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

EFSA Journal

Volumn 14, Issue 5, 2016, Pages

[No Author Info available]

Author keywords

glycidol; glycidyl fatty acid esters; MCPD; process contaminant; refined oil fat

Indexed keywords

EID: 85071644363     PISSN: None     EISSN: 18314732     Source Type: Journal    
DOI: 10.2903/j.efsa.2016.4426     Document Type: Article

References (272)

1. Abraham K, Appel KE, Berger-Preiss E, Apel E, Gerling S, Mielke H, Creutzenberg O and Lampen A, 2013. Relative oral bioavailability of 3-MCPD from 3-MCPD fatty acid esters in rats. Archives of Toxicology, 87, 649–659.
2. Abu-El-Haj S, Bogusz MJ, Ibrahim Z, Hassan H and A1 Tufail M, 2007. Rapid and simple determination of chloropropanols (3-MCPD and 1,3-DCP) in food products using isotope dilution GC-MS. Food Control, 18, 81–90.
3. Akane H, Shiraki A, Imatanaka N, Akahori Y, Itahashi M, Ohishi T, Mitsumori K and Shibutani M. 2013. Glycidol Induces Axonopathy by Adult-Stage Exposure and Aberration of Hippocampal Neurogenesis Affecting Late-Stage Differentiation by Developmental Exposure in Rats. Toxicological Sciences, 134:140–154. doi: 10.1093/toxsci/kft092. Epub 2013 Apr 17.
4. Akane H, Shiraki A, Imatanaka N, Akahori Y, Itahashi M, Abe H and Shibutani M, 2014a. Glycidol induces axonopathy and aberrations of hippocampal neurogenesis affecting late-stage differentiation by exposure to rats in a framework of 28-day toxicity study. Toxicology Letters, 224, 424–432.
5. Akane H, Saito F, Shiraki A, Imatanaka N, Akahori Y, Itahashi M, Wang L and Shibutani M, 2014b. Gene expression profile of brain regions reflecting aberrations in nervous system development targeting the process of neurite extension of rat offspring exposed developmentally to glycidol. Journal of Applied Toxicology, 34, 1389–1399. doi: 10.1002/jat.2971
6. Akane H, Saito F, Shiraki A, Takeyoshi M, Imatanaka N, Itahashi M, Murakami T and Shibutani M. 2014c. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol. Toxicology and Applied Pharmacology, 279, 150–162. doi: 10.1016/j.taap.2014.05.017 Epub 2014 Jun 8.
7. Alden CL and Frith CH, 1991. Urinary system. In: Haschek WM, Rousseaux CG (eds.). Handbook of Toxicologic Pathology. Academic Press, San Diego, CA, USA, pp. 315–387.
8. Amador A, Steger RW, Bartke A, Johns A, Siler-Khodr TM, Parker CR Jr and Shepherd AM, 1985. Testicular LH receptors during aging in Fisher 344 rats. Journal of Andrology, 6, 61–64.
9. Andres S, Appel KE and Lampen A, 2013. Toxicology, occurrence and risk characterisation of the chloropropanols in food: 2-Monochloro-1,3-propanediol, 1,3-dichloro-2-propanol and 2,3-dichloro-1-propanol. Food and Chemical Toxicology, 58, 467–478. doi:10.1016/j.fct.2013.05.024
10. Angerer J, Ewers U and Wilhelm M, 2007. Human biomonitoring: state of the art. International Journal of Hygiene and Environmental Health, 210, 201–228.
11. AOCS (The American Oil Chemists’ Society), 2013. AOCS validates three methods for MCPD-ester analysis. AOCS blog. Available online: http://www.lipidsfatsoilssurfactantsohmy.com/2013/10/aocs-validates-three-methods-for-mcpd.html
12. Appel KE, Abraham K, Berger-Preiss E, Hansen T, Apel E, Schuchardt S, Vogt C, Bakhiya N, Creutzenberg O and Lampen A, 2013. Relative oral bioavailability of glycidol from glycidyl fatty acid esters in rats. Archives of Toxicology, 87, 1649–1659.
13. Bakhiya N, Abraham K, Guertler R, Appel KE and Lampen A, 2011. Toxicological assessment of 3-chloropropane-1,2-diol and glycidol fatty acid esters in food. Molecular Nutrition and Food Research, 55, 509–521.
14. Bar A, 1992. Significance of Leydig cell neoplasia in rats fed lactitol or lactose. Journal of the American College of Toxicology, 11, 189–207.
15. Barocelli E, Corradi A, Mutti A and Petronini PG, 2011. Comparison between 3-MCPD and its palmitic esters in a 90-day toxicological study. Scientific report CFP/EFSA/CONTAM/2009/01. Available online: http://www.efsa.europa.eu/en/supporting/pub/187e.htm
16. Becalski A, Zhao T and Sit D, 2013. Cyclohexanone/sulfonated polymer catalyst: a new simple derivatizing procedure for GC-MS determination of 3- and 2-monochloropropanediols. Food Energy Security, 2, 157–165.
17. Benford D, Bolger M, Carthew P, Coulet M, DiNovi M, Leblanc JC, Renwick AG, Setzer W, Schlatter J, Smith B, Williams G and Wildemann T, 2010. Application of the Margin of Exposure (MOE) approach to substances in food that are genotoxic and carcinogenic. Food and Chemical Toxicology, 48, S34–S41.
18. BfR (Bundeninstitut fur Risikobewertung), 2007. Infant formula and follow-up formula may contain harmful 3-MCPD fatty acid esters. BfR Opinion No. 047/2007. Available online: http://www.bfr.bund.de/cm/349/infant_formula_and_follow_up_formula_may_contain_harmful_3_mcpd_fatty_acid_esters.pdf
19. BfR (Bundesinstitut für Risikobewertung), 2009. Initial evaluation of the assessment of levels of glycidol fatty acid esters detected in refined vegetable fats. Opinion No 007/2009.
20. BfR (Bundesinstitut für Risikobewertung), 2012. 3-MCPD-Fettsäureester in Lebensmitteln. Stellungnahme Nr. 006/2013 des BfR vom 3. April 2012.
21. BfR (Bundesinstitut für Risikobewertung), 2013. Collaborative Study for the determination of 3-MCPD- and 2-MCPD-Fatty Acid Esters in Fat Containing Foods. Available online: http://www.bfr.bund.de/cm/350/collaborative-study-for-the-determination-of-3-mcpd-and-2-mcpd-fatty-acid-esters-in-fat-containing-foods.pdf
22. Boden L, Lundgren M, Stensio K-E and Gorzynski M, 1997. Determination of 1,3-dichloro-propanol and 3-chloro-1,2-propanediol in papers treated with polyamidoamine-epichlorohydrin wet-strength resins by gas chromatography- mass spectrometry in selective ion monitoring mode. Journal of Chromatography A, 788, 195–203.
23. Boorman GA, Wilson JT, van Zwieten MJ and Eustis SL, 1990. Mammary gland. In: Boorman GA, Eustis SL, Elwell MR, Montgomery CA Jr and MacKenzie WF (eds.) Pathology of the Fischer Rat. Reference and Atlas. Academic Press, San Diego, New York, London, pp. 43–61.
24. Breitling-Utzmann CM, Köbler H, Herbolzheimer D and Maier A, 2003. 3-MCPD-occurrence in bread crust and various food groups as well as formation in toast. Deutsche Lebensmittel-Rundschau, 99, 280–285.
25. Breitling-Utzmann CM, Hrenn H, Haase NU and Unbehend GM, 2005. Influence of dough ingredients on 3-chloropropane-1,2-diol (3-MCPD) formation in toast. Food Additives and Contaminants, 22, 97–103.
26. Brereton P, Kelly J, Crews C, Honour S, Wood R and Davies A, 2001. Determination of 3-chloro-1,2-propanediol in foods and food ingredients by gas chromatography with mass spectrometric detection: collaborative study. Journal of AOAC International, 84, 455–465.
27. Brown-Woodman PDC, White IG and Ridley DD, 1979. The antifertility activity and toxicity of α-chlorohydrin derivatives in male rats. Contraception, 19, 517–529.
28. Burke T, Weisshaar R and Lampen A, 2011. Absorption and metabolism of the food contaminant 3-chloro-1,2-propanediol (3-MCPD) and its fatty acid esters by human intestinal Caco-2 cells. Archives of Toxicology, 85, 1201–1208.
29. Burke T, Frenzel F, Kuhlmann J and Lampen A, 2015. 2-Chloro-1,3-propanediol (2-MCPD) and its fatty acid esters: cytotoxicity, metabolism, and transport by human intestinal Caco-2 cells. Archives of Toxicology, 89(12), 2243–2251.
30. Cao X, Song G, Gao Y, Zhao J, Zhang M, Wu W and Hu Y, 2009. A novel derivatization method coupled with GC–MS for the simultaneous determination of chloropropanols. Chromatographia, 70, 661–664.
