Effects of Malaria and HIV Infection on Anemia and T-cells Levels in Children in Douala City, Cameroon.

Introduction Human immunodeficiency virus (HIV) infection and malaria are priority health issues for sub-Saharan Africa. Both diseases worsen each other through their effect on the immune and hematological systems. This study aimed to determine the effects of HIV infection and asymptomatic malaria on anemia and T-cells counts in children in the city of Douala in the republic of Cameroon. Method From May to November 2016, 197 HIV infected and 98 HIV-free non-febrile children up to 19 years old (128 male and 167 female) participated in the study. All HIV-infected children were receiving antiretroviral treatment and co-trimoxazole. Malaria diagnosis was performed using Giemsa-stained thick blood film; immunological and hematological parameters were assessed through a flow cytometer and an automated analyzer respectively. Chi-squared or Fischer's exact tests was used to compare the proportions, Mann-Whitney and ANOVA tests were used for the means. Statistical significance was set at p˂0.05. Results The prevalence of malaria was 8.8%, and that of anemia was 40.7%. CD4+-T cells were higher in malaria-infected children, both in HIV positive and negative (p=0.049). No significant association was found between malaria parasitemia and CD8+-T cell levels, both in HIV-positive and negative children (p=0.41). Anemia was higher in HIV-positive children (p=0.019), especially in those with severe immunosuppression (p=0.001) and in younger children (p=0.0083). Children on HIV treatment presented lower malaria prevalence (8.6% versus 10.10%), though the difference was not significant (p=0.7068). Malaria infection was associated with lower hemoglobin levels (10.5±1.7 versus 11.2±1.4; p=0.016). Conclusion Malaria infection may enhance CD4+-T cells. Both malaria and HIV infection lead to a drop in hemoglobin levels. The HIV treatment protocol may reduce malaria prevalence.

Toxicokinetics of bisphenol S in rats for predicting human bisphenol S clearance from allometric scaling.

Previous data obtained in piglets suggested that despite structural analogy with Bisphenol A (BPA), Bisphenol S (BPS) elimination may proceed more slowly, resulting in a much higher systemic exposure to unconjugated BPS than to BPA. Interspecies allometric scaling was applied to predict the toxicokinetic (TK) parameters of BPS, namely plasma clearance in humans from values obtained in animals, and thus contribute to assessment of the human internal exposure to BPS. Allometric scaling was performed using mean BPS plasma clearance values measured in rats after intravenous administration of 5 mg BPS /kg body weight (BW) and those previously obtained in piglets and sheep using identical IV BPS dosing and analytical procedures. The BPS plasma clearance, evaluated at 0.92 L/kg.h in rats, was proportional to species body weight, enabling the prediction of human BPS plasma clearance by extrapolating to a BW of 70 kg. The estimated BPS plasma clearance in humans was thus 0.92 L/min (0.79 L/kg.h), i.e. about two times lower than the previously estimated BPA clearance (1.79 L/min). By increasing systemic exposure to the active moiety of an environmental estrogenic chemical, this less efficient clearance of BPS in humans, as compared with BPA, might worsen the harmful consequences of replacing BPA by BPS.

Oral Systemic Bioavailability of Bisphenol A and Bisphenol S in Pigs.

BACKGROUND: Given its hormonal activity, bisphenol S (BPS) as a substitute for bisphenol A (BPA) could actually increase the risk of endocrine disruption if its toxicokinetic (TK) properties, namely its oral availability and systemic persistency, were higher than those of BPA. OBJECTIVES: The TK behavior of BPA and BPS was investigated by administering the two compounds by intravenous and oral routes in piglet, a known valid model for investigating oral TK. METHODS: Experiments were conducted in piglets to evaluate the kinetics of BPA, BPS, and their glucuronoconjugated metabolites in plasma and urine after intravenous administration of BPA, BPS, and BPS glucuronide (BPSG) and gavage administration of BPA and BPS. A population semiphysiologically based TK model describing the disposition of BPA and BPS and their glucuronides was built from these data to estimate the key TK parameters that drive the internal exposure to active compounds. RESULTS: The data indicated that almost all the BPS oral dose was absorbed and transported into the liver where only 41% of BPS was glucuronidated, leading to a systemic bioavailability of 57.4%. In contrast, only 77% of the oral dose of BPA was absorbed and underwent an extensive first-pass glucuronidation either in the gut (44%) or in the liver (53%), thus accounting for the low systemic bioavailability of BPA (0.50%). Due to the higher systemic availability of BPS, in comparison with BPA, and its lower plasma clearance (3.5 times lower), the oral BPS systemic exposure was on average about 250 times higher than for BPA for an equal oral molar dose of the two compounds. CONCLUSION: Given the similar digestive tracts of pigs and humans, our results suggest that replacing BPA with BPS will likely lead to increased internal exposure to an endocrine-active compound that would be of concern for human health. https://doi.org/10.1289/EHP4599.

