Analysis of potential influence factors on background urinary benzene concentration among a non-smoking, non-occupationally exposed general population sample.

OBJECTIVES: Analytical difficulties and lack of a biological exposure index and reference values have prevented using unmetabolized urinary benzene (UB) excretion as a biomarker of low-level environmental exposure. To explore what environmental factors beyond active smoking may contribute to environmental exposure to benzene, we monitored UB excretion in a non-smoking, non-occupationally exposed sample of the general population. METHODS: Two spot urine samples were obtained from 86 non-smoking, non-occupationally exposed subjects, selected among a random sample of the general population of the metropolitan area of Cagliari (Sardinia, Italy), at 8:00 a.m. (UBm) and 8:00 p.m. (UBe). UB was measured by headspace solid-phase microextraction (HS-SPME) followed by gas chromatography-mass spectrometry analysis. Questionnaire information on personal and environmental exposures during the sampling day was gathered with personal interviews. Multivariate analysis of variance and multiple regression model were applied to investigate the role of such variables on the level of UB. RESULTS: The ninety-fifth percentile of UBe in this population was 311.5 ng/L, which is tentatively proposed as the UB guidance value for unexposed populations. UBm and urban residence were the only predictors of a significant increase in UBe excretion. Self-reported residential vehicular traffic will not account for the excess median value among urban residents; commuting time among urban residents showed a suggestive nonsignificant linear correlation with UBe, but the small sample size prevented reliable inference to be drawn. Age, environmental tobacco smoking, employment status and body mass index did not affect UB excretion. CONCLUSIONS: Our findings support the use of unmetabolized UB as a specific and sensitive biomarker of low-level environmental exposure to benzene.

Biological monitoring of low-level exposure to benzene.

INTRODUCTION: Conflicting opinions exist about the reliability of biomarkers of low-level exposure to benzene. We compared the ability of the urinary excretion of trans,trans-muconic acid (t,t-MA), s-phenilmercapturic acid (s-PAMA) and urinary benzene (U-Benz) to detect low level occupational and environmental exposure to benzene. METHODS: We monitored airborne benzene by personal air sampling, and U-Benz, s-PMAI, t,t-MA and cotinine (U-Cotinine) in spot urine samples, collected at 8 am and 8 pm, in 32 oil refinery workers and 65 subjects, randomly selected among the general population of urban and suburban Cagliari, Italy. Information on personal characteristics, diet and events during the sampling day was acquired through in person interviews. RESULTS: The median concentration of airborne benzene was 25.2 microg/m3 in oil refinery workers, and 8.5 microg/m3 in the general population subgroup. U-Benz in morning and evening samples was significantly more elevated among oil refinery workers than the general population subgroup (p = 0.012, and p = 7.4 x 10(-7), respectively) and among current smokers compared to non-smokers (p = 5.2 x 10(-8), and p = 5.2 x 10(-5) respectively). Benzene biomarkers and their readings in the two sampling phases were well correlated to each other. The Spearman's correlation coefficient with airborne benzene was significant for U-Benz in the evening sample, while no correlation was seen with t,t-MA and s-PMA readings in either samplings. The two benzene metabolites were frequently below limit of detection (LOD), particularly among the general population study subjects (17-9% and 39%, for t,t-MA and s-PMA respectively). Morning U-Cotinine excretion showed a good correlation with U-Benz in the morning and in the evening sampling (p < 0.001), and with s-PMA in the evening sample (p < 0.001), but not with t,t-MA in either samplings. t,t-MA in the evening sample was the only biomarker showing a moderate inverse correlation with BMI (p < 0.05). The multiple regression analysis adjusting by BMI and number of cigarettes smoked during the day confirmed the results of the univariate analysis. DISCUSSION: Our results suggest that unmetabolized U-Benz would allow a more reliable biomonitoring of low-level exposure to benzene than s-PMA and t,t-MA.

Environmental and lifestyle factors affect benzene uptake biomonitoring of residents near a petrochemical plant.