31. Cavanagh JB and Nolan CC, 1993. The neurotoxicity of a-chlorohydrin in rats and mice: II. Lesion topography and factors in selective vulnerability in acute energy deprivation syndromes. Neuropathology and Applied Neurobiology, 19, 471–479.
32. Cavanagh JB, Nolan CC and Seville MP, 1993. The neurotoxicity of a-chlorohydrin in rats and mice: I. Evolution of the cellular changes. Neuropathology and Applied Neurobiology, 19, 240–252.
33. CEN (European Committee for Standardization), 2004. EN 14573 Foodstuffs – Determination of 3-monochloropropane-a,2-diol by GC/MS. Available online: file:///C:/Users/cioacgi/Downloads/EN_14573%7B2004%7D_(E).pdf
34. Chatani F, Nonoyama T, Sudo K, Miyajima H, Takeyama M, Takatsuka D, Mori H and Matsumoto K, 1990. Stimulatory effect of luteinizing hormone on the development and maintenance of 5 alpha-reduced steroid-producing testicular interstitial cell tumors in Fischer 344 rats. Anticancer Research, 10, 337–342.
35. Cho WS, Han BS, Nam KT, Park K, Choi M, Kim SH, Jeong J and Jang DD, 2008a. Carcinogenicity study of 3-monochloropropane-1,2-diol in Sprague-Dawley rats. Food and Chemical Toxicology, 46, 3172–3177.
36. Cho WS, Han BS, Lee H, Kim C, Nam KT, Park K, Choi M, Kim SJ, Jeong J and Jang DD, 2008b. Subchronic toxicity study of 3-monochloropropane-1,2-diol administered by drinking water to B6C3F1 mice. Food and Chemical Toxicology, 46, 1666–1673.
37. Chung SWC and Chan BTP, 2012. Simultaneous determination of 2-and 3-monochloropropan-1,3-diol esters in foods by enzymatic hydrolysis and GC–MS detection. Chromatographia, 75, 1049–1056.
38. Chung WC, Hui KY and Cheng SC, 2002. Sensitive method for the determination of 1,3-dichloropropan-2-ol and 3-chloropropane-1,2-diol in soy sauce by capillary gas chromatography with mass spectrometric detection. Journal of Chromatography A, 952, 185–192.
39. Chung SWC, Chan BTP, Chung HY, Xiao Y and Ho YY, 2013. Occurrence of bound 3-monochloropropan-1,2-diol content in commonly consumed foods in Hong Kong analysed by enzymatic hydrolysis and GC-MS detection. Food Additives and Contaminants: Part A, 30, 1248–1254.
40. Clayton RN and Huhtaniemi IT, 1982. Absence of gonadotropin-releasing hormone receptors in human gonadal tissue. Nature, 299, 56–59.
41. Clegg ED, Cook JC, Chapin RE, Foster PM and Daston GP, 1997. Leydig cell hyperplasia and adenoma formation: mechanisms and relevance to humans. Reproductive Toxicology, 11, 107–121.
42. Collier PD, Cromie DDO and Davies AP, 1991. Mechanism of formation of chloropropanols present in protein hydrolysates. Journal of American Oil Chemistry Society, 68, 785–790.
43. Cook JC, Murray SM, Frame SR and Hurtt ME, 1992. Induction of Leydig cell adenomas by ammonium perfluorooctanoate: a possible endocrine-related mechanism. Toxicology and Applied Pharmacology, 113, 209–217.
44. Cook JC, Klinefelter GR, Hardisty JF, Sharpe RM and Foster PM, 1999. Rodent Leydig cell tumorigenesis: a review of the physiology, pathology, mechanisms, and relevance to humans. Critical Reviews in Toxicology, 29, 169–261.
45. Cooper ERA, Jones AR and Jackson H, 1974. Effects of a-chlorohydrin related compounds on the reproductive organs and fertility of the male rat. Journal of reproduction and fertility, 38, 379–386.
46. Craft BD, Nagy K, Seefelder W, Dubois M and Destaillats F, 2012. Glycidyl esters in refined palm (Elaeis guineensis) oil and related fractions. Part II: practical recommendations for effective mitigation. Food Chemistry, 132, 73–79.
47. Craft BD, Chiodini A, Garst J and Granvogl M, 2013. Fatty acid esters of monochloropropanediol (MCPD) and glycidol in refined edible oils. Food Additives and Contaminants Part A-Chemistry Analysis Control Exposure and Risk Assessment, 30, 46–51.
48. Crews C, 2011. MCPD and glycidyl esters in food products. Summary Report of a Workshop held in November 2011 in Brussels, Belgium. Available online: http://www.ilsi.org/Europe/Documents/MCPD%20Report%202012.pdf
49. Crews C, Brereton P and Davies A, 2001. The effects of domestic cooking on the levels of 3-monochloropropanediol in foods. Food Additives and Contaminants, 18, 271–280.
50. Crews C, Hough P, Brereton P, Harvey D, Mcarthur R and Matthews W, 2002. Survey of 3-monochloropropane-1,2-diol (3-MCPD) in selected food groups, 1999–2000. Food Additives and Contaminants, 19, 22–27.
51. Crisp TM, Clegg ED, Cooper RL, Wood WR, Anderson DG, Baetcke KR, Hoffmann JL, Morrow MS, Rodier DJ, Schaeffer JE, Touart LW, Zeeman MG and Patel YM, 1998. Environmental endocrine disruption: an effects assessment and analysis. Environmental Health Perspectives, 106 (Suppl. 1), 11–56.
52. Davídek J, Velíšek J, Kubelka V, Janícek G and Šimicová Z, 1980. Glycerol chlorohydrins and their esters as products of the hydrolysis of tripalmitin, tristearin and triolein with hydrochloric acid. Lebensmittel-Untersuchung und Forschung, 171, 14–17.
53. Dayrit FM and Niñonuevo MR, 2004. Development of an analytical method for 3-monochloropropane-1,2-diol in soy sauce using 4-heptanone as derivatizing agent. Food Additives and Contaminants, 21, 204–209.
54. Dertinger SD, Phonethepswath S, Franklin D, Weller P, Torous DK, Bryce SM, Avlasevich S, Bemis JC, Hyrien O, Palis J and MacGregor JT, 2010. Integration of mutation and chromosomal damage endpoints into 28-day repeat dose toxicology studies. Toxicological Sciences, 115, 401–411.
55. Destaillats F, Craft BD, Dubois M and Nagy K, 2012. Glycidyl esters in refined palm (Elaeis guineensis) oil and related fractions. Part I: Formation mechanism. Food Chemistry, 131, 1391–1398.
56. Divinová V, Svejkovská B, Doležal M and Velíšek J, 2004. Determination of free and bound 3-chloropropane-1,2-diol by gas chromatography with mass spectrometric detection using deuterated 3-chloropropane-1,2-diol as internal standard. Czech Journal of Food Sciences, 22, 182–189.
57. Dubois M, Tarres A, Goldmann T, Loeffelmann G, Donaubauer A and Seefelder W, 2011. Determination of seven glycidyl esters in edible oils by gel permeation chromatography extraction and liquid chromatography coupled to mass spectrometry detection. Journal of Agricultural and Food Chemistry, 59, 12291–12301.
58. Dybing E, Sanner T, Roelfzema H, Kroese D and Tennant RW, 1997. T25: a simplified carcinogenic potency index: description of the system and study of correlations between carcinogenic potency and species/site specificity and mutagenicity. Pharmacology and Toxicology, 80, 272–279.
59. Dybing E, O'Brien J, Renwick AG and Sanner T, 2008. Risk assessment of dietary exposures to compounds that are genotoxic and carcinogenic – an overview. Toxicology Letters, 180, 110–117.
60. Eckert E, Drexler H and Göen T, 2010. Determination of six hydroxyalkyl mercapturic acids in human urine using hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC-ESI-MS/MS). Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 878, 2506–2514.
61. Eckert E, Schmid K, Schaller B, Hiddemann-Koca K, Drexler H and Goen T, 2011. Mercapturic acids as metabolites of alkylating substances in urine samples of German inhabitants. International Journal of Hygiene and Environmental Health, 214, 196–204.