Is bisphenol S a safer alternative to bisphenol A in terms of potential fetal exposure ? Placental transfer across the perfused human placenta.

The aim of our study was to evaluate the bidirectional transfer of Bisphenol S (BPS) and its main metabolite, BPS Glucuronide (BPSG), using the model of perfused human placenta and to compare the obtained values with those of Bisphenol A (BPA) and BPA Glucuronide. Fourteen placentas at term were perfused in an open dual circuit with deuterated BPS (1 and 5 µM) and non-labelled BPSG (2.5 µM) and a freely diffusing marker antipyrine (800 ng/ml) in the presence of albumin (25 mg/ml). In a second experiment, the potential role of P-glycoprotein in the active efflux of BPS across the placental barrier was studied using the well-established P-glycoprotein inhibitor, PSC833 (2 and 4 µM). Placental transfer of BPS was much lower than that of BPA in both directions. The placental clearance index of BPS in the materno-fetal direction was three times lower than in the opposite direction, strongly suggesting some active efflux transport. However, our results show that P-glycoprotein is not involved in limiting the materno-fetal transfer of BPS. Placental transfer of BPSG in the fetal compartment was almost non-existent indicating that, in the fetal compartment, BPSG originates mainly from feto-placental metabolism. The feto-maternal clearance index for BPSG was 20-fold higher than the materno-fetal index. We conclude that the blood-placental barrier is much more efficient in limiting fetal exposure to BPS than to BPA, indicating that the placenta has a crucial role in protecting the human fetus from BPS exposure.

Bisphenol S instead of Bisphenol A: Toxicokinetic investigations in the ovine materno-feto-placental unit.

Bisphenol S (BPS) is widely used as a substitute for Bisphenol A in consumer products. Despite its potential endocrine-disrupting effects and widespread exposure, toxicokinetic data, particularly during the critical period of pregnancy, are not available for BPS. The objectives of our study were to evaluate the mechanisms determining fetal exposure to BPS and to BPS glucuronide (BPSG) and to compare them with those prevailing for BPA. The disposition of BPS and BPSG was evaluated in the materno-fetal unit of the catheterized pregnant ewe model, following intravenous administrations of BPS and BPSG to mothers and their fetuses. In a second experiment, the rate of BPS accumulation in the fetal compartment was determined under steady-state conditions after repeated intravenous BPS administrations to the mother. In the maternal compartment, BPS was mainly metabolized into BPSG and totally eliminated in urine. Only 0.40% of the maternal dose was transferred to the fetus. However, once in the fetal compartment, 26% of the fetal dose was rapidly eliminated through placental transfer, while 46% of BPS was metabolized into BPSG which remained trapped in the fetal compartment. Thus, the elimination of BPSG from the fetal compartment required its back-conversion into bioactive BPS, leading to an 87% enhancement of the fetal BPS exposure. Our findings demonstrate that, despite the low materno-fetal placental transfer of BPS, this substitute for BPA is able to accumulate in the fetal compartment after repeated maternal exposure, leading to chronic fetal exposure to BPS in a range of concentrations similar to those of BPA.

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.

Study of the specific lipid binding properties of Abeta 11-22 fragment at endosomal pH.

