Reproductive effects, general

Reproductive Effects. The existing data in humans are insufficient to establish a causal relationship between premature delivery and higher levels of heptachlor epoxide found in pregnant women (Wassermann et al. 1982). Because the ascertainment was based on premature delivery and other risk factors were not controlled, it is not possible to relate the levels found in these women to those seen in the general population. 

Substance-related adverse effects on reproduction are always of potential concern, but it is important, where possible, to distinguish between a specific effect on reproduction as a consequence of an intrinsic property of the substance and an adverse reproductive effect, which is a nonspecific consequence of general toxicity (e.g., reduced food or water intake, maternal stress). Hence, reproductive toxicity should be assessed alongside parental toxicity in the same study (EC 2003). 

The two areas of the reproductive process that animal studies focus on are general reproductive effects and developmental effects. 

Data from repeat-dose toxicity studies are essential for CTAs in the early stages of development of a compound, but are superseded once there is a reasonable amount of human data. Any target organs that are identified in the toxicity studies should be monitored in clinical trials. Definitive data on the effects derived from clinical trials will show whether the animal studies are predictive of the effects in humans. This information can then be used to help interpret findings in reproductive toxicity studies, such as whether general toxicity in the adult is relevant. If adult toxicity in animals is deemed relevant, the exposure at which it occurs can be used to estimate the clinical relevance of any reproductive effects. If toxic effects in animals are induced at exposures greatly in excess of the clinical exposure, then they might not be clinically relevant. 

In general the adverse reproductive effects of PCBs on fertility are evident sooner in the female of a species, and at lower doses. At subtoxic doses, PCB effects on reproduction can span several generations. 

Reproduction studies in rats and rabbits Reproductive effects are evaluated on the gametes, in the developing organism (teratology), and in the progeny. These studies are generally conducted for all pharmaceuticals, but on a case-by-case basis for biopharmaceuticals. 

Excessive cobalt can potentially interfere with normal spermatogenesis, and even generalized hypoxia related to increased blood viscosity which affects the testes (Evans, 2007 Thomas, 1995). Chromium and vanadium have also been associated with adverse reproductive effects, and cis-platmum exposure has been associated with the death of spermatocytes and spermatids, as well as disruption of... 

SAFETY PROFILE A human poison by ingestion and possibly other routes. Poison experimentally by ingestion, intravenous, and rectal routes. Moderately toxic by subcutaneous, parenteral, and intraperitoneal routes. Experimental reproductive effects. Human systemic effects by ingestion general anesthetic, cardiac arrhythmias, blood pressure depression, eye effects, coma, pulse rate increase, arrhythmias. Human mutation data reported. 

SAFETY PROFILE Poison by ingestion, subcutaneous, intraperitoneal, and intravenous routes. Human systemic effects by ingestion general anesthesia and thrombocytopenia (reduction in the number of blood platelets). Human effects on newborn by an unspecified route drug dependency and Apgar score (condition of newborn). Experimental teratogenic and reproductive effects. When heated to decomposition it emits toxic fumes of CL. 

SAFETY PROFILE Poison by intraperitoneal route. Experimental teratogenic and reproductive effects. Mutation data reported. A general-purpose chelating and complexing agent. When heated to decomposition it emits toxic fumes of NOx. 

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