Toxicity studies reproductive toxicology

Reproductive Toxicity. No reproductive toxicological studies were located in the surveyed literature for HDI. Only a few animal studies examined the reproductive organs of both male and female animals, with no gross or histologieal results evident (Mobay Corporation 1984, 1988, 1989) none of the human studies of acute, intermediate, or ehronie durations directly addressed the issue of reproductive toxieity. The majority of studies used male humans and animals, presumably because hmnan males are presently the predominant sex in the automotive painting industry and, therefore, more likely to be exposed to HDI. 

Results of acute, short-term and long-term toxicity studies, reproduction studies, developmental studies, genotoxicity studies, and studies of the toxicity of metabolites and impurities, and other adverse effects. Data on human toxicology, the no observable effect level, acceptable daily intake, and proposed and safety directions... 

Schwetz, B.A., J.F. Quast, P.A. Keeler, C.G. Humiston, and R.J. Kociba. 1978. Results of two-year toxicity and reproduction studies on pentachlorophenol in rats. Pages 301-309 in K.R. Rao (ed.). Pentachlorophenol Chemistry, Pharmacology, and Environmental Toxicology. Plenum Press, New York. 

In the first step of the hazard assessment process, aU effects observed are evaluated in terms of the type and severity (adverse or non-adverse), the dose-response relationship, and NOAEL/LOAEL (or alternatively BMD) for every single effect in aU the available studies if data are sufficient, and the relevance for humans of the effects observed in experimental animals. In this last step of the hazard assessment, all this information is assessed as a whole in order to identify the critical effect(s) and to derive a NOAEL, or LOAEL, for the critical effect(s). It is usual to derive a NOAEL on the basis of effects seen in repeated dose toxicity studies and in reproductive toxicity studies. However, for acute toxicity, irritation, and sensitization it is usually not possible to derive a NOAEL because of the design of the studies used to evaluate these effects. For each toxicological endpoint, these aspects are further addressed in Sections 4.4 through 4.10. 

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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