Cancer mortality in an international cohort of reinforced plastics workers exposed to styrene: a reanalysis.

OBJECTIVE: To investigate the carcinogenicity of styrene by reanalysing data from a previous international cohort study of workers in the reinforced plastics industry. METHODS: Mortality from cancers of prior interest was analysed with more detailed consideration of exposure-response relations and an updated classification of leukaemias and lymphomas in data from a previous international cohort study of 37 021 reinforced plastics workers exposed to airborne styrene. RESULTS: Increased mortality from non-Hodgkin's lymphoma (NHL) was associated with the mean level of exposure to styrene in air (relative risk (RR) 2.31, 95% CI 1.29 to 4.12 per 100 ppm), but not with cumulative styrene exposure. Similar associations with mean exposure were observed for the oesophagus (RR 2.44, 95% CI 1.11 to 5.36 per 100 ppm) and pancreas (RR 1.89, 95% CI 1.17 to 3.09). Oesophageal cancer mortality was also associated with cumulative styrene exposure lagged 20 years (RR 1.16, 95% CI 1.03 to 1.31). No other cancer, including lung cancer, was associated with any indicator of styrene exposure. CONCLUSION: This reanalysis does not substantially change the conclusions of the original study with respect to NHL or lung cancer but new evidence concerning cancers of the oesophagus and pancreas merits further investigation.

An investigation of multiple biomarkers among workers exposed to styrene and styrene-7,8-oxide.

Investigations of cancer and cytogenetic damage among reinforced-plastics workers have produced contradictory results. In all studies, the focus has been on styrene rather than the carcinogen, styrene-7,8-oxide (SO), traces of which are generated during the manufacturing process. Because styrene is present at very high levels and is metabolized almost exclusively through SO, coexposures to SO have been discounted. This study investigated the relative contributions of airborne styrene and SO and of smoking toward several SO-specific biomarkers (DNA and albumin adducts) and sister chromatid exchanges in the blood of 48 reinforced-plastics workers. Among individual subjects, albumin and DNA adducts as well as sister chromatid exchanges were significantly correlated with styrene exposure. However, among the 20 subjects with measurements to both styrene and SO, albumin adducts were significantly correlated with exposure to SO but not to styrene. Finally, among the 10 job groups, surprisingly strong correlations (0.709 < or = r < or = 0.966) were found between all SO biomarkers and exposure to SO but not to styrene. Calculations suggest that SO was about 2000 times more effective than styrene in producing SO biomarkers. After accounting for the disparate exposures to the two chemicals, a typical worker received 71% of the systemic dose of SO via inhalation; nonetheless, 5 of the 20 subjects received the majority of the SO dose from styrene. Cigarette smoking increased levels of SO-albumin and SO-DNA adducts, suggesting that SO was a constituent of tobacco smoke. We conclude that inhalation of SO should be considered in any interventions to reduce health risks.

Behavioral effects of long-term exposure to organic solvents.

Epidemiological studies have detected an increased risk of neuropsychiatric diseases among groups occupationally exposed to organic solvents. Psychological studies of solvent exposed workers have investigated both cognitive and sensory and motors functions. Most of these studies have dealt with trichloroethylene, toluene, styrene, and mixtures of organic solvents. Most of these studies have found a decline in the sensory and motor functions. Of the cognitive functions especially short-term memory has proved to be sensitive to solvent exposure. Also some implications of declined visuoconstructive abilities have been found. It has been possible to analyze exposure-response and exposure-effect relationships between exposure and psychological findings only for some single studies, because reliable measures for long-term solvent exposure have usually not been available. The measurement of personality characteristics among solvent exposure workers has been another neglected area.

Glycophorin A somatic cell mutation frequencies in Finnish reinforced plastics workers exposed to styrene.

