Developmental Toxicity of Boric Acid in Mice and Rats

Boric acid (BORA), an ingredient of many cosmetics, pharmaceuticals,and pesticides, was tested for developmental toxicity in timed-pregnantSwiss mice and Sprague-Dawley rats (n = 26–28/group).BORA (0, 0.1, 0.2, or 0.4% in feed) was provided throughoutgestation to attain steady-state exposure as early as possibleduring prenatal development. Average doses (mg/kg/day) were248, 452, or 1003 in mice, and 78, 163, or 330 in rats. To limitprenatal mortality, BORA (0.8% or 539 mg/kg/day) was providedto an additional group of rats on Gestational Days (GD) 6 to15 only. On GD 17 (mice) or 20 (rats), fetuses were weighedand examined for malformations (external, visceral, skeletal).Mouse dams exhibited mild renal lesions (0.1%), increased waterintake and relative kidney weight (0.4%), and decreased weightgain (0.4%) during treatment. There was a reduction of fetalbody weight (0.2%) and an increased incidence of resorptionsand malformed fetuses per litter (0.4%). Morphological changesincluded an increased incidence of short rib XIII (a malformation)and a decreased incidence of rudimentary or full rib(s) at lumbarI (an anatomical variation). Maternal rats exhibited increasedliver and kidney weights at 0.2%, altered water and/or foodintake at >0.2%, and decreased weight gain at >0.4%. Averagefetal body weight/litter was reduced at all doses. Prenatalmortality was increased only at 0.8%. The incidence of fetalmalformations was significantly increased at 0.2%. The mostfrequently observed malformations were enlarged lateral ventriclesof the brain and agenesis or shortening of rib XIII. In rats,the no-observable-adverse-effect level (NOAEL) for maternaltoxicity was 78 mg/kg (0.1%), while in mice the low dose of248 mg/kg (0.1%) approached the maternal NOAEL with mild renallesions in only 2 of 10 females. Embryo/fetal toxicity occurredin all groups of rats at 78 mg/kg (0.1%) while the NOAEL fordevelopmental toxicity in mice was 248mg/kg (0.1%). Thus developmentaltoxicity occurred below maternally toxic levels in rats as wellas in the presence of maternal toxicity in mice and rats.