Breath and blood levels of benzene, toluene, cumene and styrene in non-occupational exposure.

Benzene, toluene, cumene and styrene were measured in the breath and blood of two groups of individuals. The first group included individuals belonging to a hospital staff, the second group included chemical workers who were not exposed to the abovementioned chemicals. The chemical workers were examined in plant infirmaries on the morning before the start of the workshift, and the hospital staff in the hospital infirmaries. One environmental air sample was taken in the infirmaries for each individual at the moment of the biological samplings. The environmental concentrations of benzene and styrene were significantly higher in the infirmaries of the chemical plant than in the infirmaries of the hospital. On the other hand, the environmental concentrations of toluene and cumene were not significantly different in the plant infirmaries and in the hospital infirmaries. In the hospital staff the alveolar concentrations of benzene, toluene and styrene were significantly lower than those in the chemical workers. In the hospital staff the blood concentrations of benzene, toluene and styrene were not significantly different from those in the chemical workers. Only the blood cumene concentration was significantly higher in the chemical workers. In hospital staff, smokers showed alveolar and blood concentrations of benzene and toluene that were significantly higher than those measured in the non smoker hospital staff. With reference to chemical workers, only alveolar benzene concentration was significantly higher in smokers than in non smokers.(ABSTRACT TRUNCATED AT 250 WORDS)

Soil adsorption alters bioavailability of benzene in dermally exposed male rats.

The potential for exposure to chemically contaminated soil is a concern for chemical industry and waste disposal site workers as well as for individuals living near the contamination site. Current assessment of potential health risks from these types of exposures relies almost exclusively on extrapolations from data derived with pure chemicals. Complex interactions with soil, however, may alter greatly the way in which a chemical subsequently interacts with the body. This study was conducted to determine if soil adsorption alters the way in which benzene, a common chemical contaminant, enters and is handled by the body following dermal exposure. A shallow glass cap covering approximately a 13-cm2 area was fixed tightly to the shaved skin of each adult male rat tested; 300 microL of 14C-benzene alone or with 1 g of clay or sandy soil was introduced under the cap through an opening which was sealed immediately. Pure benzene produced the highest peak plasma concentration of radioactivity, followed closely by sandy soil-adsorbed benzene, with the lowest value exhibited by clay soil-adsorbed benzene. The plasma elimination half-lives were as follows:sandy (24.5 hr), pure (23.0 hr), and clay (19.4 hr). The tissue concentrations of radioactivity 48 hr post administration were highest in treated skin (covered by the glass cap), followed by the kidney and liver in both soil-treated groups, and were highest in the kidney followed by the liver and treated skin in the pure group.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological monitoring of workers exposed to benzene in the coke oven industry.

Workers in the coke oven industry are potentially exposed to low concentrations of benzene. There is a need to establish a well validated biological monitoring procedure for low level benzene exposure. The use of breath and blood benzene and urinary phenol has been explored in conjunction with personal monitoring data. At exposures of about 1 ppm benzene, urinary phenol is of no value as an indicator of uptake/exposure. Benzene in blood was measured by head space gas chromatography but the concentrations were only just above the detection limit. The determination of breath benzene collected before the next shift is non-specific in the case of smokers. The most useful monitor at low concentrations appears to be breath benzene measured at the end-of-shift.

Saúde e trabalho industrial: valores hematológicos de trabalhadores residentes no pólo sidero-petroquímico de Cubatäo, Säo Paulo / Health and industrial work: hematological values of workers living in the siderurgical and petrochemical complex of Cubatäo, Säo Paulo

Alguns parâmetros eritro-leucocitáros foram investigados em trabalhadores dos setores secundário e terciário da economia, e em desempregados, aposentados, residentes em quatro dos principais bairros de Cubatäo: Cubatäo Sede (CS), Vila Nova Cubatäo (VNC), Jardim Casqueiro (JC) e Vila Parisi (VP). Além dos valores médios de leucócitos totais (VMLT) dos város elementos da contagem diferencial e de hemoglobina, elaboramos Classificaçäo Indicadora de Alteraçöes Leucocitárias (CIGAL) com base em dados da literatura e no critério usado pelos órgäos oficiais (INAMPS e INPS) para caracterizar os indivíduos "leucopênicos". Observou-se associaçäo entre CIGAL e ocupaçäo dos trabalhadores: a percentagem de "leucopênicos" foi menor entre os supervisores (10%) e maior entre os técnicos (28,3%). Embora näo se note associaçäo, a freqüência de leucopênicos é maior entre aposentados e desempregados (32,3 e 36,9%), menor entre os funcionáros públicos (20,0%) e intermediária entre trabalhadores de diversos ramos industriais. Os operários das indústrias sidero-petroquímicas (indústria e empreiteiras) foram os únicos trabalhadores a apresentarem diferenças significativas em relaçäo a VMLT e VMN, segundo o bairro; isto se deve ao fato de os residentes na VNC e JC terem maior estabilidade no emprego e maiores chances de apresentarem leuco-neutropenia de origem benzênica do que os residentes na VP. As diferenças de VMEo e VMHb entre as populaçöes dos quatro bairros säo explicadas pelo fato de VMEo mais alta e dos VMHb mais baixos observados na VP estarem relacionados com precárias condiçöes de vida dos moradores deste bairro. A elevada freqüência de leuco-neutropenia e alta exposiçäo ao benzeno colocam sérios problemas sociais que devem ser equacionados através de rigoroso controle dos ambientes de trabalho e da realizaçäo de estudos epidemiológicos

