Developmental and reproductive toxicology studies

CheUman GRet al (2009) Developmental and reproductive toxicology studies in nonhuman primates. Birth Defects Res B Dev Reprod Toxicol 83 1-17... 

Predictive assessment of developmental and reproductive toxicology studies... 

Another consensus recommendation was that, when possible, methods to assess DIT should be included in existing developmental and reproductive toxicology protocols.1719,30 The feasibility of this approach has been previously demonstrated in studies described by a number of investigators.34 35 36 While it could be argued that DIT methods could also be integrated into the EPA Developmental Neurotoxicity Protocol (OPPTS 870-630037) the consensus was that this approach would not be technically feasible due to the large number of animals already required to conduct that study.7,19,30... 

Kallen B (2006) Human studies — Epidemiologic techniques in developmental and reproductive toxicology. In Hood RD ed. Developmental and reproductive toxicology, a practical approach. Boca Raton, FL, CRC Press, pp 799-840. 

SOT sunset session Developmental toxicology Issues with including neurotox and immunotox assessments in reproductive toxicology studies. New Orleans, LA March, 2005... 

Ladies, G.S. et al. Developmental toxicology evaluations Issues with including neurotoxicology and immunotoxicology assessments in reproductive toxicology studies. Toxicol. Sci., 88(1), 24-29, 2005. 

Previous reproductive toxicology studies in laboratory animals examining the effects of prenatal exposure to fumonisin demonstrated a potential risk to the developing fetus. Studies using an aqueous extract of contaminated maize-culture material of F. verticillioides reported that fumonisin was developmentally toxic in hamsters (Floss et al., 1994 Penner et al., 1998). In addition, purified fumonisin Bi was shown experimentally to cause fetal toxicity in rats and mice (Collins et al., 1998 Reddy et al., 1996). In another study, pregnant CD1 mice treated with a semipurified extract... 

Adjustments are often made in the NOAEL or BMD to account for the exposure scenario of concern. In the case of inhalation exposure, for example, if a study involved exposure to 500 parts per million (ppm) for 6 hours per day (h/ d), and there are no modifying pharmacokinetic data, the adjusted NOAEL or BMD for a continuous exposure would be calculated by multiplying by 6/24, yielding 125 ppm. Adjustment to account for the duration of exposure has not been applied routinely in assessments of developmental toxicity such an adjustment is made in the case of assessments for reproductive toxicity. The Subcommittee on Reproductive and Developmental Toxicology recommends that exposure duration should be considered in developmental and reproductive toxicity assessments alike. The reason for this recommendation is that adjusting for duration of exposure is likely to be more conservative with repeated exposures than with single exposures, even for developmental toxicity data (Weller et al. 1999). In the case of occupational exposure during a 6-8 h workday, this adjustment could be unnecessary. However, if pharmacokinetic data indicate accumulation with repeated exposure, an adjustment would be appropriate. 

The test statistics from a Mann-Whitney are linearly related to those of Wilcoxon. The two tests will always yield the same result. The Mann-Whitney is presented here for historical completeness, as it has been much favored in reproductive and developmental toxicology studies. However, it should be noted that the author does not include it in the decision tree for method selection (Figure 22.2). 

H.M. Solomon, B.A. Burgess, G.L. Kennedy, R.E. Staples, l-Methyl-2-Pyrrolidone (NMP) reproductive and developmental toxcicity study by inhalation in the rat, Drug and Chemical Toxicology, 18 (1995) 271-293. 

Other types of reproductive toxicity studies, e.g., the prenatal developmental toxicity study, the reproduction/developmental toxicity screening study, and the developmental neurotoxicity study (Section 4.10.3) may give some indications of general toxicological effects arising from repeated exposure over a relatively limited period of the animal s life span as clinical signs of toxicity and... 

Developmental Toxicity. No developmental toxicological studies were located in the surveyed literature for HDI. It is not known if HDI exerts an effect on reproductive tissues in males or females or on the developing fetus however, given its short half-life in biological fluid, this seems imlikely. HDI has been reported to bind to biological tissues (protein) (Ted and Pesce 1979) however, the relevance of this observation to reproductive toxicity is not known. The toxicity of the HDI metabolite (HDA) is not known. Toxicologic studies should be devised to answer questions about HDI s potential developmental toxicity or its prepolymers in the developing human or laboratory animal. 

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