Carcinogenicity of Monochloro-1,2-Propanediol (α-Chlorohydrin, 3-MCPD)

Lynch, Barry; Bryant, Douglas W.; Hook, G. J.; Nestmann, Earle R.; Munro, I.C.

doi:10.1080/109158198226756

Cited by 113 publications

(92 citation statements)

References 58 publications

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“…3-MCPD has also been detected in various heat-processed foods, including cereal-derived products like bread crust, toast and biscuits, malt-derived products, coffee, and grilled cheese, as well as smoke-treated products (Bakhiya et al, 2011;Schallschmidt et al, 2012;Teng and Wang, 2014). The toxicity of 3-MCPD is well-documented and includes neurotoxicity (Cavanagh and Nolan, 1993), nephrotoxicity (Velisek et al, 1980), genotoxicity (Lynch et al, 1998), immunotoxicity (Lee et al, 2004) and reproductive toxicity (Lynch et al, 1998). Recently, 3-MCPD was classified by the IARC as group 2B, "possibly carcinogenic to humans" (Bakhiya et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells

Zhu²,

Sun

et al. 2017

J. Toxicol. Sci.

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-3-Chloropropane-1,2-diol (3-MCPD) is a heat-produced contaminant formed during the preparation of soy sauce worldwide. The present investigation was conducted to determine the molecular aspects of 3-MCPD toxicity on human embryonic kidney cells (HEK293). Cell viability and apoptosis were assessed in response to exposure to 3-MCPD using the MTT assay and high-content screening (HCS). DNA damage, intracellular reactive oxygen species (ROS) and apoptosis-related proteins were evaluated. Genes related with apoptosis were detected by qPCR-array for further understanding the 3-MCPD induced cell apoptosis signaling pathway. Our results clearly showed that 3-MCPD treatment inhibits cell proliferation and reactive oxygen species generation. qPCR-array indicated that nine apoptotic genes were up-regulated more than 2-fold and six down-regulated more than 2-fold. Genes associated with the mitochondrial apoptotic pathway, especially BCL2 family genes, changed significantly, indicating that the mitochondrial apoptotic pathway is activated. Death receptor pathway-related genes, TNFRS-F11B and TNFRSF1A, changed significantly, indicating that the death receptor pathway is also activated, resulting in the inhibition of cell growth and proliferation as well as induction of apoptosis. To sum up, the experiment results indicated that 3-MCPD induced HEK293 cell toxicity through the death receptor pathway and mitochondrial pathway.

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Section: Introductionmentioning

confidence: 99%

Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells

Zhu²,

Sun

et al. 2017

J. Toxicol. Sci.

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“…Consequently, there is an increasing awareness that CPN can be a risk factor for the spontaneous development of renal tubule tumors in rats (Figure 4), particularly in the male (Lipsky and Trump, 1988;Hard, 1998). Furthermore, evidence is emerging that certain chemicals can interact with CPN to increase the incidence of CPN-related proliferative lesions (Hard et al, 1997;Lynch et al, 1998;Hard, 2002). This association appears to be restricted to the most advanced stages of the disease process.…”

Section: Introductionmentioning

confidence: 99%

Invited Review: A Contemporary Overview of Chronic Progressive Nephropathy in the Laboratory Rat, and Its Significance for Human Risk Assessment

Hard¹,

2004

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CPN (chronic progressive nephropathy) is a spontaneous age-related disease that occurs in high incidence in the strains of rat commonly used in preclinical toxicology studies, exhibiting a male predisposition. Although increasing in incidence and severity with age, evidence indicates that CPN should be regarded as a specific disease entity and not just a manifestation of the aging process. A number of factors, mainly dietary manipulations, have been shown to modify the expression of CPN. Amongst these, restriction of caloric intake is the most effective for inhibiting the disease process. The precise etiology of CPN and the mechanism(s) underlying its pathogenesis remain unknown, but the long-standing assumption that glomerular dysfunction is the primary basis is challenged in the light of contemporary developments in understanding filtration and postglomerular cellular processing of albumin. CPN is not only a degenerative disease, but also has regenerative aspects with a high cell proliferative rate in affected tubules. Accordingly, evidence is emerging that advanced, particularly end-stage CPN, is a risk factor for a marginal increase in the background incidence of renal tubule tumors. Many chemicals are known to exacerbate the severity of CPN to an advanced stage, and this interaction between chemical and CPN can result in a small increase in the incidence of renal adenomas in 2-year carcinogenicity bioassays. Review of the pathological entities associated with chronic renal failure in man emphasizes that this rodent condition has no strict human counterpart. Because CPN is a rodent-specific entity, the finding of a small, statistically significant increase in renal tubule tumors, linked to exacerbation of CPN by a test chemical in a preclinical study for carcinogenicity, can be regarded as having no relevance for extrapolation in human risk assessment.

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“…A recent review of the toxicological, metabolic and mechanistic data on 3-MCPD (LYNCH et al 1998) showed its genotoxicity in vitro, but there was no evidence of genotoxicity in vivo. It was concluded that tumours reported in certain animals had de-veloped as a result of non-genotoxic mechanisms and were considered not to be relevant to humans exposed to trace amounts of 3-MCPD.…”

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confidence: 99%

Optical isomers of chloropropanediols: mechanisms of their formation and decomposition in protein hydrolysates

Velı́šek¹,

Doležal²,

Crews³

et al. 2002

Czech J. Food Sci.

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Protein hydrolysates produced by hydrochloric acid hydrolysis were analysed for 3-chloropropane-1,2-diol and its enantiomers. It was found that (R)-3-chloropropane-1,2-diol and (S)-3-chloropropane-1,2-diol were present in the hydrolysates in equimolar concentrations. Model experiments with glycerol, triolein and soy lecithin heated with hydrochloric acid in solution showed that these materials were precursors of 3-chloropropane-1,2-diol and 2-chloropropane-1,3-diol and, as expected, yielded racemic 3-chloropropane-1,2-diol. Yields of 3-chloropropane-1,2-diols decreased in the order triolein > lecithin > glycerol. The mechanisms of 3-chloropropane-1,2-diol enantiomers formation during the production of protein hydrolysates are presented and discussed as well as the reaction pathways of their decomposition in alkaline media via the corresponding intermediates, (R)-and (S)-glycidol, respectively. Both epoxides are hydrolysed to glycerol and form a variety of products with hydrolysate constituents.

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Carcinogenicity of Monochloro-1,2-Propanediol (α-Chlorohydrin, 3-MCPD)

Cited by 113 publications

References 58 publications

Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells

Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells

Invited Review: A Contemporary Overview of Chronic Progressive Nephropathy in the Laboratory Rat, and Its Significance for Human Risk Assessment

Optical isomers of chloropropanediols: mechanisms of their formation and decomposition in protein hydrolysates

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