Increasing evidence implicates interactions between Abeta peptide and lipids in the development of Alzheimer's disease. More generally, Abeta peptide interactions with membranes seem to depend on the composition of the lipid bilayer and the structural features of the peptide. One key parameter should be pH, since one site of intracellular Abeta peptide production and/or accumulation is likely to be endosomes. This intracellular endosomal accumulation was suggested to contribute to disease progression. In this paper, we report a study on the 11-22 amphiphilic domain of Abeta in interaction with model membrane; this region contains most of the charged residues of the N-terminal domain of Abeta. We show that the peptide charge, and more precisely the protonation state of histidines 13 and/or 14, is important for the interaction with lipids. Hence, it is only at endosomal pH that a conformational change of the peptide is observed in the presence of negatively charged lipid vesicles, that is, when both lipid headgroups and histidines can interact through electrostatic interactions. Specific interactions of the fragment with phosphatidylserine and to a lesser extent with phosphatidylcholine, but not phosphatidylethanolamine, are further evidenced by the Langmuir monolayer technique. From our results, we suggest that the protonation state of His residues could have a role in the pathogenic surface interaction of the whole Abeta peptide with membranes.

Lipid-destabilizing properties of the hydrophobic helices H8 and H9 from colicin E1.

Colicins are toxic proteins produced by Escherichia coli that must cross the membrane to exert their activity. The lipid insertion of their pf domain is linked to a conformational change which enables the penetration of a hydrophobic hairpin. They provide useful models to more generally study insertion of proteins, channel formation and protein translocation in and across membranes. In this paper, we study the lipid-destabilizing properties of helices H8 and H9 forming the hydrophobic hairpin of colicin E1. Modelling analysis suggests that those fragments behave like tilted peptides. The latter are characterized by an asymmetric distribution of their hydrophobic residues when helical. They are able to interact with a hydrophobic/hydrophilic interface (such as a lipid membrane) and to destabilize the organized system into which they insert. Fluorescence techniques using labelled liposomes clearly show that H9, and H8 to a lesser extent, destabilize lipid particles, by inducing fusion and leakage. AFM assays clearly indicate that H8 and especially H9 induce membrane fragilization. Holes in the membrane are even observed in the presence of H9. This behaviour is close to what is seen with viral fusion peptides. Those results suggest that the peptides could be involved in the toroidal pore formation of colicin E1, notably by disturbing the lipids and facilitating the insertion of the other, more hydrophilic, helices that will form the pore. Since tilted, lipid-destabilizing fragments are also common to membrane proteins and to signal sequences, we suggest that tilted peptides should have an ubiquitous role in the mechanism of insertion of proteins into membranes.

[Environmental exposure to inorganic lead and neurobehavioural tests among adolescents living in the Sulcis-Iglesiente, Sardinia]. / Esposizione ambientale a piombo e test neuro- comportamentali in adolescenti del Sulcis-Iglesiente.

In several recent studies blood lead levels below 100 microg/L have been associated with reduced neurocognitive capacities and neurobehavioural performances in children, with no clear evidence of the lowest "safe" level not associated to adverse effects on the CNS. We analyzed blood lead concentration and the results of 5 neurocognitive tests, two derived from the Swedish Performance Evaluating System (SPES) and three from the Wechsler Intelligence Scale for Children-Revised (WISC-R), in 139 Sardinian adolescents living in Portoscuso, a town 2 Km far from a lead smelter, and in 72 age-matched students living in S. Antioco, a town about 15 Km far from the same smelter. The blood lead concentrations were lower than 100 microg/l in almost subjects, but, in average, significantly higher particularly among males, in the Portoscuso group compared to controls. The regression coefficients derived from the multivariate stepwise analysis, adjusted for the student's age and gender and for the educational and socio-economic level of parents, showed that reduced performances in neurocognitive test were significantly associated to increasing blood lead concentrations. According to previous our surveys in the same area and to the recent scientific literature on this topic, the present study suggests the need to further low the blood lead levels, considered by the U.S. CDC in 1991 as potentially "safe" for the children's CNS, to a threshold possibly < 50 microg/L.

[Neurobehavioural testing in lead smelter workers]. / Test neurocomportamentali in lavoratori esposti a piombo inorganico.

Several recent meta-analyses, although some inconsistencies between studies, provide evidence for subtle deficits in neurobehavioural tests being associated with average blood levels (PbB) between 350 and 600 microg/l and for significant correlations between impairments in some test results and increasing indices present andlor cumulative exposure to inorganic lead. In this study we assessed the relationship between blood lead level (PbB) and results of some neurobehavioural tests derived from the SPES battery and from the WAIS-R among a sample of 94 lead smelter workers (median PbB: 302 microg/l; range: 60-690 microg/l). The stepwise multiple regression analysis shows that, even after adjusting for age, education level, score in the vocabulary test and for alcohol and cigarette consumption, the rise of PbB above 300 microg/l was significantly associated with the rise in the number of errors and in the response time of the Symbol Digit test. No significant relationship between PbB and results of the other tests was observed after adjusting for the main confounding factors. Despite the small size of this study and the few number of neurobehavioural tests applied, our results are suggestive for suble potential neurotoxic effects of inorganic lead even at the present exposure levels found in the studied sample of smelter workers and support the ACGIH BEI and the SCOEL recommendation for a biological limit of 300 microg/l of PbB.

