Start Submission

Reading: From silent spring to silent night: Agrochemicals and the anthropocene


A- A+
Alt. Display


From silent spring to silent night: Agrochemicals and the anthropocene


Tyrone B. Hayes ,

Laboratory for Integrative Studies in Amphibian Biology, Group in Endocrinology, Molecular Toxicology, Energy and Resources Group, Museum of Vertebrate Zoology, and Department of Integrative Biology, University of California, Berkeley, CA, US
X close

Martin Hansen

Laboratory for Integrative Studies in Amphibian Biology, Group in Endocrinology, Molecular Toxicology, Energy and Resources Group, Museum of Vertebrate Zoology, and Department of Integrative Biology, University of California, Berkeley, CA, US; and Aarhus University, Faculty of Science and Technology, Department of Environmental Science, Section of Environmental Chemistry and Toxicology, Laboratory for Environmental Endocrine Disruptors, 4000-Roskilde, DK
X close


We are now living in the Anthropocene, the first time in Earth’s history when synthetic chemicals—created by humans—are damaging the planet and contributing to a major loss of biodiversity. Pesticides are a particular problem in this regard. Agricultural practices changed dramatically following World War II. Methods for the production of nitrogen for manufacturing explosives were adapted for use as fertilizer in agriculture. Further, chemicals used to combat insect vectors for disease during World War II were adapted for the control of insect pests in agriculture. Eventually, herbicides used as defoliants to destroy food supplies and aid in combating soldiers using forests as cover, were customized to control weeds in agriculture. The heavy use of pesticides in agriculture has resulted in global exposure to these chemicals. Travelling through water, air, and in migrating animals, pesticides can be found in drinking water reservoirs, the atmosphere, on mountain tops, and even in remote areas in the Arctic where they are not used. The widespread exposure to agrichemicals has altered landscapes and ecosystems around the world. In addition to directly killing non-target organisms, target and non-target organisms can evolve resistance to pesticides, resulting in altered gene pools. Further, emerging data demonstrate that even low— formerly considered “non-toxic”— concentrations of pesticides can impact health, physiology, reproduction and development through endocrine-disrupting effects. The development of genetically modified crops that are resistant to pesticides and that produce pesticides themselves, and the financial incentive of the chemical companies that produce the genetically modified organisms (GMOs) have resulted in increased pesticide applications. There is probably no place on earth that is not affected by pesticides. The solution is the adoption of integrated pest management practices that reduce the use of chemical pesticides and fertilizers in agriculture and the decoupling of the agrichemical and seed industry.

Knowledge Domain: Sustainability Transitions
How to Cite: Hayes, T.B. and Hansen, M., 2017. From silent spring to silent night: Agrochemicals and the anthropocene. Elem Sci Anth, 5, p.57. DOI:
 Published on 29 Sep 2017
 Accepted on 24 Aug 2017            Submitted on 21 Sep 2016
Domain Editor-in-Chief: Anne R. Kapuscinski; Dartmouth, US
Associate Editor: Kim A. Locke; Dartmouth, US
Guest Editor: Anthony Barnosky; Stanford University, US

1. Introduction

We are in the Anthropocene and likely experiencing the Earth’s sixth mass extinction. The current mass extinction is the first to be caused by a single species, humans. Chemical contaminants in the environment, especially pesticides, are playing an important role in the Anthropocene. Over 85,000 synthetic chemicals exist today (USEPA, 2014, USEPA, 2016b, NIH, 2014, USEPA). These chemicals represent compounds used in every aspect of life and can end up in the environment (air, water, soil, and biological tissues). Even personal care products and personal use chemicals (such as pharmaceuticals) can persist in the environment (Yamamoto et al., 2009, D’Abrosca et al., 2008). Although there are many sources and types of chemicals in the environment, pesticides are a significant concern because they are applied directly in the environment in large amounts, particularly by the agricultural industry. Pesticides are defined by the U.S. Environmental Protection Agency as: “any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest; any substance or mixture of substances intended for use as a plant regulator, defoliant, or desiccant, or any nitrogen stabilizer” (USEPA, 2015c) and include herbicides, fungicides, nematocides, rodenticides, and agents to kill bacteria and viruses. Over the last 75 years, the use of pesticides has increased dramatically and continues to increase. Approximately 2.3 billion kilograms of pesticides are used annually worldwide with the U.S. alone accounting for over 0.45 billion kilograms per year (Alavanja, 2009, USEPA, 2017, USEPA, 2015b). Here, we review evidence that pesticides have altered the gene pool of target organisms and through direct toxic effects and so-called “low dose” effects (effects below concentrations considered safe) have altered landscapes and populations globally (references herein). The impact of these chemicals on non-target organisms and their impact on environmental health and public health are a growing concern. Here, we address: 1) the widespread use, transport, and persistence of pesticides in the environment; 2) growing concerns regarding low-dose effects of pesticides as endocrine disruptors: effects on reproduction, development, disease transmission, and epigenetic, trans-generational and other long-term effects; and 3) the trajectory for pesticide use and solutions to these concerns.

2. History of chemical use in agriculture

Agriculture has been a part of human civilization for over 10,000 years (IUPAC, 2010). Although pesticides have been used in agriculture for over 4,500 years, the early use of pesticides was mainly restricted to inorganic compounds, such as sulfur and copper, or even extracts from plants (e.g. pyrethrin). In the mid 1900’s new synthetic pesticides were developed, however (IUPAC, 2010). For example, Dichloro-diphenyl-trichloroethane (DDT), first synthesized in 1874, is one of the most well-known synthetic insecticides. DDT was prized because it was inexpensive, not water soluble (so it did not wash away), persistent (so it did not have to be applied frequently), and a broad spectrum pesticide. DDT’s effectiveness was discovered during World War II (WWII) where it was used to combat ticks and fleas that transmitted typhus in Europe. At the end of the war, DDT was used in agriculture (USEPA, 2015a), where over 36 million kilograms per year were produced and used worldwide. Likewise, the popular herbicide, 2,4-D was discovered during war time (Peterson et al., 2016). As one of the active components of “Agent Orange”, 2,4-D was used as an herbicide to destroy food crops to starve people (such as during the Vietnam war), then also found a purpose in agriculture (as an herbicide to control weeds) following wartime. Other widespread pesticides were developed around this time as well, including the widely used herbicides atrazine (introduced in 1958) and glyphosate, among others.

In the US, pesticides are regulated by the U.S. Environmental Protection Agency, which is responsible for assessing the safety of pesticides and the risk that they pose to the environment and to human health. The U.S. EPA came into existence during the Nixon administration in 1972. Prior to the EPA, the Food and Drug Administration (FDA) and the U.S. Department of Agriculture (USDA) were responsible for evaluating and assessing the safety of pesticides, but there was little regulation. The Federal Insecticide Fungicide and Rodenticide Act (FIFRA) of 1947 called for stricter regulations, but this mandate did not become a reality until the establishment of the U.S. EPA 25 years later. Thus, many of the pesticides used in agriculture today were never adequately tested before registration and widespread use. This history left the U.S. EPA with over 80,000 chemicals to evaluate, including (according to the U.S. EPA) 1,235 active ingredients used to formulate 16,810 pesticide products, represented by 46,147 distributed products. In addition, many of the problems associated with pesticide over-use, such as endocrine-disrupting effects at low concentrations (considered non-toxic by traditional toxicological standards) have only been recognized in the last two decades (Vandenberg et al., 2013, Vandenberg et al., 2012). So even chemicals that have been evaluated and reviewed and that are considered “safe” may cause previously unrecognized harm in the environment to a diversity of living organisms.

The size of the threat of pesticides is realized when one considers the sheer numbers of active ingredients, formulations, and environmental mixtures that have not been adequately examined or assessed. Further, the widespread use, persistence, transport and bioaccumulation in wildlife and food chain bio-magnification of these chemicals make the likely impact even more troubling.

3. Extent of chemical contamination

3.a. Wide spread use

An estimated 2.3 billion kilograms of active pesticide ingredients are used annually worldwide, with the U.S. using 22% of the total (USEPA, 2017). As an example, for three decades, DDT was heavily applied in agricultural and in public and military settings against insects to control insect-borne diseases. After 1972, many countries restricted the use of DDT and later the Stockholm Convention on Persistent Organic Pollutants in 2010 restricted its use to vector control of mosquitos (Anonymous, 2010). Still, however, the current global production volume of DDT is estimated at 3.3 million kilograms (Stockholm Covention 2010). Similarly, glyphosate, atrazine and 2,4-D are the three most applied herbicides, and also produced in the highest volumes with an estimated combined annual use of approximately 135 million kilograms in the U.S. alone (USEPA, 2017). Atrazine is used in the agricultural sector, 2,4-D in agriculture and in the non-agricultural sector (home, gardens and industry), and glyphosate in both (USEPA, 2017).

3.b. Persistence in the environment

In addition to the concerns associated with the sheer volume of pesticide ingredients produced and used each year, the persistence in the environment raises more concern. Even though environmental persistence is assessed prior to an approval, pesticides, their residues, and transformation products are omnipresent in groundwater, air, and sediment (Fenner et al., 2013). Pesticide removal processes include transport (e.g. atmospheric volatilization and deposition), abiotic processes (e.g. adsorption and photolysis), and biotic processes (e.g. by microorganisms and plants). Soil bacteria and fungi have proven most promising to degrade DDT, but still DDT and its transformation residues, such as DDE and DDD, persist in the environment (Yang et al., 2013, Turgut et al., 2012, Yang et al., 2012), animals (Beyer and Krynitsky, 1989), and in humans (Saoudi et al., 2014) for decades, if not longer. Similarly, habituated native microorganisms are key for removal processes of the three most popular herbicides, however degradation half-lives range from weeks to years (Borggaard and Gimsing, 2008, Boivin et al., 2005). The metabolites generated can survive environmental degradation, migrate into water supplies and exert similar or different toxicological actions (for example see (Sanderson et al., 2002)). Thus, assessing the impact of transformation products is also important.

3.c. Transport to remote locations

In addition to widespread use and persistence, pesticides are also a significant threat because they spread well beyond the point of application. Pesticides and their byproducts, such as DDT and DDE, have been transported to remote locations (Simonich and Hites, 1995) such as the Arctic (Thomas et al., 1992), and to mountain tops (Devi et al., 2015, Dockalova et al., 2015, Mast et al., 2007, Ren et al., 2014, Yang et al., 2013) via atmospheric deposition (Bailey et al., 2000, Halsall et al., 1998), ocean currents, magnification in food web and migratory animals, and even in bark of trees across the world (Bailey et al., 2000, Blais et al., 2005, Kallenborn et al., 2013). Animal migration patterns (Deshpande et al., 2016, Dorneles et al., 2015) and climatic changes (including increases in global temperatures and alterations in ocean currents) can enhance the transport of pesticides (Gong et al., 2015, Nadal et al., 2015). The three most commonly applied herbicides, atrazine, glyphosate and 2,4-D, are less susceptible to transport to remote locations due to low volatility. Nevertheless, atrazine is found in Arctic seawater and ice (Jablonowski et al., 2011, Chernyak et al., 1996) and can travel over 1000 kilometers carried on dust and transported in clouds with an estimated 0.225 million kilograms per year coming down in precipitation in the U.S. alone (Thurman and Cromwell, 2000, Mast et al., 2007).

3.d. Bioaccumulation and biomagnification

Once an organism is contaminated, pesticides can be transferred biologically (Becker et al., 1992, Blomqvist et al., 2006, Ewins et al., 1992, Furusawa and Morita, 2001, Furusawa, 2002, George et al., 2006, Kamata et al., 2009, Kamata et al., 2013, Meiser et al., 2003). Pesticide residues are likely present in every larger organism on Earth including trees (Simonich and Hites, 1995). Pesticides, especially highly lipophilic xenobiotics such as DDT and its residues, accumulate in animal tissues and biomagnify in food webs to higher trophic levels (Alexander, 1999, Woodwell et al., 1967). For example, DDT and its residues are present in Adélie penguins (Pygoscelis adeliae) (Geisz et al., 2008), Galapagos sea lions (Zalophus wolleabeki) (Alava et al., 2011b, Alava et al., 2011c), killer whales (Orcinus orca) (McHugh et al., 2007), earthworms (Aporrectodea turgida) (Beyer and Krynitsky, 1989), and bald eagles (Haliaeetus leucocephalus) (Stokstad, 2007), among others. Furthermore, pesticides can be transferred to offspring, including transport across the placenta (Adetona et al., 2013, Elserougy et al., 2013, Li et al., 2014, Perera et al., 2003, Tyagi et al., 2015) and through breast milk (Al-Saleh et al., 2012), and can be found in egg yolk in birds (Faruga et al., 2008, Furusawa and Morita, 2001), reptiles (Alava et al., 2011a), and fish (Faruga et al., 2008, Lorenzen et al., 2003).

Thus, the sheer amount of pesticides released into the environment annually, extensive transport, and persistence of these chemicals all raise concern. There is likely no habitat, geographical location, or organism that is free from pesticide exposure. Even if organisms could migrate away from the sources of contamination, the persistence in biological tissues for many pesticides and the transfer from parent to offspring, means that even individuals that are not exposed directly are still at risk.

4. Low-dose effects

4.a. Resistance

In addition to direct adverse impacts of pesticides on non-target organisms — e.g. the detrimental effects of BT corn (genetically modified to produce toxins from the bacteria Bacillus thuringiensis) on monarch and other “non-target” butterflies and moths (Lang and Otto, 2010, Perry et al., 2010) and the proposed role of neonicotinoid insecticides in honey bee declines (Chaimanee et al., 2016, Christen et al., 2016, Hladik et al., 2016, Long and Krupke, 2016), among others — pesticides can also alter the adaptive evolution, hence the genetic make-up, of target and non-target organisms. Widespread use of pesticides can lead to the evolution of resistance in target and non-target organisms. As a result of intense use of herbicides and insecticides in agriculture, many resistance organisms have evolved over the last 70 years.

Resistance to insecticides was noted as early as 1897 (Forgash, 1984), but only 12 insecticide-resistant insects were known in 1946. From 1946 to 1954 (following the increased use of pesticides after WW II), however, one to two new resistant species were discovered per year and by 1980, 428 insecticide-resistant insects and spiders were known. Sixty one percent of the resistant species were agricultural pests at this time, thus, the widespread use of insecticides in agriculture that began after WW II contributed significantly to the evolution of resistant species. In fact, of the 25 most damaging insect pests, 17 are insecticide-resistant (Forgash, 1984). Although resistance depends on both genetic and other biological factors, the application frequency, distribution, and amount of pesticide is also an important factor. Historically, the response to insecticide-resistance was to apply more chemicals more frequently and more broadly, thus hastening the evolution of resistance.

DDT-resistance in insects was one of the first documented cases of resistance. The evolution of resistance to DDT was noted as early as 1946 (Incho and Deonier, 1947, Barber et al., 1948). Although DDT was used for several reasons, its use in agriculture was responsible for hastening the evolution of resistant insects. Resistance to other insecticides has been documented, including resistance to pyrethrins and pyrethroids (Dai et al., 2015, Ishak et al., 2015). In fact, some insects develop cross-resistance to multiple insecticides, in some cases, to pesticides with unrelated mechanisms of action (Ishak et al., 2015). Although cross-resistance (where insects evolve the ability to metabolize the insecticides via P450 enzymes) is common, in many cases, multiple resistance is due to independent selection via glutathione reductase induction (Han et al., 2016, Jacquet et al., 2015, Kamita et al., 2016, Pavlidi et al., 2017, Yang et al., 2016, Clements et al., 2017). The harmful consequences of the evolution of insecticide resistance is not only manifest in the harm to crops and the use of even more insecticide (which leads to even more rapid and widespread evolution of resistance), but also seen in adverse impacts on public health, such as the progression of insecticide-resistance in insects that serve as vectors for human disease (e.g. malaria, yellow fever, dengue fever, and Zika virus) (Mulamba et al., 2014, Dang et al., 2015a, Dang et al., 2015b, Dang et al., 2015c, Dykes et al., 2015, Ishak et al., 2015, Owusu et al., 2015, Dalla Bona et al., 2016).