We have used the glycophorin A (GPA) in vivo somatic cell mutation assay to assess the genotoxic potential of styrene exposure in 47 reinforced plastics workers occupationally exposed to styrene and 47 unexposed controls matched for age, gender, and active smoking status. GPA variant erythrocyte frequencies (Vf), reflecting GPA allele loss (phi/N) and allele loss and duplication (N/N) somatic mutations arising in vivo in the erythroid progenitor cells of individuals of GPA M/N heterozygous genotype, were flow cytometrically determined in peripheral blood samples from these subjects. Measurements of styrene exposure of the workers at the time of blood sampling showed a mean 8-h time-weighted average (TWA8-h) styrene concentration of 155 mg/m3 (37 ppm) in the breathing zone. Mean urinary concentrations of the styrene metabolites mandelic acid (MA) and mandelic acid plus phenyl glyoxylic acid (MA+PGA) were 4.4 mmol/liter (after workshift) and 2.1 mmol/liter (next morning), respectively. Multivariate analysis of covariance on log-transformed GPA Vf data with models allowing adjustment for age, gender, smoking status, and styrene exposure showed that N/N Vf were nearly significantly increased among all of the exposed workers (adjusted geometric mean, 6.3 per million versus 5.0 in the controls; P = 0.058) and were statistically significantly elevated (adjusted geometric mean, 6.8 versus 5.0 in the controls; P = 0.036) among workers classified into a high-exposure group according to personal TWA8-h concentration of styrene in the breathing zone of > or = 85 mg/m3 (20 ppm; Finnish threshold limit value). Women in this high exposure group showed especially elevated N/N Vf (adjusted geometric mean 8.5 versus 5.3 in control women; P = 0.020); this elevation was also significant if urinary MA+PGA of > or = 1.2 mmol/liter was used as the basis of classification (adjusted geometric mean, 8.3; P = 0.030). The occupational exposure could not be shown to influence phi/N Vf. Cigarette smoking was associated with significantly elevated GPA Vf among active smokers (P = 0.042 for phi/N and P = 0.020 for N/N) and among active and ex-smokers combined (P = 0.014 for N/N). Its influence on phi/N Vf was especially clear among active smokers in the control group (P = 0.005). An effect of smoking, nearly statistically significant, was also observed for the phi/N Vf of control ex-smokers (P = 0.055) and of all active and ex-smokers combined (P = 0.050). Thus, the two characterized chemical exposures experienced by this group of workers and controls appear to produce differential effects on the two independent classes of GPA variants enumerated in the assay. This result suggests that the genotoxicity of these agents is mediated, at least in part, by different genetic mechanisms. Styrene exposure is associated with a specific increase in GPA N/N Vf; these allele loss and duplication variants reflect predominantly somatic recombination mechanisms in erythroid progenitor cells. Tobacco smoke exposure in active and ex-smokers is also associated not only with an increase in N/N Vf but also with an increase in phi/N Vf, reflecting the induction of GPA gene-inactivating mutations, including point mutations and deletions. This finding is consistent with a broad mechanistic spectrum of tobacco smoke genotoxicity associated with this complex mixture of chemical mutagens. Finally, there was no detectable effect of age on phi/N Vf; however, a highly significant (P = 0.0002) increase in N/N Vf with age, even after adjustment for other variables, was observed.

Determination of albumin and hemoglobin adducts in workers exposed to styrene and styrene oxide.

Hemoglobin and albumin adducts of the carcinogen styrene-7,8-oxide (SO) were measured in 48 workers exposed to both styrene and SO in a boat manufacturing plant. Personal exposures to both substances were measured repeatedly over the course of 1 year (styrene:0.9-235 mg/m3 with a mean of 64.3 mg/m3 for 48 subjects; S0: 13.4-525 mu g/m3 with a mean of 159 mu g/m3 for 20 subjects). Cysteine and carboxylic acid adducts of SO with hemoglobin and albumin were assayed on one or more occasions for each subject. The proteins were subjected to base hydrolysis to release styrene glycol, representing carboxylic acid-bound SO, and were then treated with Raney nickel to release 1-phenylethanol and 2-phenylethanol, representing cysteine-bound SO. These three analytes were extracted, derivatized, and analyzed by gas chromatography-mass spectrometry. No evidence was found of any exposure-related increase in hemoglobin adducts. In contrast, albumin adducts were found to increase with exposures to either styrene or SO, the latter apparently being more important. This suggests that exposure to low levels of SO in the air may be important among workers in the reinforced plastics industry. Significant levels of SO adducts of albumin and hemoglobin were also detected in proteins obtained from persons without occupational exposure to styrene or to SO. This finding opens the possibility that SO is either a dietary or an environmental contaminant or is produced endogenously.

A comparative trial of oxantel-pyrantel and mebendazole in multiple helminth infection in school children.

