Monitoring of occupational exposure to epichlorohydrin by genetic effects and hemoglobin adducts

Landin, Helena Hindsø; Grummt, Tamara; Laurent, Christian; Tates, A.D.

doi:10.1016/s0027-5107(97)00171-1

Cited by 50 publications

(22 citation statements)

References 24 publications

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“…Due to its electrophilic epoxide structure, glycidol has alkylating properties. It was shown to form the haemoglobin adduct N‐(2,3‐dihydroxypropyl)valine (diHOPrVal) which could be quantified by GCMS after detachment of the N‐terminal valines in haemoglobin via the N‐alkyl Erdman method (Hindsø Landin et al., , ). Because of the long lifespan of erythrocytes (120 days) these adducts accumulate in the human body, making them a very sensitive parameter for human biomonitoring over this time period.…”

Section: Assessmentmentioning

confidence: 99%

Risks for human health related to the presence of 3‐ and 2‐monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food

Wallace¹,

Alexander²,

Barregård³

et al. 2016

EFS2

129

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EFSA was asked to deliver a scientific opinion on free and esterified 3-and 2-monochloropropane-1, 2-diol (MCPD) and glycidyl esters in food. Esters of 3-and 2-MCPD and glycidol are contaminants of processed vegetable oils; free MCPDs are formed in some processed foods. The Panel on Contaminants in the Food Chain (CONTAM Panel) evaluated 7,175 occurrence data. Esters of 3-and 2-MCPD and glycidyl esters were found at the highest levels in palm oil/fat, but most vegetable oil/fats contain substantial quantities. Mean middle bound (MB) dietary exposure values to total 3-MCPD, 2-MCPD and glycidol, respectively, across surveys and age groups in µg/kg body weight (bw) per day were 0.2-1.5, 0.1-0.7 and 0.1-0.9; high exposure (P95) values were 0.3-2.6, 0.2-1.2 and 0.2-2.1. Animal studies show extensive hydrolysis of esterified 3-MCPD and glycidol following oral administration; esterified and free forms were assumed to contribute equally to internal exposures. Nephrotoxicity was consistently observed in rats treated with 3-MCPD. Data on 2-MCPD toxicity were insufficient for dose-response assessments. Chronic treatment with glycidol increased the incidence of tumours in several tissues of rats and mice, likely via a genotoxic mode of action. The Panel selected a BMDL 10 value for 3-MCPD of 0.077 mg/kg bw per day for induction of renal tubular hyperplasia in rats and derived a tolerable daily intake (TDI) of 0.8 µg/kg bw per day. The mean exposure to 3-MCPD was above the TDI for 'Infants', 'Toddlers' and 'Other children'. For glycidol, the Panel selected a T25 value of 10.2 mg/kg bw per day for neoplastic effects in rats. The margins of exposure (MoEs) were 11,300-102,000 and 4,900-51,000 across surveys and age groups at mean and P95 exposures, respectively. An exposure scenario for infants receiving formula only resulted in MoEs of 5,500 (mean) and 2,100 (P95). MoEs of 25,000 or higher were considered of low health concern. Amendment: A few editorial amendments were carried out that do not materially affect the contents of the outcome of this scientific output: on pages 5 and 91 'chorine' has been replaced with 'chlorine'; on page 52 the word 'it' has been replaced by 'its' in the first paragraph after Figure 7; on page 54 in the Repeated dose section the reference to MCPD has been replaced with 3-MCPD; on page 54 the 429.5 mg/kg bw day dose has been replaced with 29.5 mg/kg bw day; on page 55 in the first paragraph of the Hematology section the reference 'mg/kg per day' has been replaced with 'mg/kg bw per day; on page 55 the year for the reference Marchesini et al. has been changed from 1989 to 1986; on page 59, in the first paragraph of the Developmental toxicity section the word 'days' has been cancelled; on page 65 the reference 'Onami et al., 2014a,b' has been replaced with 'Onami et al., 2014b'; on page 85 first paragraph, reference to the lowest T25 of 10 has been replaced to 10.2. To avoid confusion, the older version has been removed from the EFSA Journal, but is available on request, as is a version sho...

