Immunotoxicity of ethyl-4-isothiocyanatobutanoate in male Wistar rats.

The immunotoxicity of ethyl-4-isothiocyanatobutanoate (E-4IB) using different immuno-pathological parameters and immune function assays in male Wistar rats was evaluated. The rats were administered intraperitoneally 12 times with E-4IB in three varying doses of 21, 28 and 35 mg/kg of body weight, over a period of 36 days. The doses of E-4IB were set according to the results of previous experiments by its anti-proliferative activity in vivo. High and medium doses of E-4IB exceeded the maximum tolerated dose after the 36-day treatment period. Symptoms of toxicity were displayed by a drop in body weight, spleen and thymus weight and in organ and bone marrow cellularity. Haematological changes displayed a dose-dependent decrease in the percentage of lymphocytes and dose-dependent increase in the percentage of polymorphonuclear leukocytes in peripheral blood. The white blood cell count in rats exposed to a high dose of E-4IB was suppressed. The immune system of rats administered 21 mg/kg of E-4IB (low dose) was unaffected. No changes in primary antibody response to sheep erythrocytes, in vitro proliferative response of spleen lymphocytes to mitogens and phagocytic activity of leukocytes were found in those rats. Our findings indicate that this newly developed anti-cancer drug is not immunotoxic.

Biomonitoring of genotoxic risk in workers in a rubber factory: comparison of the Comet assay with cytogenetic methods and immunology.

Several substances used in rubber processing are known to be genotoxic. Workers in a rubber tyre factory, exposed to a broad spectrum of contaminants such as benzo[a]pyrene, benzo-fluoranthene, naphthalene, acetonaphthene, alkenes and 1,3-butadiene have been regularly examined for several years: chromosomal aberrations in lymphocytes, mutagenicity of urine (by use of the Ames test) and various parameters of blood and urine were assessed. An elevated level of mercapturic acid derivatives was found in the urine of employees, which is indicative of environmental exposure to toxicants with alkylating activity. We have now extended this study by examining genotoxicity with the modified Comet assay in parallel with chromosomal aberrations and micronucleus formation as well as immunological endpoints. Twenty-nine exposed workers from this factory were compared with 22 non-exposed administrative staff working in the same factory, as well as with 22 laboratory workers. The absolute numbers of peripheral leukocytes were significantly higher in the exposed group than in either of the control groups (p < 0.001). The erythrocyte mean cell volume was significantly higher in exposed workers in comparison with laboratory controls (p < 0.05). Percentages of lymphocytes, polymorphonuclear leukocytes, monocytes and eosinophils were not altered. The proliferative response of T- and B-cells to mitogen treatment when calculated per number of lymphocytes and adjusted for smoking, age and years of exposure did not differ between exposed and control groups. Endogenous strand breaks (including alkali-labile sites) and altered bases (formamidopyrimidine glycosylase- and endonuclease III-sensitive sites) were measured by the Comet assay in lymphocyte DNA. Exposed workers had significantly elevated levels of DNA breaks compared with office workers (p < 0.00001) or with laboratory controls (p < 0.00001). Micronuclei occurred at significantly higher frequencies in the exposed group than in controls (p < 0.00001), though the frequencies were all within the normal range. Significant correlations were seen between individual values of strand breaks, micronuclei and chromatid/chromosome breaks and certain immunological parameters.

Determination of arsenic in geological samples by HG AAS.

A continuous hydride generation (HG) AAS procedure for the determination of As in geological samples utilizing the SH-group containing amino-acid L-cysteine for the pre-reduction of As (V) to As (III) in HNO(3) has been optimized and compared with a method utilizing KI and ascorbic acid in HCl. The influence of some transition metals (Co, Fe, Ni) on the determination of As has been investigated. Decompositions of geological certified reference materials, sediments and soils of different origin and geochemical composition with concentrated HNO(3) have been performed in open and closed systems and the resulting As content has been compared with certified and proposed data.

The influence of ascorbic acid on selected parameters of cell immunity in guinea pigs exposed to cadmium.

The study investigated the possibility of influencing immunotoxic effects of Cd through ascorbic acid. Guinea pigs with high and low intake of ascorbic acid were perorally exposed to cadmium chloride (1 mg Cd/animal/day). The daily vitamin C intake was 2 and 100 mg per animal, respectively. Phagocytic activity of polymorphonuclear leucocytes and monocytes as well as the percentage of active and total T lymphocytes in peripheral blood of animals were evaluated. Five- and 12-week experiments showed a mutual potentiation of negative effects of Cd on the immune system by suboptimal intake of ascorbic acid. Toxic effects of Cd on the immune system can be reduced by a sufficient intake of vitamin C.

Subacute immunotoxicity study of formaldehyde in male rats.

Immune functions were examined in male rats following 28 day oral administration of formaldehyde by gastric tube at dose levels of 0, 20, 40, and 80 mg/kg. Routine parameters examined included hematology, clinical chemistry, and body, thymus, kidney, and liver weights. In addition, cellularity of spleen and lymph nodes, histology of spleen, thymus, lymph nodes, liver kidney, small and large intestines, and histochemistry of spleen and lymph nodes were evaluated. Immune parameters evaluated included serum hemagglutinin antibody response; antibody plaque forming cell response to sheep erythrocytes (lymphocyte-dependent antigen); microbicidal activity of Candida albicans; and phagocytic activity by adhesion of microspheric hydrophilic synthetic particles to leukocyte cell membrane. Body weights were slightly decreased at high dose level (80 mg/kg). The difference was significant when compared to the controls. The lymph node weights were significantly increased in rats receiving formaldehyde. The cellularity of lymphoid organs was not influenced after 28 day exposure to formaldehyde.