Carcinogenicity study of 3-monochloropropane-1, 2-diol (3-MCPD) administered by drinking water to B6C3F1 mice showed no carcinogenic potential

Jeong, Jayoung; Han, Beom Seok; Cho, Wan‐Seob; Choi, Mina; Ha, Chang-Su; Lee, Byoung‐Seok; Kim, Yong-Bum; Son, Woo‐Chan; Kim, Choong-Yong

doi:10.1007/s00204-010-0552-6

Cited by 35 publications

(22 citation statements)

References 18 publications

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“…In a long-term toxicity study Jeong et al (2010) investigated the carcinogenicity of 3-MCPD in B6C3F 1 mice by administration in drinking water over a period of 104 weeks. Three groups, each comprising 50 male and 50 female mice received 3-MCPD at levels of 30, 100 or 300 mg/L up to day 100, and 200 mg/L onwards (4.2, 14.3 and 33.0 mg/kg bw per day for males; 3.7, 12.2, and 31.0 mg/kg bw per day for females).…”

Section: Long-term Toxicity and Carcinogenicitymentioning

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

127

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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: Long-term Toxicity and Carcinogenicitymentioning

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

127

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“…These data provide support to the premise that these carcinogenic effects are not confined to a specific rat strain. In contrast, no evidence has been found for carcinogenic potential of 3‐MCPD in mice (B6C3F1) after administration in drinking water for 104 weeks 11. Underlying mechanisms that may explain this species specific toxicity have not been elucidated yet.…”

Section: ‐Mcpd(esters): Toxicology and Research Needsmentioning

confidence: 99%

“…It is further oxidized to yield oxalic acid, CO 2 , and chloride. The mechanism of nephrotoxicity of 3‐MCPD has been suggested to be associated with inhibition of glycolysis by metabolites of the β‐chlorolactate pathway 9, 11. In addition, the accumulation of oxalic acid in the kidney also might contribute to chronic progressive nephropathy and subsequent stimulation of renal tubule hyperplasia 11.…”

Section: ‐Mcpd(esters): Toxicology and Research Needsmentioning

confidence: 99%

“…The mechanism of nephrotoxicity of 3‐MCPD has been suggested to be associated with inhibition of glycolysis by metabolites of the β‐chlorolactate pathway 9, 11. In addition, the accumulation of oxalic acid in the kidney also might contribute to chronic progressive nephropathy and subsequent stimulation of renal tubule hyperplasia 11. The metabolites of 3‐MCPD also have an inhibitory activity on glycolytic enzymes in spermatozoa, which may affect sperm mobility together with alkylation of spermatozoa cysteine by 3‐MCPD 11–13.…”

Section: ‐Mcpd(esters): Toxicology and Research Needsmentioning

confidence: 99%

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Identification of gaps in knowledge concerning toxicology of 3‐MCPD and glycidol esters

Habermeyer

Guth

Eisenbrand

2011

Euro J Lipid Sci & Tech

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3-Monochloropropane-1,2-diol (3-MCPD), also named 3-chloro-propanediol or a-chlorohydrin has long been known as a contaminant in certain heat-processed foods, including cereal products, coffee, fish, meat products, dairy products, and sauces on the basis of acid hydrolyzed vegetable protein [1]. There is convincing evidence that fatty acid esters of 3-MCPD are also widespread in processed foods and that concentrations of these compounds exceed those of the corresponding chloropropanols. Whereas toxicology and biological effects of 3-MCPD have been studied quite thoroughly, very little is known about 3-MCPD esters of fatty acids. Recently, it has been reported that also esters of glycidol are formed during the refining of vegetable oils. There are no toxicological data available yet on glycidol esters but glycidol itself as an industrial chemical has been investigated and is known as genotoxic carcinogen found to induce tumors in different tissues after oral application. The following summary provides a condensed overview about gaps in knowledge concerning 3-MCPD esters and glycidol esters and addresses questions concerning toxicological relevance.

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“…Jeong and others () conducted a carcinogenicity study on 3‐MCPD administered in drinking water to B6C3F1 mice and showed no carcinogenic potential. Their investigation lasted 104 wk, with 3‐MCPD concentrations of 0, 30, 100, and 300/200 ppm.…”

Section: Carcinogenicity Study In Micementioning

confidence: 99%

3‐Chloropropane‐1,2‐diol (3‐MCPD) in Soy Sauce: A Review on the Formation, Reduction, and Detection of This Potential Carcinogen

Lee

Khor

2014

Comp Rev Food Sci Food Safe

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Soy sauce, a dark-colored seasoning, is added to enhance the sensory properties of foods. Soy sauce can be consumed as a condiment or added during the preparation of food. There are 3 types of soy sauce: fermented, acid-hydrolyzed vegetable protein (acid-HVP), and mixtures of these. 3-Chloropropane-1,2-diol (3-MCPD) is a heatproduced contaminants formed during the preparation of soy sauce and was found to be a by-product of acid-HVPproduced soy sauce in 1978. 3-MCPD has been reported to be carcinogenic, nephrotoxic, and reproductively toxic in laboratory animal testing and has been registered as a chemosterilant for rodent control. 3-MCPD is classified as a possible carcinogenic compound, and the maximum tolerated limit in food has been established at both national and international levels. The purpose of this review is to provide an overview on the detection of 3-MCPD in soy sauce, its toxic effects, and the potential methods to reduce its concentration, especially during the production of acid-HVP soy sauce. The methods of quantification are also critically reviewed with a focus on efficiency, suitability, and challenges encountered in analysis.

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Carcinogenicity study of 3-monochloropropane-1, 2-diol (3-MCPD) administered by drinking water to B6C3F1 mice showed no carcinogenic potential

Cited by 35 publications

References 18 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

Identification of gaps in knowledge concerning toxicology of 3‐MCPD and glycidol esters

3‐Chloropropane‐1,2‐diol (3‐MCPD) in Soy Sauce: A Review on the Formation, Reduction, and Detection of This Potential Carcinogen

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