Subchronic toxicology studies of hexachloro-1,3-butadiene (HCBD) in B6C3F1 mice by dietary incorporation

Journal Article · Sat Jul 01 04:00:00 EDT 1989 · Journal of Environmental Pathology, Toxicology and Oncology; (USA)

OSTI ID:7005025

Yang, R S; Abdo, K M; Elwell, M R; Levy, A C; Brennecke, L H ^[1]

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1. National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)

Two-week repeated-dose and 13-week subchronic studies of HCBD were conducted in B6C3F1 mice. Groups of five mice/sex received 0, 30, 100, 300, 1,000, or 3,000 ppm HCBD in feed for 15 days. Toxic responses, primarily in the higher dose groups, included abnormal clinical signs (lethargy, hunched posture, rough coat, sensitivity to light, and/or incoordination), mortality (all mice in the top two dose groups died by day 7), body and organ weight depression, and gross and histopathological changes. The most prevalent microscopic lesion, seen in all HCBD-treated mice of both sexes, was renal tubular cell necrosis and/or regeneration. Regeneration was seen only in the lower dose groups. Thirteen-week studies were conducted in which groups of 10 mice/sex received 0, 1, 3, 10, 30, or 100 ppm HCBD in feed. No treatment-related clinical signs or mortality were observed. Body weight gain was reduced in the 30- and 100-ppm males (-49 and -56, respectively), and the 100-ppm females (-47). Significant reduction in kidney weights was seen in the 30- and 100-ppm males and 100-ppm females. A treatment-related increase in tubular cell regeneration in the renal cortex occurred in both male and female mice. This lesion was characterized by an increase both in number and basophilic staining intensity of the tubular epithelial cells. Regeneration was seen in the outer stripe of the outer medulla and extended into the medullary rays (pars recta); severity increased with dose. Female mice were more susceptible to the toxicity of HCBD than male mice. Although no adverse effects were observed at the 10-ppm level for male mice in the subchronic study, the regenerative lesion was present in female mice at 1 ppm, the lowest dose administered.

• OSTI ID: 7005025
• Journal Information: Journal of Environmental Pathology, Toxicology and Oncology; (USA), Journal Name: Journal of Environmental Pathology, Toxicology and Oncology; (USA) Vol. 9:4; ISSN 0731-8898; ISSN JEPOE
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANIMALS
BODY
BUTADIENE
DIENES
DIET
EPITHELIUM
HYDROCARBONS
KIDNEYS
MAMMALS
MICE
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
POLYENES
RODENTS
SEX DEPENDENCE
TISSUES
TOXICITY
TUBULES
VERTEBRATES