62. EFSA (European Food Safety Authority), 2005. Opinion of the Scientific Committee on a request from EFSA related to A Harmonised Approach for Risk Assessment of Substances Which are both Genotoxic and Carcinogenic. EFSA Journal 2005;3(10):282, 31 pp. doi:10.2903/j.efsa.2005.282
63. EFSA (European Food Safety Authority), 2006. Guidance of the Scientific Committee on a request from EFSA related to Uncertainties in Dietary Exposure Assessment. EFSA Journal 2006;5(1):438, 54 pp. doi: 10.2903/j.efsa.2007.438
64. EFSA (European Food Safety Authority), 2009a. Guidance of the Scientific Committee on a request from EFSA on the use of the benchmark dose approach in risk assessment. EFSA Journal 2009;7(6):1150, 72 pp. doi: 10.2903/j.efsa.2009.1150
65. EFSA (European Food Safety Authority), 2009b. Guidance of the Scientific Committee on transparency in the scientific aspects of risk assessment carried out by EFSA. Part 2: general principles. EFSA Journal 2009;7(5):1051, 22 pp. doi:10.2903/j.efsa.2009.1051
66. EFSA (European Food Safety Authority), 2010a. Standard sample description for food and feed. EFSA Journal 2010;8(1):1457, 54 pp. doi:10.2903/j.efsa.2010.1457
67. EFSA (European Food Safety Authority), 2010b. Management of left-censored data in dietary exposure assessment of chemical substances. EFSA Journal 2010;8(3):1557, 96 pp. doi:10.2903/j.efsa.2010.1557
68. EFSA (European Food Safety Authority), 2011a. Evaluation of the FoodEx, the food classification system applied to the development of the EFSA Comprehensive European Food Consumption Database. EFSA Journal 2011;9(3):1970, 27 pp. doi:10.2903/j.efsa.2011.1970
69. EFSA (European Food Safety Authority), 2011b. Use of the EFSA Comprehensive European Food Consumption Database in Exposure Assessment. EFSA Journal 2011;9(3):2097, 34 pp. doi:10.2903/j.efsa.2011.2097
70. EFSA (European Food Safety Authority), 2011c. Overview of the procedures currently used at EFSA for the assessment of dietary exposure to different chemical substances EFSA Journal 2011;9(12):2490. 33 pp. doi:10.2903/j.efsa.2011.2490
71. EFSA (European Food Safety Authority), 2013 Analysis of occurrence of 3-monochloropropane-1,2-diol (3-MCPD) in food in Europe in the years 2009-2011 and preliminary exposure assessment. EFSA Journal 2013;11(9):3381, 45 pp. doi:10.2903/j.efsa.2013.3381
72. EFSA SC (EFSA Scientific Committee), 2012a. Guidance on selected default values to be used by the EFSA Scientific Committee, Scientific Panels and Units in the absence of actual measured data. EFSA Journal 2012;10(3):2579, 32 pp. doi:10.2903/j.efsa.2012.2579
73. EFSA SC (EFSA Scientific Committee), 2012b. Scientific Opinion on Risk Assessment Terminology. EFSA Journal 2012;10(5):2664. 43 pp. doi:10.2903/j.efsa.2012.2664
74. El Ramy R, Elhkim MO, Poul M, Forest MG, Leduque P and Le Magueresse-Battistoni B, 2006. Lack of effect on rat testicular organogenesis after in utero exposure to 3-monochloropropane-1, 2-diol (3-MCPD). Reproductive Toxicology, 22, 485–492.
75. El Ramy R, Elhkim MO, Lezmi S and Poul JM, 2007. Evaluation of the genotoxic potential of 3-monochloropropane-1,2-diol (3-MCPD) and its metabolites, glycidol and beta-chlorolactic acid, using the single cell gel/comet assay. Food and Chemical Toxicology, 45, 41–48.
76. Epstein SS, Arnold E, Andrea J, Bass Y and Bishop Y, 1972. Detection of chemical mutagens by the dominant lethal assay in the mouse. Toxicology and Applied Pharmacology, 23, 288–325.
77. Ericsson RJ, 1982, University of Nebraska – Lincoln Digital Commons@University of Nebraska – Lincoln Proceedings of the Tenth Vertebrate PestConference (1982) Vertebrate Pest Conference Proceedings collection 2-23-1982. Alpha-Chlorhydrin (EPIBLOC®): a toxicant-sterilant as an alternative in rodent control.
78. Ericsson RJ and Baker VF, 1970. Male antifertility compounds: biological properties of U-5897 and U-l5,646. Journal of Reproduction and Fertility, 21, 267–273.
79. Ericsson RJ and Youngdale GA, 1970. Male antifertility compounds: structure and activity relationships of U-5897, U-15,646 and related substances. Journal of Reproduction and Fertility, 21, 263–266.
80. Ermacora A and Hrncirik K, 2013. A novel method for simultaneous monitoring of 2-MCPD, 3-MCPD and glycidyl esters in oils and fats. Journal of the American Oil Chemists Society, 90, 1–8.
81. Ermacora A and Hrncirik K, 2014. Influence of oil composition on the formation of fatty acid esters of 2-chloropropane-1,3-diol (2-MCPD) and 3-chloropropane-1,2-diol (3-MCPD) under conditions simulating oil refining. Food Chemistry, 161, 383–389.
82. FAO/WHO (Food and Agriculture Organization/World Health Organization), 2002. Safety evaluation of certain food additives and contaminants. Prepared by the fifty-seventh meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), Geneva. WHO Food Additives Series, 48. Available online: http://www.inchem.org/documents/jecfa/jecmono/v48je18.htm
83. Fellows M, 2000. 3-MCPD: measurement of unscheduled DNA synthesis in rat liver using an in vitro/in vivo procedure. Unpublished report No. 1863/1-D5140 from Covance Laboratories Ltd.
84. Fiebig H-J, 2011. Determination of ester-bound 3-chloro-1,2-propanediol and glycidol in fats and oils – a collaborative study. European Journal of Lipid Science and Technology, 113, 393–399.
85. Ford WCL and Waites GMH, 1982. Activities of various 6-chloro-6-deoxysugars and (S)a-chlorohydrinin producing spermatocoeles in rats and paralysis in mice and in inhibiting glucose metabolism in bull spermatozoa in vitro. Journal of Reproduction Fertility 177–183.
86. Frei H and Würgler FE, 1997. The vicinal chloroalcohols 1,3-dichloro-2-propanol (DC2P), 3-chloro-1,2-propanediol (3-CPD) and 2-chloro-1,3-propanediol (2-CPD) are not genotoxic in vivo in the wing spot test of Drosophila melanogaster. Mutation Research, 394, 59–68.
87. Freudenstein A, Weking J and Matthäus B, 2013. Influence of precursors on the formation of 3-MCPD and glycidyl esters in a model oil under simulated deodorization conditions. European Journal of Lipid Science and Technology, 115, 286–294.
88. Fry H, Schödel C, These A and Preiß-Weigert A, 2013. Collaborative study for the determination of 3-MCPD- and 2-MCPD- fatty acid esters in fat containing foods. Available online: http://www.bfr.bund.de/cm/350/collaborative-study-for-the-determination-of-3-mcpd-and-2-mcpd-fatty-acid-esters-in-fat-containing-foods.pdf
89. FSA (Food Standard Agency), 2009. Survey of process contaminants in retail foods 2008. Food Survey information sheet. Available online: http://tna.europarchive.org/20140306205048/http://multimedia.food.gov.uk/multimedia/pdfs/fsis0309acrylamide.pdf
90. FSCJ (Food Safety Commission of Japan), 2015. Considerations on glycidol and its fatty acid esters in foods. Risk assessment report – Novel Foods and Food Additives FS/185/2015. Available online: http://www.fsc.go.jp/english/evaluationreports/others/annex_glycidol_26-52.pdf
91. Gill SK and Guraya SS, 1993. Effects of low doses of alpha chlorohydrin on the lipid metabolism of the rat testis and epididymis – a correlative histochemical and biochemical study. International Journal of Fertility, 28, 43–48.
92. Gilliland FD and Key CR, 1995. Male genital cancer. Cancer, 75(Suppl. 1), 295–315.
93. Gingell R, Mitschke HR, Dzidic I, Beatty PW, Sawin VL and Page AC, 1985. Disposition and metabolism of [2-14C]epichlorohydrin after oral administration to rats. Drug Metabolism and Disposition, 13, 333–341.
94. Görlitz BD, 1991. In vitro mammalian cell HPRT-test with 3-chloro-1,2-propanediol. Unpublished report No. G91/3 from Fraunhofer-Institute für Toxikologie und Aerosolforschung, Hanover, Germany.
95. Haines TD, Adlaf KJ, Pierceall RM, Lee I, Venkitasubramanian P and Collison MW, 2011. Direct determination of MCPD fatty acid esters and glycidyl fatty acid esters in vegetable oils by LC-TOFMS. Journal of the American Oil Chemists Society, 88, 1–14.
96. Hamlet CG, 1998. Analytical methods for the determination of 3-chloro-1,2-propandiol and 2-chloro-1,3-propandiol in hydrolysed vegetable protein, seasonings and food products using gas chromatography/ion trap tandem mass spectrometry. Food Additives and Contaminants: Part A, 15, 451–465.
97. Hamlet CG, 2008. Chloropropanols and their fatty acid esters. In: Gilbert J and Senyuva H (eds.). Bioactive Compounds in Foods. Wiley-Blackwell, Oxford. pp. 323–377.