Likewise, intense herbicide use in agriculture has led to the evolution of herbicide-resistant weeds. The heavy use of herbicides also began post WWII. The earliest record of herbicide resistance was reported in 1957, when 2,4-D-resistant carrots were discovered (Shaner, 2014, Shaner and Beckie, 2014). 2,4-D is an herbicide that was discovered during WWII and later used as a component of Agent Orange to destroy crops of targeted populations in South East Asia. In 1968, however, widespread use of triazine herbicides (e.g. atrazine) resulted in the evolution of triazine-resistant groundsel (Senecio vulgaris) (Burgos et al., 2013, Busi et al., 2013, Shaner, 2014, Shaner and Beckie, 2014). The resistance was the result of a mutation at the target for triazine and was maternally inherited. Resistant groundsel and other triazine-resistant weeds succumbed to other herbicides, however. Concern over herbicides resistance rose, because multiple herbicide-resistance weed strains appeared. Between 1970 and 1995, at least four new triazine resistant weeds appeared per year, and by 1995, 191 herbicide-resistant weeds were identified. By 2013, over 400 herbicide-resistant weeds were described, including many with resistance to multiple herbicides (Varanasi et al., 2015, Owen et al., 2014, Shaner, 2014, Senseman and Grey, 2014). Interestingly, many of the weed species with multiple resistances are resistant as a result of alterations in the glutathione response (Cummins et al., 2013, Ma et al., 2016, Ma et al., 2013, Yu and Powles, 2014), the same mechanism that underlies cross-resistance to insecticides in insects (see references above).

In addition, Climate change increases the rate of herbicide metabolism and the frequency of herbicide resistant weeds (Matzrafi et al., 2016). To add to the concern, when mosquitos (Aedes aegypti) are exposed to herbicides (such as atrazine) as larvae, they can become insecticide resistant as adults (Jacquet et al., 2015). This species is a vector for yellow fever, dengue, and chikungumya virus. So, overuse of herbicides can lead to increased public health concerns as it renders insecticides less effective in controlling insect vectors.

4.b. Endocrine disruption

In addition to changing the genetic landscape via the evolution of resistant pests (Mulamba et al., 2014, Gellatly et al., 2015, Kudom et al., 2015, Wanjala et al., 2015) as a result of widespread heavy use, many pesticides also produce adverse effects on development, growth and reproduction at concentrations well below levels previously considered toxic. In particular, endocrine-disrupting effects have been identified in controlled laboratory studies, are correlated with effects on exposed wildlife, and are associated with adverse effects on human health (references below). Endocrine disruption can occur via a number of mechanisms, including increases or decreases in hormone production and/or hormone half-life, or via binding to hormone receptors (as agonist or antagonist), and by inhibiting, inducing, or increasing hormone action. These effects are especially concerning because endocrine-disrupting effects of pesticides can be unpredictable, due to underlying mechanisms of action that are unrelated to the mechanism by which the chemical regulates the target organism. For example, DDT kills insects by opening sodium channels in the nervous system which leads to spasms and death (Holan, 1969). DDT’s endocrine disrupting effects in vertebrates, however, are unrelated to this mechanism.

DDT is most well-known for causing eggshell-thinning in birds (Bitman et al., 1969, Burnett et al., 2013, Cecil et al., 1972, Cecil et al., 1971, Cecil et al., 1969, Holm et al., 2006). The mechanism that underlies this effect is still not completely clear, however. Early studies suggested that metabolites of DDT inhibited prostaglandin production in birds leading to decreased calcium deposition by the shell gland (Lundholm and Bartonek, 1992), even though other studies showed that ortho-para isomer of DDT (o,p’DDT) and at least one metabolite (p,p’DDD) stimulate prostaglandin production in the uterus of mammals (Juberg and Lochcaruso, 1992). More recent studies suggest that estrogenic effects of DDT lead to decreased capillaries and carbonic anhydrase expression which results in reduced calcium deposition in eggs by the shell gland in birds (Holm et al., 2006).

Also, unrelated to its mechanism of action in insects, DDT and some of its metabolites inhibit androgen action by binding to and inhibiting the androgen receptor (antagonist) (Maness et al., 1998, Zhuang et al., 2012, Song et al., 2014, Monteiro et al., 2015, Rivero et al., 2015, Wong et al., 2015). Inhibition of androgen-dependent developmental events have dramatic effects on development, including reproductive malformations in developing males and decreased reproductive behavior and function in exposed wildlife and humans (Daxenberger, 2002). Metabolites of DDT can act as estrogen agonists (mimics) as well, however (Gaido et al., 1997, Gaido et al., 2000, Miyashita et al., 2004, Hoekstra, 2006, Li et al., 2008, Naidoo et al., 2008, Katsu et al., 2010, Zhuang et al., 2012, Rivero et al., 2015). Effects are difficult to predict, because specific binding affinities of DDT and its metabolites to estrogen receptors and the ability of these compounds to activate the receptors vary between receptor types and between species (Miyagawa et al., 2014, Tohyama et al., 2015).

In addition, these dual effects of DDT and its metabolites (acting as androgen antagonists and estrogen agonists) make predicting the impact of exposure on development, physiology, reproduction and health complicated. Through its estrogenic actions, DDT and its metabolites can produce a number of effects through the estrogen receptors: ERα, ERβ, or ERγ (Zhuang et al., 2012, Pestana et al., 2015). Effects include feminization of males during developmental exposure or exposure during adulthood (Sikka and Wang, 2008). DDT metabolites also stimulate breast cancer cells in vitro (Zhuang et al., 2012) and DDT exposure is associated with breast cancer (Cohn et al., 2007, Soto and Sonnenschein, 2015). Furthermore, developmental exposure (even in utero) can affect outcomes later in life (Cohn et al., 2007). For example, DDT exposure in utero may increase the likelihood of developing breast cancer in adulthood (Cohn et al., 2007). So, measuring DDT in tissues in adulthood underestimates exposure and effects (or may not relate at all). Although the effects of DDT on breast cancer are correlational, DDT and its metabolites affect estrogen receptor-positive breast cancer cells in vitro and decrease cell proliferation and viability, but increase invasiveness (Pestana et al., 2015). These multiple effects of DDT, acting as an androgen antagonist and an estrogen agonist, also mean that exposure can produce a combination of demasculinizing and feminizing effects, depending on the timing of exposure and the mixture of metabolites, along with other pesticides present during exposure. Furthermore, the complex effects of DDT and its metabolites can cause pre-term labor by its alteration of estrogen to progesterone ratios (Longnecker et al., 2001).

DDT and its metabolites also affect the adrenal corticosteroids. Mitotane (o,p’ DDD) destroys adrenocortical tissue leading to decreased cortisol production and is, in fact, used in clinical treatments for Cushing’s disease (Komissarenko et al., 1978). Other DDT metabolites, e.g. o,p’ DDT and p,p’ DDT act as glucocorticoid antagonist to the glucocorticoid receptor (Zhang et al., 2016). In vitro o,p’ DDT, p,p’ DDT, and p,p’ DDE can all reduce expression of glucocorticoid regulated genes (Zhang et al., 2016). So DDT and its metabolites can inhibit glucocorticoids by decreasing synthesis and by directly blocking glucocorticoid action at the receptor. Given that glucocorticoids play a significant role in regulating tumor suppressor genes (An et al., 2016, Barr et al., 2009), interference with cortisol by DDT and its metabolites may be another indirect way that these compounds might influence cancer incidence. Further, although the mechanisms is still unknown, DDT also produces an effect similar to the mandibular fenestration associated with exogenous glucocorticoid exposure in amphibians (Hayes et al., 1997).

On the other hand, other studies show that DDT and its metabolites, when mixed with other pesticides, can increase glucocorticoid production: Zimmer et al. (Zimmer et al., 2011) extracted pesticide contaminants from burbots (Lota lota) exposed in the wild and then applied similar pesticides mixtures to H295R cells and examined steroidogenesis in vitro. Mixtures containing DDT increased cortisol production at low doses, and increased cortisol and estradiol at higher doses, while decreasing testosterone production. Pesticide mixtures can also increase glucocorticoid production which leads to immunosuppression and increased disease rates in amphibians (Falso et al., 2015).

DDT and its metabolites affect the thyroid axis as well. DDT and its metabolites affect thyroid action via several mechanisms: DDT and its metabolites result in hypothyroidism (Goldner et al., 2013) by decreasing thyroid stimulating hormone levels (Liu et al., 2014) (resulting in decreased circulating thyroid hormone levels (Liu et al., 2011, Tebourbi et al., 2010, Yaglova and Yaglov, 2014)), increasing thyroid hormone receptor expression in the hypothalamus (which presumably increases negative feedback and results in decreased thyroid production) (Liu et al., 2011, Liu et al., 2014, Tebourbi et al., 2010), decreasing thyroid hormone plasma binding protein levels (Liu et al., 2011, Liu et al., 2014), increasing hepatic enzymes that metabolize thyroid hormones (Liu et al., 2011, Liu et al., 2014, Tebourbi et al., 2010), decreasing enzymes that produce thyroid hormone (Liu et al., 2014), and inhibiting internalization of the TSH receptor (De Gregorio et al., 2011). Given the important role of thyroid hormones in growth, metabolism, and neural development and function, not to mention possible impediment of cross-talk mechanisms between steroid and thyroid hormones (Duarte-Guterman et al., 2014), these adverse effects are significant, especially considering that DDT and its metabolites can cross the placenta and affect developing fetuses (Li et al., 2014, Lopez-Espinosa et al., 2010, Adetona et al., 2013, Elserougy et al., 2013, Torres-Sanchez et al., 2013). DDT and its metabolites are also associated with decreased thyroid function in wildlife (Crain et al., 1997).

Likewise, herbicides can act as endocrine disrupters via mechanisms unrelated to their actions in plants and (as shown for atrazine, below) can function through many mechanisms as well. Historically, there was a false sense of safety associated with the assumption that herbicides that targeted processes specific to plants would not affect animals. This assumption has proven false. For example, atrazine kills weeds by inhibiting a protein involved in electronic transport in photosystem II in weed targets (Chereskin et al., 1984). Crop species where atrazine is used (such as corn) are resistant to atrazine due to the glutathione response (Shimabuk et al., 1971), the same mechanism associated with the evolution of resistance to herbicides in weeds. Because animals do not perform photosynthesis, it seemed that exposed animals would be unaffected by atrazine, however this is not the case. The U.S. EPA recently concluded that the herbicide, atrazine, is harmful to plants, fish, amphibians, reptiles, birds, and mammals and that harmful levels were exceeded several-fold in the environment (USEPA, 2016a). Similarly, the state of California’s Office of Environmental Health Hazzard Assessment listed atrazine and related compounds as reproductive toxins under the state’s proposition 65 (OEHHA, 2016). These decisions were based on over twenty years of studies showing that atrazine is a potent endocrine disruptor in animals, through mechanisms that are unrelated to its mode of action in plants.

Atrazine was first identified as an endocrine disruptor in studies conducted by the manufacturer, which showed that atrazine increased the incidence of mammary tumors in rats (Eldridge et al., 1999, Greiner et al., 2000, Ueda et al., 2005), potentially through its ability to increase estrogen production. Later studies showed that the mammary tumors in rats exposed to atrazine were indeed estrogen-dependent (Ueda et al., 2005). Shortly after, the mechanism by which atrazine induces aromatase and increases estrogen was shown in human cell lines (Sanderson et al., 2002, Sanderson et al., 2001, Sanderson et al., 2000, Fan et al., 2007a, Fan et al., 2007b, Suzawa and Ingraham, 2008). Atrazine inhibits a phosphodiesterase that results in increased cAMP, which in turn increases aromatase (cyp19) gene expression, and result in excess and inappropriate estrogen production. This mechanism is ubiquitous across vertebrate classes (Hayes et al., 2011), but other effects, such as decreases in androgen production and action are also observed across species (Fraites et al., 2011, Victor-Costa et al., 2010, Rey et al., 2009, Rosenberg et al., 2008, Hecker et al., 2005, Friedmann, 2002, Stoker et al., 2000, Šimic et al., 1991, Babic-Gojmerac et al., 1989, Kniewald et al., 1980, Hayes et al., 2011, Hayes et al., 2010b, Hayes et al., 2006b, Hayes et al., 2002a).

Adverse effects of atrazine on reproduction occur across vertebrates (Hayes et al., 2011). Under controlled experimental conditions, atrazine causes a decline in sperm production in fish (Moore and Waring, 1998), amphibians (Hayes et al., 2010b), reptiles (Rey et al., 2009), birds (Hussain et al., 2011), and mammals (laboratory rodents (Victor-Costa et al., 2010, Kniewald et al., 2000)) and is associated with low sperm count and decreased fertility in humans (Swan et al., 2003) exposed to atrazine at levels 24,000 times lower than levels farm workers experience (Lucas et al., 1993). These effects are all likely the result of atrazine’s inhibitory effect on androgen production and action (cited above).

The estrogenic effects of atrazine are also recognized by the mounting evidence that atrazine feminizes fish and amphibians and results in testicular oocytes in fish (Tillitt et al., 2008), amphibians (Hayes et al., 2002b, Hayes et al., 2002c), and reptiles (De Solla et al., 2006). Likely through the same mechanisms (aromatase induction), atrazine increases mammary cancer incidence (Stevens et al., 1994) and prostate disease in rodents (Stanko et al., 2010, Kniewald et al., 1978, Rayner et al., 2007). Atrazine exposure during gestation can even result in prostate disease in neonatal rodents (Stanko et al., 2010). Atrazine is also associated with breast cancer (Kettles et al., 1997) and is correlated with an 8.4 fold increase in prostate cancer incidence in men working in an atrazine production facility (Maclennan et al., 2002).

Atrazine also produces reproductive abnormalities in vertebrates under controlled laboratory conditions. For example, atrazine causes partial or complete sex reversal in fish (Tillitt et al., 2008, Suzawa and Ingraham, 2008), amphibians (Hayes et al., 2002a, Hayes et al., 2006b, Hayes et al., 2010b, Hayes et al., 2002b, Hayes et al., 2002c), and reptiles (De Solla et al., 2006). Similar effects have been documented in amphibians in the wild (Reeder et al., 1998, Hayes et al., 2002b). In addition, abnormalities in secondary sex characters (e.g. small penis) is experienced in reptiles exposed under controlled laboratory conditions (Rey et al., 2009). In humans, atrazine is likewise implicated as a cause of birth defects (Winchester et al., 2009), many of which are consistent with a decrease in androgens and/or an increase in estrogens when males are exposed in utero (Waller et al., 2010). These effects include hypospadias, cryptorchidism, and micropenis, all effects associated with a decrease in fetal androgen exposure (Gray et al., 1994, Kalfa et al., 2011, Sikka and Wang, 2008, Gray et al., 1998) or excessive fetal exposure to estrogen (Gray et al., 1998, Harrison et al., 1997, Palmer et al., 2009, Zhang et al., 2009, Agras et al., 2007, Kalfa et al., 2015, Sikka and Wang, 2008), and consistent with well-documented mechanisms and effects of atrazine across vertebrates (Hayes et al., 2011). Atrazine is also correlated with gastroschisis (Mattix et al., 2007, Waller et al., 2010) which is associated with excess estrogen production during pregnancy (Lubinsky, 2012).

