Consensus workshop on the evaluation of maternal and developmental toxicity work group III report: Low dose extrapolation and other considerations for risk assessment–models and applications

Schwetz, Bernard A.; Tyl, Rochelle W.; Buelke-Sam, J.; Bui, Quang Q.; Chinchilli, Vernon M.; Christian, Mildred S.; Costlow, Richard D.; Dapson, S.; Filler, Ron; Frankos, Vasilios H.; Gaylor, David W.; Hardin, Bryan D.; Hart, W. S.; Khera, K. S.; Levinsky, H.V.; Ottley, Myron S.; Parker, J. E. S.; Perlin, Susan A.; Rogers, John M.; Schardein, James L.; Setzer, Woodrow

doi:10.1002/tcm.1770070313

Cited by 9 publications

(2 citation statements)

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“…Neubert comprehensively discussed this topic [56]. Schwetz and Tyl [57] summarized the discussions of a working group on prenatal toxic-risk estimation. They recommended that, besides other future goals, research should focus on target dosimetry, including data on maternal and fetal blood and tissue levels, and molecular dosimetry.…”

Section: Risk Assessment Using Molecular Dosimetrymentioning

confidence: 99%

Embryotoxicity induced by alkylating agents: 7. Low dose prenatal‐toxic risk estimation based on NOAEL risk factor approach, dose‐response relationships, and DNA adducts using methylnitrosourea as a model compound

Platzek

Bochert

Meister

et al. 1993

Teratog Carcinog Mutagen

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Prenatal-toxic risk estimation for the alkylating model compound methylnitrosourea (MNU) was performed using different procedures. Risk of low doses was estimated using linear extrapolation to zero (estimated ED0.1%: 0.1 mg/kg body wt MNU) as well as extrapolation by probit analysis based on a dose-response study (estimated ED0.1%: 1.6 mg/kg body wt). Furthermore, a "virtually safe dose" was established by means of the NOAEL risk factor approach (e.g., factor 30:0.03 mg MNU per kg body wt). In previous studies in murine embryos using MNU, we combined dose-response data and DNA adduct rate measurements and deduced that O6-methylguanine is a suitable variable for molecular dosimetry. In a tentative approach, we estimated the teratogenic risk of low doses based on the adduct rates of O6-methylguanine in the DNA of the embryos. It is concluded that in the case of steep dose-response relationships, which are typical for the majority of teratogenic effects, the NOAEL risk factor approach is more conservative than extrapolation based on probit analysis. Risk estimation using dosimetry with this model compound yields estimated incidences similar to linear extrapolation.

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Section: Risk Assessment Using Molecular Dosimetrymentioning

confidence: 99%

Embryotoxicity induced by alkylating agents: 7. Low dose prenatal‐toxic risk estimation based on NOAEL risk factor approach, dose‐response relationships, and DNA adducts using methylnitrosourea as a model compound

Platzek

Bochert

Meister

et al. 1993

Teratog Carcinog Mutagen

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“…These concerns were highlighted in a 1993 report from the National Research Council titled Pesticides in the Diets of Infants and Children (National Research Council 1993), in which the immune, reproductive, and nervous systems were identified as potential targets for pesticide exposure. Although considerable attention has focused on the identification, characterization, and standardization of methods for developmental neurotoxicity and reproductive toxicity (e.g., Garman et al 2001;Levine and Butcher 1990;Schwetz and Tyl 1987) only limited discussions on developmental immunotoxicity have occurred Holsapple 2002). The present workshop extends these earlier discussions by establishing a consensus on the most appropriate experimental designs and methods to identify and characterize developmental immunotoxicity in experimental animals given our current knowledge.…”

mentioning

confidence: 99%

Consensus workshop on methods to evaluate developmental immunotoxicity.

Luster

Dean

Germolec

2003

Environ Health Perspect

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A workshop cosponsored by the National Institute of Environmental Health Sciences and the National Institute for Occupational Safety and Health was convened in Washington, DC, on 17-18 October 2001 with the goal of developing a consensus document on the most appropriate experimental approaches and assays available to assess developmental immunotoxicity. The work group was composed of scientists from academia, the chemical and pharmaceutical industries, and federal agencies with expertise in developmental immunology, developmental toxicology, immunotoxicology, and risk evaluation. This consensus document presents an overview of the major summations made by the work group. A summary of early work in the field is provided, which includes potential immunotoxic agents, followed by brief discussions of our current understanding of developmental immunology. This report concludes with the work group's consensus of the most appropriate experimental design and tests to screen for potential developmental immunotoxic agents in experimental models, including potential limitations and data gaps.

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