Derek W Gammon

Bio: Derek W Gammon is an academic researcher from FMC Corporation. The author has contributed to research in topics: Acute toxicity & Resmethrin. The author has an hindex of 9, co-authored 17 publications receiving 360 citations.

A risk assessment of atrazine use in California: human health and ecological aspects†

Abstract: A risk assessment of the triazine herbicide atrazine has been conducted by first analyzing the toxicity database and subsequently estimating exposure. Margins of safety (MOS) were then calculated. Toxicity was assessed in animal studies and exposure was estimated from occupational and dietary sources. In acute toxicity studies, atrazine caused developmental toxicity in the rabbit [no observed effect level (NOEL) 5 mg kg(-1) day(-1)] and cardiotoxicity in a dog chronic study (NOEL 0.5 mg kg(-1) day(-1)); cancer (mammary glands) resulted from lifetime exposure. The mammary tumors, which occurred specifically in female Sprague-Dawley rats, were malignant, increased in a dose-dependent manner and were also observed with other, related triazines. Evidence for a genotoxic basis for these tumors was either equivocal or negative. Triazines have been shown to be clastogenic in Chinese hamster ovary cells, in vitro, but without showing a convincing dose/response relationship. Atrazine can be converted into genotoxic N-nitrosoatrazine in the environment or the digestive system, suggesting that N-nitrosamines derived from triazines could be oncogenic. However, it was concluded that N-nitrosotriazines are unlikely to play a significant role in triazine-induced rat mammary gland tumors. An endocrine basis for the mammary tumors, involving premature aging of the female SD rat reproductive system, has been proposed. A suppression of the luteinizing hormone surge during the estrus cycle by atrazine leads to the maintenance of elevated blood levels of 17beta-estradiol (E2) and prolactin. The mechanism for tumor development may include one or more of the following: the induction of aromatase (CYP19) and/or other P450 oxygenases, an antagonist action at the estrogen feedback receptor in the hypothalamus, an agonist action at the mammary gland estrogen receptor or an effect on adrenergic neurons in the hypothalamic-pituitary pathway. None of these has been excluded as a target because there has been a lack of a rigorous attempt to address the mechanism of action for mammary tumors at the molecular level. The potential occupational exposure to atrazine was assessed during mixing, loading and application. Absorbed daily dosage values were 1.8-6.1 microg kg(-1) day(-1). The MOS values (animal NOEL/human exposure) for short-term (acute) exposure were 820-2800. Longer-term occupational exposure and risk were also calculated. Detectable crop residues are generally absent at harvest. Theoretical calculations of acute dietary exposure used tolerance levels, along with secondary residues, and water, for which there is a maximum contamination level; atrazine plus the three main chlorotriazine metabolites were combined. MOS values were above 2000 for all population subgroups. Dietary exposure to atrazine is therefore extremely unlikely to result in human health hazard. Recent publications have reported a possible feminization of frogs, measured in laboratory and field studies. This is assumed to be due to the induction of aromatase, but no measurements of enzyme activity have been reported. In field studies, the water bodies with the greatest numbers of deformed frogs sometimes had the lowest concentrations of atrazine. Other studies have also cast doubt on the feminization theory, except perhaps at very high levels of atrazine. Epidemiology studies have investigated the possibility that atrazine may result in adverse effects in humans. Although some studies have claimed that atrazine exposure results in an elevated risk of prostate cancer, the published literature is inconclusive with respect to cancer incidence.

Encyclopedia of agrochemicals

Abstract: This text is part of a three-volume encyclopaedia which provides a comprehensive compilation of agrochemicals that should be of interest to professionals and scientists in agriculture and chemistry.

Organosilane insecticides. Part I: Biological and physical effects of isosteric replacement of silicon for carbon in etofenprox and MTI‐800

Abstract: Substitution of silicon for carbon was explored in etofenprox and MTI-800, primarily to establish the suitability of silicon for pesticide construction and to probe steric effects. It was shown that silicon is an effective building block for insecticides with subtle qualitative and quantitative differences relative to the carbon analogs. The silanes were slightly less toxic to insects than the carbon analogs (relative potency of 0.2-0.6) but the silane analog of MTI-800 was considerably less toxic to fish (0% mortality at ≥50 mg liter−1) than MTI-800 itself (LC50 = 3 mg liter−1). The mode of action of both carbon and silicon compounds was similar in the intact, electrode-implanted cockroach and involved repetitive firing of a sensory nerve; potency measurements were also made using an in-vitro nerve assay. The possible metabolic and physicochemical contributions to the observed insecticide potencies were explored using synergism studies, physical chemistry measurements and quantum mechanical calculations.

Pyrethroid neurotoxicity studies with bifenthrin indicate a mixed Type I/II mode of action.

