Sensory irritating properties of cyanuric chloride as revealed with plethysmographic method.

Sensory respiratory irritation properties of cyanuric chloride (2,4,6-trichlorotriazine; CC) were studied in mice. For this purpose, the respiratory rate was measured in Balb/C male mice by means of the whole body plethysmographic method. Each animal was placed in a body plethysmograph attached to a small (0.25 m3) dynamic inhalation chamber and exposed to various concentrations (2.1, 6.7, 9.1, 11.7 and 14.6 mg/m3) of CC. Respiratory rates were recorded before, during and after termination of the exposure. It was found that exposure to CC caused a concentration-dependant decrease of respiratory rates in mice. After termination of exposure fast and full recovery of respiratory rates were observed within 5 minutes. RD50 value calculated with probit method was established as 5.9 (1.3-13.9 for 95% confidence limits) mg/m3. The slope of the dose response curve was 1.366 (0.78). It is concluded that cyanuric chloride is a strong respiratory irritant.

Reactive naphthalene metabolite binding to hemoglobin and albumin.

Earlier work has shown that the murine Clara cell cytotoxicant, naphthalene, is metabolized to reactive metabolites which deplete glutathione or, in the absence of sufficient glutathione, become bound covalently to tissue macromolecules. Correlations between bound metabolite levels in the lung with injury suggests an association between reactive metabolite binding and toxicity. In this study we examine the formation of covalent naphthalene adducts with hemoglobin and albumin in mice to determine whether these serve as useful indices of exposure and metabolism for a chemical which shows a glutathione threshold. Covalent binding of radioactivity from [3H]naphthalene to both albumin and hemoglobin was dose dependent and a glutathione threshold was observed. At early times after naphthalene administration, the formation of albumin adducts was 10- to 30-fold higher than that of hemoglobin adducts. Hemoglobin and albumin adduct levels decreased by apparent first-order processes with half-lives of 11.5 and 1.8 days, respectively. These half-lives are consistent with the turnover of these blood proteins in the mouse. Pretreatment with buthionine sulfoximine resulted in higher levels of albumin adduct but in no alteration of hemoglobin adduct levels in comparison with control. In contrast, diethylmaleate pretreatment increased the level of hemoglobin adduct but not albumin adduct. The antibody to naphthalene mercapturates recognized the hemoglobin adduct(s) but not the albumin adduct(s). Comparison of the data from ELISA (standardized using hydroxymercaptodihydronaphthalene) and radiochemical analysis yielded curves with identical slopes; the absolute levels of adduct found by ELISA were approximately half those measured with radiochemical techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute combined exposure to N-butyl alcohol and M-xylene.

The effects of combined exposure to m-xylene and n-butyl alcohol on rotarod performance and motor activity in rats and respiratory rate in mice were investigated in the condition of an acute inhalation experiment. Rotarod performance and motor activity were tested in rats exposed to various concentrations of m-xylene, n-butyl alcohol and their mixture consisting of 50 Vol-% m-xylene and 50 Vol-% n-butyl alcohol immediately after termination of a 4-hour exposure period. The respiratory rate in mice was recorded in short 6 min duration exposures to individual solvents and their 50:50 Vol-% mixture. Both solvents and mixtures caused concentration-dependent disturbances of rotarod performance in rats. The medial effective concentration (EC50) for the effect amounted 6530 ppm, 1980 ppm and 3080 ppm for n-butyl alcohol, m-xylene and their mixture, respectively. Both solvents and their mixture changed the spontaneous motor activity in the rat. Because of a two-phase effect, the concentration-dependence of the observed changes could not be defined. The evaluation of the combined effect in motor activity test was carried out by comparing experimental values with expected ones assuming the summation of individual solvent effects. The tested solvents resulted in a concentration-dependent decrease in respiratory rate in mice. The concentration which decreased the respiratory rate to 50% (RD50) was 3010 ppm, 1360 ppm and 3140 ppm for n-butyl alcohol, m-xylene and their mixture, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute toxicity of 2-butyne-1,4-diol in laboratory animals.

Acute toxicity of 2-butyne-1,4-diol (BYD) was evaluated in laboratory animals. The evaluation involved acute oral and dermal toxicity in rats, dermal and ocular irritation in rabbits and skin sensitization in guinea pigs. The oral LD50 values for BYD were 132 mg kg-1 in male rats and 176 mg kg-1 in female rats. Post-mortem histology showed severe damage in lungs, liver and kidneys. In surviving rats, moderate to severe degenerative changes were observed in the liver but only mild lesions in the kidneys. In acute dermal toxicity studies the test chemical was applied either as a solid substance or as 40% aqueous solution at a dose of 5 g kg-1 for 24 h. Within 48 h of application of the diluted test material, half of the rats died. Liver and kidneys were the primary targets and different stages of degeneration, including necrosis, were observed. No deaths occurred after application of the solid substance. In rabbits, BYD was slightly irritant to skin and eyes. No allergic contact dermatitis was observed in guinea pigs.

Subacute oral toxicity of 2-butyne-1,4-diol in rats.

