TOXIC EFFECTS AND EXCRETION IN URINE OF -CHLORO-4-(DICHLOROMETHYL)5-HYDROXY-2(5H)-FURANONE (MX) IN THE RAT AFTER A SINGLE ORAL DOSE

Toxic effects and excretion in urine of chloro-4-(dichloromethyl)-5-hy droxy-2(5H)-furanone (MX), the potent mutagenic compound in chlorinate d drinking water, was evaluated in male Wistar rats by the up-and-down method. MX was dosed by gavage in deionized water at doses between 20 0 mg/kg and 600 mg/kg, for one animal at a time, and effects were obse rved for 14 days. Urine was collected in metabolism cages up to 72 h a fter dosing for chemical analysis of MX in urine. The animals receivin g 200 mg/kg did not display clear clinical signs but at higher doses t he signs of ill effects included dyspnea, laborious, wheezing and gasp ing breathing, decreased spontaneous motor activity, ataxia, nostril d ischarges, catalepsia and cyanosis. In necropsy bronchi contained foam y liquid and the lungs appeared edematous and spongy. The stomach cavi ty was expanded due to accumulation of fluid and gas and the gastroint estinal tract from stomach to caecum was reddish. Microscopically, the main target organ of toxicity was the gastrointestinal tract (diffuse congestion and necrosis in the mucosa). Signs of toxicity were record ed also in lungs (slight edema) and kidneys (dilated tubules, thin tub ular epithelium, brownish tubular and interstitial concretion). The LD (50) in 48 h was 230 mg/kg. Only 0.03-0.07% of the dose (200 mg/kg or 300 mg/kg) was excreted in urine as intact MX. The results indicate th at at high doses MX has a strong local irritating effect in the gastro intestinal tract and it probably increases liquid permeability in lung s. MX may also cause tubular damage in kidneys. Data also indicate tha t after an oral dose only traces of MX are excreted in urine as intact compound, suggesting that MX is subjected to intense metabolism befor e excretion, even at lethal doses.