Oral 1-Generation Rat Reproduction Study of Isobornyl Acetate: An Evaluation Through Sexual Maturity in the F1 Generation

Abstract

Reproductive toxicity of isobornyl acetate (IA), a widely used fragrance ingredient, was investigated in a 1-generation reproduction study in which 25 Crl: CD (Sprague-Dawley) rats/sex/group were gavaged with dosages of 0 (corn oil vehicle), 30, 100, or 300 mg/kg/d during premating, mating, gestation, and lactation. After weaning, 25 F1 generation pups/sex/dosage group were randomly selected for evaluation until sexual maturity. The following parameters were evaluated in P generation males and females: viability, clinical signs, body weights, feed consumption, mating and fertility, organ weights, gross and microscopic observations, sperm assessments (motility and concentration), natural delivery and litter observations, and ovarian follicle counts. In F1 generation pups, viability, body weights, sexual maturation, anogenital distance (days 1 and 22 postpartum), nipple eruption (day 12 postpartum), and gross necropsy observations were recorded. Isobornyl acetate did not adversely affect any of the investigated parameters. Based on the results of this investigation, the no observable adverse effect level (NOAEL) for toxicity of IA is considered to be 300 mg/kg/d. Increased incidences of excess salivation occurred in P generation male and female rats at 100 and/or 300 mg/kg/d throughout the dosage period, and low incidences of urine-stained abdominal fur were seen in females at 300 mg/kg/d during the gestation period. These clinical signs were not considered as adverse effects of IA administration. Thus, the NOAEL for reproductive toxicity in the P generation rats and the NOAEL for viability and growth of the F1 generation offspring is considered to be ≥300 mg/kg/d.