[Intellectual quotient and environmental exposure to low doses of lead]. / Quoziente intellettivo ed esposizione ambientale a basse dosi di piombo.

The effects of low-level lead exposure on children's intelligence quotient (IQ) were investigated in 64 Sardinian adolescents (13-16 years old). To estimate potential early adverse effects on the Central Nervous System (CNS) due to very low-level lead, the Intelligence Quotient (IQ) of adolescents with present blood lead concentrations (PbB) generally below 10 microg/dl was measured. We analyzed blood lead concentration and individual IQ of 32 Sardinian children living in Portoscuso, a town 2 Km far from a lead smelter, and of other 32 controls living in S. Antioco, a town about 15 Km far from the same smelter. The Wechsler Intelligence Scale for Children Revised (WISC-R) was administered. The relation between IQ and blood lead concentration was estimated by linear multivariate models adjusting for several potential confounders, such as the educational and socio-economic level of the parents. The blood lead concentration was in average significantly higher in the Portoscuso group compared to controls. The linear model applied to the total population studied (n 64) showed that the blood lead concentration was inversely and significantly associated with IQ, with an extrapolated decline of 1.29 points in total IQ for each microg/dl increase of lead blood concentration. According to the recent scientific literature on this topic, results of our pilot study suggest the need to further lower the blood lead concentration for children to a threshold significantly below 10 microg/dl, value till now considered "safe" for the children's CNS.

[Report on the activities carried out in the research project of the Ministry of Instruction, University, and Research entitled "Environmental and occupational exposure to inorganic lead: assessment of toxic effects of current doses and related preventive measures"]. / Presentazione delle attività svolte nell'ambito del progetto di ricerca MIUR "Esposizione ambientale ed occupazionale a piombo inorganico: studio degli effetti tossici conseguenti alle dosi correnti e delle relative misure preventive".

It is here presented the project sustained by the Ministry of Public Instruction, University and Research "Environmental and Occupational Exposure to Inorganic Lead: assessment of human health effects due to current doses and preventive measures" ruled out between 2001 and 2003. The aim of the study was to investigate about the toxic effects related to current occupational exposures to inorganic lead (particularly those effects concerning blood pressure, carcinogenic risk, nervous and immunological systems), to identify hypersusceptibility conditions, particularly the ALAD genetic polymorphism and to evaluate the role of traditional biomarker and the possibility of introducing new ones. In the present article the procedures followed during the project lasting and the contribution of each Unit are described. The results of the research, presented in detail in the current issue, do confirm the inadequacy of the biological exposure index nowadays ruled by Lex 25/2002.

[Study on mortality by specific cause among workers at a lead and zinc foundry in Sardinia]. / Studio di mortalità per cause specifiche in lavoratori di una fonderia di piombo e zinco della Sardegna.

The mortality of 918 Sardinian lead-smelter workers followed between 1972 and 2001 is reported. The assessment of individual exposure to inorganic lead was based on several environmental and blood lead measurements available, for each department and task, between 1985 and 2001. The mortality for all cancers was within the expected numbers (SMR 1.01, n 108). Even if not statistically significant, the mortality for gastric cancer (SMR 1.22, n 4), for lung cancer (SMR 1.21, n 18) and for lymphomas and leukaemias (SMR 1.82, n 6) was higher than that expected from the regional rates during the follow-up. Only for the lung cancer mortality a statistically significant upward trend with increasing categories of lead exposure was observed (SMR 1.96, 95% CI 1.02-3.68 for the highest exposure group). Our study, even if of small size, suggests an association between occupational exposure to inorganic lead and lung cancer risk.

[Lead: indicators of dose and effects on heme]. / Piombo: indicatori di dose e di effetto sull'eme.