98. Hamlet CG, 2009. Chloropropanols and their fatty acid esters. In: Gilbert J and Senyuva HZ (eds.). Bioactive Compounds in Foods. Blackwell Publishing Ltd., Oxford, UK. pp. 323–357.
99. Hamlet CG and Asuncion L, 2011. Single-laboratory validation of a method to quantify bound 2-chloropropane-1,3-diol and 3-chloropropane-1,2-diol in foodstuffs using acid catalysed transesterification, HFBI derivatisation and GC/MS detection. European Journal of Lipid Science, 113, 345–355.
100. Hamlet CG and Sadd PA, 2004. Chloropropanols and their esters in cereal products. Czech Journal of Food Sciences, 22, 259–262.
101. Hamlet CG and Sadd PA, 2009. Chloropropanols and chloroesters. In: Stadler RH, Lineback DR (eds.). Process-Induced Food Toxicants: Occurrence, Formation, Mitigation and Health Risks. Wiley, Hoboken, NJ, pp. 175–214.
102. Hamlet CG, Sadd PA, Crews C, Velisek J and Baxter DE, 2002. Occurrence of 3-chloro-propane-1,2-diol (3-MCPD) and related compounds in foods: a review. Food Additives and Contaminants, 19, 619–631.
103. Hamlet CG, Sadd PA and Gray DA, 2003. Influence of composition, moisture, pH and temperature on the formation and decay kinetics of monochloropropanediols in wheat flour dough. European Food Research and Technology, 216, 122–128.
104. Hamlet CG, Sadd PA and Gray DA, 2004a. Generation of monochloropropanediols (MCPDs) in model dough systems. 1 Leavened doughs. Journal of Agricultural and Food Chemistry, 52, 2059–2066. doi:10.1021/jf035077w
105. Hamlet CG, Sadd PA and Gray DA, 2004b. Generation of monochloropropanediols (MCPDs) in model dough systems. 2 Unleavened doughs. Journal of Agricultural and Food Chemistry, 52, 2067–2072. doi:10.1021/jf035078o
106. Hamlet CG, Asuncion L, Velíšek J, Doležal M, Zelinková Z and Crews C, 2011. Formation and occurrence of esters of 3-chloro-1,2-propanediol (3-CPD) in foods: what we know and what we assume. European Journal of Lipid Science and Technology, 113, 279–303.
107. Hamlet CG, Asuncion L, Velíšek J, Doležal M, Zelinková Z, Crews C, Anderson W and Pye C, 2014. Investigation of the formation of 3-chloropropane-1-2-diol(3-MCPD) from mono-and di-esters of its fatty acids in foods(FS231006, FS231074, FS231075). Available online: https://www.food.gov.uk/sites/default/files/C04072_Final%20report_July%202014_151014.pdf
108. Hard GC, 1998. Mechanisms of chemically induced renal carcinogenesis in the laboratory rodent. Toxicologic Pathology, 26, 104–112.
109. Haseman JK, 1984. Statistical issues in the design, analysis and interpretation of animal carcinogenicity studies. Environmental Health Perspective, 58, 385–392.
110. Henderson LM, Bosworth HJ, Ransome SJ, Banks SJ, Brabbs CE and Tinner AJ, 1987. An assessment of the mutagenic potential of 1,3-dichloro-2-propanol, 3-chloro-1,2-propanediol and a cocktail of chloropropanols using the mouse lymphoma TK locus assay. Unpublished report No. ULR 130 ABC/861423 from Huntingdon Research Centre Ltd, Huntingdon, Cambridgeshire, UK.
111. Hibi D, Suzuki Y, Ishii Y, Jin M, Watanabe M, Sugita-Konishi Y, Yanai T, Nohmi T, Nishikawa A and Umemura T, 2011. Site-specific in vivo mutagenicity in the kidney of gpt delta rats given a carcinogenic dose of ochratoxin A. Toxicological Sciences, 122, 406–414.
112. Hindsø Landin H, Osterman-Golkar S, Zorcec V and Tornqvist M, 1996. Biomonitoring of epichlorohydrin by hemoglobin adducts. Analytical Biochemistry, 240, 1–6.
113. Hindsø Landin H, Grummt T, Laurent C and Tates A, 1997. Monitoring of occupational exposure to epi-chlorohydrin by genetic effects and hemoglobin adducts. Mutation Research, 381, 217–226.
114. Hindsø Landin H, Tareke E, Rydberg P, Olsson U and Tornqvist M, 2000. Heating of food and haemoglobin adducts from carcinogens: possible precursor role of glycidol. Food and Chemical Toxicology, 38, 963–969.
115. Honda H, Fujii K, Yamaguchi T, Ikeda N, Nishiyama N and Kasamatsu T, 2012. Glycidol exposure evaluation of humans who have ingested diacylglycerol oil containing glycidol fatty acid esters using hemoglobin adducts. Food and Chemical Toxicology, 50, 4163–4168.
116. Honda H, Toernqvist M, Nishiyama N and Kasamatsu T, 2014. Characterization of glycidol-hemoglobin adducts as biomarkers of exposure and in vivo dose. Toxicology and Applied Pharmacology, 275, 213–220.
117. Hrncirik K and Ermacora A, 2010. Formation of 3-MCPD esters in vegetable oils: lab-scale refining study. Paper presented at: 8th EuroFed Lipid Congress; 21–24 November 2010; Munich, Germany.
118. Hrncirik K and van Duijn G, 2011. An initial study on the formation of 3-MCPD esters during oil refining. European Journal of Lipid Science and Technology, 113, 374–379.
119. Huybrechts I, Sioen I, Boon PE, Ruprich J, Lafay L, Turrini A, Amiano P, Hirvonen T, De Neve M, Arcella D, Moschandreas J, Westerlund A, Ribas-Barba L, Hilbig A, Papoutsou S, Christensen T, Oltarzewski M, Virtanen S, Rehurkova I, Azpiri M, Sette S, Kersting M, Walkiewicz A, SerraMajem L, Volatier JL, Trolle E, Tornaritis M, Busk L, Kafatos A, Fabiansson S, De Henauw S and Van Klaveren J, 2011. Dietary exposure assessments for children in Europe (the EXPOCHI project): rationale, methods and design. Archives of Public Health, 69, 4. doi:10.1186/0778-7367-1169-1184
120. IARC (International Agency for Research on Cancer), 1987. IARC Monographs on the evaluation of the carcinogenic risk to humans. Overall evaluations of carcinogenicity: An updating of IARC Monographs Volumes 1 to 42. Supplement 7, Lyon, 10–18 March 1987.
121. IARC (International Agency for Research on Cancer) 2000. Some Industrial Chemicals. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 77. Lyon, France: International Agency for Research on Cancer. pp. 469–486.
122. IARC (International Agency for Research on Cancer), 2012. 3-Monochloro-1,2-propanediol. In: IARC Monographs Volume 101. Some Chemicals Present in Industrial and Consumer Products, Food and Drinking-water. Lyon, France, 349–374.
123. Ikeda N, Fujii K, Sarada M, Saito H, Kawabata M, Naruse K, Yuki K, Nakagiri H, Honda H, Tamaki Y, Nishiyama N and Kasamatsu T, 2012. Genotoxicity studies of glycidol fatty acid ester (glycidol linoleate) and glycidol. Food and Chemical Toxicology, 50, 3927–3933.
124. Jala RCR, Zhang X, Huang H, Gao B, Yu L and Xu X, 2015. 3-MCPD fatty acid esters: chemistry, safety, and technological approaches for their reductions. In L. Yu, S. Wang, B-G Sun, (eds.). Food Safety Chemistry: toxicant Occurrence, Analysis and Mitigation. CRC Press. ISBN 9781466597945.
125. James SP, Pue MA and Richards DH, 1981. Metabolism of 1,3-dibromopropane. Toxicology Letters, 8, 7–15.
126. Jaccaud E and Aeschbacher HU, 1989. Evaluation of 3-chloro-1,2-propanediol (3MCPD) in the bone marrow and colonic micronucleus mutagenicity tests in mice. Unpublished report No. 1265 from Nestec Ltd Research Centre, Nestlé, Switzerland.
127. Jacobs BB and Huseby RA, 1968. Transplantable Leydig cell tumors in Fischer rats: horomone responsivity and hormone production. Journal of the National Cancer Institute, 41, 1141–1153.
128. JECFA (Joint FAO/WHO Expert Committee on Food Additives), 2002. 3-Chloro-1,2-propanediol. Safety evaluation of certain food additives and contaminants. Prepared by the fifty-seventh meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), GenevaWHO Food Additives Series, 48.
