Urinary levels of free 2,5-hexanedione in Italian subjects non-occupationally exposed to n-hexane

The purpose of the study is to evaluate the urinary levels of free 2,5-hexanedione (2,5-HD) in Italian subjects non-occupationally exposed to n-hexane, in order to define background values in non-occupational settings. The study was carried out on 99 subjects of the general population. The analysis of free 2,5-HD was performed by gas chromatography-mass spectrometry. Personal information about the subjects was ascertained by means of a self-administered questionnaire. The urinary levels of free 2,5-HD were in the range of <12.0\u201377.9 g/L (5th\u201395th percentiles). The urinary excretion of the metabolite did not seem to be influenced by gender, age, smoking habit or area of residence. Statistically significant dierences (p = 0.03) were found between the free 2,5-HD urinary levels according to the vehicular trac intensity within the area of residence and to body mass index of subjects. The background levels of free 2,5-HD found in this study could contribute to the definition of reference values of general population non-occupationally exposed and could be useful to the toxicologists and industrial hygienists to determine whether workers have been exposed to higher levels of n-hexane than the general population

Unusual Domestic Source of Lead Poisoning

Non-occupational lead poisoning is not rare, mainly occurring in domestic situations in children, but also in adults. Lead poisoning was observed in a 65 years-old woman non-exposed to risk that caught our attention with a diagnostic suspicion of acute intermittent porphyria according to recurrent episodes of abdominal pain and neuropathy of upper limbs. Acute intermittent porphyria was excluded by a laboratory investigation that showed instead severe lead poisoning. After several thorough examinations of the domestic environment, the source of intoxication has been detected in some cooking pots that released high concentrations of lead. Ethylenediamine tetracetic acid disodium calcium therapy (three cycles) reduced consistently blood lead concentration and, after one year, neuropathy was almost entirely recovered

Evidence for Sub-Haplogroup H5 of Mitochondrial DNA as a Risk Factor for Late Onset Alzheimer's Disease

BACKGROUND: Alzheimer's Disease (AD) is the most common neurodegenerative disease and the leading cause of dementia among senile subjects. It has been proposed that AD can be caused by defects in mitochondrial oxidative phosphorylation. Given the fundamental contribution of the mitochondrial genome (mtDNA) for the respiratory chain, there have been a number of studies investigating the association between mtDNA inherited variants and multifactorial diseases, however no general consensus has been reached yet on the correlation between mtDNA haplogroups and AD. METHODOLOGY/PRINCIPAL FINDINGS: We applied for the first time a high resolution analysis (sequencing of displacement loop and restriction analysis of specific markers in the coding region of mtDNA) to investigate the possible association between mtDNA-inherited sequence variation and AD in 936 AD patients and 776 cognitively assessed normal controls from central and northern Italy. Among over 40 mtDNA sub-haplogroups analysed, we found that sub-haplogroup H5 is a risk factor for AD (OR=1.85, 95% CI:1.04-3.23) in particular for females (OR=2.19, 95% CI:1.06-4.51) and independently from the APOE genotype. Multivariate logistic regression revealed an interaction between H5 and age. When the whole sample is considered, the H5a subgroup of molecules, harboring the 4336 transition in the tRNAGln gene, already associated to AD in early studies, was about threefold more represented in AD patients than in controls (2.0% vs 0.8%; p=0.031), and it might account for the increased frequency of H5 in AD patients (4.2% vs 2.3%). The complete re-sequencing of the 56 mtDNAs belonging to H5 revealed that AD patients showed a trend towards a higher number (p=0.052) of sporadic mutations in tRNA and rRNA genes when compared with controls. CONCLUSIONS: Our results indicate that high resolution analysis of inherited mtDNA sequence variation can help in identifying both ancient polymorphisms defining sub-haplogroups and the accumulation of sporadic mutations associated with complex traits such as AD

Effect of Benzene Exposure on the Urinary Biomarkers of Nucleic Acid Oxidation in Two Cohorts of Gasoline Pump Attendants

