Toxicokinetics reproductive toxicity

Toxicokinetic data can also be used to make informed decisions on testing of chemical substances. In specific circumstances, valid toxicokinetic data may be used to support a decision to omit testing for systemic effects, e.g., in cases where the toxicokinetic data provide sufficient evidence that a substance is not absorbed and therefore not systemically available, i.e., no plasma/blood concentrations were measurable and no parent compound or metabolites could be detected in urine, bile, or exhaled air. For example, in vivo testing for mutagenicity, reproductive toxicity, or carcinogenicity may be omitted if toxicokinetic data or other data indicate a lack of systemic availability. 

Reproductive Toxicity. There are currently limited data available regarding the reproductive toxicity of inorganic tin or organotin compounds after inhalation, oral, or dermal exposures in either humans or animals. The limited toxicokinetic data indicate that inorganic tin is poorly absorbed and that selected organotin compounds such as trimethyl- and triethyltins appear to be absorbed slightly better. Inorganic tin dose not appear to readily cross the placenta (Hiles 1974). 

The National Institute for Occupational Safety and Health (NIOSH) develops criteria documents to describe the scientific basis for occupational safety and health standards. They contain critical reviews of the available literature on physical and chemical properties, uses and occurrence, toxicokinetics, general toxicity, toxic effects on various organs, genotoxicity, carcinogenicity, and developmental and reproductive toxicity of particular agents. Data are evaluated in the context of potential human occupational exposures, and recommendations for minimizing safety and health risks are provided. Most of these documents were written more than 10 years ago, and many are more than 20 years old. 

It is preferable that animal studies are conducted using appropriate routes of administration which relate to the potential route of human exposure. However, in practice, reproductive toxicity studies are commonly conducted using the oral route, and such studies will normally be suitable for evaluating the hazardous properties of the substance with respect to reproductive toxicity. However, if it can be conclusively demonstrated that the clearly identified mechanism or mode of action has no relevance for humans or when the toxicokinetic differences are so marked that it is certain that the hazardous property will not be expressed in humans then a substance which produces an adverse effect on reproduction in experimental animals should not be classified. 

Toxicokinetics Toxic effects of cadmium Acute toxicity Long-term exposure Reproductive toxicity Carcinogenicity Nephrotoxicity ... 

Reproductive Toxicity. No data exist on reproductive effects on humans from exposure to vanadium by any exposure route. One animal study shows that vanadium did not affect reproductive parameters in rats following oral exposure (Domingo et al. 1986). Since vanadium is poorly absorbed from the gastrointestinal tract (Conklin et al. 1982 Roschin et al. 1980) and skin (WHO 1988), exposure by these routes is unlikely to be a health risk in humans. Toxicokinetic studies in humans (Schroeder et al. 1963) and reliable studies in animals (Edel and Sabbioni 1988) do not indicate that the reproductive system accumulates vanadium. Humans are most likely to be exposed to vanadium in the air, but the reproductive system does not appear to be a sensitive target of vanadium toxicity. Further studies would not appear to be particularly useful. 

Full toxicity testing would be required on a substance shown to bioaccumulate, to establish whether it is a Class 1 specified or a safe substance. A full toxicity testing programme covers chronic toxicity, mutagenicity, carcinogenicity, reproduction toxicity, teratogenicity, toxicokinetics and pharmacology. 

Formal studies of reproductive toxicity of iodates are also lacking. In view of the toxic effects of excessive doses of iodine on the fetus and the unlikely exposure of the fetal system to iodate for the metabolic (toxicokinetic) reasons outlined above, there appears to be no need for additional studies. 

Intracutaneous reactivity Systemic toxicity (acute) Subacute/subchronic toxicity Genotoxicity Implantation Hemocompatibility Chronic toxicity Carcinogenicity Reproductive toxicity Biodegradation Toxicokinetics Immunotoxicity... 

Humans are susceptible to the acute toxic effects of 1,2-dibromoethane from various routes of exposure. Except for adverse reproductive effects in men after occupational exposure, chronic effects of 1,2-dibromoethane exposure have not been documented in humans. Based on data derived from animal studies, mechanisms of action of 1,2-dibromoethane at a cellular level, toxicokinetics, and genotoxicity tests, there is a potential for certain adverse health effects in humans exposed chronically to low environmental levels of 1,2-dibromoethane that could exist near hazardous waste sites or areas of former agricultural use. 

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