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The herbicide glyphosate has undergone multiple safety tests for developmental toxicity in rats and rabbits. The European Commission's 2002 review of available glyphosate data discusses specific heart defects observed in several individual rabbit developmental toxicity studies, but describes the evidence for a potential causal relationship as equivocal. The present assessment was undertaken to analyze the current body of information generated from seven unpublished rabbit studies in order to determine if glyphosate poses a risk for cardiovascular malformations. In addition, the results of six unpublished developmental toxicity studies in rats were considered. Five of the seven rabbit studies (dose range: 10-500 mg/kg/day) were GLP- and testing guideline-compliant for the era in which the studies were performed; a sixth study predated testing and GLP guidelines, but generally adhered to these principles. The seventh study was judged inadequate. In each of the adequate studies, offspring effects occurred only at doses that also caused maternal toxicity. An integrated evaluation of the six adequate studies, using conservative assumptions, demonstrated that neither the overall malformation rate nor the incidence of cardiovascular malformations increased with dose up to the point where severe maternal toxicity was observed (generally ≥150 mg/kg/day). Random occurrences of cardiovascular malformations were observed across all dose groups (including controls) and did not exhibit a dose-response relationship. In the six rat studies (dose range: 30-3500 mg/kg/day), a low incidence of sporadic cardiovascular malformations was reported that was clearly not related to treatment. In summary, assessment of the entire body of the developmental toxicity data reviewed fails to support a potential risk for increased cardiovascular defects as a result of glyphosate exposure during pregnancy. [ABSTRACT FROM AUTHOR]

An evaluation of the scientific literature for trichloroethylene (TCE) identified two reports of ocular defects, specifically microphthalmia/anophthalmia, following prenatal TCE exposure in rats. Herein, these reports are analyzed in detail and interpreted within the context of other developmental TCE exposure studies. The ocular findings following prenatal TCE exposure are reported in studies that were not designed specifically for developmental safety assessment, and thus did not use standard experimental practices. Furthermore, these findings most commonly occurred at TCE doses associated with considerable maternal toxicity. Among the 18 published studies using developmental TCE exposures, only 3 used doses sufficiently high enough to result in maternal toxicity, and of these, only the 2 discussed in detail in this paper demonstrated ocular defects in the offspring. Furthermore, statistically significant effects were only observed at doses that were above the currently accepted guideline limit dose of 1000 mg/kg body weight. All other TCE developmental exposure studies failed to demonstrate ocular defects as a result of prenatal exposure. These results suggest that the micro-/anophthalmia findings were likely a consequence of delivery of an extremely high bolus TCE dose that is irrelevant to human environmental exposure scenarios. [ABSTRACT FROM AUTHOR]

Assessment of risks to human health from chemical agents is a complex process that requires the assembly, careful analysis, and integration of human and animal data collected from studies performed at different times, for disparate purposes, and under varying conditions. The application of risk assessment methods to data without consideration of the relevance of critical experimental parameters such as route of exposure or magnitude of dose can lead to specious determinations of the risk posed by exposure to environmental agents. A case study of the purported risk of developmental toxicity from inorganic arsenic is presented to illustrate (1) the nature of the problem, (2) how extant data from all studies are useful, (3) how appropriately designed modern studies can clarify the situation, and (4) how conflicted data should be evaluated in terms of appropriateness for use in risk assessment. [ABSTRACT FROM AUTHOR]