Styrene-specific N-7- and O6-guanine DNA adducts and N-terminal valine adducts were determined in mice tissues after the intraperitoneal administration of styrene. Blood, liver, lungs and spleen were collected 3 h after administration of various doses (from 0 to 4.35 mmol/kg b.w.) of styrene. DNA adducts were analysed by the modified 32P-postlabelling assay and N-terminal valine adducts were detected by GC-MS according to the modified Edman degradation technique. In the dose-range studied, for all adducts a clear dose-response relationship was observed. 7-Alkylguanines and O6-styrene guanine adducts were most abundant in lungs, approximately 30% more than in liver and spleen. In all analysed tissues 7-alkylguanines were more abundant than O6-styrene guanine adducts. We found a considerably lower rate of N-terminal valine adduct formation as compared with both DNA adducts. The ratio between 7-alkylguanines and O6-guanine adducts was 1.9, 1.6 and 7.8 in liver, lung and spleen, respectively. In vitro determination of both DNA adducts by 32P-postlabelling resulted also in a lower ratio than that reported earlier using an HPLC analysis. All correlation's between dose, haemoglobin and DNA adducts were very high and significant. However, at the highest injected doses the adduct formation showed a levelling off. To explain this phenomenon a model simulation was performed revealing that 3 h after the injection of the higher doses styrene was not completely converted into styrene-7,8-oxide.

Objectives-To investigate neurobehavioural eVects and the persistence of complaints in workers exposed to styrene relative to exposure characteristics and the enzyme microsomal epoxide hydrolase (mEH) activity. Methods-A cross sectional study was performed in a retrospective cohort of workers of a polyester boat building plant 3 years after the main activity shut down in 1989. Workers still currently exposed to a much lower concentration of styrene in air than before (n=27) and formerly exposed workers (n=90) were compared with matched control workers (n=64). Currently and formerly exposed workers laminated 4700 and 3610 hours on average at mean exposure to styrene concentrations of 148 and 157 mg/m 3 respectively. A structured neurological anamnesis into former and present complaints, the NSC-60 questionnaire, and computer assisted neurobehavioural tests (NES) were administered. The mEH phenotype activity was measured in lymphocytes with a novel gas chromatography-mass spectroscopy (GC-MS) method. Results-For the period before 1989, currently and formerly exposed workers reported more complaints than control workers which related well with the mean exposure to airborn styrene concentration (p=0.03). Most complaints disappeared after the end of exposure, although the chest, equilibrium, and somatic category scores of NSC-60 and the number of workers reporting diminished sense of smell remained increased in formerly exposed workers (p<0.05). Symbol-digit substitution and digit span forwards test results were worse in currently and formerly exposed workers (p<0.01). In the combined group of currently and formerly exposed workers, the symbol-digit substitution and colour-word vigilance results related well to duration of exposure (p<0.01 and p=0.03) and mEH phenotype activity (p=0.01 and p=0.05), whereas the digit span forwards results only showed associations of borderline significance (duration of exposure (p=0.08) and mEH phenotype activity (p=0.08)).Conclusion-Most subjective symptoms were reversible but some persisted after the end of exposure to styrene, whereas dysfunction of visuomotor performance and perceptual speed seemed to persist. Duration of exposure at lamination tasks and the interaction, duration of exposure×concentration of exposure, were found to be the best predictors of worsening visuomotor and perceptual speed performances. Activity of the mEH phenotype may play a modulating part in styrene neurotoxicity. The results suggested that less than 10 years of exposure to atmospheric styrene at an average concentration of 155 mg/m 3 may result in persistent neurotoxic eVects. (Occup Environ Med 2001;58:103-112)

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