Long-term Oral Exposure Research Articles

食道癌患者に認められた化学薬品が原因と考えられる抗赤血球自己抗体と輸血

Here reported a case of esophageal cancer showing high level of anti-erythrocyte autoantibody of IgG type possibly caused by his professional long-term exposure to chemicals such as hydrogen fluoride, chloride and sulfuric acid.Case: Y. Y.,54 y. o., M.. He had been working as a house washer over twenty years using hydrogen fluoride, chloride and sulfuric acid as cleansers and bleaching agents, used to taste the mixtures of the chemicals in order to obtain the best ratio and condition of them. As he had been quite healthy since his birth, he had never used any medicines habitually, and had never received blood transfusion. On Apr.1983, he consulted our hospital, mainly complaining of dysphagia, and was diagnosed to be suffering from esophageal cancer (squamous cell carcinoma) by means of radiological and endoscopic examinations. Immunological tests detected high level of anti-erythrocyte autoantibody (IgG), i. e. positive direct and indirect anti-globulin tests using polyspecific and anti- IgG antiserum without addition of the chemicals, both his serum and eluate from his red cells showing panaggulutination against several panel cells of blood type O, and these antibodies were absorbed completely by his own red cells. None of other autoantibodies such as LE factor, anti-nuclear antibody and anti-DNA antibody were detected.For the operation to rem ove his cancer, concentrated human red blood corpuscles of 960ml in total were transfused to him, although pretransfusion cross match tests between these CRCs and his blood yielded incompatible results. The transfusion seemed not to be sufficiently effective, and caused a slight elevation of seral GOT, GPT and indirect bilirubin, suggesting extravascular hemolysis, for about two weeks thereafter, although no remarkable clinical side effects such as fever or renal dysfunction were recognized.About ten mon ths after the operation, while pulmonary metastases of the cancer occurred, the anti-erythrocyte autoantibody titers in his eluate and serum went down. During these ten months, he had never been exposed to these chemicals.The observation of this case sugges ts that a long-term oral exposure to the chemicals such as hydrogen fluoride, chloride and sulfuric acid might cause esophageal cancer, and on the other hand, it might cause production of anti-erythrocyte autoantibody. Hitherto, no papers reporting such cases as ours could be found in the literature. It should be necessary to pile up such cases, in order to provoke hygienical and experimental researches which may result the establishment of the concept of an occupational disease newly found.

Immune complex nephritis in rats induced by long-term oral exposure to cadmium

Oral administration of 100 and 200 ppm of cadmium in drinking water induced a diffuse membranous glomerulo-nephritis in rats after 30 weeks of exposure. Light microscopical, immunofluorescence and electron microscopic studies showed that the immunocomplex formed induced glomerular nephritis. The pathological changes were more pronouced in the rats treated with the lower doses of cadmium.

Observations on the oral administration and toxicity of vinyl chloride in rats

Various possibilities were studied for administering vinyl chloride monomer (VCM) orally to rats. Upon storage, solutions of VCM in soya-bean oil appeared to be stable with respect to their VCM content and the fatty acid composition of the oil. In addition no oligomers of vinyl chloride or reaction products of VCM with components of the oil were detected. Stomach intubation of such solutions was considered an acceptable method of oral administration of VCM to rats in short-term toxicity studies. Within a period of 4 hr following intragastric intubation of VCM in soya-bean oil (300 mg VCM/kg body weight), over 92% of the VCM administered was recovered from the gases excreted (mainly exhaled?) by the animals. Eructation did not appear to be involved in the excretion of VCM. VCM dissolved in soya-bean oil was administered by gavage to male and female rats at levels of 0 (controls), 30, 100 and 300 mg/kg body weight, once daily on 6 days/wk for a period of 13 wk. Several haematological, biochemical and organ weight values differed to a statistically significant degree from those of the controls, but these differences were considered to have only minor, if any, toxicological significance. A slight increase in liver-to-body weight ratio occurred in males and females on the highest dose level. This increase was not accompanied by liver damage, as was evident from histological examination, enzyme histochemistry and electron microscopy. The no-effect level in this 90-day study was conservatively placed at 30 mg VCM/kg body weight, but was probably higher since the effects occurring at 100 and 300 mg/kg body weight were of doubtful toxicological significance. Indications were obtained that the feeding of rats on diets containing polyvinyl chloride (PVC) powder with a high VCM content is a more practical method for the long-term oral exposure of rats to VCM than is stomach intubation of VCM in oil. VCM was almost completely released from PVC powder during passage through the digestive tract.

Metabolic fate of dichlorvos in swine.

The metabolic fate of dichlorvos in swine has been studied by short- and long-term oral and inhalation exposure studies utilizing32P-,36Cl-, or14C-labeled dichlorvos. In dietary studies slowrelease formulations in PVC were used. No intact dichlorvos could be determined in the blood or tissues of treated animals, and, of the recognized metabolites, only dichloroethanol was found in measurable quantities under some conditions. Studies with36Cl-dichlorvos demonstrated that no organochlorine metabolic residues accumulated in tissues. The cumulative evidence from all studies indicates that the detoxification and degradation of dichlorvos in swine proceeds by essentially the same route whether the compound is administered orally or by inhalation exposure. This degradation proceeds almost exclusively via cleavage of the vinyl-phosphate bond and subsequent dechlorination of the dichlorovinyl product. Evidence is presented for the presence of a symmetrical two-carbon intermediate prior to the formation of glycine, an early metabolic product utilizing the vinyl carbons of the dichlorvos melocule. The isolation and identification of numerous14C-labeled normal biochemical cell constituents implies that further degradation proceeds via well-recognised metabolic pathways.