129. Jeong J, Han BS, Cho WS, Choi M, Ha CS, Lee BS, Kim YB, Son WC and Kim CY, 2010. Carcinogenicity study of 3-monochloropropane-1,2-diol (3-MCPD) administered by drinking water to B6C3F1 mice showed no carcinogenic potential. Archives of Toxicology, 84, 719–729.
130. Jones AR, 1975. The metabolism of 3-chloro,- 3-bromo- and 3-iodoprpan-1,2-diol in rats and mice. Xenobiotica, 5, 155–165.
131. Jones AR, Bashir AA and Low SJ, 1974. The comparative metabolism of 3-bromo-propane-1,2-diol and 3-bromopropanol in the rat. Experientia, 30, 1238–1239.
132. Jones AR, 1983. Antifertility actions of alpha-chlorohydrin in the male. Australian Journal of Biological Sciences, 36, 333–350.
133. Jones AR and Cooper TG, 1999. A re-appraisal of the posttesticular action and toxicity of chlorinated antifertility compounds. International Journal of Andrology, 22, 130–138. doi: 10.1046/j.1365-2605.1999.00163.x
134. Jones AR, Davies P, Edwards K and Jackson H, 1969. Antifertility effects and metabolism of alpha- and epi-chlorohydrins in the rat. Nature, 224, 83.
135. Jones AR and Fakhouri G, 1979. Epoxides as obligatory intermediates in the metabolism of α-halohydrins. Xenobiotica, 9, 595–599.
136. Jones P and Jackson H, 1976. Antifertility and dominant lethal mutation studies in male rats with a-O(-chlorohydrin) and an amino-analogue. Contraception, 13, 639–646.
137. Jones AR and O'Brien RW, 1980. Metabolism of three active analogues of the male antifertility agent α-chlorohydrin in the rat. Xenobiotica, 10, 365–370.
138. Jones AR and Porter LM, 1995. Inhibition of glycolysis in boar spermatozoa by alpha-chlorohydrin phosphate appears to be mediated by phosphatase activity. Reproduction, Fertility, and Development, 7, 1089–1094.
139. Jones AR, Milton DH and Murcott C, 1978. The oxidative metabolism of alpha-chlorohydrin in the male rat and the formation of spermatocoeles. Xenobiotica, 8, 573–582.
140. Jones AR, Gadiel P and Stevenson D, 1981. The fate of oxalic acid in the Wistar rat. Xenobiotica, 11, 385–390.
141. Karasek L, Wenzl T and Ulberth F, 2013. Proficiency test on the determination of 3-MCPD esters in edible oil Final Report. Available online: https://ec.europa.eu/jrc/sites/default/files/eur_24356_en_3-mpcd_esters_in_edible_oil.pdf
142. Kaur S and Guraya SS, 1981a. Effect of low doses of alpha chlorohydrin on the enzymes of glycolytic and phosphogluconate pathways in the rat testis and epididymis. International Journal of Andrology, 4, 196–207.
143. Kaur S and Guraya SS, 1981b. Biochemical observations on the protein and nucleic acid metabolism of the rat testis and epididymis after treatment with low doses of alphachlorohydrin. International Journal of Fertility, 26, 8–13.
144. Kim K, 2008. Differential expression of neuronal and inducible nitric oxide synthase in rat brain after subchronic administration of 3- Monochloro-1,2-propanediol. Food and Chemical Toxicology, 46, 955–960.
145. Kim K, Song C, Park Y, Koh S, Kim J, Kim S, Kim Y, Kim SU and Jung H, 2004. 3-Monochloropropane-1,2-diol does not cause neurotoxicity in vitro or neurobehavioral deficits in rats. NeuroToxicology, 25, 377–385.
146. Kirton KT, Ericsson RJ, Ray JA and Forbes AD, 1970. Male antifertility compounds: efficacy of U-5897 in primates (Macaca mulatta). Journal of Reproduction and Fertility, 21, 275–278.
147. Kissa E, 1992. Determination of 3-chloropropanediol and related dioxolanes by gas chromatography. Journal of Chromatography A, 605, 134–138.
148. Kluwe WM, Gupta BN and Lamb JC 4th, 1983. The comparative effects of 1,2-dibromo-3-chloropropane (DBCP) and its metabolites, 3-chloro-1,2-propaneoxide (epichlorohydrin), 3-chloro-1,2-propanediol (alphachlorohydrin), and oxalic acid, on the urogenital system of male rats. Toxicology and Applied Pharmacology, 70, 67–86. doi: 10.1016/0041-008X(83)90180-1
149. Konishi H, Okajima H, Okada Y, Yamamoto H, Fukai K and Watanabe H, 1991. High levels of cholesteryl esters, progesterone and estradiol in the testis of aging male Fischer 344 rats: feminizing Leydig cell tumors. Chemical & Pharmaceutical Bulletin (Tokyo), 39, 501–504.
150. Kuballa T and Ruge W, 2004. Analysis and detection of 3-monochloropropane-1,2-diol (3-MCPD) in food by GC/MS/MS. Varian GC/MS Application Note, 73, 1–2.
151. Kuhlmann J, 2011. Determination of bound 2,3-epoxy-1-propanol (glycidol) and bound monochloropropanediol (MCPD) in refined oils. European Journal of Lipid Science and Technology, 113, 335–344.
152. Kuntzer J and Weißhaar R, 2006. The smoking process – a potent source of 3-chloropropane-12-diol 3-MCPD in meat products. Deutsche Lebensmittel-Rundschau, 102, 397–400.
153. Küsters M, Bimber U, Ossenbrüggen A, Reeser S, Gallitzendörfer R and Gerhartz M, 2010. Rapid and simple micromethod for the simultaneous determination of 3-MCPD and 3-MCPD esters in different foodstuffs. Journal of Agricultural and Food Chemistry, 58, 6570–6577.
154. Küsters M, Bimber U, Reeser S, Gallitzendörfer R and Gerhartz M, 2011. Simultaneous determination and differentiation of glycidyl esters and 3-monochloropropane-1,2-diol (MCPD) esters in different foodstuffs by GC-MS. Journal of Agricultural and Food Chemistry, 59, 6263–6270.
155. Kwack SJ, Kim SS, Choi YW, Rhee GS, Da Lee R, Seok JH, Chae SY, Won YH, Lim KJ, Choi KS, Park KL and Lee BM, 2004. Mechanism of antifertility in male rats treated with 3-monochloro-1,2-propanediol (3-MCPD). Journal of Toxicology and Environmental Health A, 67, 2001–2011.
156. Larsen JC 2009. 3-MCPD esters in food products. Summary Report of a Workshop held in February 2009 in Brussels, Belgium. Available at: http://www.ilsi.org/europe/publications/final%20version%203%20mcpd%20esters.pdf
157. León N, Yusà V, Pardo O and Pastor A, 2008. Determination of 3-MCPD by GC-MS/MS with PTV-LV injector used for a survey of Spanish foodstuffs. Talanta, 75, 824–831.
158. Li Y, Liu S, Wang C, Li K, Shan YJ, Wang XJ and Sun CH, 2010. Novel biomarkers of 3-chloro-1,2-propanediol exposure by ultra performance liquid chromatography/mass spectrometry based metabonomic analysis of rat urine. Chemical Research in Toxicology, 23, 1012–1017.
159. Li J, Wang S, Wang M, Shi W, Du X and Sun C, 2013. The toxicity of 3-chloropropane-1,2-dipalmitate in Wistar rats and a metabonomics analysis of rat urine by ultra-performance liquid chromatography-mass spectrometry. Chemico-Biological Interactions, 206, 337–345.
160. Liu M, Gao BY, Qin F, Wu PP, Shi HM, Luo W, Ma AN, Jiang YR, Xu XB and Yu LL, 2012. Acute oral toxicity of 3-MCPD mono- and dipalmitic esters in Swiss mice and their cytotoxicity in NRK-52E rat kidney cells. Food and Chemical Toxicology, 50, 3785–3791.
161. LMBG (1995) Bestimmung von 3-Chlor-1,2-Propandiol (3-MCPD) in Speisewürzen (Eiweißhydrolysate). Amtliche Sammlung von Untersuchungsverfahren nach § 35, Beuth Verlag, Berlin, Germany.
162. Lohika NK and Arya M, 1979. Antifertility activity of alpha-chlorohydrin (3-chloro-1, 2 propanediol, U-5897) on the female rats. Acta Europaea fertilitatis, 10, 23–27.
163. Lucas TF, Siu ER, Esteves CA, Monteiro HP, Oliveira CA, Porto CS and Lazari MF, 2008. 17beta-estradiol induces the translocation of the estrogen receptors ESR1 and ESR2 to the cell membrane, MAPK3/1 phosphorylation and proliferation of cultured immature rat Sertoli cells. Biology of Reproduction, 78, 101–114.
164. Lynch BS, Bryant DB, Hook GJ, Nestmann ER and Munro IC, 1998. Carcinogenicity of monochloro-1,2-propanediol (alpha-chlorohydrin, 3-MCPD). International Journal of Toxicology, 17, 47–76.