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Section: Assessmentmentioning

confidence: 99%

Risks for human health related to the presence of 3‐ and 2‐monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food

Wallace¹,

Alexander²,

Barregård³

et al. 2016

EFS2

129

View full text Add to dashboard Cite

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“…Also, the stability of the adduct in vivo might be low: in rats treated with ECH, Hindsø Landin et al [15] observed that the concentration of the globin adduct S-(3-chloro-2-hydroxypropyl)cysteine decreased faster in blood than would have been expected from the half-life of rat erythrocytes, while the potential secondary adduct S-(2,3-dihydroxypropyl)cysteine slightly increased for some time before dropping due to the erythrocyte turnover. While a straightforward conversion of the primary into the secondary cysteine adduct could not be shown in these experiments, Hindsø Landin et al [34] supposed that the corresponding N-(3-chloro-2-hydroxypropyl)valine adduct in human haemoglobin might be rapidly hydrolysed to N-(2,3-dihydroxypropyl)valine under physiological conditions. Despite the unfavourable perspectives and analytical problems described by Hindsø Landin et al [14] for the determination of N-(3-chloro-2-hydroxypropyl) adducts and in view of the contradictory encouraging results from recent in vitro and in vivo studies on these specific primary adducts of ECH, our work aimed on the development, validation and application of a GC-tandem MS method for the quantitative determination of CHPV, i.e.…”

Section: Introductionmentioning

confidence: 87%

“…8. Partial GC-tandem MS chromatograms from the analysis of blood samples of two subjects who were potentially exposed to ECH during a freight train accident [33,34]. The CHPV adduct was detected in the blood of subject #2 (80 pmol/g globin), but not in that of subject #1 (non-detectable).…”

Section: Stability Of the Dipeptide Calibrator And The Internal Standardmentioning

confidence: 99%

“…Thus, the hydrolysis of the chlorine-carrying methylene group at C-3 does not seem to be an immanent, but a work-up dependent problem. The in vivo stability of the 3-chloro-2-hydroxypropyl adducts is largely unknown, but the results of Hindsø Landin et al [34] with S-(3-chloro-2-hydroxy)cysteine in rat haemoglobin could support the assumption that the life-time of CHPV in the body may be shorter than adducts of other toxins. This aspect should be considered in sampling strategies for CHPV and other relatives.…”

Section: General Remarks Concerning Ech Adducts Analysis In Biomonitomentioning

confidence: 99%

See 1 more Smart Citation

Quantification of N-(3-chloro-2-hydroxypropyl)valine in human haemoglobin as a biomarker of epichlorohydrin exposure by gas chromatography–tandem mass spectrometry with stable-isotope dilution☆

Bader

Rosenberger

Gutzki

et al. 2009

Journal of Chromatography B

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“…In der zweiten Studie an Epichlorhydrin-exponierten Personen wurde das Hämo-globin-Addukt N-(2,3-Dihydroxypropyl)-valin (DHPV) als Biomonitoringparameter verwendet (Hindsø Landin et al 1997). Dabei wurde dieser Parameter in den Blutproben von 14 beruflich gegen Epichlorhydrin exponierten Personen, 14 Büro-angestellten des gleichen Betriebes ohne Epichlorhydrin-Belastung sowie 10 externen Kontrollpersonen ohne Epichlorhydrin-Belastung bestimmt.…”

Section: Belastung Und Beanspruchungunclassified

1‐Chlor‐2,3‐epoxypropan (Epichlorhydrin) [BAT Value Documentation in German language, 2017]

Göen

Bader

Drexler

et al. 2017

The MAK‐Collection for Occupational Health and Safety

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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated EKA (exposure equivalents for carcinogenic substances) for epichlorohydrin (CAS‐No 106‐89‐8) in 2017. Available publications are described in detail. In rodents, epichlorohydrin induces malignant lymphomas, hyperplasias, forestomach papillomas and carcinomas, subcutaneous fibromas and lung and pituitary tumours. Epichlorohydrin was classified in category 2 for carcinogenic substances. The substance can easily pass through the skin, so biological monitoring is indicated for a valid individual risk assessment. In several biomonitoring studies the mercapturic acids derivatives N‐acetyl‐S‐(3‐chloro‐2‐hydroxypropyl)‐L‐cysteine (CHPMA) and N‐acetyl‐S‐(2,3‐dihydroxypropyl)‐L‐cysteine (DHPMA) in urine as well as the hemoglobin adducts N‐(3‐chloro‐2‐hydroxypropyl)valine and N‐(2,3‐dihydroxypropyl)valine are suggested as biomarkers after epichlorohydrin exposure. Validated analytical procedures for their quantification are available. Data of a correlation of epichlorohydrin in the air and the CHPMA‐excretion in urine were considered for the evaluation of exposure equivalents for carcinogenic substances. Sampling time is at the end of exposure or end of shift and after long term exposure at the end of the shift after several shifts.

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Monitoring of occupational exposure to epichlorohydrin by genetic effects and hemoglobin adducts

Cited by 50 publications

References 24 publications

Risks for human health related to the presence of 3‐ and 2‐monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food

Risks for human health related to the presence of 3‐ and 2‐monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food

Quantification of N-(3-chloro-2-hydroxypropyl)valine in human haemoglobin as a biomarker of epichlorohydrin exposure by gas chromatography–tandem mass spectrometry with stable-isotope dilution☆

1‐Chlor‐2,3‐epoxypropan (Epichlorhydrin) [BAT Value Documentation in German language, 2017]

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