In the present study the role of the traditional biomarkers of exposure and effect on haeme system during lead exposure was analysed: the opportunity of introducing new biomarkers such as lead and delta-aminolevulinic acid in plasma was also evaluated, especially by considering the current levels of exposure. The population in study was constituted by 371 males owning to different production fields and selected by five national units. The results suggest caution in the use of lead in plasma as a biomarker of lead exposure in the biological monitoring procedures, mainly in reason of its great variability affecting in particular the sampling time and the pre-analytical treatment of the sample. The other biomarkers were well correlated between them and with the exposure biomarkers for lead in blood >300 microg/L, suggesting the BEI to which the protection of workers exposed to lead would be guaranteed (instead the actual of 600 microg/L).

[Cognitive and performance capacity among adolescents living near a lead and zinc smelter]. / Capacità cognitive e di performance in adolescenti residenti in prossimità di una fonderia di piombo e zinco.

To estimate potential early adverse effects on the Central Nervous System (CNS) due to very low exposure to inorganic lead, the Intelligence Quotient (IQ) of adolescents with present blood lead concentrations (PhB) generally below 10 micrograms/dl was measured. We analyzed blood lead concentration and individual IQ of 32 Sardinian adolescents living in Portoscuso, a town 2 Km far from a lead smelter, and of other 32 controls living in S. Antioco, a town about 15 Km far from the same smelter. The Wechsler Intelligence Scale for Children Revised (WISC-R) was administered. The relation between IQ and blood lead concentration was estimated by linear multivariate models adjusting for several potential confounders, such as the educational and socio-economic level of the parents. The blood lead concentration was in average significantly higher in the Portoscuso group compared to controls. The linear model applied to the total population studied (n 64) showed that the blood lead concentration was inversely and significantly associated with IQ, with an extrapolated decline of 1.29 points in total IQ for each microgram/dl increase of blood concentration. According to the recent scientific literature on this topic, results of our pilot study suggest the need to further lower the definition of an elevated blood lead concentration for children to a threshold significantly below 10 micrograms/dl, value till now considered "safe" for the children's CNS.

[Mortality from lung cancer among workers of a Sardinian lead smelter [Follow-up: 1972-2001]]. / Mortalità per cancro polmonare in lavoratori di una fonderia di piombo della Sardegna [Follow-up: 1972-2001].

The mortality of 918 Sardinian lead-smelter workers followed between 1972 and 2001 is reported. The assessment of individual exposure to inorganic lead was based on several environmental and blood lead measurements available, for each department and task, between 1985 and 2001. The mortality for all cancers was within the expected numbers (SMR 1.01, n 108). Even if not statistically significant, the mortality for gastric cancer (SMR 1.22, n 4), for lung cancer (SMR 1.21, n 18) and for lymphomas and leukaemias (SMR 1.82, n 6) was higher than that expected from the regional rates during the follow-up. Only for the lung cancer mortality a statistically significant upward trend with increasing categories of lead exposure was observed (SMR 1.96, 95% CI 1.02-3.68 for the highest exposure group). Our study, even if of small size, suggests an association between occupational exposure to inorganic lead and lung cancer risk.

[Evaluation of the dose of mercury in exposed and control subjects]. / Valutazione delle dosi di mercurio negli esposti e nei controlli.

OBJECTIVES: The aim of this paper was to analyse the concentrations of HgU and HgB in three different groups: 122 workers exposed, 18 workers formerly exposed and 196 subjects not occupationally or environmentally exposed to mercury. METHODS: All the subjects filled out a questionnaire concerning personal data, lifestyle, occupational or non-occupational exposure to Hg and medical history. The amalgam fillings area was measured by a standardised method. RESULTS: Urinary mercury excretion was significantly greater in the group of the exposed workers respect to the group of subjects not occupationally exposed (Median value of 8.3 micrograms/g creatinine and the 5 degrees and 95 degrees percentile respectively of 2.66 e 23.50 micrograms/g creatinine against Median value of 1.2 micrograms/g creatinine and the 5 degrees and 95 degrees percentile respectively of 0.18 and 5.42 micrograms/g creatinine). U-Hg in formerly exposed workers were comparable to U-Hg in non-occupationally exposed subjects, with a median value of 1.6 micrograms/g creatinine. B-Hg values were similar in the three groups: the median value was 3.1 micrograms/l in the non-occupationally exposed, 4.0 micrograms/l in the exposed workers and 3.9 micrograms/l in the past exposed. These value were not significantly different. Among the considered variables (amalgam fillings, fish consumption, age, sex, alcohol intake, chewing-gum and smoking) dental amalgam and fish consumption were significantly related with the Hg urinary excretion and the B-Hg levels. This is particularly true considering the subjects altogether: for the exposed workers, indeed, the occupational exposure was the most relevant variable. CONCLUSIONS: The results of the present research confirmed that the U-Hg excretion in non-occupationally exposed subjects is influenced by amalgam dental fillings. Furthermore, in our study Hg urinary excretion was significantly related with fish consumption. This fact can be explained, according to several recent experimental human and animal trials, considering that methylmercury contained in fish is partially converted, through breakage of the carbon-Hg bond, into Hg inorganic forms, which accumulate in the kidney and have a urinary excretion pathway.