165. MacMahon S, Mazzola E, Begley TH and Diachenko GW, 2013a. Analysis of processing contaminants in edible oils. part 1. liquid chromatography − tandem mass spectrometry method for the direct detection of 3–monochloropropanediol monoesters and glycidyl esters. Journal of Agricultural and Food Chemistry, 61, 4737–4747.
166. MAK (Maximale Arbeitsplatzkonzentrationen), 2000. Deutsche Forschungsgemeinschaft, Senatskommission zur Prüfung Gesundheitsschädlicher Arbeitsstoffe: “MAK- und BAT-Werte-Liste: maximale Arbeitsplatzkonzentrationen und biologische Arbeitsstofftoleranzwerte”. Wiley-VCH, Weinheim 2000, 30. Lieferung.
167. Marchesini M and Stalder R, 1983. Toxicity of 3-chloro-1,2-propanediol in a 4 weeks gavage study on rats. Part I. Unpublished report No. LA 70/1082 from the Société d'Assistance Technique Pour Produits Nestlé SA, Switzerland.
168. Marchesini M, Stalder R and Perrin I, 1989. Subchronic toxicity of 3-chloro-1,2-propanediol, 90 days administration in drinking water of Fischer F344 rats. Unpublished report No. 1264 from Nestec Ltd Research Centre, Nestlé, Switzerland.
169. Marchesini M and Huggett A, 1992. The acute toxicity of 2-chloropropan 1,2 diol (up and down test) Unpublished report No. FS-RN920011 submitted to WHO by Nestec Ltd, Research & Development, Switzerland.
170. Marks TA, Gerling FS and Staples RE, 1982. Teratogenic evaluation of epichlorohydrin in the mouse and rat and glycidol in the mouse. Journal of Toxicology and Environmental Health, Part A Current Issues, 9, 87–96.
171. Marshall RM, 2000. 3-MCPD: induction of micronuclei in the bone-marrow of treated rats. Unpublished report No. 1863/2-D5140 from Covance Laboratories Ltd.
172. Masukawa Y, Shiro H, Nakamura S, Kondo N, Jin N, Suzuki N, Ooi N and Kudo N, 2010. A new analytical method for the quantification of glycidol fatty acid esters in edible oils. Journal of Oleo Science, 2010, 81–88.
173. Matthäus B, 2012. Organic or not organic – that is the question: how the knowledge about the origin of chlorinated compounds can help to reduce formation of 3-MCPD esters. European Journal of Lipid Science and Technology, 114, 1333–1334.
174. Matthäus B, Pudel F, Fehling P, Vosmann K and Freudenstein A, 2011. Strategies for the reduction of 3-MCPD esters and related compounds in vegetable oils. European Journal of Lipid Science and Technology, 113, 380–386.
175. Matthäus B, Freundenstein A, Vosmann K, Pudel F and Rudolph T, 2012. Deodorization for edible oils Investigate the influences on the formation related by 3-MCPD fatty acid esters and connections. Deutsche Lebensmittel-Rundschau, 108, 510–515.
176. Meierhans DC, Bruehlmann S, Meili J and Taeschler C, 1998. Sensitive method for the determination of 3-chloro-propane-1,2-diol and 2-chloropropane-1,3-diol by capillary gas chromatography with mass spectrometric detection. Journal of Chromatography A, 802, 325–333.
177. Melnick RL, 2002. Carcinogenicity and mechanistic insights on the behavior of epoxides and epoxide-forming chemicals. Annals of the New York Academy of Sciences, 982, 177–189.
178. Merten C, Ferrari P, Bakker M, Boss A, Hearty A, Leclercq C, Lindtner O, Tlustos C, Verger P, Volatier JL and Arcella D, 2011. Methodological characteristics of the dietary surveys carried out in the European Union as included in the European Food Safety Authority (EFSA) Comprehensive European Food Consumption Database, Food Additives and Contaminants. Part A, 28, 975–995.
179. Montaldo C, Dore M and Congiu L, 1984. Glycidol, a new depletory of liver glutathione. IRCS Medical Science, 12, 135–136.
180. Montgomery CA Jr and Seely JC, 1990. Kidney. In: Boorman GA, Eustis SL, Elwell MR, Montgomery CA Jr, Mackenzie WF (eds.). Pathology of the Fischer Rat. Reference and Atlas. Academic Press, Inc., San Diego, CA, USA, pp. 127–153.
181. Morgenthaler P, 1993. Evaluation of the genotoxicity of 2-Chloro-1,2-propanediol (2-MCPD) using the V79 mutation assay. Nestlé Research Center – Unpublished Report No RE-SR93073.
182. Morris ID and Jackson CM, 1978. Gonadotrophin changes in male rats following a sterilising dose of alpha-chlorohydrin. International Journal of Andrology, 1, 85–95.
183. Morris ID and Williams LM, 1980. Some preliminary observations of the nephrotoxicity of the male antifertility drug (-) a-chlorohydrin. Journal of Pharmacy and Pharmacology, 32, 35–38.
184. Nagy K, Sandoz L, Craft BD and Destaillats F, 2011. Mass-defect filtering of isotope signatures to reveal the source of chlorinated palm oil contaminants. Food Additives and Contaminants, 28, 1492–1500.
185. Neumann F, 1991. Early indicators for carcinogenesis in sex-hormone-sensitive organs. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 248, 341–356.
186. Nomeir AA, Silveira DM, Ferrala NF, Markham PM and McComish MF, 1995. Comparative disposition of 2,3-epoxy-1-propanol (glycidol) in rats following oral and intravenous administration. Journal of Toxicology and Environment Health, 44, 203–217.
187. NTP (National Toxicology Program), 1990. National Toxicology Program, Toxicology and carcinogenesis studies of glycidol (CAS No. 556-52-5) in F344/N rats and B6C3F1 mice (gavage studies). Technical Report Series No. 374. National Institutes of Health Publication No. 90-2829. Research Triangle Park, NC.
188. Arf mice (gavage study). Technical Report Series No. 13. National Institutes of Health Publication No. 08-5962. Research Triangle Park, NC.
189. Nyman PJ, Diachenko GW and Perfetti GA, 2003. Survey of chloropropanols in soy sauces and related products. Food Additives and Contaminants, 20, 909–915.
190. Ohkubo T, Hayashi T, Watanabe E, Endo H, Goto S, Endo O, Mizoguchi T and Mori Y, 1995. Mutagenicity of chlorohydrins. Nippon Suisan Gakkaishi, 61, 596–601 (in Japanese).
191. Onami S, Cho YM, Toyoda T, Horibata K, Ishii Y, Umemura T, Honma M, Nohmi T, Nishikawa A and Ogawa K, 2014a. Absence of in vivo genotoxicity of 3-monochloropropane-1,2-diol and associated fatty acid esters in a 4-week comprehensive toxicity study using F344 gpt delta rats. Mutagenesis, 29, 295–302.
192. Onami S, Y-m Cho, Toyoda T, Mizuta Y, Yoshida M, Nishikawa A and Ogawa K, 2014b. A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats. Archives of Toxicology, 88, 871–880.
193. Onami S, Cho YM, Toyoda T, Akaqi J, Fujiwara S, Tsujino K, Nishikawa A and Ogawa K, 2015. Orally administered glycidol and its fatty acid esters as well as 3-MCPD fatty acid esters are metabolized to 3-MCPD in the F344 rat. Regulatory Toxicology and Pharmacology, 73, 726–731.
194. Patel JM, Wood JC and Leibman KC, 1980. The biotransformation of allyl alcohol and acrolein in rat liver and lung preparations. Drug Metabolism and Disposition, 8, 305–308.
195. Painter RB and Howard R, 1982. The HeLa DNA synthesis inhibition test as a rapid screen for mutagenic carcinogens. Mutation Research, 92, 427–437.
196. Paz G, Carmon A and Homonnai ZT, 1985. Effect of alpha-chlorohydrin on metabolism and testosterone secretion by rat testicular interstitial cells. International Journal of Andrology, 8, 139–146.
197. Perrin I, Marchesini M and Sunahara G, 1994. Repeated dose oral toxicity 28 day gavage in Sprague Dawley rats of 2-chloropropan-1,3 diol (2-MCPD). Unpublished report No. RE-SR94026 submitted to EFSA by Nestec Ltd, Research & Development, Switzerland.
198. Pesselman RL and Feit MJ, 1988. Determination of residual epichlorohydrin and 3-chloropropanediol in water by gas chromatography with electron-capture detection. Journal of Chromatography A, 439, 448–452.
199. Piasecki A, Ruge A and Marquardt H, 1990. Malignant transformation of mouse M2-fibroblasts by glycerol chlorohydrines contained in protein hydrolysate and commercial food. Arzneim.-Forsch./Drug Res., 40, 1054–1055.