In a pilot study in 17 children, oxantel-pyrantel as one single dose of 10 to 20mg/kg of each, gave good results in ascariasis but poor cure rates in both trichuriasis and necatoriasis. However in the latter groups the infection was extremely heavy. In a controlled trial in 51 children, using oxantel-pyrantel at the same dose, but given daily for 3 consecutive days, or mebendazole 100mg twice daily for 3 days, the drugs gave similar response rates. Both gave 100% cure rates, as assessed by the absence of ova by both Beaver and brine-flotation techniques, in Ascaris lumbricoides infection. The percentage cures and egg reduction rates were 66.7 and 94.5 in trichuriasis and 53 and 93.6 in necatoriasis respectively. Those for mebendazole were 52 and 91.2 in trichuriasis and 37.5 and 89.7 in necatoriasis. Oxante-pyrantel treatment was associated with more cures, and a marginally greater reduction in ovum excretion than mebendazole but the differences were not statistically significant. No side-effects were seen with either treatment.

Influence of the level of cytosolic epoxide hydrolase on the induction of sister chromatid exchanges by trans-beta-ethylstyrene 7,8-oxide in human lymphocytes.

trans-beta-Ethylstyrene 7,8-oxide, a substrate of cytosolic epoxide hydrolase, and 4-fluorochalcone oxide, an inhibitor of this enzyme, were investigated on induction of sister chromatid exchanges (SCE) in human lymphocytes. Both epoxides enhanced the frequency of SCE. 4-Fluorochalcone oxide at low concentration (2.5 microM) inhibited cytosolic epoxide hydrolase activity towards trans-beta-ethylstyrene 7,8-oxide in lymphocytes by 74% and had no effect on glutathione transferase activity using this substrate. At this concentration it did not induce SCE itself, but it potentiated the effect of trans-beta-ethylstyrene 7,8-oxide several fold. In lymphocytes from different subjects, the number of SCE induced by a low concentration of trans-beta-ethylstyrene 7,8-oxide correlated negatively with the individual cytosolic epoxide hydrolase activity (r = -0.72; -0.73 in two series of experiments). The number of SCE induced by a high concentration of trans-beta-ethylstyrene 7,8-oxide did not correlate with cytosolic epoxide hydrolase activity (r = 0.004; -0.24), but a negative correlation was found with glutathione transferase activity (r = -0.50). This finding is consistent with the results of biochemical studies in lymphocytes in which we determined the relative contribution of cytosolic epoxide hydrolase and glutathione transferase to the metabolism of trans-beta-ethylstyrene 7,8-oxide at varying substrate concentrations. The study demonstrates that the level of genotoxic effects induced in human lymphocytes is influenced by the individual level of detoxifying enzymes. At low concentrations, cytosolic epoxide hydrolase was more important than glutathione transferase activity.

An investigation of the association between exposure to styrene and hearing loss.

The importance of the association between advancing age and hearing loss is well recognized. Further, prolonged significant noise exposures are also known to result in permanent hearing loss. However, little is known of the contribution of industrial chemical exposures to hearing loss. Information available, from both animal and human studies, raises the possibility that certain aromatic hydrocarbons are ototoxic. The purpose of this study was to assess whether occupational styrene exposure causes hearing loss in a group of workers in the fiber-reinforced plastics manufacturing industry. The hearing acuity of 299 subjects was determined, using pure-tone screening audiometry, at the beginning of a single workshift and again at the end of the shift. On the same day, the personal, time-weighted average exposures of each subject to both styrene and noise were measured. In addition, information on the following factors was obtained from each participant: previous work history, including exposures to noise and chemicals; use of personal protective equipment for noise or solvents; personal and family history of hearing problems; and smoking history. Current exposures together with work histories were used to construct lifetime noise and styrene exposure indices. No conclusive evidence was found for a chronic styrene-induced effect on hearing acuity, when both noise and styrene lifetime exposures were taken into account. As expected, age and noise exposures were highly important variables, both positively associated with hearing loss. In addition, the detrimental effect of noise exposure on hearing acuity was found to be strengthened with increased age. Noise and styrene exposures were highly correlated, clearly illustrating the importance of considering all associated variables in analysis of such data. No evidence was found for a relationship between smoking, recreational noise, solvent exposures, and hearing loss.

Use of the glycophorin A human mutation assay to study workers exposed to styrene.