[Urinary and blood markers of internal mercury dose in workers from a chlorakali plant and in subjects not occupationally exposed: relation to dental amalgam and fish consumption]. / Indicatori urinari ed ematici di dose interna di mercurio in lavoratori di un impianto clorosoda e in soggetti non professionalmente esposti: relazione con gli amalgami dentali ed il consumo di pesce di mare.

OBJECTIVES: The aim of this paper was both to evaluate the internal dose of Hg in occupationally exposed workers (35 Chloralkali workers) compared to that of non occupationally exposed controls (40 workers of the same plant of Portotorres and 22 residents on the island of Carloforte, usual consumers of local fish, mostly tuna fish with relatively high Hg levels) and to assess the relevance of environmental and individual exposure factors linked to lifestyle, sea fish consumption and amalgam fillings. METHODS: All subjects filled out a questionnaire concerning the working history and lifestyle. The amalgam fillings area was measured by medical inspection using a standardised schedule attached to the questionnaire. Mercury in urine (HgU) was measured in all cases, while in a subgroup of our study total blood mercury (HgB) and its organic and inorganic component were also assessed. Furthermore, for 8 of the Carloforte group mercury in hair was also available. RESULTS: Values of urinary mercury excretion of the Chloralkali workers were significantly higher (median value of 15.4, range 4.8-35.0 micrograms/g creatinine, 94.3% of the cases having values > 5 micrograms/g creatinine) than those observed both among the reference group (median value of 1.9, range 0.4-5.6 micrograms/g creatinine, 12.5% of the cases having values a little greater than 5 micrograms/g creatinine) and among the residents in Carloforte (median value of 6.5, range 1.8-21.5 micrograms/g creatinine, 59.1% of the cases having values > 5 mcg/g creatinine). The HgU values observed in this group were in turn significantly higher than those of the non occupationally exposed workers living near Sassari (p = 0.03). Only in this last group were the HgU concentrations statistically significantly related to the extension of the amalgam fillings area (Pearson r = 0.53, p < 0.01). In the Carloforte group HgU was significantly related to the number of fish meal consumed per week (Pearson r = 0.48, p < 0.02). HgB (median value of 5.9, range 3.4-21.6 micrograms/l) as well as its inorganic component (median value of 2.4, range 1.8-4.6 micrograms/l) were significantly higher in the Chloralkali group compared to the other two groups. In all cases of the Carloforte group the ratio between the organic component and the total HgB was higher than 85%, while this ratio was significantly lower in the other two groups. The relationship between HgU and HgB was statistically significant, considering both total blood mercury and the inorganic and the organic components separately. A statistically significant relationship between the sea fish consumption per week and both total HgB (Pearson r = 0.82) and the organic component in this matrix (Pearson r = 0.84, p < 0.001) was observed among 16 non-occupationally exposed subjects. However, the significant relationship between organic blood mercury and sea fish consumption was almost entirely supported by the data observed in the Carloforte group. Total hair mercury levels analysed in 8 subjects of the Carloforte group were high (median value of 9.6, range 1.4-34.5 micrograms/g) and significantly related to sea fish consumption, and to both the individual Hg urinary excretion (Pearson r = 0.83) and to the organic component of blood mercury (Pearson r = 0.87). CONCLUSIONS: According to several experimental human and animal trials and to some recent studies on methylmercury toxicokinetic models, our results suggest that the organic compounds absorbed by usual sea fish consumption may be partially demethylated, increasing the inorganic Hg concentration in the kidney and consequently its urinary excretion, as was observed in the Carloforte group.