2-Butyne-1,4-diol was given to male and female Wistar Imp:DAK rats by oral gavage for 28 consecutive days in daily doses of 1, 10 or 50 mg kg-1 day-1. After 28 days all animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examination. Treatment-related effects in the high-dose group consisted of: fatal cases in both sexes; depressed body weight gain in males; increase of absolute and/or relative weights of liver and kidneys in both sexes; decreased red blood cell count, haematocrit value and haemoglobin concentration in female rats and elevated reticulocyte count and leukocyte count in both sexes; increased total serum protein content in females, elevated glucose concentration in males and higher activity of sorbitol dehydrogenase in both sexes; and histopathological evidence of hepatotoxicity and nephrotoxicity in decedents, and hepatic and splenic changes in survivors. Minor hepatic, splenic and erythrocytic changes were also found in some females given the middle dose. The dose of 1 mg kg-1 day-1 was considered to be the no-observed-effect level (NOEL), and 10 mg kg-1 day-1 the lowest-observed-effect level (LOEL).

Acute toxicity of 1,4-butanediol in laboratory animals.

Acute toxicity of 1,4-butanediol (BAD) was evaluated in laboratory animals. The evaluation involved acute oral and dermal toxicity in rats, dermal and ocular irritation in rabbits, and skin sensitization in guinea pigs. The oral LD50 values for BAD were 1.83 g/kg and 2.00 g/kg, respectively for male and female rats. The histopathological changes were observed in the liver and kidneys. No mortality was observed in female rats after dermal application of BAD at a dose of 5 g/kg. The histopathological lesions were comparable to those observed in rats after oral gavage. BAD was slightly irritant to the skin and eye of rabbits. No allergic contact dermatitis was observed in guinea pigs.

Subacute oral toxicity of 1,4-butanediol in rats.

1,4-Butanediol (BAD) was administered to male and female Wistar Imp:DAK rats by oral gavage for 28 consecutive days. Treated rats received BAD at daily doses of 5, 50 or 500 mg/kg/day. After 28 days all animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examination. Subacute oral administration of BAD resulted in an overall low degree of systemic toxicity. There were no changes in body weight, food consumption, and absolute and relative organ weights. Slightly higher activities of sorbitol dehydrogenase and alanine aminotransferase were observed in male rats given BAD at the highest dose of 500 mg/kg/day. Some disturbances in hematological parameters, characterized by macrocytosis and thrombocytopenia were observed in treated rats. Mild to moderate inflammation of the liver, characterized by proliferation of bile ducts and periportal infiltrations with fibroblasts and mononuclear cells, were found in treated animals. A statistically significant difference for histopathological changes was found in animals treated with BAD at the dose of 500 mg/kg/day only in the case where both sexes were jointly taken for comparison.

[Evaluation of vinyl chloride toxicity based on its metabolism]. / Ocena toksycznosci chlorku winylu na podstawie jego metabolizmu.

Discussed in the paper are the processes of absorption, distribution and metabolization of vinyl chloride in the living organism. The latest views on the occurrence and excretion of vinyl chloride metabolites, possible indices of occupational exposure to this compound, have been presented.

Comparison of the impact of continuous and intermittent exposure to vinyl chloride, including phenobarbital effect.

Rats were subjected to 4 h continuous and intermittent exposure to vinyl chloride (VC) at the time-weighted average concentration of 50,000 mg/m3. Prior to exposure, half of the animals obtained water, whereas the other half 0.1% sodium phenobarbital (PB) solution for seven consecutive days. The studies were focussed on: body weight, liver weight, activity of enzymes in the blood serum, activity of glutathione S-transferase in the liver cytoplasmatic and microsomal fraction, content of free non-protein sulfhydryl groups (NPSH) in the liver and urinary excretion of thiodiglycolic acid (TDGA). VC exposure, both continuous and intermittent, resulted in a decrease of body weight, NPSH depletion in the liver and TDGA urinary excretion. PB effects were manifested by the persistent decrease in rats' body weight, increase in the liver weight, increase in the cytoplasmatic activity of glutathione S-transferase in the liver and increase in TDGA urinary excretion. With none of the tested parameters, except TDGA, statistically significant differences between the continuous and intermittent VC exposure at the same time-weighted average concentration of 50,000 mg/m3, were found. TDGA urinary excretion was higher in rats poisoned in continuous exposure, as compared to the intermittent one.

Influence of exposure mode on vinyl chloride action.

Rats were subjected to 4 h continuous or intermittent exposure to vinyl chloride (VC) at different time-weighted average concentrations (15, 50, 150, 500 and 15,000 mg/m3). Hepatic non-protein sulfhydryl content (NPSH) and excretion of thiodiglycolic acid (TdGA) in urine were determined. VC at concentrations from 50 mg/m3 to 15,000 mg/m3 caused a dose-dependent depression of NPSH, but no difference in the magnitude of this depression induced by continuous of VC was noted. At average concentrations of 50 mg/m3 and 150 mg/m3, the urinary excretion of TdGA under continuous exposure did not differ from that under intermittent exposure, whereas at VC concentrations of 500 mg/m3 and 15,000 mg/m3 it was higher following continuous exposure.