| toxicity summary | IDENTIFICATION AND USE: 1,4-Butanediol is a colorless, oily liquid. It is used as an industrial solvent, intermediate in organic synthesis, and polymer feedstock. Two studies have been identified concerning the experimental use of 1,4-butanediol as a sedative. HUMAN STUDIES: It was reported that sleep is induced by intravenous administration or by infusion. Undesirable side-effects which may occur include restlessness and clonic spasms of the muscle of the extremities. Cases of abuse and fatal intoxication have been reported. ANIMAL STUDIES: Gauze patches with undiluted 1,4-butanediol were applied to the intact and abraded skin of rabbits with occlusive dressing for 24 hours. After 1, 24, 48 and 72 hours, no reaction was observed on the intact and abraded skin. The main signs of toxicity seen in mice and rats were accelerated breathing, dyspnea, spasmodic breathing, bradycardia, exsiccosis, exophthalmus, apathy, hyperreflexia, hyporeflexia, areflexia, ataxia, atonia, twitching, reduced motility, analgesia, lying on the side, loss of righting reflexes, sedation, narcosis, hair loss and ruffled fur. Death occurred within 24 hours. Respiratory failure was thought to be the cause of death. Signs of intoxication appeared more quickly after rectal than after oral administration. In rat developmental studies, administration was conducted by gavage at doses of 200, 400 or 800 mg/kg/day from 14 days before mating to 14 days after mating in males and from 14 days before mating to day 3 of lactation in females. The parental animals exhibited no alteration in reproductive parameters including the copulation index, fertility index, gestation length, numbers of corpora lutea or implantation, implantation index, gestation index, delivery index, and behavior at delivery and lactation. Although neither the pup viability nor the incidence of morphological abnormalities was changed by administration of the compound, pup body weight was slightly but significantly decreased in the 800 mg/kg group. In a gene mutation assay using CHO cells, 1,4-butanediol did not induce any reproducible statistically or biologically significant increase in the mutant frequency of the HPRT locus with and without metabolic activation. A gene reverse mutation test was negative in S. typhimurium TA 100, TA 98, TA 1535, TA 1537 and E.coli WP2 uvrA with and without metabolic activation. ECOTOXICITY STUDIES: Toxicity of this chemical to aquatic organisms seems to be low, because all toxicity data obtained were higher than 85 mg/L or 1000 mg/L which were the maximum concentrations of exposure. No fish died, and no toxic symptoms were observed in fish exposed to 92.5 mg/L of this chemical throughout 14 day test period. Also, any reproduction impairment was not observed in D. magna exposed to 85 mg/L. |