The glycophorin A (GPA) assay is a human mutation assay that is potentially useful for large epidemiological studies. The assay is rapid and requires a minimal amount of blood, which can be stored before analysis. The data presented here were collected from workers exposed to styrene in a boat manufacturing plant. This study was the first to apply the GPA assay to an occupationally exposed population. Subjects with a mean styrene exposure of 30 ppm had a higher frequency of GPA N phi variant cells than subjects with mean exposure of 1 ppm, but the subjects differed in respect to smoking and age distribution. Results indicate that the original 1-W-1 version of the assay may not be suitable for studies of small numbers of exposed subjects due to variability and artifacts. The newer BR6 version, however, has much lower variability and shows promise for use in the occupational setting.

Mortality of a cohort of workers in the styrene-butadiene polymer manufacturing industry (1943-1982).

A cohort of 12,110 male workers employed 1 or more years in eight styrene-butadiene polymer (SBR) manufacturing plants in the United States and Canada has been followed for mortality over a 40-year period, 1943 to 1982. The all-cause mortality of these workers was low [standardized mortality ratio (SMR) = 0.81] compared to that of the general population. However, some specific sites of cancers had SMRs that exceeded 1.00. These sites were then examined by major work divisions. The sites of interest included leukemia and non-Hodgkin's lymphoma in whites. The SMRs for cancers of the digestive tract were higher than expected, especially esophageal cancer in whites and stomach cancer in blacks. The SMR for arteriosclerotic heart disease in black workers was significantly higher than would be expected based on general population rates. Employees were assigned to a work area based on job longest held. The SMRs for specific diseases differed by work area. Production workers showed increased SMRs for hematologic neoplasms and maintenance workers, for digestive cancers. A significant excess SMR for arteriosclerotic heart disease occurred only in black maintenance workers, although excess mortality from this disease occurred in blacks regardless of where they worked the longest. A significant excess SMR for rheumatic heart disease was associated with work in the combined, all-other work areas. For many causes of death, there were significant deficits in the SMRs.

Environmental epidemiologic investigations in the styrene-butadiene rubber production industry.

A review of the literature and an update that is in progress of a previous retrospective cohort mortality study of the styrene-1,3-butadiene industry are discussed. The follow-up has now been extended from April 1, 1976, through December 31, 1981, for plant B and December 31, 1982, for plant A. The person-years at risk of death have gone from 34,187 to 43,341 in plant A and from 19,742 to 26,314 in plant B. Among the death certificates received to date, observed deaths have increased in both plants, with increases in cancers of the trachea, bronchus and lung and in lymphosarcomas, reticulosarcomas, and cancers of the overall lymphatic and hematopoietic system.

Certain styrene oligomers have proliferative activity on MCF-7 human breast tumor cells and binding affinity for human estrogen receptor.

To examine the estrogenic activities of styrene oligomers, we carried out cell proliferation assays with estrogen-sensitive MCF-7 cells and competitive binding assays to human estrogen receptor [alpha] (hER[alpha]). The styrene oligomers tested were 1,3-diphenyl propane (SD-1), 2,4-diphenyl-1-butene (SD-2), cis-1,2-diphenyl cyclobutane (SD-3), trans-1,2-diphenyl cyclobutane (SD-4), 2,4,6-triphenyl-1-hexene (ST-1), 1a-phenyl-4a-(1'-phenylethyl)tetralin (ST-2), 1a-phenyl-4e-(1'-phenylethyl)tetralin (ST-3), 1e-phenyl-4a-(1'-phenylethyl)tetralin (ST-4), 1e-phenyl-4e-(1'-phenylethyl)tetralin (ST-5), 1e,3e,5a-triphenylcyclohexane (ST-6), and 1e,3e,5e-triphenylcyclohexane (ST-7). In the MCF-7 cell proliferation assay, styrene trimers (ST-1, ST-3, ST-4, and ST-5) had the highest proliferative activities of the compounds tested. The relative potency of these chemicals was 0.0002-0.0015%, which was comparable with that of bisphenol A (0.0001-0.0025%), and their relative proliferative effect was 51-104%. Styrene dimers (SD-3 and SD-4) also significantly increased the cell yields. However, SD-1, SD-2, ST-2, ST-6, and ST-7 had insignificant proliferative activities. The competitive binding assay revealed the binding affinity of some styrene oligomers for hER[alpha]. The order of their binding potency for hER[alpha] was as follows: ST-4 > ST-2 > ST-3 > ST-5 > ST-1 > SD-3 > SD-4 > SD-2 > SD-1. ST-6 and ST-7 did not appear to bind to hER[alpha]. The present studies indicate that styrene dimers SD-3 and SD-4 and styrene trimers ST-1, ST-3, ST-4, and ST-5 have estrogenic activity on MCF-7 cells and binding affinity for hER[alpha]. These compounds might be endocrine disrupters.