Quantitative analysis of benzene by selected ion monitoring/gas chromatography/mass spectrometry.

A selected ion monitoring gas chromatographic/mass spectrometric method for the quantitative determination of benzene in air, breath, and blood was developed utilizing a headspace assay with benzene-d3 as an internal standard. Limits of detection for 2 ng/mL in blood and 0.1 ppb in a 5-L sample of air or breath were attained. The influence of contamination by background benzene on the analytical process was studied carefully. For cases where background contamination could not be adequately controlled, the assay was modified for the quantitative determination of labelled benzenes six mass units heavier than natural benzene (benzene-d6 or benzene-13C6). Use of the method for the analysis of natural benzene was illustrated for the measurement of background levels in urban smokers and nonsmokers.

Placental transfer and distribution of toluene, xylene and benzene, and their metabolites during gestation in mice.

The distribution of radioactivity in pregnant mice was registered at different time intervals (0-24 h) after a 10 min period of inhalation of 14C-toluene, -xylene, and -benzene. Autoradiographic and liquid scintillation methods were used to make possible the distinction between volatile, water-soluble and firmly tissue-bound radioactivity. Toluene, xylene, as well as benzene reached high concentrations immediately after inhalation in lipid-rich tissues (brain and fat) and well perfused organs (e.g., liver and kidney) but were rapidly eliminated resulting in low concentrations at 1 h in all maternal tissues, except fat. Metabolites reached peak levels around 30 min to 1 h after inhalation, but were also relatively rapidly eliminated. One exception from this general trend was a retention of firmly tissue-bound metabolites in maternal liver and kidney after benzene inhalation. Another exception was the very strong accumulation of water-soluble metabolites at 4 and 24 h in the nasal mucosa and olfactory bulb after inhalation of toluene and xylene. Volatile radioactivity was observed in the placenta and fetuses immediately and up to 1 h after inhalation of all the three studied solvents at all stages of gestation. The fetal levels were, however, much lower than in maternal tissues. In early gestation an even distribution pattern was observed, while the fetal liver reached higher concentration than other fetal tissues in late gestation. In similarity with maternal tissues, fetal tissues reached the highest levels of metabolites 30 min to 1 h after inhalation. A retention in uterine fluid was seen at 4 h. Otherwise no retention of metabolites was observed in the feto-placental unit.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of ethanol ingestion and repeated benzene exposures on benzene pharmacokinetics.

Two groups of C57Bl/6J mice were exposed to 300-ppm benzene vapor, 6 hr/day, 5 days/week for 20 exposures. One group received 10% ethanol (EtOH) in the drinking water commencing 20 hr prior to the initial exposure and continuing 5 days/week throughout the study. The second group received tap water. The uptake and clearance of benzene was followed in the blood during and after the 1st and 20th exposures. During the first benzene exposures, the mean steady state benzene concentrations in benzene/EtOH-treated mice and benzene/water-treated mice were 5.2 and 10.7 micrograms/ml, respectively. The mean elimination rate constants for the benzene/EtOH- and benzene/water-treated groups were 0.124 and 0.042 min-1, respectively. By 20 exposures, the benzene/EtOH group showed no change in mean blood steady state concentration (Css); however, the Css of the benzene/water group was reduced to 7.9 micrograms/ml. The mean elimination rate constants for the two groups were not different after the 20th exposure. The benzene/water mice exhibited a shift from mono-to biexponential clearance between the 1st and 20th exposures. Monoexponential clearances were observed for the benzene/EtOH group at both time points. These results indicate that 1 day of 10% EtOH consumption causes dramatic effects on benzene kinetics. After 20 days of treatment, the benzene/water and benzene/EtOH animals are kinetically similar. These changes in kinetics can be explained by the ability of ethanol and benzene to alter benzene metabolism.

An hypothesis for the induction of leukemia by benzene.