Although many of the effects of atrazine are explained by its ability to induce aromatase, like DDT, atrazine acts through many other mechanisms (Hayes et al., 2011) including adverse effects on the hypothalamus, the anterior pituitary, and gonads (see references in (Hayes et al., 2011)) that involve alterations in hormone synthesis and/or secretion that appear independent of action on aromatase or androgen synthesis and action. Also atrazine affects the stress axis (Fraites et al., 2009, Laws et al., 2009), behavior (Carr et al., 2003, Rohr et al., 2003, Alvarez and Fuiman, 2005, Belloni et al., 2011, Britson and Threlkeld, 1998, Dessi-Fulgheri et al., 2007, Fraites et al., 2011, Kunze, 1989, Liu et al., 2016, Mendez et al., 2009, Neuman-Lee and Janzen, 2005, Neuman-Lee and Janzen, 2003, Rodriguez et al., 2005, Saglio and Trijasse, 1998, Walters et al., 2015, Tierney et al., 2007) and immune function (Brodkin et al., 2007, Cantemir et al., 1987, Christin et al., 2003, Filipov et al., 2005, Forson and Storfer, 2006a, Forson and Storfer, 2006b, Gendron et al., 2003, Hooghe et al., 2000, Whalen et al., 2003, Zeljezic et al., 2006, Schwab et al., 2005) in addition to its adverse effects on reproduction. Thus, given the many mechanisms by which atrazine can act as an endocrine disruptor, there can be multiple developmental and physiological cascade effects which can be difficult to predict. Given the ubiquity of atrazine contamination and the severity of effects at low ecologically relevant doses, these findings are a significant concern for both wildlife and humans.

Less information is known about the other two heavily used herbicides 2,4-D and glyphosate. Like atrazine, glyphosate was considered safe because its herbicidal mechanism of action was through a pathway not present in vertebrates (Myers et al., 2016). Recently designated a probable carcinogen (Guyton et al., 2015), glyphosate is also a potent endocrine disruptor (Gasnier et al., 2009, Mesnage et al., 2015). Glyphosate alters the structure of the ovaries and affects expression of SF1, a gene important in sex differentiation and regulation of sex steroid production (Armiliato et al., 2014), which is also affected by atrazine (Fan et al., 2007c, Fan et al., 2007a). Glyphosate alters aromatase expression in testes and adversely affects sperm production (Cassault-Meyer et al., 2014). Glyphosate also decreases male fertility by inhibiting gonadotropin expression (Romano et al., 2012), again similar to effects of atrazine. Furthermore, glyphosate causes a decrease in male fertility because it causes necrosis and apoptosis in testicular cells and a decrease in testosterone (Clair et al., 2012, Romano et al., 2010). Glyphosate also alters estrogen-regulated genes (Hokanson et al., 2007) and stimulates breast cancer cells via the estrogen receptor (Thongprakaisang et al., 2013). Data regarding endocrine disrupting effects of 2,4-D are lacking. The studies simply have not been conducted (or published).

Fungicides are also potentially important endocrine disruptors, but have not been adequately addressed in the literature. Miconazole and related fungicides disrupt steroidogenesis, however, and can reduce both androgen and estrogen production (Kjaerstad et al., 2010, Trosken et al., 2006). The fungicide tebuconazole also decreased estrogen production and resulted in elevated androgens in the gonads and plasma of an amphibian Xenopus laevis (Poulsen et al., 2015). Another fungicide, vinclozolin (Benachour et al., 2007, Gray et al., 1994, Hecker et al., 2006, Makynen et al., 2000, Rivers et al., 2016, Sanderson et al., 2002, Thibaut and Porte, 2004, Uzumcu et al., 2004) may act as a direct antagonist to the androgen receptor and interfere with reproductive development and function in exposed males. This field of study is worthy of more attention.

4.c. Transgenerational effects

In addition to the effects associated with direct exposure, pesticides can have transgenerational effects. For example, atrazine retards growth and development in rodents for two generations even without exposure to F2 (Rayner et al., 2005, Rayner et al., 2004, Rayner et al., 2007, Stanko et al., 2007). This effect across two generations is the result of impaired mammary development in females exposed in utero. The resulting F1 are unable to provide adequate milk to the F2 generation which then suffer from retarded growth and development. In addition, there is a growing concern for epigenetic effects in exposed organisms. For example, altered gene expression and effects on development and physiology after the maternal or even paternal parent is exposed to a chemical, can be observed in the next generation even though the individuals in the next generation are not exposed themselves (Heindel et al., 2006, Nilsson and Skinner, 2015, Perera and Herbstman, 2011, Skinner, 2011, Stuppia et al., 2015, Vandegehuchte and Janssen, 2011). For example, atrazine inhibits meiosis in mice, but also affects gene expression in ways that can be inherited through the germline in the next generation (Gely-Pernot et al., 2015). Similarly, DDT exposure can result in transgenerational effects (Skinner et al., 2013b, Kabasenche and Skinner, 2014, Song et al., 2014) and at least two fungicides can have transgenerational effects (Skinner, 2011, Skinner et al., 2013a, Skinner et al., 2011, Skinner et al., 2014). These observations create an even greater concern. Not only are pesticides widespread, effectively ubiquitous, but even after their use is restricted, they can persist in the environment for decades if not longer. Furthermore, even after they no longer persist, effects can occur across generations even without direct exposure.

5. The future and solutions

Rachel Carson warned in Silent Spring (Carson, 1962) that the decline of birds (primarily due to DDT-exposure) was a warning of environmental collapse and that human health was intricately tied to environmental health. Extinction rates have increased continuously over the last 100 years. The loss is exemplified by amphibians, a vertebrate class that survived the last four mass extinctions. As much as 70% of all amphibian species are threatened globally (Alford and Richards, 1999, Blaustein and Wake, 1990, Vredenburg et al., 2008, Wake and Vredenburg, 2008). This sixth mass extinction, experienced in the Anthropocene (Waters et al., 2016, Williams et al., 2016, Zalasiewicz et al., 2015, Barnosky, 2014, Barnosky et al., 2011, Wake and Vredenburg, 2008), is inarguably due to human activity. While habitat loss is surely the most direct cause of amphibian declines (and other animals and plants), environmental contaminants, especially pesticides, which contaminate the remaining refuges in degrading habitats and remote areas where many species persist, are key factors in declines (Hayes et al., 2010a, Lenhardt et al., 2015, Wagner et al., 2014, Bruhl et al., 2013, Hayes et al., 2006a, Hayes, 1997). Even in cases where disease (Berger et al., 1998, Bosch et al., 2007, Bovero et al., 2008, Briggs et al., 2005, Fellers et al., 2007, Fellers et al., 2001, Frias-Alvarez et al., 2008, Garner et al., 2005, Goldberg et al., 2007, Green and Dodd, 2007) and invasive species (which in many cases introduce pathogens) (Silvano and Segalla, 2005, Woodhams et al., 2006) directly impact amphibian populations, the immunosuppressive effects of pesticides play a synergistic role as does climate change (Bosch et al., 2007, Rohr et al., 2003, Hayes et al., 2006a). These interactions are very important, because there is no single cause for amphibian decline. Likewise, several interactions between changes associated with the Anthropocene and pesticides will inevitably result in collapse if not mitigated: Climate change is increasing the development and evolution of resistance to herbicides and likely insecticides (Matzrafi et al., 2016), increased use of pesticides (in response) will increase the number of resistant pests, increased pesticide use will exacerbate the damage, resulting in more resistance weed species which will decrease productivity and more resistant insects which will both decrease crop yields and increase the spread of vector-borne diseases.

It is not clear if lessons were learned from our Silent Spring (bird decline) and likely our Silent Night (amphibian decline) is occurring because of many of the same concerns and practices (increasing pesticide use) addressed by Carson. Now, there is virtually no habitat or organism that is free from pesticide exposure or effects of pesticides. It is clear that increasing pesticide applications (sheer volume and number of active ingredients) increases the evolution of resistance (and ultimately render the active ingredients ineffective) and increases the widespread low-level contamination that leads to endocrine disruption and transgenerational effects.

Despite lessons from over-use of pesticides (e.g. more is not better), the current genetically modified organism (GMO) crop strategy rapidly moves us towards increased pesticide applications and more widespread use, as more crop species are rendered pesticide-resistant. The production of GMO crops has increased and will continue to increase the use of pesticides, in particular, herbicides. Although the earliest promise of GMO technology was to develop drought resistant (Hanson et al., 1994, Newton et al., 1991) or frost resistant crops (Jain and Pehu, 1992, Nichols et al., 1992), to increase yields, to increase nutritional value of the crop (Burkhardt et al., 1997, Chopra and Vageeshbabu, 1996, George and Delumen, 1991), or to decrease insecticide applications into the environment with the use of BT crops (Peferoen, 1997) the strategy has changed. In fact GMO technology has increased and will continue to increase pesticide use and applications. For example, corn and soy are the top two crops in the U.S. and the number one and sixth (respectively) most planted crops in the world. At present, 80–90% of all corn and soy planted in the U.S. are glyphosate resistant (“Roundup-ready”) crops (Dill, 2005, Dill et al., 2008) and, more GMO crops are being developed with the use of “stacking” where plants are rendered resistant or tolerant to more than one herbicide. These herbicide resistant varieties will permit (and require) the use of even more herbicides (see the case for glyphosate (Benbrook, 2016)). As Dill concluded in 2008, regarding glyphosate resistant crops (GRCs): “GRCs represent one of the more rapidly adopted weed management technologies in recent history. Current use patterns would indicate that GRCs will likely continue to be a popular weed management choice that may also include the use of other herbicides to complement glyphosate. Stacking with other biotechnology traits will also give farmers the benefits and convenience of multiple pest control and quality trait technologies within a single seed.” (Dill et al., 2008). Thus, all of the problems associated with heavy pesticide use (evolution of resistant weeds, endocrine-disrupting effects, carcinogenicity, transgenerational effects, etc.), will become even more widespread and problematic.

In addition, since Silent Spring, science has uncovered many of the mechanisms of action on non-target organisms, yet manufacturers and regulators seem to ignore this new information. The manufacturers (and the scientists that support them) have even been accused of misreporting science (Rohr et al., 2009, Hayes, 2004, Sass and Colangelo, 2006) or misrepresenting science (Hakim, 2017) and released chemicals with the knowledge that they are harmful. For example, after a ban on atrazine by the European Union in 2003 (Sass and Colangelo, 2006), an almost chemically identical triazine herbicide, terbuthylazine was approved for use in Europe, even though the manufacturer had knowledge that it had even greater adverse effects than atrazine. The manufacturer wrote, regarding the herbicide terbuthylazine (TBA), “TBA may be a bit more potent than atrazine, lower doses cause same effects” and commented that terbuthylazine caused an “increase in mammary tumors” and an “increase in testicular tumors” (Syngenta, 2004). In addition, terbuthylazine can persist in soils three times as long as atrazine (Stipicevic et al., 2015). The U.S. EPA seems complicit in accepting the manufacturers’ misrepresentation of data: “It is unfortunate but not uncommon for registrants to ‘sit’ on data that may be considered adverse to the public’s perception of their products…science can be manipulated to serve certain agendas. All you can do is practice suspended disbelief.” (Tom Steeger, U.S. Environmental Protection Agency, personal communication (USEPA, 2003)) and accept that chemicals cause harm: “a monetary value is assigned to disease, impairments, and shortened lives and weighed against the benefits of keeping a chemical in use” (Aviv, 2014). The problem is that the cost of these chemicals is paid by wildlife and individuals from low income and minority populations, while the benefits are reaped by others. Many health disparities between minority populations (African Americans and Hispanic Americans) and Caucasians in the U.S. are likely related to differential exposure to environmental factors (Bonner et al., 2005, DeLancey et al., 2008, Demicheli et al., 2007, Gatto et al., 2007, Gerend and Pai, 2008, Jones, 1989, Lantz et al., 2006, Menashe et al., 2009, Sarker et al., 2007). The impact on human health is manifested both by the effects of direct exposure (e.g. cancer, impaired fertility, birth defects etc.) and by the increase in pesticide-resistant insect vectors for human diseases.

Finally, at the heart of the problem is the intertwining of the chemical industry and the seed industry. An overwhelming percentage of the seeds used in agriculture are distributed by six chemical companies (Howard 2009). Thus, the financial incentive to generate pesticide resistant crops (or chemically dependent agriculture) is driving the increased use of chemical pesticides. This strategy is in direct opposition to an integrated pest management (IPM) approach, which first emerged under the Nixon administration. Completely eradicating pests is usually unrealistic and certainly not possible without harming other non-pest species. IPM practices (which may incorporate chemical control methods), instead seeks to reduce yield loss to an economically acceptable level and limit damage to the environment by chemical practices. The increased use of GMO technology to produce crops that require pesticide application will continue to limit the ability to use an IPM approach. The solution is to decouple the seed industry and the pesticide industry (a regulatory ruling to require the separation of the chemical industry and seed industry) and to provide incentives to growers to use less and fewer chemical pesticides. This is the only way to avoid more widespread damage due to overuse of pesticides.

Funding information

Hayes’ research program is supported by funding from the Kapor Foundation, the Ceres Foundation, Beyond Pesticides, and the office of the Executive Vice Chancellor and Provost of UCB.

Competing interests

Hayes has served as a consultant to Ecorisk Inc, Novartis, and Syngenta. Hayes’ research has been supported in the past by Ecorisk, Novartis, and Syngenta and is currently supported by the Ceres Foundation and Beyond Pesticides.

Author contributions

Hayes wrote the majority of the manuscript with contributions and edits from Hansen.


  1. Adetona O, Horton K, Sjodin A, Jones R, Hall DB, Aguillar-Villalobos M, Cassidy BE, Vena JE, Needham LL and Naeher LP 2013. Concentrations of select persistent organic pollutants across pregnancy trimesters in maternal and in cord serum in Trujillo, Peru. Chemosphere 91: 1426–1433, DOI: 

  2. Agras K, Willingham E, Shiroyanagi Y, Minasi P and Baskin LS 2007. Estrogen receptor-alpha and beta are differentially distributed, expressed and activated in the fetal genital tubercle. Journal of Urology 177: 2386–2392, DOI: 

  3. Alava JJ, Keller JM, Wyneken J, Crowder L, Scott G and Kucklick JR 2011a. Geographical variation of persistent organic pollutants in eggs of threatened loggerhead sea turtles (Caretta caretta) from southeastern United States. Environmental Toxicology and Chemistry 30: 1677–1688, DOI: 

  4. Alava JJ, Ross PS, Ikonomou MG, Cruz M, Jimenez-Uzcategui G, Dubetz C, Salazar S, Costa DP, Villegas-Amtmann S, Howorth P and Gobas F 2011b. DDT in Endangered Galapagos sea lions (Zalophus wollebaeki). Marine Pollution Bulletin 62: 660–671, DOI: 

  5. Alava JJ, Salazar S, Cruz M, Jimenez-Uzcategui G, Villegas-Amtmann S, Paez-Rosas D, Costa DP, Ross PS, Ikonomou MG and Gobas F 2011c. DDT strikes back: Galapagos sea lions face increasing health risks. Ambio 40: 425–430, DOI: 

  6. Alavanja M 2009. Pesticides use and exposure extensive worldwide. Reviews on Environmental Health 24: 303–309, DOI: 

  7. Alexander DE 1999. Environmental Geology; Encyclopedia of Earth Science In: Springer Netherlands: Dordrecht.  

  8. Alford RA and Richards SJ 1999. Global amphibian declines: a problem in applied ecology. Annu. Rev. Ecol. Syst 30: 133–165, DOI: 

  9. Al-Saleh I, Al-Doush I, Alsabbaheen A, Mohamed GED and Rabbah A 2012. Levels of DDT and its metabolites in placenta, maternal and cord blood and their potential influence on neonatal anthropometric measures. Science of the Total Environment 416: 62–74, DOI: 

  10. Alvarez MD and Fuiman LA 2005. Environmental levels of atrazine and its degradation products impair survival skills and growth of red drum larvae. Aquatic Toxicology 74: 229–241, DOI: 

  11. An BC, Jung NK, Park CY, Oh IJ, Choi YD, Park JI and Lee SW 2016. Epigenetic and glucocorticoid receptor-mediated regulation of glutathione peroxidase 3 in lung cancer cells. Molecules and Cells 39: 631–638, DOI: 

  12. Armiliato N, Ammar D, Nezzi L, Straliotto M, Muller YMR and Nazari EM 2014. Changes in Ultrastructure and Expression of Steroidogenic Factor-1 in Ovaries of Zebrafish Danio rerio Exposed to Glyphosate. Journal of Toxicology and Environmental Health-Part a-Current Issues 77: 405–414.  

