Interleukin 1 alpha hematological examination in mechanics exposed to low benzene concentrations.

OBJECT: To examine the hypothesis of Renz and Kalf relative to the involvement of interleukin 1 alpha (IL-1 alpha) in the development of anemia in benzene-exposed workers. According to this hypothesis, benzene inhibits the cleavage of the IL-1 alpha precursor (proIL-1 alpha) to mature IL-1 alpha and the lack of this cytokine is responsible for benzene-induced bone marrow suppression. This inhibition of the processing of proIL-1 alpha is attributed to an inhibition of calpain. METHOD: Selection of a population of mechanics exposed to low levels of benzene from fuels, assessment of usual exposure and lifetime exposure duration, and measurements of concentrations of workplace-air benzene and urinary benzene metabolites. Determination of IL-1 alpha concentrations was done by a whole-blood assay after lipopolysaccharide stimulation and a hematological examination was carried out. Statistical analysis considered several possible confounding factors, particularly smoking and drinking habits. DESIGN: Cross-sectional study. RESULTS: The level of exposure of the mechanics to benzene from fuels was mostly well below 1 ppm. IL-1 alpha production was not decreased in mechanics exposed to benzene from fuels, and no correlation between IL-1 alpha concentrations and red blood cell counts appeared. With the exception of a slight decrease in red blood cell counts in mechanics, no hint of a toxic effect of exposure on hematological parameters was found. CONCLUSIONS: The hypothesis of Renz and Kalf could not be confirmed. Although the low level exposure of the study population and methodological factors are possible explanations, it cannot be excluded that the hypothesis of Renz and Kalf is not generalizable to benzene-exposed humans. Presently, one cannot advise the measurement of IL-1 alpha production for biological effect monitoring of workers exposed to low concentrations of benzene.

Relationships between smoking habits, smoking-associated hematological changes, and urinary benzene metabolites.

It has been suggested that benzene metabolites might be good indicators of smoking. Moreover, benzene could stimulate the neutrophil lineage while depressing the lymphocytic and erythroid lineages, possibly by an interference with cytokines. The effect on the neutrophil lineage could explain the smokers' leukocytosis, the mechanism of which is presently unknown. Therefore, the usefulness of benzene metabolites as indicators of smoking was compared to that of cotinine and thiocyanate, and the relationships between benzene metabolites, the hematological parameters of smokers, and interleukin 1 alpha production were examined. The results show that benzene metabolites are not better indicators of smoking status than cotinine or thiocyanate. Furthermore, it seems unlikely that the smokers' leukocytosis is benzene induced.

Biological monitoring of vehicle mechanics and other workers exposed to low concentrations of benzene.

It has been suggested that the threshold limit value (TLV) for the time-weighted average (TWA), of benzene be lowered because of its possible leukemogenic effect at low exposure concentrations. This requires the development of new methods of biological monitoring. In this cross-sectional study the diagnostic power of blood and breath benzene and of urinary phenol, catechol, hydroquinone, S-phenylmercapturic acid, and muconic acid were compared in a population of 410 male workers exposed to benzene in garages, in two coke plants, and in a by-product plant. Benzene exposure was assessed by personal air sampling (charcoal tube and passive dosimeter). In all, 95% of the workers were exposed to less than 0.5 ppm benzene. According to the multiple regression equation, the muconic acid and S-phenylmercapturic acid concentrations detected in nonsmokers exposed to 0.5 ppm benzene were 0.3 mg/g and 6 micrograms/g, respectively (range 0.2-0.6 mg/g and 1.2-8.5 micrograms/g, respectively). With muconic acid very few false-positive test results were found, and this determination remained reliable even around a cutoff level of 0.1 ppm benzene. Moreover, the diagnostic power of this test proved to be good even when diluted or concentrated urine samples were not excluded. S-Phenylmercapturic acid (S-PMA) also performed fairly well. Blood and breath benzene as well as urinary phenol (PH) and hydroquinone (HQ) were clearly less suitable biomarkers than muconic acid (MA). Catechol (CA) was not associated with occupational benzene exposure. According to the results of biological monitoring, the skin resorption of benzene from gasoline or other fuels seems negligible. Correlation, multiple regression, and likelihood ratios consistently showed that MA and S-PMA concentrations were fairly good indicators of benzene exposure in the 0.1- to 1-ppm range, even in a population comprising both smokers and nonsmokers. PH, HQ, CA, and blood and breath benzene were less suitable, if at all, in the same exposure range.

Assessment for Subclinical Kidney Damage in Workers Exposed to Low Concentrations of Hydrocarbons.

It has been suggested the risk of hydrocarbon-induced chronic nephropathy is negligible at low exposure levels. The first purpose of the study was to test this hypothesis by selecting a population slightly exposed to hydrocarbons. Moreover, as hypertension might be associated with an increased excretion of nephrotoxic mercapturates, the association between blood pressure and urinary concentration of S-phenylmercapturic acid (S-PMA) was also examined. Lifetime exposure assessment, main tests of subclinical kidney damage, and statistical approach were taken from a previous study that had included primarily moderately or heavily exposed workers and had found hydrocarbon-induced nephrotoxic effects. No nephrotoxic effect of exposure could be ascertained in the present study. S-PMA concentration was not increased in hypertensive workers. Thus, the risk of hydrocarbon-induced chronic nephropathy might be extremely low in workers slightly exposed to hydrocarbons. The negative results of some studies might be due to the low lifetime hydrocarbon exposures of the study populations.