(1) Background: The oxidized guanine derivatives excreted into urine, products of DNA and RNA oxidation and repair, are used as biomarkers of oxidative damage in humans. This study aims to evaluate oxidative damage in gasoline pump attendants occupationally exposed to benzene. Benzene is contained in the gasoline but it is also produced from traffic and from smoking. (2) Methods: Twenty-nine gasoline pump attendants from two major cities of Saudi Arabia and 102 from Italy were studied for urinary 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydro-2&prime;-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and S-phenyl-mercapturic acid (SPMA) for benzene exposure and urinary cotinine for smoking status assessment by liquid chromatography-tandem mass spectrometry. Airborne benzene was also assessed in the Italian group by gas-chromatography with flame ionization detector (GC-FID). (3) Results: The results suggest that high levels of benzene exposure can cause an accumulation of SPMA and bring about the formation of the oxidation biomarkers studied to saturation. At low exposure levels, SPMA and oxidation biomarker levels were correlated among them and were associated with the smoking habit. (4) Conclusions: The study confirms the association between benzene exposure and the excretion of nucleic acid oxidation biomarkers and enhances the importance of measuring the smoking habit, as it can significantly influence oxidative damage, especially when the exposure levels are low

Assessment of exposure to oak wood dust using gallic acid as a chemical marker.

Objectives: The American Conference of Governmental Industrial Hygienists (ACGIH) has classified oak dusts as human carcinogens (A1), based on increased sinus and nasal cancer rates among exposed workers. The aims of this study were to investigate the use of gallic acid (GA) as chemical marker of occupational exposure to oak dusts, to develop a high-performance liquid chromatography\u2013diode array detector (HPLC\u2013DAD) method to quantify it, and to apply the method in the analysis of oak dust samples collected in some factories.Methods: A high performance liquid chromatography (HPLC) method was developed to detect GA in oak wood dust. The method was tested on field, and GA was extracted from oak wood dust sampled in the air of five wood-working plants where only oak wood is used. Results: A total of 57 samplings was taken in the dust concentration range 0.271-11.138 mg/m3. Five of these exceeded the Italian threshold limit value of 5 mg/m3, and 30 exceeded the ACGIH TLV of 1 mg/m3. GA concentrations were in the range 0.017-4.178 \ub5g/m3. The total oak dust sampled was correlated with GA contents with a coefficient of 0.95. Conclusions: The GA in tannic extracts of oak wood turned out to be specific for this type of wood, showing that its concentration in wood dust sampled in the work environment is useful in assessing true exposure to carcinogenic oak dust

Biomonitoring occupational sevoflurane exposure at low levels by urinary sevoflurane and hexafluoroisopropanol.

This study aimed to correlate environmental sevoflurane levels with urinary concentrations of sevoflurane (Sev-U) or its metabolite hexafluoroisopropanol (HFIP) in order to discuss the main issues relating to which biomarker of sevoflurane exposure is best, and possibly suggest the corresponding biological equivalent exposure limit values. Individual sevoflurane exposure was measured in 100 healthcare operators at five hospitals in north-east Italy using the passive air sampling device Radiello\uae, and assaying Sev-U and HFIP concentrations in their urine collected at the end of a session in the operating room. All analyses were performed by gas chromatography-mass spectrometry. Environmental sevoflurane levels in the operating rooms were also monitored continuously using an infrared photoacoustic analyzer. Our results showed very low sevoflurane individual exposure levels, generally below 0.5 ppm (mean 0.116 ppm; range 0.007-0.940 ppm). Sev-U and HFIP concentrations were in the range of 0.1-17.28 \ub5g/l and 5-550 \ub5g/l, respectively. Both biomarkers correlated statistically with the environmental exposure levels (Sev-U, r=0.49; HFIP, r=0.52), and with each other (r = 0.27), albeit with fairly scattered values. Sev-U values seem to be influenced by peaks of exposure, especially at the end of the operating-room session, whereas HFIP levels by exposure on the previous day, the data being consistent with the biomarkers\u2019 half-lives (2.8 and 19 h, respectively). According to our results, both Sev-U and HFIP are appropriate biomarkers for assessing sevoflurane exposure at low levels, although with some differences in times/patterns of exposure. More work is needed therefore to identify the best biomarker of sevoflurane exposure and the corresponding biological equivalent exposure limit value