Analysis and Integration of Developmental Neurotoxicity and Ancillary Data into Risk Assessment: A Case Study of Dimethoate

DeSesso, John M.; Watson, Rebecca; Keen, Carl L.; Hazelden, Keith P.; Haws, Laurie C.; Li, Abby A.

doi:10.1080/15287390802477452

Cited by 12 publications

(8 citation statements)

References 22 publications

(24 reference statements)

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“…Maternal influences during gestation and lactation may exert significant effects on developmental outcomes. Therefore, the litter of origin needs to be accounted for in evaluating neurodevelopmental outcomes for both gestational and postnatal exposures (DeSesso et al, 2009; Holson et al, 2008; Holson and Pearce, 1992). Studies that selected one offspring per original litter exposed or included litter of origin as a factor in the statistical analyses met this criterion.…”

Section: Approach To Evaluation Of Animal Studiesmentioning

confidence: 99%

“…One rationale for this practice is “to distribute any maternal caretaking differences randomly across litters and treatment groups” (Aldridge et al, 2003). This rationale may not fully consider that maternal caretaking has much more impact during early lactation when pups are fully dependent on the dam (DeSesso et al, 2009). It is also possible for maternal care in treated groups to be disproportionally impacted by the combination of (a) repeated disruption of dams and reconstituted litters and (b) sc injection of pups postnatally with test material that might cause acute toxicity in pups (e.g., 75% AChE inhibition 2 h after PND 1 dosing with 1 mg/kg CPF in Dam et al, 2000) as well as potentially causing the pups to taste or smell different.…”

Section: Approach To Evaluation Of Animal Studiesmentioning

confidence: 99%

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Pesticide Exposure and Neurodevelopmental Outcomes: Review of the Epidemiologic and Animal Studies

Burns

McIntosh²,

Mink

et al. 2013

Journal of Toxicology and Environmental Health, Part B

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157

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Assessment of whether pesticide exposure is associated with neurodevelopmental outcomes in children can best be addressed with a systematic review of both the human and animal peer-reviewed literature. This review analyzed epidemiologic studies testing the hypothesis that exposure to pesticides during pregnancy and/or early childhood is associated with neurodevelopmental outcomes in children. Studies that directly queried pesticide exposure (e.g., via questionnaire or interview) or measured pesticide or metabolite levels in biological specimens from study participants (e.g., blood, urine, etc.) or their immediate environment (e.g., personal air monitoring, home dust samples, etc.) were eligible for inclusion. Consistency, strength of association, and dose response were key elements of the framework utilized for evaluating epidemiologic studies. As a whole, the epidemiologic studies did not strongly implicate any particular pesticide as being causally related to adverse neurodevelopmental outcomes in infants and children. A few associations were unique for a health outcome and specific pesticide, and alternative hypotheses could not be ruled out. Our survey of the in vivo peer-reviewed published mammalian literature focused on effects of the specific active ingredient of pesticides on functional neurodevelopmental endpoints (i.e., behavior, neuropharmacology and neuropathology). In most cases, effects were noted at dose levels within the same order of magnitude or higher compared to the point of departure used for chronic risk assessments in the United States. Thus, although the published animal studies may have characterized potential neurodevelopmental outcomes using endpoints not required by guideline studies, the effects were generally observed at or above effect levels measured in repeated-dose toxicology studies submitted to the U.S. Environmental Protection Agency (EPA). Suggestions for improved exposure assessment in epidemiology studies and more effective and tiered approaches in animal testing are discussed.

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Section: Approach To Evaluation Of Animal Studiesmentioning

confidence: 99%

Section: Approach To Evaluation Of Animal Studiesmentioning

confidence: 99%

Pesticide Exposure and Neurodevelopmental Outcomes: Review of the Epidemiologic and Animal Studies

Burns

McIntosh²,

Mink

et al. 2013

Journal of Toxicology and Environmental Health, Part B

Self Cite

157

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“…Additional studies and analyses indicate the increased pup mortality at 3.0 mg/kg in this developmental neurotoxicity study was due to clustering of pup deaths in a few litters and was likely related to maternal care deficits in affected litters (357,358). Three other studies in which dams were dosed with 0, 0.1, 0.5, 3.0, or 6.0 mg/kg on gestation days 6 through postnatal day 10 observed increased pup mortality only at 6.0 mg/kg/day (357).…”

