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.2009.04.056

Cited by 12 publications

(25 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These authors confirmed previous reports that the DNT guidelines are capable of detecting known human developmental neurotoxicants 18) . Multiple independent expert scientific peer reviews affirm these conclusions 3,17,19) . However, the large cost and time required for DNT testing means that a large percentage of environmental contaminants remain unevaluated for their potential DNT risks.…”

Section: Introductionmentioning

confidence: 79%

“…It is important to note that the neurobehavioral testing conducted in these pharmaceutical safety studies did address all of the neuro-endpoints required for DNT guideline studies. A latter study of 69 DNT studies submitted to the U.S. EPA Office of Pesticide Programs (OPP) in support of pesticide registration found that 15 had been used to determine the point of departure for one or more risk assessment scenarios, and an additional 13 were determined to have the potential for use as a point of departure for future risk assessments 3) . Neuro-endpoints affected at the lowest doses indicated that no single parameter was consistently more sensitive than another, but early postnatal assessments tended to be more sensitive than adult assessments.…”

Section: Basic Concept Of Developmental Neurotoxicitymentioning

confidence: 99%

“…Not a little concern has been growing on adverse effects of xenobiotics which would be taken through maternal and/ or children's foods and drinks on the developing nervous system of fetuses, infants and/or children [1][2][3][4] . One of the most well-known examples is the neurological abnormalities caused by developmental exposures to methyl mercury.…”

Section: Introductionmentioning

confidence: 99%

“…Children's exposures to developmental neurotoxicants also occur via both inhalation and dermal exposures to environmental contaminants. Other well-known or suspected developmental neurotoxicants include ethanol, antidepressant or anticonvulsant pharmaceuticals, arsenic, lead, toluene, polychlorinated biphenyls (PCBs), organophosphate or organochlorine pesticides and a variety of industrial chemicals 3,[9][10][11][12][13][14][15] . The number of chemicals known to be developmentally neurotoxic in humans is limited at present.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Developmental Neurotoxicology: History and Outline of Developmental Neurotoxicity Study Guidelines

Aoyama¹,

Takahashi²,

Shutoh³

et al. 2015

Food Safety

View full text Add to dashboard Cite

The present work provides a brief review of basic concepts in developmental neurotoxicology, as well as current representative testing guidelines for evaluating developmental neurotoxicity (DNT) of xenobiotics. Historically, DNT was initially recognized as a "functional" teratogenicity: the main concern was that prenatal and/or early postnatal exposures to chemicals during critical periods of central nervous system (CNS) development would cause later functional abnormalities of the brain. Current internationally harmonized DNT study guidelines are thus intended to predict adverse effects of test compounds on the developing CNS by observing such postnatal parameters as motor activity, startle response, and learning and memory, as well as neuropathological alterations. The reliability of current DNT study guidelines and sensitivity of testing methodologies recommended in these guidelines have been confirmed by retrospective evaluations of the many international and domestic collaborative validation studies in developed nations including Japan.

show abstract

Section: Introductionmentioning

confidence: 79%

Section: Basic Concept Of Developmental Neurotoxicitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Developmental Neurotoxicology: History and Outline of Developmental Neurotoxicity Study Guidelines

Aoyama¹,

Takahashi²,

Shutoh³

et al. 2015

Food Safety

View full text Add to dashboard Cite

show abstract

“…The paradigm for regulatory testing of developmental neurotoxicology (DNT) has been the subject of much scientific debate and has been reviewed by expert groups (Raffaele et al, 2010, Makris et al, 2009). On-going discussions concern matters such as whether or not the OECD Test Guideline (TG) 426 for DNT testing (OECD, 2007) is sensitive and/or reliable enough to serve as a basis for the risk assessment of DNT in humans, and if corresponding guidance documents (OECD, 2008, OECD, 2004 are detailed enough.…”

Section: Discussion and Recommendationsmentioning

confidence: 99%

Literature review on in vitro and alternative Developmental Neurotoxicity (DNT) testing methods

Fritsche

Alm

Baumann

et al. 2015

EFSA Supporting Publications

View full text Add to dashboard Cite

The goal of this systematic review performed under a contract with EFSA was the evaluation of information on assessment methods in the field of developmental neurotoxicity (DNT). Therefore, a systematic and comprehensive literature search and collection of scientific literature and all other relevant grey literature and website information (in English) from past 20 years until mid of April 2014 on the state of the art of in vivo DNT testing methods including novel and alternative non-mammalian models, in vitro test methods, in silico methods, read across and combination of testing methods in test batteries was performed. This systematic review identified a variety of methods covering early and later stages of neurodevelopment that have the ability to predict DNT of chemicals. Few in vivo models alternative to OECD TG 426 were identified. In general, the available published in vivo data is scattered and heterogeneous, making comparisons across exposure paradigms and compounds very difficult. Thus, to make more useful evaluations, publications with more consistent experimental designs are needed, and more focused in vivo-in vitro comparisons are needed to establish useful effect biomarkers and testing models. From the alternative methods, a testing strategy covering early and later neurodevelopmental stages (from stem cell to zebrafish larvae motor behaviour) can be assembled. For gaining regulatory acceptance, definition of biological application domains of alternative methods by performing e.g. in vitro -in vivo validation is needed. Moreover, protocols for cell-based and zebrafish assays need international standardization. With such standardized protocols, the test battery needs to be tested for its sensitivity and specificity by testing concentration-responses of known DNT positive and negative compounds across the different assays. Such data might then be used either for regulatory decision-making or compound prioritization in favour of a reduction of rodent guideline in vivo testing.

show abstract