Chloroform

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

other: review

Adequacy of study:

weight of evidence

Study period:

2108

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

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

Author:

Williams AL, Bates CA, Pace ND, Leonhard MJ, Chang ET, DeSesso JM

Year:

2018

Bibliographic source:

Birth Defects Res. 110(17), 1267-1313

Applicant's summary and conclusion

Conclusions:

The available animal data suggest that exposures lower than those causing maternal toxicity should be without developmental effects in the offspring.

Executive summary:

Review

Williams et al (2017) conducted a systemic assessment of the animal and epidemiological data for chloroform to determine if the available evidence indicates that chloroform causes developmental and/or reproductive toxicity. As a first step in this effort, a scoping exercise was undertaken to identify the primary developmental/reproductive concern(s) for chloroform (i.e., female reproductive toxicity, male reproductive toxicity, or developmental toxicity). Based on the results of this scoping effort, a more focused analysis was conducted on the developmental toxicity potential of chloroform. This evaluation involved separate analyses of the animal and epidemiological studies, followed by an integrated assessment of the data.

Initial scoping identified developmental toxicity was 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 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.

The available animal data suggest that exposures lower than those causing maternal toxicity should be without developmental effects in the offspring.