Biomarker research in neurotoxicology: the role of mechanistic studies to bridge the gap between the laboratory and epidemiological investigations.

There is an increasing interest in the development and validation of biomarkers for use in biochemical/molecular epidemiological studies. Though the area of neurotoxicology has received much attention in the past several years, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility. This review discusses several aspects of biomarker research as it relates to neurotoxic compounds and focuses on selected agents (organophosphorus insecticides, styrene, n-hexane, carbon disulfide, acrylamide), which have been the subject of a number of investigations in animals and humans. While traditional biomonitoring approaches and novel techniques (e.g., hemoglobin adducts) provide several measurements for monitoring exposure to neurotoxic chemicals, potential markers of genetic susceptibility have been seldom investigated in a neurotoxicology context. Furthermore, the complexity of the nervous system, together with the multiplicity of end points and the limited knowledge of the exact mechanism(s) of action of neurotoxicants, has led to only limited advancements in the development of biomarkers for neurotoxic effects. Significant progress in this area will depend upon an increased understanding of the cellular, biochemical, and molecular targets directly involved in neurotoxicity.

Clinical studies of styrene workers: initial findings.

Styrene monomer is a high volume chemical used chiefly in production of polystyrene. A clinical survey of 493 production workers was undertaken at the oldest and largest monomer production, polymerization, and extrusion facility in the U.S. Relative exposure durations and levels were obtained from occupational histories. Significant differences between the high and low exposure groups were found with regard to history of acute prenarcotic symptoms, acute lower respiratory symptoms, prevalence of FEV 1/FV less than 75 per cent, and elevated GCTP. Other liver function tests, chest x-ray, FVC less than 80 per cent, and hematological parameters showed no distinct pattern. A concomitant mortality study has been mounted and is in progress.

DNA adducts and related biomarkers in populations exposed to environmental carcinogens.

Prevention of environmentally related cancer will be enhanced by the availability of sensitive early warning systems and by improvements in quantitative assessment of human risks. Accordingly, we have carried out a series of molecular epidemiologic studies aimed at validating a panel of biologic markers, including carcinogen-DNA and -protein adducts, sister chromatid exchange, micronucleus formation, DNA strand breaks, and DNA repair capacity. Results from three such studies illustrate the usefulness of these biomarkers in elucidating low-dose-response relationships, correlations between biomarkers, and the range of variation in biomarkers between individuals exposed to similar concentrations of carcinogens. Low-level workplace or ambient exposures to styrene, ethylene oxide, and polycyclic aromatic hydrocarbons (PAH) were associated with significant increases in both molecular dose of carcinogens (adducts) and various markers of preclinical effects. Correlations between biomarkers varied by exposure. For example, in the styrene study, sister chromatid exchange frequency was not correlated with any of the markers, in contrast to the studies of ethylene oxide and PAH. Significant molecular effects were observed not only in occupationally exposed people but also in residents of an area in Poland characterized by high levels of air pollution. For example, the mean PAH-DNA level in exposed residents (winter sample) was 30.4 adducts per 10(8) nucleotides. This level was significantly higher than that of adducts seen in summer samples from the same area (4.2/10(8), or in winter samples from residents of a rural area (11.01/10(8). Significant seasonal variation in PAH-DNA adduct formation in this group was consistent with recorded fluctuations in air pollution levels. Striking interindividual variation was observed in all three exposed populations.

Variability in human sensitivity to 1,3-butadiene: Influence of the allelic variants of the microsomal epoxide hydrolase gene.