  13. Aviv R 2014. A Valuable reputation. The New Yorker,  

  14. Babic-Gojmerac T, Kniewald Z and Kniewald J 1989. Testosterone metabolism in neuroendocrine organs in male rats under atrazine and deethylatrazine influence. Steroid Biochem 33: 141–146.  

  15. Bailey R, Barrie LA, Halsall CJ, Fellin P and Muir DCG 2000. Atmospheric organochlorine pesticides in the western Canadian Arctic: Evidence of transpacific transport. Journal of Geophysical Research-Atmospheres 105: 11805–11811, DOI: 

  16. Barber GW, Starnes O and Starnes EB 1948. Resistance of house flies to insecticides. Soap and sanitary chemicals 24: 120–120.  

  17. Barnosky AD 2014. Dodging Extinction: Power, Food, Money, and the Future of Life on Earth,  

  18. Barnosky AD, Matzke N, Tomiya S, Wogan GOU, Swartz B, Quental TB, Marshall C, Mcguire JL, Lindsey EL, Maguire KC, Mersey B and Ferrer EA 2011. Has the Earth’s sixth mass extinction already arrived?. Nature 471: 51–57, DOI: 

  19. Barr FD, Krohmer LJ, Hamilton JW and Sheldon LA 2009. Disruption of Histone Modification and CARM1 recruitment by arsenic represses transcription at glucocorticoid receptor-regulated promoters. Plos One 4DOI: 

  20. Becker PH, Heidmann WA, Buthe A, Frank D and Koepff C 1992. Chemical residues in eggs of birds from the southern coast of the North Sea-trends 1981–1990. Journal Fur Ornithologie 133: 109–124, DOI: 

  21. Belloni V, Dessi-Fulgheri F, Zaccaroni M, Di Consiglio E, De Angelis G, Testai E, Santochirico M, Alleva E and Santucci D 2011. Early exposure to low doses of atrazine affects behavior in juvenile and adult CD1 mice. Toxicology 279: 19–26, DOI: 

  22. Benachour N, Moslemi S, Sipahutar H and Seralini G-E 2007. Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination. Toxicology and Applied Pharmacology 222: 129–140, DOI: 

  23. Benbrook CM 2016. Trends in the use of glyphosate herbicide in the U.S. and globally. Environmental Sciences Europe 28 

  24. Berger L, Speare R, Daszak P, Green D and Cunningham A 1998. Chytridiomycosis causes amphibian mortality associated with population declines in the rain forests of Australia and Central America. Proc. Natl. Acad. Sci. USA 95: 9031–9036, DOI: 

  25. Beyer WN and Krynitsky AJ 1989. Long-term persistence of dieldrin, DDT and heptachlor epoxide in earthworms. Ambio 18: 271–273.  

  26. Bitman J, Cecil HC, Harris SJ and Fries GF 1969. DDT induces a decrease in eggshell calcium. Nature 224: 44–46, DOI: 

  27. Blais JM, Kimpe LE, Mcmahon D, Keatley BE, Mallory ML, Douglas MSV and Smol JP 2005. Tracing contaminants with delta N-15 measurements – Response. Science 310: 443–443, DOI: 

  28. Blaustein AR and Wake DB 1990. Amphibian declines: Judging stability, persistence and susceptibility of populations to local and global extinction. Trends Ecol. Evol 5: 203–204, DOI: 

  29. Blomqvist A, Berg C, Holm L, Brandt I, Ridderstrale Y and Brunstrom B 2006. Defective reproductive organ morphology and function in domestic rooster embryonically exposed to o,p’-DDT or ethynylestradiol. Biology of Reproduction 74: 481–486, DOI: 

  30. Boivin A, Amellal S, Schiavon M and Van Genuchten MT 2005. 2,4-Dichlorophenoxyacetic acid (2,4-D) sorption and degradation dynamics in three agricultural soils. Environmental Pollution 138: 92–99, DOI: 

  31. Bonner MR, Lee WJ, Sandler DA, Hoppin JA, Dosemeci M and Alavanja MCR 2005. Occupational exposure to carbofuran and the incidence of cancer in the Agricultural Health Study. Environmental Health Perspectives 113: 285–289, DOI: 

  32. Borggaard OK and Gimsing AL 2008. Fate of glyphosate in soil and the possibility of leaching to ground and surface waters: a review. Pest Management Science 64: 441–456, DOI: 

  33. Bosch J, Carrascal LM, Duran L, Walker S and Fisher MC 2007. Climate change and outbreaks of amphibian chytridiomycosis in a montane area of Central Spain; is there a link?. Proceedings of the Royal Society Biological Sciences Series B 274: 253–260, DOI: 

  34. Bovero S, Sotgiu G, Angelini C, Doglio S, Gazzaniga E, Cunningham AA and Garner TWJ 2008. Detection of chytridiomycosis caused by Batrachochytrium dendrobatidis in the endangered sardinian newt (Euproctus platycephalus) in Southern Sardinia, Italy. Journal of Wildlife Diseases 44: 712–715, DOI: 

  35. Briggs CJ, Vredenburg VT, Knapp RA and Rachowicz LJ 2005. Investigating the population-level effects of chytridiomycosis: An emerging infectious disease of amphibians. Ecology 86: 3149–3159, DOI: 

  36. Britson C and Threlkeld S 1998. Abundance, Metamorphosis, developmental, and behavioral abnormalities in Hyla chrysoscelis tadpoles following exposure to three agrichemicals and methyl mercury in outdoor mesochosms. Bull. Environ. Contam. Toxicol 61: 154–161, DOI: 

  37. Brodkin M, Madhoun H, Muthuramanan R and Itzick V 2007. Atrazine is an immune disruptor in adult northern leopard frogs (Rana pipiens). Environ. Toxicol. Chem 26: 80–84, DOI: 

  38. Bruhl CA, Schmidt T, Pieper S and Alscher A 2013. Terrestrial pesticide exposure of amphibians: An underestimated cause of global decline?. Scientific Reports 3DOI: 

  39. Burgos NR, Tranel PJ, Streibig JC, Davis VM, Shaner D, Norsworthy JK and Ritz C 2013. Review: Confirmation of Resistance to Herbicides and Evaluation of Resistance Levels. Weed Science 61: 4–20, DOI: 

  40. Burkhardt PK, Beyer P, Wunn J, Kloti A, Armstrong GA, Schledz M, Vonlintig J and Potrykus I 1997. Transgenic rice (Oryza sativa) endosperm expressing daffodil (Narcissus pseudonarcissus) phytoene synthase accumulates phytoene, a key intermediate of provitamin A biosynthesis. Plant Journal 11: 1071–1078, DOI: 

  41. Burnett LJ, Sorenson KJ, Brandt J, Sandhaus EA, Ciani D, Clark M, David C, Theule J, Kasielke S and Risebrough RW 2013. Eggshell thinning and depressed hatching success of California condors reintroduced to central California. Condor 115: 477–491, DOI: 

  42. Busi R, Vila-Aiub MM, Beckie HJ, Gaines TA, Goggin DE, Kaundun SS, Lacoste M, Neve P, Nissen SJ, Norsworthy JK, Renton M, Shaner DL, Tranel PJ, Wright T, Yu Q and Powles SB 2013. Herbicide-resistant weeds: from research and knowledge to future needs. Evolutionary Applications 6: 1218–1221, DOI: 

  43. Cantemir C, Cozmei C, Scutaru B, Nicoara S and Carasevici E 1987. p53 Protein expression in peripheral lymphocytes from atrazine chronically intoxicated rats. Toxicol. Letters 93: 87–94, DOI: 

  44. Carr J, Gentles A, Smith E, Goleman W, Urquidi L, Thuett K, Kendall R, Giesy J, Gross T, Solomon K and Van Der Kraak G 2003. Response of larval Xenopus laevis to atrazine: Assessment of growth, metamorphosis, and gonadal and laryngeal morphology. Environ. Toxicol. Chem 22: 396–405, DOI: 

  45. Carson R 1962. Silent Spring. Boston, MA: Houghton Mifflin.  

  46. Cassault-Meyer E, Gress S, Seralini G-E and Galeraud-Denis I 2014. An acute exposure to glyphosate-based herbicide alters aromatase levels in testis and sperm nuclear quality. Environmental Toxicology and Pharmacology 38: 131–140, DOI: 

  47. Cecil HC, Bitman J, Fries GF, Denton CA, Lillie RJ and Harris SJ 1972. Dietary p,p’-DDT, o,p’DDT or p,p’-DDE and changes in egg-shell characteristics and pesticide accumulation in egg contents and body fat of caged white leghorns. Poultry Science 51: 130–139.  

  48. Cecil HC, Bitman J and Harris SJ 1971. Effects of dietary p,p’-DDT and p,p’DDE on egg production and egg shell characteristis of Japanese quail receiving and adequate calcium diet. Poultry Science 50: 657–659, DOI: 

  49. Cecil HC, Bitman J, Harris SJ and Fries GF 1969. DDT-induced decrease in egg shell calcium. Poultry Science 48: 1794. 

  50. Chaimanee V, Evans JD, Chen YP, Jackson C and Pettis JS 2016. Sperm viability and gene expression in honey bee queens (Apis mellifera) following exposure to the neonicotinoid insecticide imidacloprid and the organophosphate acaricide coumaphos. Journal of Insect Physiology 89: 1–8, DOI: 

  51. Chereskin BM, Clement-Metral JD and Gantt E 1984. Atrazine Inhibition of oxygen evolution in a purified photosystem II particle from Porphyridium cruentumPlant Physiology 75: 90–90.  

  52. Chernyak SM, Rice CP and Mcconnell LL 1996. Evidence of currently used pesticides in air, ice, fog, seawater and surface microlayer in the Bering and Chukchi seas. Marine Pollution Bulletin 32: 410–419, DOI: 

  53. Chopra VL and Vageeshbabu HS 1996. Metabolic engineering of plant lipids. Journal of Plant Biochemistry and Biotechnology 5: 63–68, DOI: 

  54. Christen V, Mittner F and Fent K 2016. Molecular Effects of Neonicotinoids in Honey Bees (Apis mellifera). Environmental Science & Technology 50: 4071–4081, DOI: 

  55. Christin MS, Gendron AD, Brousseau P, Menard L, Marcogliese DJ, Cyr D, Ruby S and Fournier M 2003. Effects of agricultural pesticides on the immune system of Rana pipiens and on its resistance to parasitic infection. Environmental Toxicology and Chemistry 22: 1127–1133, DOI: 

  56. Clair E, Mesnage R, Travert C and Seralini G-E 2012. A glyphosate-based herbicide induces necrosis and apoptosis in mature rat testicular cells in vitro, and testosterone decrease at lower levels. Toxicology in Vitro 26: 269–279, DOI: 

  57. Clements J, Schoville S, Peterson N, Huseth AS, Lan Q and Groves RL 2017. RNA interference of three up-regulated transcripts associated with insecticide resistance in an imidacloprid resistant population of Leptinotarsa decemlineataPesticide Biochemistry and Physiology 135: 35–40, DOI: 

  58. Cohn BA, Wolff MS, Cirillo PM and Sholtz RI 2007. DDT and breast cancer in young women: new date on the significance of age at exposure. Environmental Health Perspectives 115: 1406–1414, DOI: 

  59. Crain D, Guillette LJ, Rooney AA and Pickford D 1997. Alterations in steroidogenesis in alligators (Alligator mississippiensis) exposed naturally and experimentally to environmental contaminants. Environ. Health Perspect 105: 528–533, DOI: 

  60. Cummins I, Wortley DJ, Sabbadin F, He ZS, Coxon CR, Straker HE, Sellars JD, Knight K, Edwards L, Hughes D, Kaundun SS, Hutchings SJ, Steel PG and Edwards R 2013. Key role for a glutathione transferase in multiple-herbicide resistance in grass weeds. Proceedings of the National Academy of Sciences of the United States of America 110: 5812–5817, DOI: 

  61. D’Abrosca B, Fiorentino A, Izzo A, Cefarelli G, Pascarella MT, Uzzo P and Monaco P 2008. Phytotoxicity evaluation of five pharmaceutical pollutants detected in surface water on germination and growth of cultivated and spontaneous plants. Journal of Environmental Science and Health Part a-Toxic/Hazardous Substances & Environmental Engineering 43: 285–294.  

  62. Dai Y, Huang X, Cheng P, Liu L, Wang H, Wang H and Kou J 2015. Development of insecticide resistance in malaria vector Anopheles sinensis populations from Shandong province in China. Malaria journal 14: 592–592, DOI: 

  63. Dalla Bona AC, Chitolina RF, Fermino ML, Poncio LD, Weiss A, Lima JBP, Paldi N, Bernardes ES, Henen J and Maori E 2016. Larval application of sodium channel homologous dsRNA restores pyrethroid insecticide susceptibility in a resistant adult mosquito population. Parasites & Vectors 9 

  64. Dang K, Lilly DG, Bu W and Doggett SL 2015a. Simple, rapid and cost-effective technique for the detection of pyrethroid resistance in bed bugs, Cimex spp. (Hemiptera: Cimicidae). Austral Entomology 54: 191–196, DOI: 

  65. Dang K, Toi CS, Lilly DG, Bu W and Doggett SL 2015b. Detection of knockdown resistance mutations in the common bed bug, Cimex lectularius (Hemiptera: Cimicidae), in Australia. Pest Management Science 71: 914–922, DOI: 

  66. Dang K, Toi CS, Lilly DG, Lee C-Y, Naylor R, Tawatsin A, Thavara U, Bu W and Doggett SL 2015c. Identification of putative kdr mutations in the tropical bed bug, Cimex hemipterus (Hemiptera: Cimicidae). Pest Management Science 71: 1015–1020, DOI: 

  67. Daxenberger A 2002. Pollutants with androgen-disrupting potency. European Journal of Lipid Science & Technology 104: 124–130, DOI:<124::AID-EJLT124>3.0.CO;2-T 

  68. De Gregorio F, Pellegrino M, Picchietti S, Belardinelli MC, Taddei AR, Fausto AM, Rossi M, Maggio R and Giorgi F 2011. The insecticide 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT) alters the membrane raft location of the TSH receptor stably expressed in Chinese hamster ovary cells. Toxicology and Applied Pharmacology 253: 121–129, DOI: 

  69. Delancey JOL, Thun MJ, Jemal A and Ward EM 2008. Recent trends in Black-White disparities in cancer mortality. Cancer Epidemiology, Biomarkers & Prevention 17: 2908–2912, DOI: 

  70. Demicheli R, Retsky MW, Hrushesky WJM, Baum M, Gukas ID and Jatoi I 2007. Racial disparities in breast cancer outcome – Insights into host-tumor interactions. Cancer 110: 1880–1888, DOI: 

  71. Deshpande AD, Dickhut RM, Dockum BW, Brill RW and Farrington C 2016. Polychlorinated biphenyls and organochlorine pesticides as intrinsic tracer tags of foraging grounds of bluefin tuna in the northwest Atlantic Ocean. Marine Pollution Bulletin 105: 265–276, DOI: 

  72. De Solla SR, Martin PA, Fernie KJ, Park BJ and Mayne G 2006. Effects of environmentally relevant concentrations of atrazine on gonadal development of snapping turtles (Chelydra serpentine). Environmental Toxicology and Chemistry 25: 520–526, DOI: 

  73. Dessi-Fulgheri F, Belloni V, Seta DD, Porrini S, Zaccaroni M, Farabollini F and Santucci D 2007. Exposition to environmentally relevant doses of endocrine disrupters: effects on behavior. Evolutionary molecular strategies and plasticity, : 261–272.  