BACKGROUND: We monitored urinary benzene excretion to examine factors affecting benzene uptake in a sample of the general population living near a petrochemical plant. METHODS: Our study population included 143 subjects: 33 petrochemical plant workers (W) with low level occupational benzene exposure; 30 residents in a small town 2 km from the plant (2kmR); 26 residents in a second small town located 2 to 4 km from the plant (4kmR); and 54 urban residents 25km from the plant (25kmR). Exposure to benzene was evaluated by personal air sampling during one work-shift for the W group, and from 8.00 to 20:00 for general population subgroups, and by urinary benzene (BEN-U). RESULTS: Median airborne benzene exposure was 25, 9, 7 and 6 µg/m(3) benzene among the W, 2kmR, 4kmR, and 25kmR subgroups, respectively; the highest level was found among the workers, while there was no significant difference among the other groups. Median BEN-U was 2 to 14-fold higher in smokers compared to non-smokers; among non-smokers BEN-U was the highest in W (median 236 ng/L), and lower in the 2kmR (48 ng/L) and 4kmR (63 ng/L) subgroups than in the 25kmR (120 ng/L) subgroup. A multiple linear regression analysis, explaining up to 73% of BEN-U variability, confirmed that active smoking and airborne benzene most strongly affected BEN-U. Among the non-smoking, non-occupationally exposed study subjects, a positive association was found between BEN-U and the distance of residence from the plant. This association was explained by increased exposure to urban traffic emissions in the study group residing at a greater distance from the plant. Environmental tobacco smoke had a marginally positive role. CONCLUSION: Among factors affecting benzene uptake in non-occupationally exposed individuals, urban residence contributes to benzene exposure more than residing in close proximity to a petrochemical plant.

[Urinary benzene in biological monitoring of environmental exposure to low benzene concentrations]. / Il benzene urinario nel monitoraggio biologico dell'esposizione a bassi livelli ambientali.

INTRODUCTION: Conflicting opinions exist about urinary benzene (UB) as a reliable biomarker of exposure. Objective of our study is to evaluate the effect of low-level environmental exposure on UB levels. METHODS: We monitored UB excretion in 74 non-smoking non- occupationally exposed subjects; a questionnaire interview gathered information on relevant exposures during the day of monitoring. RESULTS: UB excretion was related (p < 0.05) to gender, sampling time, residence, and reported vehicular traffic, but not to passive smoking and body mass index. CONCLUSION: Our findings support the use of unmetabolized UB as a specific and sensitive biomarker of low-level exposure to benzene.

Reproductive outcomes in DDT applicators.

OBJECTIVES: To explore reproductive outcomes in relation to occupational exposure to DDT. METHODS: We inquired into the reproductive history, including total number of children, sex distribution in the offspring, time-to-pregnancy, and number of spontaneous abortions and stillbirths, of the spouses of 105 men first exposed to DDT in a 1946-1950 anti-malarial campaign in Sardinia, Italy. The time-to-pregnancy in months at the first successful conception was estimated from population Registrars. Cumulative DDT exposure during the anti-malarial campaign was retrospectively estimated. RESULTS: The stillbirth rate was elevated and the male/female ratio in the offspring was reversed among DDT-exposed workers, and particularly among DDT applicators, compared to the unexposed subjects. Among DDT applicators, the stillbirth rate increased and the male/female ratio decreased by the tertile of cumulative DDT exposure. The fecundity ratio among spouses of DDT applicators was 0.72 (95% CI, 0.41,1.21) compared to the unexposed. The average number of children and abortion rate were unaffected by DDT exposure. CONCLUSIONS: The low statistical power of our study does not allow definitive conclusions. However, the results prompt further in-depth research into adverse reproductive outcomes and reduced fertility among men heavily exposed to DDT.

Serum sex hormones in men occupationally exposed to dichloro-diphenyl-trichloro ethane (DDT) as young adults.