The carcinogenic effects of 1,3-butadiene (BD), a chemical widely used in the rubber industry, are thought to be due to its epoxide metabolites. In humans, these epoxides are detoxified predominantly by hydrolysis, a reaction mediated by the microsomal epoxide hydrolase (mEH) enzyme. The mEH gene is polymorphic and the most common mEH coding-region variants detected in human populations are the two amino acid polymorphisms Tyr113His and His139Arg. Polymorphic amino acid substitutions at residues 113 and 139 in the human mEH protein can associate in four distinct combinations: Tyr113/His139, Tyr113/Arg139, His113/His139, and His113/Arg139. In vitro studies have shown that each of these genotypes has a unique mEH protein level that can affect net mEH enzymatic activity. In the current study, we examined the relationships among the genotypes involving these two polymorphisms and the mutagenic responses associated with occupational exposure to BD. We studied 49 nonsmoking workers from two styrene-butadiene rubber facilities in southeast Texas using the autoradiographic HPRT mutant lymphocyte assay as a biomarker of genotoxic effect. We genotyped the study participants simultaneously for both polymorphisms, using a multiplex PCR assay developed in our laboratory, and the subjects were assigned to a specific group based on the predicted mEH activity associated with their genotypes (low, intermediate, and high). In the study population, 67% were exposed to low BD levels of <150 ppb (measured by personal badge dosimeters) and 33% were exposed to >150 ppb (mean 2,244 ppb). In the BD low-exposure group, the mEH genotypes had no significant effect on the HPRT variant (mutant) frequency (Vf). In the high-exposure group (BD > 150 ppb), individuals with genotypes associated with low mEH activity had a significant (P < 0.05) 3-fold increase in HPRT Vf (Vf +/- SEM = 13.95 +/- 2.15 x 10(-6)) compared to high-activity individuals (4.41 +/- 1.19 x 10(-6)), and a 2-fold increase in Vf compared to intermediate-activity individuals (6.44 +/- 2.09 x 10(-6)). Our results indicate that mEH genotypes may play a significant role in human sensitivity to the genotoxic effects of exposure to BD.

Ocular toxicity of styrene.

We completed histories and ocular examinations of 345 workers in a styrene plant in order to determine the ocular toxicity of styrene. Despite previous case reports of retrobulbar neuritis and central retinal vein occlusion (associated with a toxic hematopoietic disorder), no such conditions were found in these workers. Conjunctival irritation from styrene was found in 22% of the workers and correlated with intensity of exposure, thus confirming previous reports.

Thrombogenicity of Teflon versus copolymer-coated guidewires: evaluation with scanning electron microscopy.

Utilizing the scanning electron microscope, we compared a new guidewire with copolymer coating with standard Teflon-coated, coiled-spring guidewires in both clinical and in vitro settings. Intense thrombogenicity was observed with the Teflon-coated guidewires with formed thrombi ranging in size from 50-100 microns. No formed thrombus was noted on any of the specimens of the copolymer guidewire, although isolated clumps of platelets and erythrocytes without fibrin strands were seen infrequently. We conclude that the copolymer guidewire is markedly less thrombogenic than Teflon-coated guidewires.

DNA adducts in environmental, occupational and life-style studies in human biomonitoring.

The importance of DNA adducts in carcinogenesis had been discussed. The 32P-postlabelling method was developed as a quantitative technique to measure the level of different DNA adducts including adducts in human DNA. The elevated level of DNA adducts was found in white blood cells in persons exposed environmentally and occupationally to high concentrations of PAHs (polycyclic aromatic hydrocarbons) in the ambient air. Tobacco also generated higher level of DNA adducts both in lymphocytes and laryngeal tissues of smokers. Exposure to styrene has been of interest world-wide because of the very high exposure and persistence of adducts in DNA of lamination workers.

Chemotactic activity of human polymorphonuclear leukocytes and industrial xenobiotics: a brief review.

This review deals with some of our contributions to the use of chemotaxis, as a tool in evaluating effects of industrial xenobiotics on PMN, either in vitro or ex vivo. In vitro experiments have shown that lead, arsenic, styrene and 2,5-hexanedione, a major neurotoxicant metabolite of n-hexane, reduce chemotaxis. The most important results of ex vivo experiments have confirmed those obtained in vitro with styrene and 2,5-hexanedione: a significant reduction of chemotaxis was indeed observed in PMN harvested from workers exposed to low levels of n-hexane or styrene who did not show any sign of biochemical or clinical alteration. After 3 weeks under non-exposed conditions, the chemotactic indexes were markedly increased in most of the workers which were exposed to styrene and in all the workers exposed to n-hexane, all of whom have shown a reduced chemotaxis at the first blood sampling. Moreover chemotaxis was found to be significantly reduced at relative low levels of lead: results of the in vitro and ex vivo experiments show a comparable ranking of midpoint inhibition concentrations. We are only at the dawn of the understanding of the relation between occupational xenobiotics and PMN chemotaxis. This research area is still promising for the future, since PMN chemotaxis seems to be adequate and it must therefore enter in well-defined study protocols for investigating the potential immunotoxicity of occupational chemicals to which humans are exposed at low levels.