  74. Devi NL, Yadav IC, Raha P, Qi SH and Dan Y 2015. Spatial distribution, source apportionment and ecological risk assessment of residual organochlorine pesticides (OCPs) in the Himalayas. Environmental Science and Pollution Research 22: 20154–20166, DOI: 

  75. Dill GM 2005. Glyphosate-resistant crops: history, status and future. Pest Management Science 61: 219–224, DOI: 

  76. Dill GM, Cajacob CA and Padgette SR 2008. Glyphosate-resistant crops: adoption, use and future considerations. Pest Management Science 64: 326–331, DOI: 

  77. Dockalova K, Holubcova J, Bacardit M, Bartrons M, Camarero L, Gallego E, Grimalt JO, Hardekopf D, Horicka Z, Rosseland BO, Tatosova J and Stuchlik E 2015. Brown and brook trout populations in the Tatra Mountain lakes (Slovakia, Poland) and contamination by long-range transported pollutants. Biologia 70: 516–529, DOI: 

  78. Dorneles PR, Lailson-Brito J, Secchi ER, Dirtu AC, Weijs L, Dalla Rosa L, Bassoi M, Cunha HA, Azevedo AF and Covaci A 2015. Levels and profiles of chlorinated and brominated contaminants in Southern Hemisphere humpback whales. Megaptera novaeangliae. Environmental Research 138: 49–57, DOI: 

  79. Duarte-Guterman P, Navarro-Martin L and Trudeau VL 2014. Mechanisms of crosstalk between endocrine systems: Regulation of sex steroid hormone synthesis and action by thyroid hormones. General and Comparative Endocrinology 203: 69–85, DOI: 

  80. Dykes CL, Kushwah RBS, Das MK, Sharma SN, Bhatt RM, Veer V, Agrawal OP, Adak T and Singh OP 2015. Knockdown resistance (kdr) mutations in Indian Anopheles culicifacies populations. Parasites & Vectors 8DOI: 

  81. Eldridge JC, Wetzel LT, Stevens JT and Simpkins JW 1999. The mammary tumor response in triazine-treated female rats: A threshold-mediated interaction with strain and species-specific reproductive senescence. Steroids 64: 672–678, DOI: 

  82. Elserougy S, Beshir S, Saad-Hussein A and Abouarab A 2013. Organochlorine pesticide residues in biological compartments of healthy mothers. Toxicology and Industrial Health 29: 441–448, DOI: 

  83. Ewins PJ, Weseloh DV and Mineau P 1992. Geographical-distribution of contaminants and productivity of herring-gulls in the Great Lakes- Lake Huron 1980. Journal of Great Lakes Research 18: 316–330, DOI: 

  84. Falso PG, Noble CA, Diaz JM and Hayes TB 2015. The effect of long-term corticosterone treatment on blood cell differentials and function in laboratory and wild-caught amphibian models. General and Comparative Endocrinology 212: 73–83, DOI: 

  85. Fan W, Yanase T, Morinaga H, Gondo S, Okabe T, Nomura M, Hayes TB, Takayanagi R and Nawata H 2007a. Herbicide atrazine activates SF-1 by direct affinity and concomitant co-activators recruitments to induce aromatase expression via promoter II. Biochemical and Biophysical Research Communications 355: 1012–1018, DOI: 

  86. Fan W, Yanase T, Morinaga H, Gondo S, Okabe T, Nomura M, Komatsu T, Morohashi K-I, Hayes T, Takayanagi R and Nawata H 2007b. Atrazine-induced aromatase expression is SF-1 dependent: Implications for endocrine disruption in wildlife and reproductive cancers in humans. Environ. Health Perspect 115: 720–727, DOI: 

  87. Fan W, Yanase T, Morinaga H, Gondo S, Okabe T, Nomura M, Komatsu T, Morohashi K-I, Hayes TB, Takayanagi R and Nawata H 2007c. Atrazine-induced aromatase expression is SF-1 dependent: Implications for endocrine disruption in wildlife and reproductive cancers in humans. Environmental Health Perspectives 115: 720–727, DOI: 

  88. Faruga A, Pudyszak K, Borejszo Z, Smoczynski S and Pietrzak-Fiecko R 2008. Concentration of chlorinated hydrocarbons in turkey hens’ blood and egg yolk compared to their reproductivity traits. Medycyna Weterynaryjna 64: 1401–1403.  

  89. Fellers GM, Bradford DF, Pratt D and Long Wood L 2007. Demise of repatriated populations of mountain yellow-legged frogs (Rana muscos) in the Sierra Nevada of California. Herpetological Conservation and Biology 2: 5–21.  

  90. Fellers GM, Green DE and Longcore JE 2001. Oral chytridiomycosis in the mountain yellow-legged frog (Rana muscosa). Copeia, : 945–953, DOI:[0945:OCITMY]2.0.CO;2 

  91. Fenner K, Canonica S, Wackett LP and Elsner M 2013. Evaluating Pesticide Degradation in the Environment: Blind Spots and Emerging Opportunities. Science 341: 752–758, DOI: 

  92. Filipov N, Pinchuk L, Boyd B and Crittenden P 2005. Immunotoxic effects of short-term atrazine exposure in young male C57BL/6 mice. Toxicol. Sci 86DOI: 

  93. Forgash AJ 1984. History, Evolution, and Consequences of Insecticide Resistance. Pesticide Biochemistry and Physiology 22: 178–186, DOI: 

  94. Forson D and Storfer A 2006a. Atrazine increases Ranavirus susceptibility in the tiger salamander. Ambystoma tigrinum. Ecol. Appl 16: 2325–2332, DOI:[2325:AIRSIT]2.0.CO;2 

  95. Forson D and Storfer A 2006b. Effects of atrazine and iridovirus infection on survival and lifehistory traits of the long-toed salamander (Ambystoma macrodatylum). Environ. Toxicol. Chem 25: 168–173, DOI: 

  96. Fraites MJP, Cooper RL, Buckalew A, Jayaraman S, Mills L and Laws SC 2009. Characterization of the Hypothalamic-Pituitary-Adrenal Axis response to atrazine and metabolites in the female rat. Toxicological Sciences 112: 88–99, DOI: 

  97. Fraites MJP, Narotsky MG, Best DS, Stoker TE, Davis LK, Goldman JM, Hotchkiss MG, Klinefelter GR, Kamel A, Qian Y, Podhorniak L and Cooper RL 2011. Gestational atrazine exposure: Effects on male reproductive development and metabolite distribution in the dam, fetus, and neonate. Reproductive Toxicology 32: 52–63, DOI: 

  98. Frias-Alvarez P, Vredenburg VT, Familiar-Lopez M, Longcore JE, Gonzalez-Bernal E, Santos-Barrera G, Zambrano L and Parra-Olea G 2008. Chytridiomycosis survey in wild and captive Mexican amphibians. Ecohealth 5: 18–26, DOI: 

  99. Friedmann A 2002. Atrazine inhibition of testosterone production in rat males following peripubertal exposure. Reproductive Toxicology 16: 275–279, DOI: 

  100. Furusawa N 2002. Transferring and distributing profiles of p,p’-(DDT) in egg-forming tissues and eggs of laying hens following a single oral administration. Journal of Veterinary Medicine Series a-Physiology Pathology Clinical Medicine 49: 334–336.  

  101. Furusawa N and Morita Y 2001. Residual profile of DDT in egg yolks of laying hens following an oral application. New Zealand Journal of Agricultural Research 44: 297–300, DOI: 

  102. Gaido KW, Leonard LS, Lovell S, Gould JC, Babai D, Portier CJ and Mcdonnell DP 1997. Evaluation of chemicals with endocrine modulating activity in a yeast-based steroid hormone receptor gene transcription assay. Toxicology and Applied Pharmacology 143: 205–212, DOI: 

  103. Gaido KW, Maness SC, Mcdonnell DP, Dehal SS, Kupfer D and Safe S 2000. Interaction of methoxychlor and related compounds with estrogen receptor alpha and beta, and androgen receptor: structure-activity studies. Molecular Pharmacology 58: 852–858.  

  104. Garner TWJ, Walker S, Bosch J, Hyatt AD, Cunningham AA and Fisher MC 2005. Chytrid fungus in Europe. Emerging Infectious Diseases 11: 1639–1641, DOI: 

  105. Gasnier C, Dumont C, Benachour N, Clair E, Chagnon M-C and Seralini G-E 2009. Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Toxicology 262: 184–191, DOI: 

  106. Gatto NM, Longnecker MP, Press MF, Sullivan-Halley J, Mckean-Cowdin R and Bernstein L 2007. Serum organochlorines and breast cancer: a case-control study among African-American women. Cancer Causes & Control 18: 29–39, DOI: 

  107. Geisz HN, Dickhut RM, Cochran MA, Fraser WR and Ducklow HW 2008. Melting glaciers: A probable source of DDT to the Antarctic marine ecosystem. Environmental Science & Technology 42: 3958–3962, DOI: 

  108. Gellatly KJ, Yoon KS, Doherty JJ, Sun W, Pittendrigh BR and Clark JM 2015. RNAi validation of resistance genes and their interactions in the highly DDT-resistant 91-R strain of Drosophila melanogaster. Pesticide Biochemistry and Physiology 121: 107–115, DOI: 

  109. Gely-Pernot A, Hao C, Becker E, Stuparevic I, Kervarrec C, Chalmel F, Primig M, Jegou B, Smagulova F and Hao CX 2015. The epigenetic processes of meiosis in male mice are broadly affected by the widely used herbicide atrazine. BMC Genomics October 30 201516 

  110. Gendron AD, Marcogliese DJ, Barbeau S, Christin MS, Brousseau P, Ruby S, Cyr D and Fournier M 2003. Exposure of leopard frogs to a pesticide mixture affects life history characteristics of the lungworm Rhabdias ranaeOecologia 135: 469–476, DOI: 

  111. George AA and Delumen BO 1991. A novel methionine-rich protein in soybean seed-Identification, amino-acid composition and N-terinal sequence. Journal of Agricultural and Food Chemistry 39: 224–227, DOI: 

  112. George VT, Pazhanivel N and Manohar BM 2006. Residues of DDT in the chicken egg. Indian Veterinary Journal 83: 832–833.  

  113. Gerend MA and Pai M 2008. Social Determinants of Black-White Disparities in Breast Cancer Mortality: A Review. Cancer Epidemiology Biomarkers & Prevention 17: 2913–2923, DOI: 

  114. Goldberg TL, Readel AM and Lee MH 2007. Chytrid fungus in frogs from an equatorial African montane forest in western Uganda. Journal of Wildlife Diseases 43: 521–524.  

  115. Goldner WS, Sandler DP, Yu F, Shostrom V, Hoppin JA, Kamel F and Levan TD 2013. Hypothyroidism and Pesticide Use Among Male Private Pesticide Applicators in the Agricultural Health Study. Journal of Occupational and Environmental Medicine 55: 1171–1178.  

  116. Gong P, Wang XP, Xue YG, Sheng JJ, Gao SP, Tian LD and Yao TD 2015. Influence of atmospheric circulation on the long-range transport of organochlorine pesticides to the western Tibetan Plateau. Atmospheric Research 166: 157–164, DOI: 

  117. Gray LE Jr., Ostby JS and Kelce WR 1994. Developmental effects of an environmental antiandrogen: The fungicide vinclozolin alters sex differentiation of the male rat. Toxicology and Applied Pharmacology 129: 46–52, DOI: 

  118. Gray LE, Ostby J, Wolf C, Lambright C and Kelce W 1998. The value of mechanistic studies in laboratory animals for the prediction of reproductive effects in wildlife: Endocrine effects on mammalian sexual differentiation. Environmental Toxicology and Chemistry 17: 109–118, DOI: 

  119. Green D and Dodd C Jr. 2007. Presence of amphibian chytrid fungus Batrachochytrium dendrobatidis and other amphibian pathogens at warmwater fish hatcheries in southeastern North America. Herpetological Conservation and Biology 2: 43–47.  

  120. Greiner S, Youngblood G and Fenton S 2000. Estrogen-independent effects of atrazine (ATR) on mammary gland (MG) development in rats. Toxicologist 54: 332. 

  121. Guyton KZ, Loomis D, Grosse Y, El Ghissassi F, Benbrahim-Tallaa L, Guha N, Scoccianti C, Mattock H, Straif K and Int Agcy Res Canc Monog, W 2015. Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate. Lancet Oncology 16: 490–491, DOI: 

  122. Hakim D 2017. Monsanto weed killer Roundup faces new doubts on safety in unsealed documents. New York Time,  

  123. Halsall CJ, Bailey R, Stern GA, Barrie LA, Fellin P, Muir DCG, Rosenberg B, Rovinsky FY, Kononov EY and Pastukhov B 1998. Multi-year observations of organohalogen pesticides in the Arctic atmosphere. Environmental Pollution 102: 51–62, DOI: 

  124. Han JB, Li GQ, Wan PJ, Zhu TT and Meng QW 2016. Identification of glutathione S-transferase genes in Leptinotarsa decemlineata and their expression patterns under stress of three insecticides. Pesticide Biochemistry and Physiology 133: 26–34, DOI: 

  125. Hanson AD, Rathinasabapathi B, Rivoal J, Burnet M, Dillon MO and Gage DA 1994. Osmoprotective compounds in the plumbaginaceae – A natural experiment in metabolic engineering of stress tolerance. Proceedings of the National Academy of Sciences of the United States of America 91: 306–310, DOI: 

  126. Harrison PTC, Holmes P and Humfrey CDN 1997. Reproductive health in humans and wildlife: are adverse trends associated with environmental chemical exposure?. Science of the Total Environment 205: 97–106, DOI: 

  127. Hayes TB 1997. Steroid-mimicking environmental contaminants: Their potential role in amphibian declines. Herpetologia Bonnensis. SEH Bonn, : 145–150.  

