Costantino Flore

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.

Proportional Mortality of Dichloro-Diphenyl-Trichloroethane (DDT) Workers: A Preliminary Report

The authors conducted a proportional mortality study of 1,043 deaths that occurred between 1956 and 1992 among men who used mainly dichloro-diphenyl-trichloroethane (DDT) in an anti-malarial campaign in Sardinia, Italy, during the late 1940s. For each cause of interest, investigators compared observed deaths with expected deaths. The estimated DDT exposure ranged from 170 to 600 mg/m3 in indoor operations and from 24 to 86 mg/m3 in outdoor operations. Workers directly exposed to DDT had a significant increase in risk for liver and biliary tract cancers (PMR = 228; 95% confidence interval = 143, 345) and multiple myeloma (PMR = 341; 95% confidence interval = 110, 795). However, the PMR for liver and biliary tract cancers was also elevated among workers who did not have direct occupational contact with DDT, and the authors observed no increase in either PMR, by number of days in exposed jobs. Perhaps DDT did not increase the risk or perhaps occupational exposure, although quite high, did not further increase the risk, compared with the heavy baseline exposure of the entire Sardinian population, (i.e., mainly through diet and drinking water). Expansion of the cohort to include all exposed workers, and collection of information to improve exposure assessment are needed to clarify these findings.

Neurotoxic effect of lead at low concentrations

The effects of lead exposure at low concentrations were evaluated by studying the post-rotatory nystagmus (PRN) in two groups of rats exposed for 3 months to 50 parts per million (ppm) of sodium acetate and 50 ppm of lead acetate, respectively, in the drinking water. Only animals treated with lead acetate showed changes of the PRN parameters which were significantly related to the concentration of lead in the blood and in brain structures. The patterns of PRN responses were characterized and classified into four types: progressively inhibitory (40%), prematurely inhibitory (25%), late inhibitory (25%), and excitatory-inhibitory (10%). No alterations of the PRN parameters were observed in the animals treated with sodium acetate. The results show that exposure to lead, even at low concentrations, impairs both sensory and motor functions. The findings also point out that the vestibular system and brain stem structures which generate and control the PRN represent targets of the action of this heavy metal. Finally, the results indicate that the evaluation of the vestibulo-ocular-reflex can provide a test suited for the screening of the neurotoxic effects of lead even in the absence of clinical signs typical of lead intoxication.

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.

Causes of death among lead smelters in relation to the glucose-6-phosphate dehydrogenase polymorphism

Objective: To assess, by updating a follow-up mortality study of a lead smelters cohort in Sardinia, Italy, the adverse health effects following occupational lead exposure in relation to the glucose-6-phosphate dehydrogenase (G6PD) polymorphism. Method: The 1973–2003 mortality of 1017 male lead smelters were followed-up, divided into two subcohorts according to the G6PD phenotype: whether G6PD deficient (G6PD−) or wild-type (wtG6PD). Deaths observed in the overall cohort and the two subcohorts were compared with those expected, on the basis of the age-, sex- and calendar year-specific mortality in the general male population of the island. Directly standardised mortality rates (sr) in the two subcohorts were also compared. Results: Cardiovascular mortality was strongly reduced among production and maintenance workers, which is most related to the healthy worker effect. However, the sr for cardiovascular diseases was substantially lower among the G6PD− subcohort (5.0×10−4) than among the wtG6PD subcohort (33.6×10−4; χ2 = 1.10; p = NS). Neoplasms of the haemopoietic system exceeded the expectation in the G6PD− subcohort (SMR = 388; 95% CI 111 to 1108). No other cancer sites showed any excess in the overall cohort or in the two subcohorts. No death from haemolytic anaemia occurred in the G6PD− subcohort. Conclusion: With due consideration of the limited statistical power of our study, previous results suggesting that in workplaces where exposure is under careful control, expressing the G6PD− phenotype does not convey increased susceptibility to lead toxicity are confirmed. The observed excess risk of haematopoietic malignancies seems to have most likely resulted from chance.

Risk of specific lymphoma subtypes is associated to polymorphism in genes implicated in the metabolism of workplace carcinogens

Objectives Exploring lymphoma risk associated with metabolic gene polymorphisms might provide clues on the role of gene-environment interactions in lymphomagenesis. Methods We assessed polymorphisms in genes encoding for the metabolic enzymes CYP1A2, CYP2E1, GSTM1, GSTT1, NAT1, NAT2, NQ01, and PON1 in 255 incident lymphoma cases and 204 population controls. The OR for lymphoma overall, B lymphoma, and the diffuse large B cell lymphoma (DLBCL) and chronic lymphocytic leukaemia (CLL) subtypes, associated to the less frequent allele was calculated along with the respective 95% CI, adjusting by age and gender. Results GSTT1 gene polymorphism significantly increased risk of DLBCL (OR = 5.0, IC 95% 3.0 to 8.3). An excess risk of DLBCL was also related to polymorphisms in the CYP1A2, PON1, NAT1 and NAT2genes. CLL risk was reduced in relation to CYP1A2 polymorphisms, increased in relation to GSTM1 deletion, and strongly associated with NAT1, and NAT2 mutant haplotypes. Conclusions Caution is recommended in interpreting the high risks in our study, due its small size. However, our results suggest that polymorphisms in genes encoding for the metabolic enzymes might affect risk of specific lymphoma subtypes associated with exposure to workplace carcinogens.