© 1992 Oxford University Press
research-article |
Developmental Toxicity of Boric Acid in Mice and Rats1
,2;
*Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences, National Toxicology Program Research Triangle Park, North Carolina 27709
Chemistry and Life Sciences, Center for Life Sciences and Toxicology Research Triangle Park, North Carolina 27709
Received January 28, 1991; accepted August 7, 1991
Boric acid (BORA), an ingredient of many cosmetics, pharmaceuticals, and pesticides, was tested for developmental toxicity in timed-pregnant Swiss mice and Sprague-Dawley rats (n = 26–28/group). BORA (0, 0.1, 0.2, or 0.4% in feed) was provided throughout gestation to attain steady-state exposure as early as possible during prenatal development. Average doses (mg/kg/day) were 248, 452, or 1003 in mice, and 78, 163, or 330 in rats. To limit prenatal mortality, BORA (0.8% or 539 mg/kg/day) was provided to an additional group of rats on Gestational Days (GD) 6 to 15 only. On GD 17 (mice) or 20 (rats), fetuses were weighed and examined for malformations (external, visceral, skeletal). Mouse dams exhibited mild renal lesions (
0.1%), increased water intake and relative kidney weight (0.4%), and decreased weight gain (0.4%) during treatment. There was a reduction of fetal body weight (0.2%) and an increased incidence of resorptions and malformed fetuses per litter (0.4%). Morphological changes included an increased incidence of short rib XIII (a malformation) and a decreased incidence of rudimentary or full rib(s) at lumbar I (an anatomical variation). Maternal rats exhibited increased liver and kidney weights at 0.2%, altered water and/or food intake at >0.2%, and decreased weight gain at >0.4%. Average fetal body weight/litter was reduced at all doses. Prenatal mortality was increased only at 0.8%. The incidence of fetal malformations was significantly increased at 0.2%. The most frequently observed malformations were enlarged lateral ventricles of the brain and agenesis or shortening of rib XIII. In rats, the no-observable-adverse-effect level (NOAEL) for maternal toxicity was 78 mg/kg (0.1%), while in mice the low dose of 248 mg/kg (0.1%) approached the maternal NOAEL with mild renal lesions in only 2 of 10 females. Embryo/fetal toxicity occurred in all groups of rats at 78 mg/kg (0.1%) while the NOAEL for developmental toxicity in mice was 248mg/kg (0.1%). Thus developmental toxicity occurred below maternally toxic levels in rats as well as in the presence of maternal toxicity in mice and rats.