  128. Hayes TB 2004. There is no denying this: Defusing the confusion about atrazine. Bioscience 54: 1138–1149, DOI:[1138:TINDTD]2.0.CO;2 

  129. Hayes TB, Anderson LL, Beasley VR, De Solla SR, Iguchi T, Ingraham H, Kestemont P, Kniewald J, Kniewald Z, Langlois VS, Luque EH, Mccoy KA, Munoz-De-Toro M, Oka T, Oliveira CA, Orton F, Ruby S, Suzawa M, Tavera-Mendoza LE, Trudeau VL, Victor-Costa AB and Willingham E 2011. Demasculinization and feminization of male gonads by atrazine: Consistent effects across vertebrate classes. Journal of Steroid Biochemistry and Molecular Biology 127: 64–73, DOI: 

  130. Hayes TB, Case P, Chui S, Chung D, Haefele C, Haston K, Lee M, Mai V-P, Marjuoa Y, Parker J and Tsui M 2006a. Pesticide mixtures, endocrine disruption, and amphibian declines: Are we underestimating the impact?. Environ. Health Perspect 114: 40–50, DOI: 

  131. Hayes TB, Collins A, Lee M, Mendoza M, Noriega N, Stuart AA and Vonk A 2002a. Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses. Proc. Natl. Acad. Sci. USA 99: 5476–5480, DOI: 

  132. Hayes TB, Falso P, Gallipeau S and Stice MJ 2010a. The cause of global amphibian declines: A developmental endocrinologist’s perspective. J. Exp. Biol 213: 921–933, DOI: 

  133. Hayes TB, Haston K, Tsui M, Hoang A, Haeffele C and Vonk A 2002b. Atrazine-induced hermaphroditism at 0.1 ppb in American leopard frogs (Rana pipiens): Laboratory and field evidence. Environ. Health Perspect 111: 568–575, DOI: 

  134. Hayes TB, Haston K, Tsui M, Hoang A, Haeffele C and Vonk AA 2002c. Feminization of male frogs in the wild. Nature 419: 895–896, DOI: 

  135. Hayes TB, Khoury V, Narayan A, Nazir M, Park A, Brown T, Adame L, Chan E, Buchholz D, Stueve T and Gallipeau S 2010b. Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis). Proc. Natl. Acad. Sci. USA 107: 4612–4617, DOI: 

  136. Hayes TB, Stuart A, Mendoza G, Collins A, Noriega N, Vonk A, Johnston G, Liu R and Kpodzo D 2006b. Characterization of atrazine-induced gonadal malformations and effects of an androgen antagonist (cyproterone acetate) and exogenous estrogen (estradiol 17β): Support for the demasculinization/feminization hypothesis. Environ. Health Perspect 114: 134–141, DOI: 

  137. Hayes TB, Wu TH and Gill TN 1997. DDT-like effects as a result of corticosterone treatment in an anuran amphibian: Is DDT a corticoid mimic or a stressor?. Environmental Toxicology and Chemistry 16: 1948–1953, DOI: 

  138. Hecker M, Kim W, Park J-W, Murphy M, Villeneuve D, Coady K, Jones P, Solomon K, Van Der Kraak G, Carr J, Smith E, Du Preez L, Kendall R and Giesy J 2005. Plasma concentrations of estradiol and testosterone, gonadal aromatase activity and ultrastructure of the testis in Xenopus laevis exposed to estradiol or atrazine In: Aquat. Toxicol Amsterdam: 72: 383–396, DOI: 

  139. Hecker M, Newsted JL, Murphy MB, Higley EB, Jones PD, Wu R and Giesy JP 2006. Human adrenocarcinoma (H295R) cells for rapid in vitro determination of effects on steroidogenesis: Hormone production. Toxicology and Applied Pharmacology 217: 114–124, DOI: 

  140. Heindel JJ, Mcallister KA, Worth L Jr. and Tyson FL 2006. Environmental Epigenomics, Imprinting and Disease Susceptibility. Epigenetics 1: 1–6, DOI: 

  141. Hladik ML, Vandever M and Smalling KL 2016. Exposure of native bees foraging in an agricultural landscape to current-use pesticides. Science of the Total Environment 542: 469–477, DOI: 

  142. Hoekstra HE 2006. Genetics, development and evolution of adaptive pigmentation in vertebrates. Heredity 97: 222–234, DOI: 

  143. Hokanson R, Fudge R, Chowdhary R and Busbee D 2007. Alteration of estrogen-regulated gene expression in human cells induced by the agricultural and horticultural herbicide glyphosate. Human & Experimental Toxicology 26: 747–752, DOI: 

  144. Holan G 1969. New halocyclopropane insecticides and the mode of action of DDT. Nature 5185: 1025–1029, DOI: 

  145. Holm L, Blomqvist A, Brandt I, Brunstrom B, Ridderstrale Y and Berg C 2006. Embryonic exposure to o,p ‚-DDT causes eggshell thinning and altered shell gland carbonic anhydrase expression in the domestic hen. Environmental Toxicology and Chemistry 25: 2787–2793, DOI: 

  146. Hooghe R, Devos S and Hooghe-Peters E 2000. Effects of selected herbicides on cytokine production in vitroLife Sciences 66: 2519–2525, DOI: 

  147. Howard PH 2009. Visualizing Consolidation in the Global Seed Industry: 1996–2008. Sustainability 1: 1266–1287, DOI: 

  148. Hussain R, Mahmood F, Khan MZ, Khan A and Muhammad F 2011. Pathological and genotoxic effects of atrazine in male Japanese quail (Coturnix japonica). Ecotoxicology 20: 1–8, DOI: 

  149. Incho HH and Deonier CC 1947. Comparative toxicity of DDT to three representative species of mosquito larvae. Mosquito News 7: 67–70.  

  150. Ishak IH, Zairi J, Ranson H and Wondji CS 2015. Contrasting patterns of insecticide resistance and knockdown resistance (kdr) in the dengue vectors Aedes aegypti and Aedes albopictus from Malaysia. Parasites and Vectors 8: 94–100, DOI: 

  151. IUPAC 2010. History of Pesticide Use.  Available at: 

  152. Jablonowski ND, Schaeffer A and Burauel P 2011. Still present after all these years: persistence plus potential toxicity raise questions about the use of atrazine. Environmental Science and Pollution Research 18: 328–331, DOI: 

  153. Jacquet M, Tilquin M, Ravanel P and Boyer S 2015. Increase in tolerance of Aedes aegypti larvae (Diptera: Culicidae) to the insecticide temephos after exposure to atrazine. African Entomology 23: 110–119, DOI: 

  154. Jain SM and Pehu E 1992. The prospects of tissue-culture and genetic-engineering for strawberry improvement. Acta Agriculturae Scandinavica Section B-Soil and Plant Science 42: 133–139, DOI: 

  155. Jones L 1989. Minorities and Cancer. NY: Springer-Verlag, DOI: 

  156. Juberg DR and Lochcaruso R 1992. Investigation of the Role of Estrogenic Action and Prostaglandin-E2 in Ddt-Stimulated Rat Uterine Contractions Exvivo. Toxicology 74: 161–172, DOI: 

  157. Kabasenche WP and Skinner MK 2014. DDT, epigenetic harm, and transgenerational environmental justice. Environmental Health 13: 62.DOI: 

  158. Kalfa N, Paris F, Philibert P, Orsini M, Broussous S, Fauconnet-Servant N, Audran F, Gaspari L, Lehors H, Haddad M, Guys J-M, Reynaud R, Alessandrini P, Merrot T, Wagner K, Kurzenne J-Y, Bastiani F, Breaud J, Valla J-S, Lacombe GM, Dobremez E, Zahhaf A, Daures J-P and Sultan C 2015. Is Hypospadias Associated with Prenatal Exposure to Endocrine Disruptors? A French Collaborative Controlled Study of a Cohort of 300 Consecutive Children Without Genetic Defect. European Urology 68: 1023–1030, DOI: 

  159. Kalfa N, Philibert P, Baskin LS and Sultan C 2011. Hypospadias: Interactions between environment and genetics. Molecular and Cellular Endocrinology 335: 89–95, DOI: 

  160. Kallenborn R, Breivik K, Eckhardt S, Lunder CR, Mano S, Schlabach M and Stohl A 2013. Long-term monitoring of persistent organic pollutants (POPs) at the Norwegian Troll station in Dronning Maud Land, Antarctica. Atmospheric Chemistry and Physics 13: 6983–6992, DOI: 

  161. Kamata R, Shiraishi F, Takahashi S, Shimizu A, Nakajima D, Kageyama S, Sasaki T and Temma K 2013. The effects of transovarian exposure to p,p’-DDT and p,p’-DDE on avian reproduction using Japanese quails. Journal of Toxicological Sciences 38: 903–912, DOI: 

  162. Kamata R, Shiraishi F, Takahashi S, Shimizu A and Shiraishi H 2009. Reproductive and Developmental Effects of Transovarian Exposure to O,P’-Ddt in Japanese Quails. Environmental Toxicology and Chemistry 28: 782–790, DOI: 

  163. Kamita SG, Mulligan S, Cornel AJ and Hammock BD 2016. Quantification of GST and esterase activities in pyrethrin-resistant mosquitoes using pyrethroid-like fluorescent substrates. International Journal of Pest Management 62: 276–283, DOI: 

  164. Katsu Y, Taniguchi E, Urushitani H, Miyagawa S, Takase M, Kubokawa K, Tooi O, Oka T, Santo N, Myburgh J, Matsuno A and Iguchi T 2010. Molecular cloning and characterization of ligand- and species-specificity of amphibian estrogen receptors. General and Comparative Endocrinology 168: 220–230, DOI: 

  165. Kettles MA, Browning SR, Prince TS and Hostman SW 1997. Triazine exposure and breast cancer incidence: An ecologic study of Kentucky counties. Environ. Health Perspect 105: 1222–1227, DOI: 

  166. Kjaerstad MB, Taxvig C, Nellemann C, Vinggaard AM and Andersen HR 2010. Endocrine disrupting effects in vitro of conazole antifungals used as pesticides and pharmaceuticals. Reproductive Toxicology 30: 573–582, DOI: 

  167. Kniewald J, Jakominic M, Tomljenovic A, Šimic B, Romac P, Vranešic Ð and Kniewald Z 2000. Disorders of male rat reproductive tract under the influence of atrazine. J. Appl. Toxicol 20: 61–68, DOI:<61::AID-JAT628>3.0.CO;2-3 

  168. Kniewald J, Mildner P and Kniewald Z 1980. Effects of s triazine herbicides on 5α dihydrotestosterone receptor complex formation in hypothalamus and ventral prostate.  

  169. Kniewald Z, Kniewald J, Kordic D and Mildner P 1978. Effects of atrazine on hormone-dependent reactions in hyppothalamus, pituitary and prostate gland. Journal of Steroid Biochemistry and Molecular Biology 9: 449–453, DOI: 

  170. Komissarenko VP, Chelnakova IS and Mikosha AS 1978. Effect of o’p DDD and perthane on glutathione reductase activity in dog and guniea pig adrenal glands in vitroByulleten’ Eksperimental’noi Biologii i Meditsiny 85: 159–161.  

  171. Kudom AA, Mensah BA, Froeschl G, Rinder H and Boakye D 2015. DDT and pyrethroid resistance status and laboratory evaluation of bio-efficacy of long lasting insecticide treated nets against Culex quinquefasciatus and Culex decens in Ghana. Acta Tropica 150: 122–130, DOI: 

  172. Kunze P 1989. Change of behavior with atrazine in an electric fish. Zeitschrift Fur Wasser Und Abwasser Forschung-Journal for Water and Wastewater Research 22: 108–111.  

  173. Lang A and Otto M 2010. A synthesis of laboratory and field studies on the effects of transgenic Bacillus thuringiensis (Bt) maize on non-target Lepidoptera. Entomologia Experimentalis Et Applicata 135: 121–134, DOI: 

  174. Lantz PM, Mujahid M, Schwartz K, Janz NK, Fagerlin A, Salem B, Liu LH, Deapen D and Katz SJ 2006. The influence of race, ethnicity, and individual socioeconomic factors on breast cancer stage at diagnosis. American Journal of Public Health 96: 2173–2178, DOI: 

  175. Laws SC, Hotchkiss M, Ferrell J, Jayaraman S, Mills L, Modic W, Tinfo N, Fraites M, Stoker T and Cooper R 2009. Chlorotriazine herbicides and metabolites activate an ACTH-dependent release of corticosterone in male Wistar rats. Toxicological Sciences 112: 78–87, DOI: 

  176. Lenhardt PP, Bruhl CA and Berger G 2015. Temporal coincidence of amphibian migration and pesticide applications on arable fields in spring. Basic and Applied Ecology 16: 54–63, DOI: 

  177. Li CC, Cheng YB, Tang Q, Lin SB, Li YH, Hu X, Nian J, Gu H, Lu YF, Tang H, Dai SG, Zhang HQ, Jin C, Zhang HJ, Jin YY and Jin YL 2014. The association between prenatal exposure to organochlorine pesticides and thyroid hormone levels in newborns in Yancheng, China. Environmental Research 129: 47–51, DOI: 

  178. Li J, Li N, Ma M, Giesy JP and Wang Z 2008. In vitro profiling of the endocrine disrupting potency of organochlorine pesticides. Toxicology Letters 183: 65–71, DOI: 

  179. Liu C, Shi Y, Li H, Wang Y and Yang K 2011. p,p’-DDE disturbs the homeostasis of thyroid hormones via thyroid hormone receptors, transthyretin, and hepatic enzymes. Hormone and Metabolic Research 43: 391–396, DOI: 

  180. Liu CJ, Ha M, Li LB and Yang K 2014. PCB153 and p,p’-DDE disorder thyroid hormones via thyroglobulin, deiodinase 2, transthyretin, hepatic enzymes and receptors. Environmental Science and Pollution Research 21: 11361–11369, DOI: 

  181. Liu ZZ, Wang YY, Zhu ZH, Yang EL, Feng XY, Fu ZW and Jin YX 2016. Atrazine and its main metabolites alter the locomotor activity of larval zebrafish (Danio rerio). Chemosphere 148: 163–170, DOI: 

  182. Long EY and Krupke CH 2016. Non-cultivated plants present a season-long route of pesticide exposure for honey bees. Nature Communications 7: 11629–11629, DOI: 

  183. Longnecker MP, Klebanoff MA, Zhou HB and Brock JW 2001. Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth. Lancet 358: 110–114, DOI: 

  184. Lopez-Espinosa MJ, Vizcaino E, Murcia M, Fuentes V, Garcia AM, Rebagliato M, Grimalt JO and Ballester F 2010. Prenatal exposure to organochlorine compounds and neonatal thyroid stimulating hormone levels. Journal of Exposure Science and Environmental Epidemiology 20: 579–588, DOI: 

  185. Lorenzen A, Williams KL and Moon TW 2003. Determination of the estrogenic and antiestrogenic effects of environmental contaminants in chicken embryo hepatocyte cultures by quantitative-polymerase chain reaction. Environmental Toxicology and Chemistry 22: 2329–2336, DOI: 

  186. Lubinsky M 2012. Hypothesis: Estrogen related thrombosis explains the pathogenesis and epidemiology of gastroschisis. American Journal of Medical Genetics Part A 158A: 808–811, DOI: 

  187. Lucas A, Jones A, Goodrow M, Saiz S, Blewett C, Seiber J and Hammock B 1993. Determination of atrazine metabolites in human urine: Development of a biomarker of exposure. Chemic. Research Toxicol 6: 107–116, DOI: 

  188. Lundholm CE and Bartonek M 1992. Effects of p,p’-DDE and some other chlorinated hydrocarbons on the formation of prostaglandins by the avian egglshell gland mucosa. Archives of Toxicology 66: 387–391, DOI: 

  189. Ma R, Evans AF and Riechers DE 2016. Differential responses to preemergence and postemergence atrazine in two atrazine-resistant waterhemp populations. Agronomy Journal 108: 1196–1202, DOI: 

  190. Ma R, Kaundun SS, Tranel PJ, Riggins CW, Mcginness DL, Hager AG, Hawkes T, Mcindoe E and Riechers DE 2013. Distinct detoxification mechanisms confer resistance to mesotrione and atrazine in a population of waterhemp. Plant Physiology 163: 363–377, DOI: 

  191. Maclennan P, Delzell E, Sathiakumar N, Myers S, Cheng H, Grizzle W, Chen V and Wu X 2002. Cancer incidence among triazine herbicide manufacturing workers. JOEM 44: 1048–1058, DOI: 

  192. Makynen E, Kahl M, Jensen K, Tietge J, Wells K, Van Der Kraak G and Ankley G 2000. Effects of the mammalian antiandrogen vinclozolin on development and reproduction of the fathead minnow (Pimephales promelas) In: Aquat.Toxicol Amsterdam: 48: 461–475, DOI: 

  193. Maness SC, Mcdonnell DP and Gaido KW 1998. Inhibition of androgen receptor-dependent transcriptional activity by DDT isomers and methoxychlor in HepG2 human hepatoma cells. Toxicology and Applied Pharmacology 151: 135–142, DOI: 

  194. Mast MA, Foreman WT and Skaates SV 2007. Current-use pesticides and organochlorine compounds in precipitation and lake sediment from two high-elevation national parks in the Western United States. Archives of Environmental Contamination and Toxicology 52: 294–305, DOI: 

  195. Mattix KD, Winchester PD and Scherer LR 2007. Incidence of abdominal wall defects is related to surface water atrazine and nitrate levels. Journal of Pediatric Surgery 42: 947–949, DOI: 

  196. Matzrafi M, Seiwert B, Reemtsma T, Rubin B and Peleg Z 2016. Climate change increases the risk of herbicide-resistant weeds due to enhanced detoxification. Planta 244: 1217–1227, DOI: 

  197. Mchugh B, Law RJ, Allchin CR, Rogan E, Murphy S, Foley MB, Glynn D and Mcgovern E 2007. Bioaccumulation and enantiomeric profiling of organochlorine pesticides and persistent organic pollutants in the killer whale (Orcinus orca) from British and Irish waters. Marine Pollution Bulletin 54: 1724–1731, DOI: 

  198. Meiser H, Hagedorn HW, Ruf J and Schulz R 2003. Antiandrogen p,p’-DDE, principal metabolite of DDT and PCBs in curlew eggs (Numenius arquata). Tierarztliche Umschau 58: 155–156.  

