Evaluation of the Developmental Toxicity Potential. of 2-Ethyl-1, 3-Hexanediol in the Rat by Cutaneous Application

Abstract

2-Ethyl-1,3-hexanediol (EHD; CAS No. 94-96-2) is an insect repellent and industrial chemical with skin as a major route of exposure. Groups of 25 timed-pregnant CD rats received cutaneous applications of undiluted EHD at dosages of 1.0, 2.0 and 4.0 ml/kg/day for 6 hr/day under occlusion on gestational days 6-15 inclusive. A. similar-sized control group received 4.0 ml/kg/day of deionized water with the same exposure regimein. Maternal toxicity was present at 4.0 ml/kg/day (reduced body weight gains and mild skin irritation that were not statistically significant, and increased liver weight that was statistically significant), and also minimally at 1.0 and 2.0 ml/kg/day (mild skin irritation and slightly increased but statistically significant relative liver weight to body weight ratio). At 4.0 ml/kg/day there was one visceral malformiation (unilateral hydroureter), increased incidences of three visceral variants (atelectasis, dilated lateral cerebral ventricle, and bilateral dilated ureter), and 13 skeletal variants affecting several skeletal districts. At 2.0 ml/kg/day no malformations were observed, but the incidence of two visceral variants (dilated lateral cerebral ventricle and bilateral dilated ureter) and one skeletal variant (reduced caudal segments) was increased. Under the conditions of this study, EHD was considered to be a weak developmental toxicant at 4.0 and 2.0 ml/kg/day, and 1 ml/kg/day was a “no-observed effect level” for developmental toxicity.