Benzene has the sad privilege of being the only industrial chemical inducing leukemia in susceptible individuals chronically exposed to its vapors. Hence, benzene has been included in the list of human carcinogens. Acute myeloblastic leukemia and erythroleukemia are typical examples of benzene leukemia. Most cases show some features in common: 1) development after many years of exposure and, in some cases many months after leaving the toxic atmosphere; 2) leucopenia or moderate degree of leucocytosis; and 3) splenohepatomegaly discrete or absent. Finding of an antecedent of pancytopenia reinforces the suspicion of benzene as the causative agent. There is still no agreement about the role played by benzene in chronic types of leukemia. In assessing diagnosis of benzene leukemia much importance has been attached by French authors and by myself to the demonstration of benzene in blood or in bone marrow aspirates or biopsies. Treatment of benzene hemopathy based on the oral administration of "anti-benzene compounds" such as methyl-donors and thiol-aminoacids is proposed here based on personal research in rabbits, in leukemic patients treated by benzene in the past and on myself as a volunteer. In pre-leukemic states, lowering the benzene burden of the bone marrow might prevent the further development of acute leukemia. Recently, I found out that: 1) benzene can be converted to phenol in the bone marrow independently of liver oxidizing enzymes; 2) benzene injected in the femoral artery of the rabbit can provoke histological changes at the isolated tibial marrow.

Benzene in blood and phenol in urine in monitoring benzene exposure in industry.

Determinations of benzene concentration in blood and of phenol in urine were made by head-space gas chromatography techniques on samples taken near the end of the work day from two groups of workers potentially exposed to low levels of benzene in the work-place atmosphere. Preliminary results suggest that benzene in blood is more reliable than phenol tests for assessing both exposure and uptake of benzene. Normal values of phenol in urine (10 mg/liter or less) were found in nearly all those cases in which benzene was detected in the blood.

[Haematological data relating to phenol excretion in urine with chronic benzene exposure. I. Epidemiological studies of adults (author's transl)]. / Haematologische Daten in Bezug zur Phenolausscheidung im Urin bei chronischer Benzolbelastung. I. Epidemiologische Studien bei Erwachsenen.

The phenol excretion in 24-h-urine has proved in epidemiological studies of normal population as a parameter, which can be measured very well and is sufficient exact as a parameter for a benzene burden. For an exact assessment of healthy impairment of the investigated collectives only the height of the phenol level is not sufficient. Therefore in the presented study the parameters little blood picture, differential blood picture, thrombocytes and reticulocytes were measured relating to the phenol excretion. 60-65 years old male and female adults from six districts of a large city in the strong industrialized North-West of the Ruhr-Area were investigated. The districts were differently exposed (i.e. 55 t/a benzene) to emissions. Adults at the same age from a little residential town (approx. 16 km apart) were investigated as a comparative collective. In the nearer environs there are no industrial emittents existing. - The different exposure situation is reflected well in the mean values of the collective exposure parameters. In the residential town you can find a lower phenol excretion, statistically guarded, corresponding with higher values of thrombocytes and leukocytes. Corresponding with phenol levels in urine the exposed districts presents the more adverse blood parameters. - The reticulocytes and MCHC values, like the MCV and MCH values show a similar trend corresponding with phenol values, statistically guarded. The other parameters, especially the differential blood picture, show no or little relation to the phenol values and give no indication of the exposure situation. - The combination of lower thrombocytes and leucocytes values, the trend to lower erythrocytes values (only females) and to higher MCH values in the industrial districts indicate a pancytopenic influence on the bone marrow as a characteristic for a benzene burden. - The higher reticulocytes count and its influence on the MCHC and MCV values suggest a reactive activity of the bone marrow. The absence of left displacement in the white blood picture let us suppose a compensated reaction. An acute healthy impairment of the population is not provable; therefore benzene is a certain carcinogen, it is not possible to estimate the potential hazard of the population for a longer period. For better registration of the real endangering of the population further more investigations are proposed.

Partial hepatectomy reduces both metabolism and toxicity of benzene.

Removal of 70--80% of the liver reduced both the metabolism and the toxicity of benzene in rats. Metabolism was evaluated by measuring the levels of urinary metabolites in both sham-operated and partially hepatectomized rats given 2200 mg/kg [3H]benzene sc. Toxicity was evaluated by measuring the incorporation of 59Fe into circulating erythrocytes according to the method of Lee et al. The observation that partial hepatectomy decreases benzene metabolism and protects against benzene toxicity indicates that the liver may play a primary role in the development of benzene-induced bone marrow toxicity. The fact that benzene administration also reduces the ability of the liver to regenerate after partial hepatectomy suggests that the regenerating liver may serve as a model system in lieu of the bone marrow for studying the mechanism by which benzene inhibits cell proliferation.