Toxicity of formaldehyde and acrolein mixtures: in vitro studies using nasal epithelial cells.

In vitro studies with human and rat nasal epithelial cells were carried out to investigate the combined toxicity of formaldehyde and acrolein and the role of aldehyde dehydrogenases in this process. These studies showed that the toxic effect of mixtures of aldehydes was additive. In addition, aldehyde dehydrogenases were inhibited by disulfiram and acrolein in S9 incubation but disulfiram did not influence the toxicity in vitro (cell culture). This study does not support the idea that aldehyde dehydrogenases play a major role in the detoxification of exogenous aldehydes.

Effect of short-term dietary administration of eugenol in humans.

1. In order to study the antigenotoxic potential of eugenol in humans, ten healthy non-smoking males ingested a daily amount of 150 mg eugenol or the placebo for seven consecutive days. After a washout period of one week, groups ingesting eugenol or the placebo were crossed and received the other treatment for seven consecutive days. 2. On days 8 and 22 blood samples were taken for the assessment of standard clinical biochemical parameters. To study the possible antigenotoxic effect of eugenol, on day 8 and 22 blood samples were collected and exposed in vitro to the established genotoxic agents mitomycin C and vinblastine. After exposure the percentage of cells with chromosome aberrations and micronuclei was determined in cultured white blood cells. On days 8 and 22 paracetamol (500 mg p.o.) was administered as test substance to measure phase-II biotransformation capacity. Glutathione-S-transferase (GST) activities were determined in erythrocytes and blood plasma. 3. No significant differences in the clinical biochemical parameters were detected between the eugenol-period and the placebo-period, indicating that daily administration of 150 mg eugenol for 7 days has no toxic affects. 4. No significant differences on the cytogenetic parameters were found after ingestion of eugenol. Thus, there are no indications for an antigenotoxic potential of eugenol in humans, consuming daily 150 mg eugenol for 7 days. 5. A significant reduction in alpha-class GSTs in plasma (P < 0.05), but not in the other measured biotransformation parameters, was found in volunteers during the eugenol-periods as compared to the placebo-period. This may either reflect GST-inhibition by eugenol or protection against background damage of liver cells by eugenol.

Antimutagenicity of eugenol in the rodent bone marrow micronucleus test.

The antimutagenic effect of eugenol on the mutagenicity of cyclophosphamide (CP), mitomycin C (MMC), ethyl methanesulfonate (EMS) and benzo[a]pyrene (B[a]P) was assessed in the rodent bone marrow micronucleus test using male Swiss mice. Oral administration of eugenol (0.4% in the diet) for 15 days was found to decrease significantly the frequency of micronucleated polychromatic erythrocytes (MPEs) elevated by CP. No effect was found on the frequency of MPEs elevated by MMC, EMS and B[a]P. The results provide some support for antimutagenic potency of eugenol in vivo.

Comparison of renal toxicity after long-term oral administration of cadmium chloride and cadmium-metallothionein in rats.

There is a clear lack of information on the toxicological risk of dietary intake of cadmium-metallothionein (CdMt). The present study aimed at establishing dose-dependent cadmium (Cd) disposition and to investigate differences in renal toxicity after long-term dietary exposure to CdMt or cadmium chloride (CdCl2) in rats. Male Wistar rats were fed diets containing 0.3, 3, 30, or 90 mg Cd/kg either as CdMt or as CdCl2 for 10 months. In rats fed 30 and 90 mg/kg Cd as CdCl2 the Cd concentrations in intestine, liver, and kidneys were all higher than in rats fed the same doses in the form of CdMt. The kidney/liver Cd concentration ratio was higher with CdMt than with CdCl2. At the lower Cd concentrations (0.3 and 3 mg/kg), no differences in Cd accumulation between CdMt and CdCl2 groups were observed and the kidney/liver Cd ratio was also similar. When based on the amount of CdMt per milligram Cd in the tissue, rats fed CdMt and those fed CdCl2 had a similar relative CdMt concentration in liver and kidney. First signs of renal injury, indicated by an increase of urinary lactate dehydrogenase (LDH) activity, were seen 4 months after exposure to 90 mg/kg Cd as CdCl2. After 8 and 10 months the renal effect of 90 mg/kg Cd as CdCl2 became more pronounced and urinary enzyme activities of LDH, N-acetyl-beta-D-glucosaminidase and alkaline phosphatase were all elevated. The only clinical effect of CdMt at the dose level of 90 mg/kg was a slight increase in urinary gamma-glutamyl transpeptidase activity at 8 and 10 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Passive smoking and sister-chromatid exchanges in lymphocytes.

The object of this study was to determine whether exposure to environmental tobacco smoke is associated with DNA damage reflected by the frequency of sister-chromatid exchange (SCE) in lymphocytes. Within a cross-sectional design, 106 male non-smoking adults, employees of two administrative companies, were divided on the basis of self-reported exposure into high and low passive smoking groups. The high exposed subjects (passive smokers, n = 50) lived with smokers, worked with smokers and were exposed to tobacco smoke for an average of 70 h/week. The low exposed non-smokers (n = 56) were exposed for an average of 5 h/week. Plasma cotinine levels for the passive smokers ranged between 0.4 and 9.0 ng/ml (median 1.4 ng/ml), and for the low exposed group between 0.0 and 1.9 ng/ml (median 0.4 ng/ml) (p less than 0.0001; Mann-Whitney test). No difference was observed between the two groups in the frequency of SCEs in lymphocytes: 4.66 +/- 0.05 for passive smokers and 4.68 +/- 0.04 for low exposed non-smokers (mean +/- SEM) (p = 0.80; t-test). Reclassification of subjects on the basis of plasma cotinine levels did not change the results substantially. These results are in accordance with observations that the increase in cancer risk due to passive smoking is small in comparison with the increase due to active smoking. The SCE test may be too insensitive to be useful for the evaluation of possible cytogenetic effects related to passive smoking.