200. Plantinga WJ, Van Toorn WG and Van Der Stegen GHD, 1991. Determination of 3-chloropropane-l,2-diol in liquid hydrolysed vegetable proteins by capillary gas chromatography with Same ionisation detection. Journal of Chromatography, 555, 311–314.
201. Porter KG and Jones AR, 1982. The effect of the isomers of alpha-chlorohydrin and racemic beta-chlorolactate on the rat kidney. Chemico-Biological Interactions, 41, 95–104.
202. Prentice DE and Meikler AW, 1995. A review of drug-induced Leydig cell hyperplasia and neoplasia in the rat and some comparison with man. Human and Experimental Toxicology, 14, 562–572.
203. Qian G, Zhang H, Zhang G and Yin L, 2007. [Study on acute toxicity of R, S and (R,S)3monchloropropane1,2diol]. Journal of Hygiene Research, 36, 13740.
204. Racamonde I, Gonzalez P, Lorenzo RA and Carro AM, 2011. Determination of chloropropanols in foods by one-step extraction and derivatization using pressurized liquid extraction and gas chromatography-mass spectrometry. Journal of Chromatography A, 1218, 6878–6883.
205. Rahmaniah, 1999. The effects of a-Chlorohydrin on the gestation of the Wistar rat (Rattus norvegicus). BIOTROPIA, 12, 25–30.
206. Rahn A and Yaylayan VA, 2010. Thermal degradation of sucralose and its potential in generating chloropropanols in the presence of glycerol. Food Chemistry, 118, 56–61.
207. Rahn AKK and Yaylayan VA, 2011. What do we know about the molecular mechanism of 3-MCPD ester formation? European Journal of Lipid Science and Technology, 113, 323–329.
208. Reece P, Crews C, Hasnip S, Hamlet CG, Sadd P, Baxter D, Slaiding I, Muller R, Velišek J and Dolezal M, 2005. The origin and formation of 3-MCPD in foods and food ingredients. Available online: http://www.foodbase.org.uk//admintools/reportdocuments/43_84_FINAL_REPORT.pdf
209. Reece P, 2005. The origin and formation of 3-MCPD in foods and food ingredients. FSA Project: C03017,18,19. Food Standards Agency, London, UK. Available online: http://www.foodbase.org.uk//admintools/reportdocuments/43_84_FINAL_REPORT.pdf
210. Reddy JK and Rao MS, 1987. Xenobiotic-induced peroxisome proliferation: role of tissue specificity and species differences in response in the evaluation of the implications for human health. Archives of Toxicology. Supplement, 10, 43–53.
211. Rétho C and Blanchard F, 2005. Determination of 3-chloropropane-1,2-diol as its 1,3-dioxolane derivative at the microg kg-1 level: application to a wide range of foods. Food Additives and Contaminants, 22, 1189–1197.
212. Roberts SA, Nett TM, Hartman HA, Adams TE and Stoll RE, 1989. SDZ 200–110 induces Leydig cell tumors by increasing gonadotropins in rats. International Journal of Toxicology, 8, 487–505.
213. Robjohns S, Marshall R, Fellows M and Kowalczyk G, 2003. In vivo genotoxicity studies with 3-monochloropropan-1,2-diol. Mutagenesis, 18, 401–404.
214. Rodman LE and Ross RD, 1986. Gas-liquid chromatography of 3-chloropropanediol. Journal of Chromatography, 369, 97–103.
215. Rooney FR and Jackson H, 1980. The contraceptive action of aliphatic diesters of alpha chlorohydrin in male rats. IRCS Medical Science: Biochemistry, 8, 65.
216. Rossi AM, Migliore L, Lascialfari D, Sbrana I, Lorieno N, Tortoreto M, Bidioli F and Pantarotto C, 1983. Genotoxicity, metabolism and blood kinetics of epichlorohydrin in mice. Mutation Research, 118, 213–226.
217. Sawada S, Meckert C, Potkura J, Oberemm A and Lampen A, 2013. Proteomic investigations into mechanisms of nephrotoxicity induced by 3-MCPD and its dipalmitate in rat kidney. Toxicology Letters, 221(Suppl. 28), S196.
218. Sawada S, Oberemm A, Buhrke T, Merschenz J, Rozycki C, Braeunning A and Lampen A, 2015. Proteomic analysis of 3-MCPD and 3-MCPD dipalmitate toxicity in rat testis. Food and Chemical Toxicology2015; 83: 84–92.
219. SCF (Scientific Committee on Food), 1994. Opinion on 3-Monochloropropane 1,2-diol (3-MCPD). Expressed 16 December 1994. Reports of the Scientific Committee for Food (thirty-sixth series).
220. SCF (Scientific Committee on Food) 2001. Opinion on 3-monochloro-propane-1,2-diol (3-MCPD), Updating the SCF opinion of 1994 adopted on 30 May 2001. European Commission, Brussels. Available online: http://ec.europa.eu/food/fs/sc/scf/out91_en.pdf (accessed October 2010).
221. Schilter B, Scholz G and Seefelder W, 2011. Fatty acid esters of chloropropanols and related compounds in food: toxicological aspects. European Journal of Lipid Science and Technology, 113, 309–313.
222. Seefelder W, Varga N, Studer A, Williamson G, Scanlan FP and Stadler RH, 2008. Esters of 3-chloro-1,2-propanediol (3-MCPD) in vegetable oils: significance in the formation of 3-MCPD. Food Additives and Contaminants, 25, 391–400.
223. Segal A, Solomon JJ and Mukai F, 1990. In vitro reactions of glycidol with pyrimidine bases in calf thymus DNA. Cancer Biochemistry Biophysics, 11, 59–67.
224. Sheline CT and Choi DW, 1998. Neuronal death in cultured murine cortical cells is induced by inhibition of GAPDH and triosephosphate isomerase. Neurobiology of Disease, 5, 47–54.
225. Shimizu M, Vosmann K and Matthäus B, 2012. Generation of 3-monochloro-1,2-propanediol and related materials from tri-, di-, and monoolein at deodorization temperature. European Journal of Lipid Science and Technology, 2012, 1268–1273.
226. Shimizu M, Weitkamp P, Vosmann K and Matthäus B, 2013a. Influence of chloride and glycidyl-ester on the generation of 3-MCPD- and glycidyl-esters. European Journal of Lipid Science and Technology, 115, 735–739.
227. Shimizu M, Weitkamp P, Vosmann K and Matthäus B, 2013b. Temperature dependency when generating glycidyl and 3-MCPD esters from diolein. Journal of the American Oil Chemists’ Society, 90(10), 1449–1454.
228. Silhankova L, Smid F, Cerna M, Davidek J and Velisek J, 1982. Mutagenicity of glycerol chlorohydrines and of their esters with higher fatty acids present in protein hydrolysates. Mutation Research, 103, 77–81.
229. Skamarauskas J, Carter W, Fowler M, Madjd A, Lister T, Mavroudis G and Ray DE, 2007. The selective neurotoxicity produced by 3-chloropropanediol in the rat is not a result of energy deprivation. Toxicology, 232, 268–276.
230. Slott VL and Hales BF, 1985. Teratogenicity and embryo lethality of acrolein and structurally related compounds in rats. Teratology, 32, 65–72.
231. Spyres G, 1993. Determination of 3-chloropropane-1, 2-diol in hydrolysed vegetable proteins by capillary gas chromatography with electrolytic conductivity detection. Journal of Chromatography A, 638, 71–74.
232. Stolzenberg SJ and Hine CH, 1979. Mutagenicity of halogenated and oxygenated three-carbon compounds. Journal of Toxicology and Environment Health, 5, 1149–1158.
233. Stolzenberg SJ and Hine CH, 1980. Mutagenicity of 3- and 2-carbon halogenated compounds in the Salmonella/mammalian-microsome test. Environmental Mutagenesis, 2, 59–66.
234. Sun J, Bai S, Bai W, Zou F, Zhang L, Su Z, Zhang Q, Ou S and Huang Y, 2013. Toxic mechanisms of 3-monochloropropane-1,2-diol on progesterone production in R2C rat Leydig cells. Journal of Agriculture and Food Chemistry, 61, 9955–9960.
235. Sunahara G, Perrin I and Marchesini M 1993. Carcinogenicity study on 3-monochloropropane-1,2-diol (3-MCPD) administered in drinking water to Fischer 344 rats. Unpublished report No. RE-SR93003 submitted to EFSA by Nestec Ltd, Research & Development, Switzerland.
236. Svejkovská B, Novotny O, Divinová V, Réblová Z, Doležal M and Velíšek J, 2004. Esters of 3-chloropropane-1,2-diol in foodstuffs. Czech Journal of Food Sciences 2004; 22, 190–196.
