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      Biological Exposure Indices of Pyrrole Adducts in Serum and Urine for Hazard Assessment of n-Hexane Exposure

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          Abstract

          Background

          Pyrrole adducts might be used as a biomarker for monitoring occupational exposure to n-hexane, but the Biological Exposure Indices of pyrrole adducts in serum and urine are still unknown. The current study was designed to investigate the biological exposure limit of pyrrole adducts for hazard assessment of n-hexane.

          Methods

          Male Wistar rats were given daily dose of 500, 1000, 1500, 2000, 4000 mg/kg bw n-hexane by gavage for 24 weeks. The levels of pyrrole adducts in serum and urine were determined at 8, 24 hours postdose once a week. The Biological Exposure Indices was evaluated by neurological evaluation and the levels of pyrrole adducts. The difference in pyrrole adducts formation between humans and rats were estimated by using in vitro test.

          Results

          Dose-dependent effects were observed between the doses of n-hexane and pyrrole adducts in serum and urine, and the levels of pyrrole adduct in serum and urine approached a plateau at week 4. There was a significantly negative correlation between the time to paralysis and the level of pyrrole adducts in serum and urine, while a positive correlation between gait score and levels of pyrrole adducts in serum and urine was observed. In vitro, pyrrole adducts formed in human serum was about two times more than those in rat serum at the same level of 2,5-HD.

          Conclusion

          It was concluded that the BEIs of pyrrole adducts in humans were 23.1±5.91 nmol/ml in serum 8 h postdose, 11.7±2.64 nmol/ml in serum 24 h postdose, 253.8±36.3 nmol/ml in urine 8 h postdose and 54.6±15.42 nmol/ml in urine 24 h postdose.

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          Most cited references45

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          The enlarging view of hexacarbon neurotoxicity.

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            Degeneration in central and peripheral nervous systems produced by pure n-hexane: an experimental study.

            Rats intoxicated with pure n-hexane, either by repetitive subcutaneous injection or by continuous inhalation, developed clinical and/or pathological evidence of peripheral neuropathy. Animals intoxicated by inhalation (400-600 ppm) developed clinical signs after forty-five days and displayed giant axonal swellings and fibre degeneration both in the central and peripheral nervous systems. The changes were most strking in tibial nerves supplying calf muscles and in selected areas of the cerebellum, medulla and spinal cord. In contrast to the usual picture associated with dying-back disease, the distal regions of proximal nerve fibres supplying calf muscles degenerated before equivalent regions of longer fibres supplying the hindfeet. The relevance of the central nervous changes to individuals recovering from toxic neuropathies and the need for a reduction of the present Threshold Limit Value (500 ppm) for human exposure are discussed.
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              Exposure to benzene and urinary concentrations of 8-hydroxydeoxyguanosine, a biological marker of oxidative damage to DNA.

              Benzene is an established animal and human carcinogen. The mechanism of benzene toxicity, particularly its leukaemogenic effect, is not fully understood. The modified base 8-hydroxy-deoxyguanosine (8-OHdG) is a sensitive marker of the DNA damage due to hydroxyl radical attack at the C8 of guanine. This damage, if left unrepaired, has been proposed to contribute to mutagenicity and cancer promotion. We conducted this biomonitoring study with the aim of evaluating the association between excretion of 8-OHdG and level of exposure to benzene and other aromatic compounds among occupationally exposed people. A random sample of 65 filling station attendants from Rome, Italy was studied for personal exposure to benzene, toluene, and xylenes, and excretion of 8-OHdG. Information about age, length of employment, smoking habits, and diagnostic exposure to x rays was collected by questionnaire. An average yearly level of exposure to benzene and methylbenzenes was calculated for each filling station attendant on the basis of about seven repeated personal samples collected during one year. A spot sample of 20 ml of urine was collected from each worker. Concentrations of 8-OHdG were determined by high performance liquid chromatography (HPLC) with coupled columns. A mean (SD) concentration of 1.36 (0.49) mumol of 8-OHdG/mol of creatinine was measured. A significant correlation was found between urinary 8-OHdG and exposure to benzene (r = 0.34). In a multiple regression analysis relating the concentration of urinary 8-OHdG with the age, length of employment, smoking, diagnostic exposure to x rays and personal exposure to benzene, an increase of 0.15 mumol/mol creatinine in urinary 8-OHdG/unit increase in the natural logarithm of the average yearly benzene concentration was estimated. This study shows a dose-response effect between personal exposure to benzene and urinary 8-OHdG concentration; further studies are needed to clarify the biological significance of 8-OHdG as a marker of cancer risk.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                22 January 2014
                : 9
                : 1
                : e86108
                Affiliations
                [1 ]Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong Province, China
                [2 ]Jinan Municipal Center for Disease Control & Prevention, Jinan, Shandong Province, China
                [3 ]Nutrition Department, Shandong Jiaotong Hospital, Jinan, Shandong Province, China
                The Ohio State University, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: KQX. Performed the experiments: HYY CLZ YG TZ XYS. Analyzed the data: XLZ. Contributed reagents/materials/analysis tools: HYY YG TZ. Wrote the paper: HYY.

                Article
                PONE-D-13-32216
                10.1371/journal.pone.0086108
                3899213
                d195e7e6-ced7-451a-8adc-f1fb7c12d046
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 August 2013
                : 5 December 2013
                Page count
                Pages: 9
                Funding
                This research was supported by grants from Doctoral Fund of Ministry of Education of China (20120131110058) and National Natural Science Foundation of China(81373044): ( http://www.cutech.edu.cn/cn/kyjj/gdxxbsdkyjj/2012/12/1354173228937804.htm), ( http://www.nsfc.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Model Organisms
                Animal Models
                Rat
                Medicine
                Anatomy and Physiology
                Neurological System
                Diagnostic Medicine
                Pathology
                General Pathology
                Biomarkers
                Global Health
                Public Health
                Health Screening
                Occupational and Industrial Health
                Toxicology
                Neurotoxicology

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