Developmental toxicity of oral n-butylamine hydrochloride and inhaled n-butylamine in rats.
Pregnant Wistar rats were administered 0, 100, 400 or 1000 mg mono-n-butylamine hydrochloride/kg body weight/day by gavage on days 6 through 15 post coitum (sperm-positive=day 0), or inhaled mono-n-butylamine 0, 17, 50 or 152 ppm (whole-body exposure), 6 h/day on days 6 through 19 post coitum. Oral n-butylamine HCl 1000 mg/kg reduced maternal feed consumption, increased early post-implantation losses (embryonic resorptions), reduced fetal and placental weight, and retarded skeletal development (incomplete skull and sternebral ossification), and produced malformations (filiform/kinked tail, enlarged cardiac ventricular chamber(s), malpositioned heart, aortic arch atresia, diaphragmatic hernia); 100 mg/kg was the no-observed-adverse effect level (NOAEL) for prenatal developmental toxicity; 400 mg/kg, the maternal no-effect level, produced only malformations (aortic arch atresia, malpositioned heart, diaphragmatic hernia). Inhaled n-butylamine produced concentration-dependent nasal epithelial hyperplasia and squamous metaplasia, inflammation and necrosis; the maternal NOAEL was less than 17 ppm. There were no treatment-related signs of embryo/fetotoxicity, particularly, no effects on fetal morphology. The developmental NOAEL was 152 ppm. The neutralization of n-butylamine by hydrochloride converts it from a strong alkali causing tissue burns into a weak acid/base which is fetotoxic. Possible mechanisms of fetotoxicity are free radical production, metabolic acidosis, and lysosomotrophy.
Gamer
A O
AO
Department of Product Safety, BASF Aktiengesellschaft, 67056 Ludwigshafen, Germany.
Hellwig
J
J
van Ravenzwaay
B
B
Heliwig
J
J
D000014:Abnormalities, Drug-Induced; D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002082:Butylamines / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005327:Fetal Resorption; D005333:Fetus / Q000002:abnormalities*; D006863:Hydrogen-Ion Concentration; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D002082:Butylamines; C032462:n-butylamine