Dimethyl hydrogen phosphite (DMHP) has been found by NTP to be a lung and forestomach carcinogen in Fischer 344/N rats but not in B6C3F1 mice. The objectives of this study are to examine various factors which may be involved in these tissue and species selectivities. DMHP was stable in aqueous solutions for a period of time before decomposition began. The period of stability and the rate of decomposition were dependent upon the pH, concentration of DMHP and the storage temperature. The degradation products were identified as methanol, monomethyl hydrogen phosphite and phosphorus acid. DMHP was metabolized in vitro to formaldehyde by the microsomal fraction of liver, lungs, kidneys, forestomach and glandular stomach. Daily treatment with DMHP at 200 mg/kg for 6 weeks resulted in the detection of pathological and biochemical changes in the lungs and forestomach but not in the liver, kidneys and glandular stomach of treated rats. There was a significant increase in the weight of the forestomach of treated rats which was associated with hyperplasia and hyperkeratosis. There was also a significant increase in the levels of nonprotein sulfhydrals in the forestomachs of daily treated animals. The activity of angeotensin converting enzyme in the serum of treated rats significantly increased suggesting early lung injury. Carboxylesterase activity significantly was decreased in the lungs and forestomach but no other tissues of daily treated rats. No treatment related effects were observed in the activities of the microsomal p-nitroanisole demethylase, soluble glutathione S-transferase and soluble superoxide dismutase in liver, lungs, kidneys, forestomach, and glandular stomach. Rats treated with a single oral dose of 200 mg/kg of [14C]DMHP expelled 50% of the dose as 14CO2, excreted 30% of the dose in the urine while 20% remained in the tissues 2r hr after dosing.