Section: Genetic and Related Cellular Effect Studiesmentioning

confidence: 79%

Organophosphorus Pesticides

Storm¹

2012

Patty's Toxicology

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Most organophosphorus compounds today fall into two general groups: the so‐called nerve agents, that are very acutely toxic and organophosphorus pesticides that are less toxic. Nerve agents were generally the first toxic organophosphorus developed, and were the original basis for organophosphorus pesticides. Interest about nerve agents has increased lately given concerns about their potential use in terrorist acts. Organophosphate nerve agents and pesticides are a highly diverse group of chemicals. They are all characterized by their ability to inhibit the enzyme acetylcholinesterase (AChE) that deactivates the neurotransmitter acetylcholine (ACh). At present, the widest use of organophosphorus compounds is as pesticides, although they have also been used as therapeutic agents, gasoline additives, hydraulic fluids, cotton defoliants, fire retardants, plastic components, growth regulators, and industrial intermediates to a much smaller extent. Compounds in this class are numerous and have been categorized in many ways according to the nature of the substituents. Gallo and Lawryk (1991) [2], for example, categorized them into four main groups I–IV based on the characteristics of the leaving group (X). Group I compounds, phosphorylcholines, have a leaving group that contains a quaternary nitrogen and are among the most potent organophosphates (e.g., Shradan). Group II compounds, fluorophosphates, have a fluoride leaving group and are also generally highly toxic (e.g., diisopropyl fluorophosphate). Group III compounds have leaving groups that contain cyanide or a halogen other than fluoride and are generally less potent than group I or II (e.g., Parathion). Group IV contains most of the organophosphates used as insecticides today. These compounds have alkoxy, alkylthio, aryloxy, arylthio, or heterocyclic leaving groups and a wide variety of other substituents. Another classification scheme is based on the nature of the atoms that immediately surround the central phosphorus atom and results in 14 different categories. According to this scheme, phosphates are the prototype for the entire class and are those compounds where all four atoms that surround the phosphorus atom are oxygen (e.g., dichlorvos, mevinphos). Sulfur‐containing organophosphate compounds (phosphorothioates, phosphorothiolates, phosphorodithioates, and phosphorodithiolates) are far more numerous than phosphates and include well‐recognized organophosphate insecticides such as parathion, diazinon, chlorpyrifos, etc. Other groups contain nitrogen (phosphoramides and phosphorodiamides), nitrogen and sulfur (phosphoramidothionates and phosphoramidothiolates), carbon (phosphonates and phosphinates), or carbon and sulfur (phosphonothionates, phosphonothionothiolates, and phosphinothionates). All aspects of organophosphate chemistry, toxicity, analysis, and exposure potential have been previously and comprehensively reviewed. In addition, information regarding the toxicity of organophosphorus pesticides in particular has expanded greatly in recent years as a result of toxicity data supplied by registrants to the U.S. EPA's Office of Pesticides to support reregistration. These data have been made publicly available by the U.S. EPA on its Internet Web site ( www.epa.gov/pesticides ). The following discussion draws heavily from recent reviews and also includes summaries of relevant toxicity data submitted to, and made available by, the U.S. EPA.

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“…Statistical analysis was conducted using SPSS v.10 (SPSS, Inc.) software. The litter was the statistical unit for all analysis (Desesso et al, 2009). Parametric data were analyzed by one-way analysis of variance (ANOVA).…”

Section: Discussionmentioning

confidence: 99%

The effects of marginal maternal vitamin A status on penta‐brominated diphenyl ether mixture‐induced alterations in maternal and conceptal vitamin A and fetal development in the Sprague Dawley rat

Ellis-Hutchings

Cherr

Hanna

et al. 2009

Birth Defects Research Pt B

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Analysis and Integration of Developmental Neurotoxicity and Ancillary Data into Risk Assessment: A Case Study of Dimethoate

Cited by 12 publications

References 22 publications

Pesticide Exposure and Neurodevelopmental Outcomes: Review of the Epidemiologic and Animal Studies

Pesticide Exposure and Neurodevelopmental Outcomes: Review of the Epidemiologic and Animal Studies

Organophosphorus Pesticides

The effects of marginal maternal vitamin A status on penta‐brominated diphenyl ether mixture‐induced alterations in maternal and conceptal vitamin A and fetal development in the Sprague Dawley rat

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