| Abstract |
From previously preformed studies, experimental animals were observed to biotransform methyl chloride (MeCl2) in the body to carbon monoxide (CO) resulting in increased carboxyhemoglobin (COHb) levels and also reported were increased COHb in the blood of human subject inhaling MeCl2. The formation of COHb causes a shift in the oxyhemoglobin dissociation curve (OD-Curve), theoretically resulting in a diminished ability to release oxygen at the tissue level. The ability of MeCl2 to alter the OD-Curve was evaluated with and without CO as measured by the P50 (pressure of oxygen which causes 50% saturation of Hb). In vitro studies werepreformed with blood (from male Sprague-Dawley rats & from male and female human) which was equilibrated with room air (control), MeCl2 alone (800ppm), CO alone (2500ppm) or MeCl2 (800ppm) plus CO (2500ppm). The in vivo studies consisted of five male Sprague Dawley receiving a nominal concentration of MeCl2 at 500ppm for 3 hours in a dynamic air flow chamber. At the end of the three hour exposure, blood was drawn by cardiac puncture and was incubated with MeCl2 (800ppm). Exposure to MeCl2 in vitro or in vivo did not cause a significant change in the P50 value relative to the controls. An acute oral toxicity study was conducted with male Fischer 344 rats (6 rats/exposure) receiving methylene chloride (technical grade) orally by gavage. Each group of animals received methylene chloride at doses of 630, 1300, 2500 or 5000mg/kg resulting in the following mortality data (no. animals dead/no. animals tested): 0/6, 0/6, 3/6 and 6/6, respectively. Most of the deaths occurred within 6 hours of treatment. Surviving animals were observed for 14 days post treatment. Signs of toxicity included, lethargy (all animals), blackening of the tip of the tail along with sloughing and/or brakeage at the tip of the tail (630-2500mg/kg groups), palpebral closure, rapid shallow breathing (1300-5000mg/kg groups) and exudate staining of the nares (630mg/kg group). The animals surviving the 14 day post treatment period appeared to recover based on weight gain data during that period. Gross pathological examination of the animals surviving the 14 day post treatment observation period revealed treatment related gastric ulcers and fibrous adhesions between the stomach, liver, spleen and adjacent peritoneum (1300 and 2500 and to a lesser extent 630mg/kg rats). The oral LD50 of methylene chloride for rats was calculated by the moving averages method to be 2524mg/kg with a 95% confidence limit of 1867 - 3414mg/kg. A slope of 4.4 was also determined. Methylene chloride (CAS No. 75-09-2) was evaluated for subchronic toxicity after partial hepatectomy. The test substance was administered by inhalation to male partially hepatectomized rats (5/group) for 6 hours/day for 3 days at 0, 1,500, or 3,500 ppm. Livers were subjected to microscopic examination after sacrifice the day following the last exposure. There were no statistically significant differences between treated and control rats in body weights, absolute and relative liver weights, or histopathology. Methylene chloride (CAS No. 75-09-2) was evaluated for chronic toxicity. The test substance was administered to rats (number not reported) in drinking water (dose not reported) for 27-months. In this interim report completed 26 weeks into the study, dose-related increases in relative adrenal weights were noted. Also observed were suppression of weight gain and food and water consumption in treated groups. No further information was provided.The ability of dichloromethane to induce morp |