Abstract: Background Bifenthrin is usually considered a Type I pyrethroid, because it lacks an α-CN group present in Type II pyrethroids, but some previous studies suggest a mixed Type I/II mode-of-action. Results are presented for bifenthrin in a rat developmental neurotoxicity (DNT) study along with effects on Na currents in human VGSC subtypes. Molecular modeling comparisons were also made for bifenthrin and other pyrethroids. Results In a rat DNT study, bifenthrin produced tremors and clonic convulsions in dams and pups and slightly reduced acoustic startle response amplitude, and increased Tmax, at PND20 in females. Similar blood levels of bifenthrin were measured in dams and pups at each dose level i.e. no concentration in pups. In human VGSC experiments, using the Nav1.8 subtype, bifenthrin's effects on inactivation were slight, as for Type II pyrethroids, but without large prolongation of the tail current (deactivation) seen with Type II. Molecular modeling of bifenthrin indicates that the o-Me group may occupy a similar space to the α-CN group of cypermethrin and fenpropathrin. Conclusion In a DNT study and on human Nav1.8 tail currents bifenthrin showed Type I and II effects, similar to some published studies. Overall, bifenthrin acts as a mixed Type I/II pyrethroid. © 2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Carbofuran occupational dermal toxicity, exposure and risk assessment

Abstract: BACKGROUND: Carbofuran is a carbamate insecticide that inhibits AChE. Although toxic by ingestion in mammals, it has low dermal toxicity, with relatively few confirmed worker illnesses. This risk assessment describes its time of onset, time to peak effect and time to recovery in rats using brain AChE inhibition in acute and 21 day dermal studies; in vitro rat/human relative dermal absorption for granular (5G) and liquid (4F) formulations; occupational exposure estimates using the Pesticide Handlers' Exposure Database and Agricultural Handlers' Exposure Database (PHED/AHED). RESULTS: The point of departure for acute risk calculation (BMDL10) was 6.7 mg kg−1 day−1 for brain AChE inhibition after 6 h exposure. In a 21 day study, the BMDL10 was 6.8 mg kg−1 day−1, indicating reversibility. At 75 mg kg−1 day−1, time of onset was ⩽30 min and time to peak effect was 6–12 h. Rat skin had ca tenfold greater dermal absorption of carbofuran (Furadan® 5G or 4F) than human skin. Exposure estimates for 5G in rice and 4F in ten crops had adequate margins of exposure (>100). CONCLUSION: Rat dermal carbofuran toxicity was assessed in terms of dose and time-related inhibition of AChE. Comparative dermal absorption in rats was greater than in humans. Worker exposure estimates indicated acceptable risk for granular and liquid formulations of carbofuran. Copyright © 2011 Society of Chemical Industry

EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

Abstract: The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions.

The Unique Role of Fluorine in the Design of Active Ingredients for Modern Crop Protection

Abstract: The task of inventing and developing active ingredients with useful biological activities requires a search for novel chemical substructures. This process may trigger the discovery of whole classes of chemicals of potential commercial interest. Similar biological effects can often be achieved by completely different compounds. However, compounds within a given structural family may exhibit quite different biological activities depending on their interactions with different intracellular proteins like enzymes or receptors. By varying the functional groups and structural elements of a lead compound, its interaction with the active site of the target protein, as well as its physicochemical, pharmacokinetic, and dynamic properties can be improved. In this context, the introduction of fluorine into active ingredients has become an important concept in the quest for a modern crop protection product with optimal efficacy, environmental safety, user friendliness, and economic viability. Fluorinated organic compounds represent an important and growing family of commercial agrochemicals. A number of recently developed agrochemical candidates represent novel classes of chemical compounds with new modes of action; several of these compounds contain new fluorinated substituents. However, the complex structure-activity relationships associated with biologically active molecules mean that the introduction of fluorine can lead to either an increase or a decrease in the efficacy of a compound depending on its changed mode of action, physicochemical properties, target interaction, or metabolic susceptibility and transformation. Therefore, it is still difficult to predict the sites in a molecule at which fluorine substitution will result in optimal desired effects.

Effects of Atrazine on Fish, Amphibians, and Aquatic Reptiles: A Critical Review

Abstract: The herbicide atrazine is widely used in agriculture for the production of corn and other crops. Because of its physical and chemical properties, atrazine is found in small concentrations in surface waters—habitats for some species. A number of reports on the effects of atrazine on aquatic vertebrates, mostly amphibians, have been published, yet there is inconsistency in the effects reported, and inconsistency between studies in different laboratories. We have brought the results and conclusions of all of the relevant laboratory and field studies together in this critical review and assessed causality using procedures for the identification of causative agents of disease and ecoepidemiology derived from Koch’s postulates and the Bradford‐Hill guidelines. Based on a weight of evidence analysis of all of the data, the central theory that environmentally relevant concentrations of atrazine affect reproduction and/or reproductive development in fish, amphibians, and reptiles is not supported by the vast majority of observations. The same conclusions also hold for the supporting theories such as induction of aromatase, the enzyme that converts testosterone to estradiol. For other responses, such as immune function, stress endocrinology, parasitism, or population-level effects, there are no indications of effects or there is such a paucity of good data that definitive conclusions cannot be made.