National Toxicology Program

TOX-1
Toxicity Studies of Hexachloro-1,3-butadienein B6C3F₁ Mice (Feed Studies) (CAS No. 87-68-3)

Two-week and 13-week toxicity studies of hexachloro-1,3-butadieneincorporated in the diet were conducted in B6C3F₁ mice. Groups of five miceof each sex received diets containing 0, 30, 100, 300, 1,000, or 3,000 ppmhexachloro-1,3-butadiene for 15 days. Toxic responses in the 2-weekstudies, primarily in the higher dose groups, included abnormal clinicalsigns (lethargy, hunched posture, rough hair coats, light sensitivity,and/or in coordination), deaths (all mice in the two highest dose groupsdied by day 7), body and organ weight depression, and gross andhistopathologic changes. The most prevalent microscopic lesion, seen in allhexachloro-1,3-butadiene-dosed mice, was renal tubular cell necrosis and/orregeneration. Regeneration was seen in lower dose groups. In addition tokidney lesions, histopathologic changes were also seen in the liver(hepatocyte necrosis, cytoplasmic vacuolization), lymphoid tissues (lymphnode necrosis, depletion), and testis (seminiferous tubule giant cells) ofmice in the two highest dose groups which died during the first week of thestudies.

Thirteen-week studies were conducted in which groups of 10 mice per sexreceived 0,1, 3,10, 30, or 100 ppm hexachloro-1,3-butadiene in feed(corresponding to doses of 0, 0.1, 0.4, 1.5, 4.9, or 16.8 mg/kg per day formales and 0.2, 0.5, 1.8, 4.5, or 19.2 mg/kg per day for females). Nocompound-related clinical signs or deaths were observed. Compared withcontrols, body weight gain was reduced in males receiving 30 and 100 ppm(-49% and -56%, respectively) and females receiving 100 ppm (-47%).Kidney weights were reduced in the males receiving 30 and 100 ppm andfemales receiving 100 ppm. A compound-related increase in tubular cellregeneration in the renal cortex occurred in male and female mice. Thislesion, characterized by a diffuse increase in basophilia of the tubularepithelial cytoplasm and an increase in the number of nuclei, increased inseverity with increased dose. The motility of sperm from dosed mice waslower, though not dose related, than that from controls. Female mice weremore susceptible to the toxicity of hexachloro-1,3-butadiene than malemice. Based on the histopathologic evaluations, theno-observed-adverse-effect levelappeared to be 10 ppm for the male mice in this 13-week study; no such level was identified for the female mice.

Synonyms: HCBD; hexachlorobutadiene; 1,1,2,3,4,4-hexachloro-1,3-butadiene; perchlorobutadiene
Trade Names: C 46; Dolen-Pur

Report Date: January 1991

(NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagencyagreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.)

Growth & Survival Curves for NTP 13-Week Toxicity Studies

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