The developmental toxicity of bromochloroacetonitrile in pregnant long‐evans rats

Abstract

Bromochloroacetonitrile (BCAN) is a by‐product of the chlorine disinfection of water containing natural organic material. Adverse effects of BCAN in an in vivo teratology screen (i.e. neonatal survival assay) gave reason for further investigation into the developmental toxicity of this compound. BCAN was administered orally to pregnant Long‐Evans rats on gestation days 6–18 (vaginal plug = day 0). Four groups of approximately 20 females received BCAN at 5, 25, 45 or 65 mg/kg/day in a tricaprylin vehicle. Endpoints assessed at necropsy (day 20) included maternal organ weights, number of corpora lutea and uterine contents (number of implants and fetuses); live fetuses were weighed, measured and subsequently examined for external, skeletal and soft tissue malformations. Gestational maternal weight gain was reduced at 45 and 65 mg kg‐1. Maternal toxicity, manifested as increased organ weights and deaths, occurred at 65 mg kg‐1. Postimplantation loss was elevated at 45 mg kg‐1 while total litter loss was observed at both 45 and 65 mg kg‐1. Fetal crown‐rump lengths were shorter for all BCAN doses tested and fetal weights were reduced at all but the lowest dose level. The frequency of cardiovascular malformations was increased for all levels of BCAN tested; urogenital and skeletal malformations were observed only at the higher dose levels. This pattern of developmental effects is similar to that seen with trichloro‐ and dichloroacetonitrile (TCAN and DCAN), closely related compounds examined previously in our laboratory.