Developmental toxicity of boric acid in mice and rats

• Published in: Fundamental and applied toxicology 1992-02, Vol.18 (2), p.266-277
• Main Authors: Heindel, Jerrold J., Price, Catherine J., Field, Elizabeth A., Marr, Melissa C., Myers, Christina B., Morrissey, Richard E., Schwetz, Bernard A.
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced - etiology; Animals; Biological and medical sciences; Boric Acids - toxicity; Embryology: invertebrates and vertebrates. Teratology; Embryonic and Fetal Development - drug effects; Female; Fetal Death - chemically induced; Fundamental and applied biological sciences. Psychology; Male; Mice; Mice, Inbred ICR; Pregnancy; Rats; Rats, Inbred Strains; Teratology. Teratogens
• ISSN: 0272-0590; 1095-6832
• DOI: 10.1016/0272-0590(92)90055-M

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 248 mg/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.