Prenatal developmental toxicity studies of inhaled methyl iodide vapor in rabbits reveal a susceptible window of exposure inducing late gestational fetotoxicity

Abstract

Methyl iodide (MeI), an intermediate used in the manufacture of some insecticides and pharmaceuticals, is under review for U.S. registration as a non-ozone-depleting alternative to methyl bromide in the pre-plant soil fumigation market. Guideline (OPPTS 870.3700) developmental toxicity studies in New Zealand White (NZW) rabbits showed dose-dependent increases in the litter proportions of late fetal deaths and postimplantation loss and/or decreased fetal body weight following inhalation exposure of pregnant rabbits to MeI during gestation days (GD) 6–28. A subsequent phased-exposure study was performed to pinpoint the critical window of gestational exposure that produced the rabbit fetotoxicity. Artificially inseminated NZW female rabbits were exposed to 20 ppm MeI vapors by whole-body inhalation (6 h/day) throughout major organogenesis and fetal development (GD 6–28), during early gestation (GD 6–14) or mid-gestation (GD 15–22) only, or during 2-day intervals late in gestation (GD 23–24, 25–26, or 27–28). No maternal or developmental toxicity was elicited from maternal exposure during GD 6–14, 15–22, or 27–28. However, MeI-related fetotoxicity, including increased litter proportions of late fetal deaths with or without corresponding decreases in fetal body weight, were observed for females exposed during GD 6–28 (p < .01), 23–24 and 25–26. Although the increase in late-stage fetal death for each of the 2-day exposures on GD 23–24 and GD 25–26 was not statistically significant, as noted for the combined total of fetal deaths during the GD 6–28 exposure, it can be deduced that the gestational window of GD 23–26 was the most susceptible window of exposure for eliciting developmental toxicity in rabbits exposed to MeI vapors.

Acknowledgments

This work, performed at WIL Research Laboratories under the funding of Arysta LifeScience Corporation (formerly Arvesta Corporation), has been presented in part at the Society of Toxicology Annual Meeting, March 2005. The authors thank Lewis E. Kaufman, MS (Consultant to WIL Research, 123 Park Avenue, Wooster, OH, USA), for help in the preparation of this article.

Declaration of interest: The authors report no conflicts of interest.