  199. Menashe I, Anderson WF, Jatoi I and Rosenberg PS 2009. Underlying causes of the Black-White racial disparity in breast cancer mortality: A population-based analysis. Journal of the National Cancer Institute 101: 993–1000, DOI: 

  200. Mendez SIS, Tillitt DE, Rittenhouse TAG and Semlitsch RD 2009. Behavioral response and kinetics of terrestrial atrazine exposure in American toads (Bufo americanus). Archives of Environmental Contamination and Toxicology 57: 590–597, DOI: 

  201. Mesnage R, Defarge N, De Vendomois JS and Seralini GE 2015. Potential toxic effects of glyphosate and its commercial formulations below regulatory limits. Food and Chemical Toxicology 84: 133–153, DOI: 

  202. Miyagawa S, Lange A, Hirakawa I, Tohyama S, Ogino Y, Mizutani T, Kagami Y, Kusano T, Ihara M, Tanaka H, Tatarazako N, Ohta Y, Katsu Y, Tyler CR and Iguchi T 2014. Differing Species Responsiveness of Estrogenic Contaminants in Fish Is Conferred by the Ligand Binding Domain of the Estrogen Receptor. Environmental Science & Technology 48: 5254–5263, DOI: 

  203. Miyashita M, Shimada T, Nakagami S, Kurihara N, Miyagawa H and Akamatsu M 2004. Enantioselective recognition of mono-demethylated methoxychlor metabolites by the estrogen receptor. Chemosphere 54: 1273–1276, DOI: 

  204. Monteiro MS, Pavlaki M, Faustino A, Rema A, Franchi M, Gediel L, Loureiro S, Domingues I, Von Osten JR and Soares A 2015. Endocrine disruption effects of p,p’-DDE on juvenile zebrafish. Journal of Applied Toxicology 35: 253–260, DOI: 

  205. Moore A and Waring C 1998. Mechanistic effects of a triazine pesticide on reproductive endocrine function in mature male Atlantic salmon (Salmo salar L.) parr. Pesticide Biochem. Physiol 62: 41–50, DOI: 

  206. Mulamba C, Riveron JM, Ibrahim SS, Irving H, Barnes KG, Mukwaya LG, Birungi J and Wondji CS 2014. Widespread pyrethroid and DDT resistance in the major malaria vector Anopheles funestus in East Africa is driven by metabolic resistance mechanisms. PLOS ONE 9: e110058–e110058, DOI: 

  207. Myers JP, Antoniou MN, Blumberg B, Carroll L, Colborn T, Everett LG, Hansen M, Landrigan PJ, Lanphear BP, Mesnage R, Vandenberg LN, Vom Saal FS, Welshons WV and Benbrook CM 2016. Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement. Environmental Health 15DOI: 

  208. Nadal M, Marques M, Mari M and Domingo JL 2015. Climate change and environmental concentrations of POPs: A review. Environmental Research 143: 177–185, DOI: 

  209. Naidoo V, Katsu Y and Iguchi T 2008. The influence of non-toxic concentrations of DDT and DDE on the old world vulture estrogen receptor alpha. General and Comparative Endocrinology 159: 188–195, DOI: 

  210. Neuman-Lee LA and Janzen FJ 2003. Effects of atrazine on the performance, survival, and behavior of embryonic map turtles (Graptemys). Integrative and Comparative Biology 43: 1049–1049.  

  211. Neuman-Lee LA and Janzen FJ 2005. Effects of atrazine on map turtle (Graptemys) development and behavior. Integrative and Comparative Biology 45: 1171–1171.  

  212. Newton RJ, Funkhouser EA, Fong F and Tauer CG 1991. Molecular and physiological genetics of drought tolerance in forest species. Forest Ecology and Management 43: 225–250, DOI: 

  213. Nichols JB, Dalton CC, Todd GA and Broughton NW 1992. Genetic-engineering of sugar beet. Zuckerindustrie 117: 797–800.  

  214. NIH 2014. Roundtable on Environmental Health Sciences, Research, and Medicine; Board on Population Health and Public Health Practice; Institute of Medicine. Identifying and Reducing Environmental Health Risks of Chemicals in Our Society: Workshop Summary. Washington (DC): The Challenge: Chemicals in Today’s Society, [Online]. 

  215. Nilsson EE and Skinner MK 2015. Environmentally Induced Epigenetic Transgenerational Inheritance of Reproductive Disease. Biology of Reproduction 93 

  216. OEHHA 2016. Atrazine, Propazine, Simazine and their Chlorometabolites DACT, DEA And DIA Listed as Reproductive Toxicants, [Online]. Available: 

  217. Owen MJ, Martinez NJ and Powles SB 2014. Multiple herbicide-resistant Lolium rigidum (annual ryegrass) now dominates across the Western Australian grain belt. Weed Research 54: 314–324, DOI: 

  218. Owusu HF, Jancaryova D, Malone D and Mueller P 2015. Comparability between insecticide resistance bioassays for mosquito vectors: time to review current methodology?. Parasites & Vectors 8DOI: 

  219. Palmer JR, Herbst AL, Noller KL, Boggs DA, Troisi R, Titus-Ernstoff L, Hatch EE, Wise LA, Strohsnitter WC and Hoover RN 2009. Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study. Environmental Health 8DOI: 

  220. Pavlidi N, Khalighi M, Myridakis A, Dermauw W, Wybouw N, Tsakireli D, Stephanou EG, Labrou NE, Vontas J and Van Leeuwen T 2017. A glutathione-S-transferase (TuGSTd05) associated with acaricide resistance in Tetranychus urticae directly metabolizes the complex II inhibitor cyflumetofen. Insect Biochemistry and Molecular Biology 80: 101–115, DOI: 

  221. Peferoen M 1997. Progress and prospects for field use of Bt genes in crops. Trends in Biotechnology 15: 173–177, DOI: 

  222. Perera F and Herbstman J 2011. Prenatal environmental exposures, epigenetics, and disease. Reproductive Toxicology 31: 363–373, DOI: 

  223. Perera F, Rauh V, Tsai W-Y, Kinney P, Camann D, Barr D, Bernert T, Garfinkel R, Tu Y-H, Diaz D, Dietrich J and Whyatt R 2003. Effects of transplacental exposure to environmental pollutants on birth outcomes in a multiethnic population. Environ. Health Perspect 111: 201–205, DOI: 

  224. Perry JN, Devos Y, Arpaia S, Bartsch D, Gathmann A, Hails RS, Kiss J, Lheureux K, Manachini B, Mestdagh S, Neemann G, Ortego F, Schiemann J and Sweet JB 2010. A mathematical model of exposure of nontarget Lepidoptera to Bt-maize pollen expressing Cry1 Ab within Europe. Proceedings of the Royal Society B-Biological Sciences 277: 1417–1425, DOI: 

  225. Pestana D, Teixeira D, Faria A, Domingues V, Monteiro R and Calhau C 2015. Effects of Environmental Organochlorine Pesticides on Human Breast Cancer: Putative Involvement on Invasive Cell Ability. Environmental Toxicology 30: 168–176, DOI: 

  226. Peterson MA, Mcmaster SA, Riechers DE, Skelton J and Stahlman PW 2016. 2,4-D past, present, and future: A review. Weed Technology 30: 303–345, DOI: 

  227. Poulsen R, Luong X, Hansen M, Styrishave B and Hayes T 2015. Tebuconazole disrupts steroidogenesis in Xenopus laevisAquatic Toxicology 168: 28–37, DOI: 

  228. Rayner JL, Enoch R and Fenton S 2005. Adverse effects of prenatal exposure to atrazine during a critical period of mammary gland growth. Toxicol. Sci 87: 255–266, DOI: 

  229. Rayner JL, Enoch RR, Wolf DC and Fenton SE 2007. Atrazine-induced reproductive tract alterations after transplacental and/or lactational exposure in male Long-Evans rats. Toxicology and Applied Pharmacology 218: 238–248, DOI: 

  230. Rayner JL, Wood C and Fenton S 2004. Exposure parameters necessary for delayed puberty and mammary gland development in Long–Evans rats exposed in utero to atrazine. Toxicol. Appl. Pharmacol 195DOI: 

  231. Reeder A, Foley G, Nichols D, Hansen L, Wikoff B, Faeh S, Eisold J, Wheeler M, Warner R, Murphy J and Beasley V 1998. Forms and prevalence of intersexuality and effects of environmental contaminants on sexuality in cricket frogs (Acris crepitans). Environ. Health Perspect 106: 261–266, DOI: 

  232. Ren J, Wang XP, Xue YG, Gong P, Joswiak DR, Xu BQ and Yao TD 2014. Persistent organic pollutants in mountain air of the southeastern Tibetan Plateau: Seasonal variations and implications for regional cycling. Environmental Pollution 194: 210–216, DOI: 

  233. Rey F, Gonzalez M, Zayas MA, Stoker C, Durando M, Luque EH and Munoz-De-Toro M 2009. Prenatal exposure to pesticides disrupts testicular histoarchitecture and alters testosterone levels in male Caiman latirostrisGeneral and Comparative Endocrinology 162: 286–292, DOI: 

  234. Rivero J, Luzardo OP, Henriquez-Hernandez LA, Machin RP, Pestano J, Zumbado M, Boada LD, Camacho M and Valeron PF 2015. In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case-control study. Science of the Total Environment 537: 197–202, DOI: 

  235. Rivers J, Amato C and Mccoy K 2016. The effects of sulforaphane on vinclozolin exposed mice. Integrative and Comparative Biology 56: E358–E358.  

  236. Rodriguez V, Thiruchelvam M and Cory-Slechta D 2005. Sustained exposure to the widely used herbicide atrazine: Altered function and loss of neurons in brain monoamine systems. Environ. Health Perspect 113: 708–715, DOI: 

  237. Rohr JR, Elskus A, Shepherd B, Crowley P, Mccarthy T, Niedzwiecki J, Sager T, Sih A and Palmer B 2003. Lethal and sublethal effects of atrazine, carbaryl, endosulfan, and octylphenol on the streamside salamander (Ambystoma barbouri). Environ. Toxicol. Chem 22: 2385–2392, DOI: 

  238. Rohr JR, Swan A, Raffel TR and Hudson PJ 2009. Parasites, info-disruption, and the ecology of fear. Oecologia 159: 447–454, DOI: 

  239. Romano RM, Oliveira CA and Romano MA 2012. Glyphosate alters reproductive function by affecting the gonadotropin expression and spermatic function. Animal Reproduction (Belo Horizonte) 9: 837–1037.  

  240. Romano RM, Romano MA, Bernardi MM, Furtado PV and Oliveira CA 2010. Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology. Archives of Toxicology 84: 309–317, DOI: 

  241. Rosenberg BG, Chen HL, Folmer J, Liu J, Papadopoulos V and Zirkin BR 2008. Gestational exposure to atrazine: Effects on the postnatal development of male offspring. Journal of Andrology 29: 304–311, DOI: 

  242. Saglio P and Trijasse S 1998. Behavioral response to atrazine and diuron in goldfish. Arch. Environ. Contam. Toxicol 35: 484–491, DOI: 

  243. Sanderson JT, Boerma J, Lansbergen G and Van Den Berg M 2002. Induction and inhibition of aromatase (CYP19) activity by various classes of pesticides in H295R human adrenocortical carcinoma cells. Toxicol. Appl. Pharmacol 182: 44–54, DOI: 

  244. Sanderson JT, Letcher RJ, Heneweer M, Giesy JP and Van Den Berg M 2001. Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes. Environ. Health Perspect 109: 1027–1031, DOI: 

  245. Sanderson JT, Seinen W, Giesy JP and Van Den Berg M 2000. 2-chloro-triazine herbicides induce aromatase (CYP19) activity in H295R human adrenocortical carcinoma cells: A novel mechanism for estrogenicity?. Toxicol. Sci 54: 121–127, DOI: 

  246. Saoudi A, Frery N, Zeghnoun A, Bidondo ML, Deschamps V, Goen T, Gamier R and Guldner L 2014. Serum levels of organochlorine pesticides in the French adult population: The French National Nutrition and Health Study (ENNS), 2006–2007. Science of the Total Environment 472: 1089–1099, DOI: 

  247. Sarker M, Jatoi I and Becher H 2007. Racial differences in breast cancer survival in women under age 60. Breast Cancer Research and Treatment 106: 135–141, DOI: 

  248. Sass JB and Colangelo A 2006. European Union bans atrazine, while the United States negotiates continued use. International Journal of Occupational and Environmental Health 12: 260–267, DOI: 

  249. Schwab CL, Fan RP, Zheng Q, Myers LP, Hebert P and Pruett SB 2005. Modeling and predicting stress-induced immunosuppression in mice using blood parameters. Toxicological Sciences 83: 101–113, DOI: 

  250. Senseman SA and Grey TL 2014. The future of herbicides and genetic technology: Ramifications for environmental stewardship. Weed Science 62: 382–384, DOI: 

  251. Shaner DL 2014. Lessons learned from the history of herbicide resistance. Weed Science 62: 427–431, DOI: 

  252. Shaner DL and Beckie HJ 2014. The future for weed control and technology. Pest Management Science 70: 1329–1339, DOI: 

  253. Shimabuk RH, Frear DS, Swanson HR and Walsh WC 1971. Glutathione conjugation - enzymatic basis for atrazine resistance in corn. Plant Physiology 47: 10–14, DOI: 

  254. Sikka SC and Wang R 2008. Endocrine disruptors and estrogenic effects on male reproductive axis. Asian Journal of Andrology 10: 134–145, DOI: 

  255. Silvano D and Segalla M 2005. Conservation of Brazilian amphibians. Conserv. Biol 19: 653–658, DOI: 

  256. Šimic B, Kniewald Z, Davies J and Kniewald J 1991. Reversibility of inhibitory effect of atrazine and lindane on 5 -dihydrotestosterone receptor complex formation in rat prostate. Bull. Environ. Contam. Toxicol 46: 92–99, DOI: 

  257. Simonich SL and Hites RA 1995. Global distribution of persistent organochlorine compounds. Science 269: 1851–1854, DOI: 

  258. Skinner MK 2011. Role of epigenetics in developmental biology and transgenerational inheritance. Birth Defects Research Part C-Embryo Today-Reviews 93: 51–55, DOI: 

  259. Skinner MK, Haque C, Nilsson E, Bhandari R and Mccarrey JR 2013a. Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line. Plos One 8 

  260. Skinner MK, Manikkam M and Guerrero-Bosagna C 2011. Epigenetic transgenerational actions of endocrine disruptors. Reproductive Toxicology 31: 337–343, DOI: 

  261. Skinner MK, Manikkam M, Tracey R, Guerrero-Bosagna C, Haque M and Nilsson EE 2013b. Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity. Bmc Medicine 11DOI: 

  262. Skinner MK, Savenkova MI, Zhang B, Gore AC and Crews D 2014. Gene bionetworks involved in the epigenetic transgenerational inheritance of altered mate preference: environmental epigenetics and evolutionary biology. Bmc Genomics 15DOI: 

  263. Song Y, Wu NX, Wang SM, Gao M, Song P, Lou JL, Tan YF and Liu KC 2014. Transgenerational impaired male fertility with an Igf2 epigenetic defect in the rat are induced by the endocrine disruptor p,p’-DDE. Human Reproduction 29: 2512–2521, DOI: 

  264. Soto AM and Sonnenschein C 2015. Endocrine disruptors DDT, endocrine disruption and breast cancer. Nature Reviews Endocrinology 11: 507–508, DOI: 

  265. Stanko J, Enoch R, Rayner J, Davis C, Wolf D and Fenton S 2007. Effects of prenatal exposure to a low dose atrazine metabolite mixture on the reproductive development of male Long Evans rats. Biology of Reproduction, : 215–215, DOI: 

  266. Stanko J, Enoch R, Rayner J, Davis C, Wolf D, Malarkey D and Fenton S 2010. Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long Evans rats. Reprod. Toxicol, Aug 2 2010 Accepted Article Online. 

