The use of developmental neurotoxicity data in pesticide risk assessments

Raffaele, Kathleen C.; Rowland, Jess; May, Brenda; Makris, Susan L.; Schumacher, Kelly; Scarano, Louis

doi:10.1016/j.ntt.2010.04.053

Cited by 64 publications

(34 citation statements)

References 30 publications

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“…In contrast, a few observations report of in vitro and in vivo effects of OPs at concentrations or doses below those required to inhibit brain AChE catalytic activity [95, 99]. These findings, together with results of biomonitoring studies that indicate exposure of children, particularly in inner cities and in farming communities, to Ops [100, 101], have led to regulatory restrictions on the residential use of certain OPs (e.g., diazinon, chlorpyrifos), and to heightened concern for their potential neurotoxic effects in children [98, 102–104]. For example, a series of studies in different cohorts in New York City and California have reported associations between developmental exposure to chlorpyrifos and other OPs and neurodevelopmental abnormalities in the domains of reflexes and cognitive performance [105–108].…”

Section: Organophosphorus (Op) Insecticidesmentioning

confidence: 99%

Developmental Neurotoxicity: Some Old and New Issues

Giordano

Costa

2012

ISRN Toxicology

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The developing central nervous system is often more vulnerable to injury than the adult one. Of the almost 200 chemicals known to be neurotoxic, many are developmental neurotoxicants. Exposure to these compoundsin uteroor during childhood can contribute to a variety of neurodevelopmental and neurological disorders. Two established developmental neurotoxicants, methylmercury and lead, and two classes of chemicals, the polybrominated diphenyl ether flame retardants and the organophosphorus insecticides, which are emerging as potential developmental neurotoxicants, are discussed in this paper. Developmental neurotoxicants may also cause silent damage, which would manifest itself only as the individual ages, and may contribute to neurodegenerative diseases such as Parkinson’s or Alzheimer’s diseases. Guidelines for developmental neurotoxicity testing have been implemented, but there is still room for their improvement and for searching and validating alternative testing approaches.

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Section: Organophosphorus (Op) Insecticidesmentioning

confidence: 99%

Developmental Neurotoxicity: Some Old and New Issues

Giordano

Costa

2012

ISRN Toxicology

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“…Only about 200 chemicals and pesticides have undergone testing according to the Organisation for Economic Co-operation and Development (OECD) Test Guideline 426 for animal-based developmental neurotoxicity testing (OECD 2007) or its precursor documents (Makris et al 2009). The available comparative toxicity data for these compounds indicate that mammals are often particularly sensitive to this form of hazard compared to other forms of toxicity (Raffaele et al 2010). …”

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confidence: 99%

Evaluation of Developmental Toxicants and Signaling Pathways in a Functional Test Based on the Migration of Human Neural Crest Cells

Zimmer

Lee

Balmer

et al. 2012

Environ Health Perspect

115

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Background: Information on the potential developmental toxicity (DT) of the majority of chemicals is scarce, and test capacities for further animal-based testing are limited. Therefore, new approaches with higher throughput are required. A screening strategy based on the use of relevant human cell types has been proposed by the U.S. Environmental Protection Agency and others. Because impaired neural crest (NC) function is one of the known causes for teratologic effects, testing of toxicant effects on NC cells is desirable for a DT test battery.Objective: We developed a robust and widely applicable human-relevant NC function assay that would allow for sensitive screening of environmental toxicants and defining toxicity pathways.Methods: We generated NC cells from human embryonic stem cells, and after establishing a migration assay of NC cells (MINC assay), we tested environmental toxicants as well as inhibitors of physiological signal transduction pathways.Results: Methylmercury (50 nM), valproic acid (> 10 µM), and lead-acetate [Pb(CH3CO2)4] (1 µM) affected the migration of NC cells more potently than migration of other cell types. The MINC assay correctly identified the NC toxicants triadimefon and triadimenol. Additionally, it showed different sensitivities to various organic and inorganic mercury compounds. Using the MINC assay and applying classic pharmacologic inhibitors and large-scale microarray gene expression profiling, we found several signaling pathways that are relevant for the migration of NC cells.Conclusions: The MINC assay faithfully models human NC cell migration, and it reveals impairment of this function by developmental toxicants with good sensitivity and specificity.

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“…organophoshates (OP) and carbamates, pyrethroids, and organochlorines, although other groups or individual compounds might also show neurotoxic properties. Consequently, the issue of possible effects by pesticides on the normal development of the central nervous system was raised and ways of addressing the identification and prevention of these effects have been discussed (Barlow et al, 2007; Eskenazi et al, 2008; Fitzpatrick et al, 2008; Raffaele et al, 2010). In particular, in the USA the passage in 1996 of the Food Quality Protection Act mandated an increased effort on the assessment of the potential toxicity of pesticides to children, and a special focus was given to developmental neurotoxicity (Raffaele et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…According Raffaele et al (2010), as of December 2008, DNT studies on 72 pesticide active ingredients have been performed and submitted for review to the EPA. The study design included treatment of rat dams from gestational day 6 to post-natal day 11 or 21, the latter being the experimentally preferred one.…”

Section: Introductionmentioning

confidence: 99%

Neurobehavioral and neurodevelopmental effects of pesticide exposures

et al. 2012

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The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective and neurodevelopmental outcomes amongst occupational (both adolescent and adult workers) and non-occupational populations (children). The symposium discussion highlighted many challenges for researchers concerned with the prevention of neurotoxic illness due to pesticides and generated a number of directions for further research and policy interventions for the protection of human health, highlighting the importance of examining potential long-term effects across the lifespan arising from early adolescent, childhood or pre-natal exposure.

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The use of developmental neurotoxicity data in pesticide risk assessments

Cited by 64 publications

References 30 publications

Developmental Neurotoxicity: Some Old and New Issues

Developmental Neurotoxicity: Some Old and New Issues

Evaluation of Developmental Toxicants and Signaling Pathways in a Functional Test Based on the Migration of Human Neural Crest Cells

Neurobehavioral and neurodevelopmental effects of pesticide exposures

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