237. Svejkovská B, Doležal M and Velíšek J, 2006. Formation and decomposition of 3-chloropropane-1,2-diol esters in models simulating processed foods. Czech Journal of Food Sciences 2006; 24, 172–179.
238. Tee VP, Shahrim Z and Nesaretnam K, 2001. Cytotoxicity Assays and Acute Oral Toxicity of 3-MCPD Esters. Malaysian Palm Oil Board, Kajang, Malaysia.
239. Teng Z and Wang Q, 2015. Chemistry and safety of 3-MCPD. In: Yu L, Wang S, Sun B-G, (eds.). Food Safety Chemistry: Toxicant Occurrence, Analysis and Mitigation. CRC Press. ISBN 9781466597945.
240. Tennant RW, Stasiewicz S, Mennear J, French JE and Spalding JW, 1999. Genetically altered mouse models for identifying carcinogens. In: McGregor D, Rice J, Venitt S (eds.). The Use of Short- and Medium-term Tests for Carcinogens and Data on Genetic and Related Effects in Carcinogenic Hazard Evaluation. IARC, Lyon, pp. 123–150.
241. Thompson ED and Hiles RA, 1981. A method for determining the maximum tolerated dose for in vivo cytogenetic analysis. Food Cosmet. Toxicol., 19, 347–351.
242. Thompson ED, Coppinger WJ, Piper CE, McCarroll N, Oberly TJ and Robinson D, 1981. Mutagenicity of alkyl glycidyl ethers in three short-term assays. Mutation Research, 90, 213–231.
243. Thompson ED and Gibson DP, 1984. A method for determining the maximum tolerated dose for acute In vivo cytogenetic studies. Food and Chemical Toxicology, 22, 665–676.
244. Turek FW and Desjardins C, 1979. Development of Leydig cell tumors and onset of changes in the reproductive and endocrine systems of aging F344 rats. Journal of the National Cancer Institute, 63, 969–975.
245. UK COC (UK Committee on Carcinogenicity of chemicals in food, consumer products and the environment), 2000. Annual report 2000. Available online: http://cot.food.gov.uk/sites/default/files/cot/cotcomcocrep_coc.pdf
246. US EPA, 2005a. US Environmental Protection Agency Guidelines for Carcinogen Risk Assessment EPA/630/P-03/001F Washington, DC.
247. US EPA, 2005b. US Environmental Protection Agency Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens, EPA/630/R-03/003F, 2005. Washington, DC.
248. Ushijima K, Deguchi Y, Kikukawa K, Nomur AT and Adachi TJ, 1995. Analysis for residual 3-chloro-1,2-propan ediol in seasonings after derivatization with phenylboronic acid. Food Hygiene and Safety Science (Shokuhin Eiseigaku Zasshi), 36, 360–364.
249. Van Bergen CA, Collier PD, Cromie DDO, Lucas RA, Preston HD and Sissons DJ, 1992. Determination of chloropropanols in protein hydrolysates. Journal of Chromatography A, 589, 109–119.
250. Van den Wijngaard AJ, Janssen D and Witholt B, 1989. Degradation of epichlorohydrin and halohydrins by bacterial cultures isolated from freshwater sediments. Journal of General Microbiology, 135, 2199–2208.
251. Velíšek J, 2009. Chloropropanols. In: Stadler RH and Lineback DR (eds.). Process-Induced Food Toxicants: Occurrence, Formation, Mitigation and Health Risks. Wiley, Hoboken, NJ. pp. 539–562.
252. Velíšek J, Davídek J, Hajšlová J, Kubelka V, Janíček G and Mankova B, 1978. Chlorohydrins in protein hydrolysates. Z Lebensm Unters Forsch., 167, 241–244.
253. Velíšek J, Davídek J, Kubelka V, Bartošová J, Tucková A, Hajšlová J and Janícek G, 1979. Formation of volatile chlorohydrins from glycerol (triacetin,tributyrin) and hydrochloric acid. Lebensmittel-Wissenshaftund- Technology, 12, 234–236.
254. Velíšek J, Davídek T, Davídek J, Kubelka V and Víden I, 1991. 3-Chloro-1,2-propanediol derived amino acids in protein hydrolysates. Journal of Food Science, 56, 139–142. doi: 10.1111/j.1365-2621.1991.tb07995.x
255. Velíšek J, Davídek J, Kubelka V, Janícek G, Svobodova Z and Simicova V, 1980. New chlorine-containing organic compounds in protein hydrolysates. Journal of Agriculture and Food Chemistry, 1980, 1142–1144.
256. Wade MJ, Moyer JW and Hine CH, 1979. Mutagenic action of a series of epoxides. Mutation Research, 66, 367–371.
257. Wakabayashi K, Kurata Y, Harada T, Tamaki Y, Nishiyama N and Kasamatsu T, 2012. Species differences in toxicokinetic parameters of glycidol after a single dose of glycidol or glycidol linoleate in rats and monkeys. The Journal of Toxicological Sciences, 37, 691–698.
258. Wang NG, Sundaram K, Pavlou S, Rivier J, Vale W and Bardin CW, 1983. Mice are insensitive to the anti-testicular effects of luteinizing hormone-releasing hormone agonists. Endocrinology, 112, 331–335.
259. Weber GL, Steenwyk RC, Nelson SD and Pearson PG, 1995. Identification of N-acetylcysteine conjugates of 1,2-dibromo-3-chloropropane: evidence for cytochrome P450 and glutathione mediated bioactivation pathways. Chemical Research in Toxicology, 8, 560–573.
260. Weißhaar R, 2008. Determination of total 3-chloropropane-1,2-diol (3-MCPD) in edible oils by cleavage of MCPD esters with sodium methoxide. European Journal of Lipid Science and Technology, 110, 183–186. doi: 10.1002/ejlt.200700197
261. Weißhaar R and Perz R, 2010. Fatty acid esters of glycidol in refined fats and oils. European Journal of Lipid Science and Technology, 112, 158–165.
262. Wenzl T, Lachenmeier DW and Gökmen V, 2007. Analysis of heat-induced contaminants (acrylamide, chloropropanols and furan) in carbohydrate-rich food. Analytical and Bioanalytical Chemistry, 389, 119–137.
263. Wenzl T, Samaras V, Giri A, Buttinger G, Karasek L and Zelinkova Z, 2015. Development and validation of analytical methods for the analysis of 3-MCPD (both in free and ester form) and glycidyl esters in various food matrices and performance of an ad-hoc survey on specific food groups in support to a scientific opinion on comprehensive risk assessment on the presence of 3-MCPD and glycidyl esters in food. EFSA supporting publication 2015: EN-779, 78 pp. Available online: http://www.efsa.europa.eu/en/supporting/pub/779e
264. WHO/IPCS (World Health Organisation/International Programme on Chemical Safety), 2008. Uncertainty and data quality in exposure assessment. Harmonisation project document No. 6. ISBN 978 92 4 156376 5.U.
265. WHO/IPCS (World Health Organization/International Programme on Chemical Safety), 2009. Principles and Methods for the Risk Assessment of Chemicals in Food, International Programme on Chemical Safety, Environmental Health Criteria 240. Chapter 6: Dietary Exposure Assessment of Chemicals in Food. Available online: http://www.inchem.org/documents/ehc/ehc/ehc240_index.htm
266. Wilkinson CF and Killeen JC, 1996. A mechanistic interpretation of the oncogenicity of chlorothalonil in rodents and an assessment of human relevance. Regulatory Toxicology and Pharmacology, 24, 69–84.
267. Wittmann R, 1991. Determination of dichloropropanols and monochloropropanediols in seasonings and in foodstuffs containing seasonings. Z. Lebensm. Unters. Forsch., 193, 224–229.
268. Xu X, Ren Y, Wu P, Han J and Shen X, 2006. The simultaneous separation and determination of chloropropanols in soy sauce and other flavoring with gas chromatography-mass spectrometry in negative chemical and electron impact ionization modes. Food Additives and Contaminants: Part A, 23, 110–119.
269. Zeiger E, Anderson B, Haworth S, Lawlor T and Mortelmans K, 1988. Salmonella mutagenicity tests: IV. Results from the testing of 300 chemicals. Environmental and Molecular Mutagenesis, 11 Suppl. 12, 1–157.
270. Zelinková Z, Svejkovská B, Velíšek J and Doležal M, 2006. Fatty acid esters of 3-chloropropane-1,2-diol in edible oils. Food Additives and Contaminants, 23, 1290–1298.
271. Zelinková Z, Doležal M and Velíšek J, 2009. 3-Chloropropane-1,2-diol fatty acid esters in potato products. Czech Journal of Food Science, 27, S421–S424.
272. Zhang X, Gao B, Qin F, Shi H, Jiang Y, Xu X and Yu L, 2013. Free radical mediated formation of 3-monochloropropanediol (3-MCPD) fatty acid diesters. Journal of Agricultural and Food Chemistry, 61, 2548–2555.