Determination of toluenediamines in urine of workers occupationally exposed to isocyanates by high-performance liquid chromatography.

In recent years, epidemiological evidence that exposure to toluene diisocyanate (TDI) is associated with adverse health effects has led to the development of useful analytical methods for the biological monitoring of TDI. In this paper, an HPLC method is presented that allows accurate determinations of toluenediamines (TDA), urinary metabolites of TDI, in hydrolysed human urine without complicated or time-consuming sample treatment. The procedure requires 5.0 ml of urine and involves the extraction with toluene of TDA and the hydrolysable conjugate fraction followed by further purification with a strong cation-exchange sorbent. Strongly alkaline conditions are chosen for the hydrolysis of urine samples and phenylene-1,3-diamine is used as internal standard to control the sample extraction and clean-up. Separation is performed on a base-deactivated octadecyl reversed-phase column by either ion-suppression or ion-pair chromatography. Chromatographic analysis is complete in less than 20 min and chromatograms with no interfering peaks are obtained. High sensitivity and selectivity are achieved by using electrochemical detection: 2,6- and 2,4-TDA can be detected at the 0.1 and 0.15 microgram l-1 levels, respectively. Absolute recoveries of the method tested with urine samples spiked at 10 micrograms l-1 with phenylene-1,3-diamine and from 1 to 25 micrograms l-1 with 2,6-and 2,4-TDA are greater than 87.6% and 88.3%, respectively. The assay is linear from 0 to 50 micrograms l-1. Within-run precisions evaluated on 10 urine samples ranging from 0 to 10 micrograms l-1 are 7.9% and 5.3% for 2,6- and 2,4-TDA, respectively. Results obtained with urine samples from 12 controls and 15 exposed workers from a flexible polyurethane foam factory indicate that the method is appropriate for the biological monitoring of occupational exposure to TDI.

Physicochemical mechanism of the interaction between cobalt metal and carbide particles to generate toxic activated oxygen species.

Hard metal alloys (or cemented carbides) are made of a mixture of tungsten carbide particles (WC, more than 80%) cemented in cobalt metal powder (Co, 5-10%). The inhalation of hard metal particles may cause an interstitial pulmonary disease, the mechanism of which involves an interaction between Co and WC particles. Some epidemiological data also suggest that hard metal dust can induce lung cancer in workers. In a macrophage culture model, butylated hydroxytoluene (1 mM) protected from the cytotoxicity of hard metal particles, suggesting a possible involvement of lipid peroxidation in the toxicity of these powders. In a biochemical system, a mixture of Co and WC particles, but not Co or WC alone, stimulated the production of thiobarbituric acid-reactive substances from arachidonic acid. Using a spin trapping system applied to aqueous particulate suspensions and electrochemical techniques, we present experimental evidence that the association of Co and carbide particles represents a specific toxic entity producing large amounts of activated oxygen species. The mechanism of this interaction proceeds through the oxidation of cobalt metal catalyzed at the surface of carbide particles and resulting in the reduction of dissolved oxygen. This physicochemical property of hard metal particles provides a new basis for interpreting their inflammatory action and their possible carcinogenic effect on the lung.

Effect of the benzene metabolite, hydroquinone, on interleukin-1 secretion by human monocytes in vitro.

Decreased interleukin-1 (IL-1) production by mononuclear phagocytes has been shown to contribute to benzene myelotoxicity in animals. The study presented here was designed to examine the relevance of this mechanism in humans. Fresh human blood monocytes were exposed to 0.001-10 microM hydroquinone (HQ) and assessed for their ability to release IL-1 alpha and IL-1 beta in response to a stimulation with endotoxin. Both cytokines were measured by specific ELISA. Exposure of human monocytes to micromolar concentrations of HQ for 2 hr resulted in a dose-dependent reduction of IL-1 secretion. For both IL-1 alpha and IL-1 beta, the decreases were statistically significant at concentrations of 5 microM and above. HQ also inhibited RNA and protein synthesis in a dose-dependent manner, with 50% inhibitory concentrations of 21 +/- 11 and 10 +/- 9 microM, respectively. Furthermore, monocytes treated with 5 microM HQ also displayed a reduced total protein content when compared with control cells. These data suggest that the reduction of IL-1 production caused by HQ results from a global impairment of monocyte essential functions such as transcription or translation. Taken as a whole, our results support a mechanism whereby HQ may contribute to the myelotoxicity of benzene in humans by inhibiting the production by mononuclear phagocytes of cytokines involved in the regulation of hematopoiesis.

[Epidemiology and prevention of tuberculous contamination in bacteriology laboratories. Results of a survey on 23 laboratories]. / Epidémiologie et prévention des contaminations tuberculeuses dans les laboratoires de bactériologie. Résultats d'une enquête effectuée dans 23 laboratoires

The authors have carried out a survey of 23 bacteriology laboratories to investigate tuberculous contaminations which took place from 1967 to 1972 in these laboratories. They have reviewed 20 accidents in 74 technicians who performs searches for tuberculous bacilli, and 29 accidents in the total amount of 379 technicians working in these 23 laboratories. A comparison of these results with the previous published investigations shows a rather high number of cases reported in our country. A review of the possible causes of contaminations leads to suspect bacterial aerosols and to put forward the use of laminar flow enclosures as a prevention. The authors have tested several vertical flow instruments built to different patterns. All three convenient enclosures have an architectural characteristic: their blowing ceiling overhangs the working plane. As these instruments have been under examination for three years in a laboratory where contaminations are very likely to happen, they have obtained interesting results.