Methylene chloride: a 2-year inhalation toxicity and oncogenicity study in rats

Journal Article · Fri Jul 01 04:00:00 EDT 1988 · Fundam. Appl. Toxicol.; (United States)

DOI:https://doi.org/10.1016/0272-0590(88)90269-2· OSTI ID:6349965

Nitschke, K D; Burek, J D; Bell, T J; Kociba, R J; Rampy, L W; McKenna, M J

Male and female Sprague-Dawley rats were exposed to 0, 50, 200, or 500 ppm methylene chloride for 6 hr/day, 5 days/week for 2 years. Blood carboxyhemoglobin levels were elevated in a dose-dependent (less than linear) manner in rats exposed to 50-500 ppm methylene chloride. Histopathologic lesions related to methylene chloride exposure were confined to the liver and mammary tissue of rats. An increased incidence of hepatocellular vacuolization was observed in male and female rats exposed to 500 ppm methylene chloride. Female rats exposed to 500 ppm methylene chloride also had an increased incidence of multinucleated hepatocytes and number of spontaneous benign mammary tumors/tumor-bearing rat (adenomas, fibromas, and fibroadenomas with no progression toward malignancy); the incidence of benign mammary tumors in female rats exposed to 50 or 200 ppm methylene chloride was comparable to historical control values. No increase in the number of any malignant tumor type was observed in rats exposed to concentrations as high as 500 ppm methylene chloride. Additional groups of female rats were exposed to 500 ppm methylene chloride for the first 12 months or the last 12 months of the 24-month study. The response observed in female rats exposed to 500 ppm for the first 12 months was the same as that observed in female rats exposed to 500 ppm for 2 years. Conversely, the response observed in female rats exposed to 500 ppm during the last 12 months of the study was similar to that observed in control animals. Based upon the results of this study, the no-adverse-effect level for chronic inhalation exposure of Sprague-Dawley rats was judged to be 200 ppm methylene chloride.

• Research Organization: Dow Chemical Company, Midland, MI (USA)
• OSTI ID: 6349965
• Journal Information: Fundam. Appl. Toxicol.; (United States), Journal Name: Fundam. Appl. Toxicol.; (United States) Vol. 11:1; ISSN FAATD
• 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.
ANIMALS
BODY
CARBOXYHEMOGLOBIN
CARCINOGENS
DIGESTIVE SYSTEM
DISEASE INCIDENCE
DNA
DOSE-RESPONSE RELATIONSHIPS
GLANDS
HORMONES
INHALATION
INTAKE
LIVER
MAMMALS
METHYLENE CHLORIDE
NUCLEIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
RATS
RODENTS
TOXICITY
VERTEBRATES