| toxicity summary | IDENTIFICATION AND USE: Dichloromethane is a clear colorless, volatile, sweet-smelling lipophilic liquid. It is commonly used as a solvent in wood varnishes, paints, strippers, cements, vapor degreasing of metal parts. Methylene chloride is also widely used as a process solvent in the manufacture of a variety of products including food, textiles, insecticides, herbicides, steroids, antibiotics and vitamins. Not registered for current pesticide use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. HUMAN EXPOSURE AND TOXICITY: Methylene chloride is rapidly absorbed following inhalation, through the alveoli of the lungs into the systemic circulation. It is also absorbed from the gastrointestinal tract, and dermal exposure results in absorption but at a slower rate than via the other routes of exposure. Methylene chloride is quite rapidly excreted, mostly via the lungs in the exhaled air. It can cross the blood-brain barrier and be transferred across the placenta, and small amounts can be excreted in urine or in milk. Its biotransformation by the hepatic mixed function oxidases leads to formation of carbon monoxide and elevated blood carboxyhemoglobin . Human exposure is mainly due to inhalation but there are incidences of toxicity from oral and dermal contact.Dermally, dichloromethane irritates the skin and eyes especially when evaporation is prevented; prolonged contact may cause chemical burns. Following inhalation of dichloromethane pulmonary edema, hearing loss, CNS depression, liver dysfunction, renal dysfunctions, cardiac stress, and effects on hematological parameters have been reported. Exposure at extremely high levels from use as a paint stripper by consumers or in an occupational setting, has been fatal. Dichloromethane is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals. ANIMAL STUDIES: Dichloromethane is not teratogenic in rats or mice at concentrations up to 16,250 mg/cu m. Developmentally, dichloromethane is able to cross the placental barrier, and minor skeletal variations, fetal weight reduction, and more rapid behavioral habituation was evident in rats exposed before and during gestation. Single ip injection of dichloromethane into adult male rats caused renal proximal tubular degeneration. Morphological effects were observed in the cortex and the outer medulla. Prolonged exposure to high concentrations of methylene chloride caused reversible CNS effects, slight eye irritation and mortality in several laboratory species. Neurological damage was reversible in rats exposed to 7, 100 mg/cu m dichloromethane for 13 weeks via inhalation. Body weight reduction was observed in rats at 3500 mg/cu m and in mice from 17,700 m/cu m. Effects on the liver were noted in dogs continuously exposed to 3,500 mg/cu m for up to 100 days. After intermittent exposure, effects on the liver were observed in rats at 3500 mg/cu m and in mice at 14,100 mg/cu m. Other target organs are the lungs and the kidneys. Dichloromethane is considered a carcinogen. When administered at levels of 0, 60, 125, 185 and 250 mg/kg body weight/day to mice in deionized drinking water for 104 wk, the high dose male and female mice showed a transitory increase in mean leucocyte counts. There was a slight elevation of proliferative hepatocellular lesions in the treated males but no dose related trend was apparent and the effect was absent in the females. Neoplastic lesions observed in the study were homogeneous among all groups and were within the range of incidence in historical controls. The results of this study demonstrated a toxicological no observable effect level of 185 mg/kg body weight/day in both sexes. In a 2 year study, female rats exposed to 500, 1500, or 3500 ppm had an increase in the total number of benign mammary tumors in an exposure-related manner. This effect was also evident in male rats in the 1500- and 3500-ppm exposure groups. Male rats exposed to 1500 or 3500 ppm had an increased number of sarcomas located in or around the salivary glands. In contrast, hamsters exposed to the same concentrations had less extensive spontaneous geriatric changes, decreased mortality , and lacked evidence of definite target organ toxicity. Dichloromethane is mutagenic in prokaryotic microorganisms with or without metabolic activation . In eukaryotic systems it gives either negative or, in one case, weakly positive results.Methylene chloride targets the lungs, blood system, and nervous system. In the lungs its metabolites damage Clara cells. It is also metabolized into carbon monoxide, which binds to hemoglobin to produce dose-dependent increases in carboxyhemoglobin. This results in the reduced oxygen transport and neurological dysfunction characteristic of carboxyhemoglobinemia . Methylene chloride is also believed to cause neurotoxicity by interfering with signal transmission in a manner similar to general anesthetics. Certain metabolites, such as formaldehyde, may result in carcinogenic effects by causing DNA single strand breaks, DNA-protein crosslinks, and other mutations. |