To explore endocrine effects in relation to para,para'-dichloro-diphenyl-dichloro ethylene (p,p'-DDE) body burden and past occupational exposure to its precursor dichloro-diphenyl-trichloro ethane (DDT), we assayed serum sex hormones, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17beta-estradiol (E2), testosterone and sex hormone binding globulin (SHBG), and p,p'-DDE levels in 107 male participants in a 1946-1950 anti-malarial campaign in Sardinia, Italy. Cumulative DDT exposure during the anti-malarial operations was retrospectively estimated from detailed reports of the anti-malarial agency. Ortho,para-DDE, and its precursor ortho,para-DDT were always below the detection limit. p,p'-DDT was detected in 14/107 subjects, and p,p'-DDE in 106/107 subjects. The median lipid-adjusted p,p'-DDE serum concentration over the total study population was 396 parts per billion (interquartile range 157-1045), and it did not vary according to the job at the time of anti-malarial operations, nor was it affected by cumulative DDT exposure. LH, FSH, and SHBG, but not testosterone or E2, showed a significant positive correlation with age. Neither current serum p,p'-DDE nor past cumulative DDT exposure affected sex hormone concentrations. Our results suggest that (1) the low current p,p'-DDE serum concentration does not affect serum hormone levels, and (2) past cumulative DDT exposure is not correlated with the current p,p'-DDE serum level, nor does it show persistent effects on serum hormone levels.

Sub-clinical neurobehavioral abnormalities associated with low level of mercury exposure through fish consumption.

In order to assess early neurotoxic effects associated with relatively low levels of mercury absorbed through fish eating, two groups of 22 adult male subjects, habitual consumers of tuna fish, and 22 controls were examined using a cross-sectional field study. The assessment included neurobehavioral tests of vigilance and psychomotor function, hand tremor measurements and serum prolactin assessment. Mercury in urine (U-Hg) and serum prolactin (sPRL) were measured in all exposed subjects and controls, whereas measurements of the organic component of mercury in blood (O-Hg) were available for only 10 exposed and six controls. U-Hg was significant higher among exposed subjects (median 6.5 microg/g of creatinine, range 1.8-21.5) than controls (median 1.5 microg/g of creatinine, range 0.5-5.3). The median values of O-Hg were 41.5 microg/l among the tuna fish eaters and 2.6 microg/l in the control group. Both U-Hg and O-Hg were significantly correlated with the quantity of fish consumed per week. Significant differences in sPRL were found between exposed (12.6 ng/ml) and controls (9.1 ng/ml). Individual sPRL were significantly correlated with both U-Hg and O-Hg levels. The neurobehavioral performance of subjects who consumed tuna fish regularly was significantly worse on color word reaction time, digit symbol reaction time and finger tapping speed (FT). After considering the education level and other covariates, the multiple stepwise regression analysis indicated that O-Hg concentration was most significantly associated with individual performance on these tests, accounting for about 65% of the variance in test scores.

trans,trans-Muconic acid excretion in relation to environmental exposure to benzene.

OBJECTIVES: Potential environmental sources of benzene exposure, and intake of foods and beverages susceptible to being preserved with sorbic acid, were investigated in relation to their contribution to the inter-individual variation in background urinary trans,trans-muconic acid ( t,t-MA) excretion among subjects non-occupationally exposed to benzene. METHODS: We measured urinary t,t-MA excretion in 65 subjects, 34 women and 31 men. A spot sample of morning urine was collected for each subject 10-12 h after they had consumed their last meal. Questionnaire information was collected on diet and possible sources of environmental benzene exposure in the surroundings of the subjects' residences. For each subject, an estimate of the average daily intake of sorbic acid with diet was calculated, based on questionnaire information and laboratory data on samples of local food items. RESULTS: The t,t-MA geometric mean was significantly higher among women (28.7 vs 11.5 microg/g creatinine, P<0.05) and among smokers (37.6 vs 15.6 microg/g creatinine, P<0.05), and increased by years of education among women, but not among men. In the multivariate analysis, smoking was the only significant predictor of elevated t,t-MA excretion. In our study, the average estimated daily sorbic-acid intake with diet was 0.33 ppm (standard deviation: 0.28), and it did not show a correlation with t,t-MA excretion. Urban traffic and residence within 100 m of a fuel station also did not show an association with elevated t,t-MA values. CONCLUSIONS: Our study confirms that, among subjects non-occupationally exposed to benzene, smoking contributes significantly to increased background t,t-MA excretion. Further studies should be addressed to confirm our observation of elevated t,t-MA levels among women.