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A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats

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Abstract

3-monochloropropane-1,2-diol (3-MCPD), a rat renal and testicular carcinogen, has been reported to occur in various foods and food ingredients as free or esterified forms. Since reports about toxicity of 3-MCPD esters are limited, we conducted a 13-week rat subchronic toxicity study of 3-MCPD esters (palmitate diester: CDP, palmitate monoester: CMP, oleate diester: CDO). We administered a carcinogenic dose (3.6 × 10−4 mol/kg B.W./day) of 3-MCPD or these esters at equimolar concentrations and two 1/4 lower doses by gavage with olive oil as a vehicle five times a week for 13 weeks to F344 male and female rats. As a result, five out of ten 3-MCPD-treated females died from acute renal tubular necrosis, but none of the ester-treated rats. Decreased HGB was observed in all high-dose 3-MCPD fatty acid ester-treated rats, except CDO-treated males. The absolute and relative kidney weights were significantly increased in the ester-treated rats at medium and high doses. Relative liver weights were significantly increased in the esters-treated rat at high dose, except for CMP females. Significant increase in apoptotic epithelial cells in the initial segment of the epididymis of high-dose ester-treated males was also observed. The results suggested that although acute renal toxicity was lower than 3-MCPD, these three 3-MCPD fatty acid esters have the potential to exert subchronic toxicity to the rat kidneys and epididymis, to a similar degree as 3-MCPD under the present conditions. NOAELs (no-observed-adverse-effect levels) of CDP, CMP and CDO were suggested to be 14, 8 and 15 mg/kg B.W./day, respectively.

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Abbreviations

3-MCPD:

3-monochloropropane-1,2-diol

CDP:

3-MCPD palmitate diester

CMP:

3-MCPD palmitate monoester

CDO:

3-MCPD oleate diester

HVP:

Hydrolyzed vegetable proteins

JECFA:

Joint FAO/WHO Expert Committee on Food Additives

NOAEL:

No-observed-adverse-effect level

LOEL:

Lowest observed effect level

PMTDI:

Provisional maximum tolerable daily intake

BMDL:

Lower confidence limit of benchmark dose

BMD:

Benchmark dose

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Acknowledgments

We thank Ms. A. Saikawa and Ms. Y. Komatsu for their expert technical assistance in processing histological materials and Dr. G. Matsui for useful discussion and comments on histopathological analysis. This study was funded by the Food Safety Commission of Japan.

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The authors declare that they have no conflicts of interest regarding this work.

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Correspondence to Kumiko Ogawa.

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Onami, S., Cho, Ym., Toyoda, T. et al. A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats. Arch Toxicol 88, 871–880 (2014). https://doi.org/10.1007/s00204-013-1190-6

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  • DOI: https://doi.org/10.1007/s00204-013-1190-6

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