Impact of chloroform exposures on reproductive and developmental outcomes: A systematic review of the scientific literature.

Aims: We assessed the animal and epidemiological data to determine if chloroform exposure causes developmental and/or reproductive toxicity.

Results And Discussion: Initial scoping identified developmental toxicity as the primary area of concern. At levels producing maternal toxicity in rats and mice, chloroform caused decrements in fetal weights and associated delays in ossification. In a single mouse inhalation study, exposure to a high concentration of chloroform was associated with small fetuses and increased cleft palate. However, oral exposure of mice to chloroform at a dose 4 times higher was negative for cleft palate; multiple inhalation studies in rats were also negative. Epidemiologic data on low birth weight and small for gestational age were generally equivocal, preventing conclusions from being drawn for humans. The animal data also show evidence of very early (peri-implantation) total litter losses at very high exposure levels. This effect is likely maternally mediated rather than a direct effect on the offspring. Finally, the epidemiologic data indicate a possible association of higher chloroform exposure with lower risk of preterm birth (<37 weeks gestation).

Conclusions: The available animal data suggest that exposures lower than those causing maternal toxicity should be without developmental effects in the offspring. Also, most studies in humans rely on group-level geographic exposure data, providing only weak epidemiologic evidence for an association with development outcomes and fail to establish a causal role for chloroform in the induction of adverse developmental outcomes at environmentally relevant concentrations.