  267. Stevens J, Breckenridge C, Wetzel L, Gillis JH, Luempert L III and Eldridge JC 1994. Hypothesis for mammary tumorigenesis in Sprague-Dawley rats exposed to certain triazine herbicides. J. Toxicol. Environ. Health 43: 139–154, DOI: 

  268. Stipicevic S, Galzina N, Udikovic-Kolic N, Jurina T, Mendas G, Dvorscak M, Petric I, Baric K and Drevenkar V 2015. Distribution of terbuthylazine and atrazine residues in crop-cultivated soil: The effect of herbicide application rate on herbicide persistence. Geoderma 259: 300–309, DOI: 

  269. Stockholm Convention 2010. Stockholm Convention on Persistent Organic Pollutants.  Available at: 

  270. Stoker T, Laws S, Guidici D and Cooper R 2000. The effect of atrazine on puberty in male Wistar rats: An evaluation in the protocol for the assessment of pubertal development and thyroid function. Toxicol. Sci 58: 50–59, DOI: 

  271. Stokstad E 2007. Species conservation – Can the bald eagle still soar after it is delisted?. Science 316: 1689–1690, DOI: 

  272. Stuppia L, Franzago M, Ballerini P, Gatta V and Antonucci I 2015. Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health. Clinical Epigenetics 7DOI: 

  273. Suzawa M and Ingraham H 2008. The herbicide atrazine activates endocrine gene networks via non-steroidal NR5 A nuclear receptors in fish and mammalian cells. PLOS ONE 3(E2): 117. 

  274. Swan S, Kruse R, Liu F, Barr D, Drobnis E, Redmon J, Wang C, Brazil and Overstreet J 2003. Semen quality in relation to biomarkers of pesticide exposure. Environ. Health Perspect 111: 1478–1484, DOI: 

  275. Syngenta 2004.  Available: 

  276. Tebourbi O, Hallegue D, Yacoubi MT, Sakly M and Ben Rhouma K 2010. Subacute toxicity of p,p’-DDT on rat thyroid: Hormonal and histopathological changes. Environmental Toxicology and Pharmacology 29: 271–279, DOI: 

  277. Thibaut R and Porte C 2004. Effects of endocrine disrupters on sex steroid synthesis and metabolism pathways in fish. Journal of Steroid Biochemistry and Molecular Biology 92: 485–494, DOI: 

  278. Thomas DJ, Tracey B, Marshall H and Norstrom RJ 1992. Arctic terrestrial ecosystem contamination. Science of the Total Environment 122: 135–164, DOI: 

  279. Thongprakaisang S, Thiantanawat A, Rangkadilok N, Suriyo T and Satayavivad J 2013. Glyphosate induces human breast cancer cells growth via estrogen receptors. Food and Chemical Toxicology 59: 129–136, DOI: 

  280. Thurman E and Cromwell A 2000. Atmospheric transport, deposition, and fate of triazine herbicides and their metabolites in pristine areas at Isle Royale National Park. Environ. Sci. Tech 34: 3079–3085, DOI: 

  281. Tierney KB, Singh CR, Ross PS and Kennedy CJ 2007. Relating olfactory neurotoxicity to altered olfactory-mediated behaviors in rainbow trout exposed to three currently-used pesticides. Aquatic Toxicology 81: 55–64, DOI: 

  282. Tillitt DE, Papoulias DM, Whyte JJ and Richter CA 2008. Atrazine reduces reproduction in fathead minnow. Marine Environmental Research 66: 51–51.  

  283. Tohyama S, Miyagawa S, Lange A, Ogino Y, Mizutani T, Tatarazako N, Katsu Y, Ihara M, Tanaka H, Ishibashi H, Kobayashi T, Tyler CR and Iguchi T 2015. Understanding the molecular basis for differences in responses of fish estrogen receptor subtypes to environmental estrogens. Environmental Science & Technology 49: 7439–7447, DOI: 

  284. Torres-Sanchez L, Schnaas L, Rothenberg SJ, Cebrian ME, Osorio-Valencia E, Hernandez MD, Garcia-Hernandez RM and Lopez-Carrillo L 2013. Prenatal p,p’-DDE Exposure and neurodevelopment among children 3.5–5 years of age. Environmental Health Perspectives 121: 263–268.  

  285. Trosken ER, Fischer K, Volkel W and Lutz WK 2006. Inhibition of human CYP19 by azoles used as antifungal agents and aromatase inhibitors, using a new LC-MS/MS method for the analysis of estradiol product formation. Toxicology 219: 33–40, DOI: 

  286. Turgut C, Atatanir L, Mazmanci B, Mazmanci MA, Henkelmann B and Schramm KW 2012. The occurrence and environmental effect of persistent organic pollutants (POPs) in Taurus Mountains soils. Environmental Science and Pollution Research 19: 325–334, DOI: 

  287. Tyagi V, Garg N, Mustafa MD, Banerjee BD and Guleria K 2015. Organochlorine pesticide levels in maternal blood and placental tissue with reference to preterm birth: a recent trend in North Indian population. Environmental Monitoring and Assessment 187: 471–480, DOI: 

  288. Ueda M, Imai T, Takizawa T, Onodera H, Mitsumori K, Matsui T and Hirose M 2005. Possible enhancing effects of atrazine on growth of 7,12-dimethylbenz(a) anthracene induced mammary tumors in ovariectomized Sprague–Dawley rats. Cancer Sci 96: 19–25, DOI: 

  289. USEPA . The Toxic Substances Control Act (TSCA) Chemical Substance Inventory, Available at: [Online]. 

  290. USEPA 2003. Environmental Protection Agency.  FOIA Request Identification Number, HQ-RIN-0045-04. 

  291. USEPA 2015a. DDT – A Brief History and Status.  Available at: 

  292. USEPA 2015b. 

  293. USEPA 2015c. What is a Pesticide? In: EPA. Available at: 

  294. USEPA 2016a. Atrazine, Propazine, Simazine and their Chlorometabolites DACT, DEA And DIA Listed as Reproductive Toxicants, [Online]. Available: 

  295. USEPA 2016b. [Online]. 

  296. USEPA 2017. Pesticides Industry Sales and Usage: 2008–2012 Market Estimates. 

  297. Uzumcu M, Suzuki H and Skinner M 2004. Effect of the anti-androgenic endocrine disruptor vinclozolin on embryonic testis cord formation and postnatal testis development and function. Reprod. Toxicol 18: 765–774, DOI: 

  298. Vandegehuchte MB and Janssen CR 2011. Epigenetics and its implications for ecotoxicology. Ecotoxicology 20: 607–624, DOI: 

  299. Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR, Lee DH, Myers JP, Shioda T, Soto AM, Vom Saal FS, Welshons WV and Zoeller RT 2013. Regulatory decisions on endocrine disrupting chemicals should be based on the principles of endocrinology. Reproductive Toxicology 38: 1–15, DOI: 

  300. Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR, Lee DH, Shioda T, Soto A, Vom Saal F, Welshons W, Zoeller R and Myers J 2012. Hormones and endocrine disrupting chemicals: Low dose effects and non-monotonic dose responses. Endocrine Reviews 33: 378–455, DOI: 

  301. Varanasi VK, Godar AS, Currie RS, Dille AJ, Thompson CR, Stahlman PW and Jugulam M 2015. Field-evolved resistance to four modes of action of herbicides in a single kochia (Kochia scoparia L. Schrad.) population. Pest Management Science 71: 1207–1212, DOI: 

  302. Victor-Costa AB, Bandeira SMC, Oliveira AG, Mahecha GAB and Oliveira CA 2010. Changes in testicular morphology and steroidogenesis in adult rats exposed to atrazine. Reproductive Toxicology 29: 323–331, DOI: 

  303. Vredenburg VT, Koos MS, Wake DB, Stuart SN, Hoffmann M, Chanson J, Cox N, Berridge R, Ramani P and Young B 2008. Amphibian declines in California. Threatened Amphibians of the World 91 

  304. Wagner N, Rodder D, Bruhl CA, Veith M, Lenhardt PP and Lotters S 2014. Evaluating the risk of pesticide exposure for amphibian species listed in Annex II of the European Union Habitats Directive. Biological Conservation 176: 64–70, DOI: 

  305. Wake DB and Vredenburg VT 2008. Are we in the midst of the sixth mass extinction? A view from the world of amphibians. Proc. Natl. Acad. Sci. USA 105: 11466–11473, DOI: 

  306. Waller SA, Paul K, Peterson SE and Hitti J 2010. Agricultural-related chemical exposures, season of conception, and risk of gastroschisis in Washington State. American Journal of Obstetrics and Gynecology 203: 183–183.  

  307. Walters JL, Lansdell TA, Lookingland KJ and Baker LE 2015. The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats. Toxicology and Applied Pharmacology 289: 185–192, DOI: 

  308. Wanjala CL, Mbugi JP, Ototo E, Gesuge M, Afrane YA, Atieli HE, Zhou G, Githeko AK and Yan G 2015. Pyrethroid and DDT Resistance and Organophosphate Susceptibility among Anopheles spp. Mosquitoes, Western Kenya. Emerging Infectious Diseases 21: 2178–2181, DOI: 

  309. Waters CN, Zalasiewicz J, Summerhayes C, Barnosky AD, Poirier C, Galuszka A, Cearreta A, Edgeworth M, Ellis EC, Ellis M, Jeandel C, Leinfelder R, Mcneill JR, Richter DD, Steffen W, Syvitski J, Vidas D, Wagreich M, Williams M, An ZS, Grinevald J, Odada E, Oreskes N and Wolfe AP 2016. The Anthropocene is functionally and stratigraphically distinct from the Holocene. Science 351: 137–140, DOI: 

  310. Whalen M, Loganathan B, Yamashita N and Saito T 2003. Immunomodulation of human natural killer cell cytotoxic function by triazine and carbamate pesticides. Chemico-Biological Interactions 145: 311–319, DOI: 

  311. Williams M, Zalasiewicz J, Waters CN, Edgeworth M, Bennett C, Barnosky AD, Ellis EC, Ellis MA, Cearreta A, Haff PK, Do Sul JAI, Leinfelder R, Mcneill JR, Odada E, Oreskes N, Revkin A, Richter DD, Steffen W, Summerhayes C, Syvitski JP, Vidas D, Wagreich M, Wing SL, Wolfe AP and An ZS 2016. The Anthropocene: a conspicuous stratigraphical signal of anthropogenic changes in production and consumption across the biosphere. Earths Future 4: 34–53, DOI: 

  312. Winchester PD, Huskins J and Ying J 2009. Agrichemicals in surface water and birth defects in the United States. Acta Paediatrica 98: 664–669, DOI: 

  313. Wong LIL, Labrecque MP, Ibuki N, Cox ME, Elliott JE and Beischlag TV 2015. p,p’-Dichlorodiphenyltrichloroethane (p,p’-DDT) and p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE) repress prostate specific antigen levels in human prostate cancer cell lines. Chemico-Biological Interactions 230: 40–49, DOI: 

  314. Woodhams DC, Rollins-Smith LA, Carey C, Reinert L, Tyler MJ and Alford RA 2006. Population trends associated with skin peptide defenses against chytridiomycosis in Australian frogs. Oecologia 146: 531–540, DOI: 

  315. Woodwell GM, Wurster CF and Isaacson PA 1967. DDT residues in an east coast estuary- A case of biological concentration of a persistent pesticide. Science 156: 821–824, DOI: 

  316. Yaglova NV and Yaglov VV 2014. Changes in Thyroid Status of Rats after Prolonged Exposure to Low Dose Dichlorodiphenyltrichloroethane. Bulletin of Experimental Biology and Medicine 156: 760–762, DOI: 

  317. Yamamoto H, Nakamura Y, Moriguchi S, Nakamura Y, Honda Y, Tamura I, Hirata Y, Hayashi A and Sekizawa J 2009. Persistence and partitioning of eight selected pharmaceuticals in the aquatic environment: Laboratory photolysis, biodegradation, and sorption experiments. Water Research 43: 351–362, DOI: 

  318. Yang LJ, Li XQ, Zhang PF, Melcer ME, Wu YX and Jans U 2012. Concentrations of DDTs and dieldrin in Long Island Sound sediment. Journal of Environmental Monitoring 14: 878–885, DOI: 

  319. Yang RQ, Zhang SJ, Li A, Jiang GB and Jing CY 2013. Altitudinal and spatial signature of persistent organic pollutants in soil, lichen, conifer needles, and bark of the southeast Tibetan Plateau: Implications for sources and environmental cycling. Environmental Science & Technology 47: 12736–12743, DOI: 

  320. Yang X, He C, Xie W, Liu YT, Xia JX, Yang ZZ, Guo LT, Wen YN, Wang SL, Wu QJ, Yang FS, Zhou XM and Zhang YJ 2016. Glutathione S-transferases are involved in thiamethoxam resistance in the field whitefly Bemisia tabaci Q (Hemiptera: Aleyrodidae). Pesticide Biochemistry and Physiology 134: 73–78, DOI: 

  321. Yu Q and Powles S 2014. Metabolism-Based Herbicide Resistance and Cross-Resistance in Crop Weeds: A Threat to Herbicide Sustainability and Global Crop Production. Plant Physiology 166: 1106–1118, DOI: 

  322. Zalasiewicz J, Waters CN, Williams M, Barnosky AD, Cearreta A, Crutzen P, Ellis E, Ellis MA, Fairchild IJ, Grinevald J, Haff PK, Hajdas I, Leinfelder R, Mcneill J, Odada EO, Poirier C, Richter D, Steffen W, Summerhayes C, Syvitski JPM, Vidas D, Wagreich M, Wing SL, Wolfe AP, Zhisheng A and Oreskes N 2015. When did the Anthropocene begin? A mid-twentieth century boundary level is stratigraphically optimal. Quaternary International 383: 196–203, DOI: 

  323. Zeljezic D, Garaj-Vrhovac V, Perkovic P and Daya S 2006. Evaluation of DNA damage induced by atrazine and atrazine-based herbicide in human lymphocytes in vitro using a comet and DNA diffusion assay. Toxicol. In Vitro 20: 923–935, DOI: 

  324. Zhang J, Zhang J, Liu R, Gan J, Liu J and Liu W 2016. Endocrine-Disrupting Effects of Pesticides through Interference with Human Glucocorticoid Receptor. Environmental Science & Technology 50: 435–443, DOI: 

  325. Zhang L, Zheng X-M, Zheng H, Yang Z-W and Li S-W 2009. The effect of diethylstilbestrol on inducing abdominal cryptorchidism and relevant genetic expression in rats. Zhonghua Yufang Yixue Zazhi 43: 413–417.  

  326. Zhuang S, Zhang J, Wen Y, Zhang C and Liu W 2012. Distinct mechanisms of endocrine disruption of DDT-related pesticides toward estrogen receptor alpha and estrogen-related receptor gamma. Environmental Toxicology and Chemistry 31: 2597–2605, DOI: 

  327. Zimmer KE, Montano M, Olsaker I, Dahl E, Berg V, Karlsson C, Murk AJ, Skaare JU, Ropstad E and Verhaegen S 2011. In vitro steroidogenic effects of mixtures of persistent organic pollutants (POPs) extracted from burbot (Lota lota) caught in two Norwegian lakes. Science of the Total Environment 409: 2040–2048, DOI: 

comments powered by Disqus