Toxicity value for 3-monochloropropane-1,2-diol using a benchmark dose methodology.

Abstract

3-Monochloropropane-1,2-diol (alpha-chlorohydrin, 3-MCPD) is a well-known contaminant that has been detected in a wide range of foods, and that is principally generated in foods prepared by hydrochloric acid hydrolysis, such as acid-hydrolyzed vegetable protein (acid-HVP). 3-MCPD is nephrotoxic to animals at high doses and induced tumors in some organs in both sexes of rodents. NITR have recently reported on the carcinogenicity of 3-MCPD in SD rats that were exposed for 2 years to drinking water. We considered that the kidney was the main target organ for 3-MCPD in SD rats and that renal tubular hyperplasia was the most sensitive endpoint. Benchmark dose analysis of the dose-response data for renal tubular hyperplasia in male and female rats exposed to 3-MCPD in drinking water for 2 years was conducted. We applied this to the benchmark dose (BMD) methodology to yield a point of departure for developing tolerable daily intakes (TDIs). The calculated BMDs and lower-bound confidence limits (BMDLs) for the critical endpoint were estimated using the seven different models. Predicted doses associated with 10% extra risk were calculated. The smallest Akaike's Information Criterion (AIC) was used in selecting the appropriate model. The model chosen by AIC for males was the logistic and for females it was the multistage. In summary, the predicted BMD(10) and BMDL(10) were 1.21 mg/kg bw/day and 0.87 mg/kg bw/day for the male rat incidence data, and values for female rats were 26.31 mg/kg bw/day and 19.47 mg/kg bw/day. In this study, the BMDL(10) of 0.87 mg/kg bw/day for male rats was suggested as the point of departure for deriving the human tolerable daily intake level of 3-MCPD.

• Authors: Myungsil Hwang, Eunkyung Yoon, Jayoung Kim, Dong Deuk Jang, Tae Moo Yoo
• Journal: Regulatory toxicology and pharmacology : RTP (Regul Toxicol Pharmacol) Vol. 53 Issue 2 Pg. 102-6 (Mar 2009) ISSN: 1096-0295 [Electronic] Netherlands
• PMID: 19133308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• alpha-Chlorohydrin
• Glycerol

Topics

• Animals
• Benchmarking
• Carcinogens (administration & dosage, toxicity)
• Dose-Response Relationship, Drug
• Female
• Food Contamination (analysis)
• Glycerol (administration & dosage, analogs & derivatives, toxicity)
• Humans
• Hyperplasia (chemically induced)
• Kidney Tubules (drug effects, pathology)
• Male
• Maximum Allowable Concentration
• Mice
• Models, Statistical
• Neoplasms (chemically induced)
• Rats
• Rats, Inbred F344
• Rats, Sprague-Dawley
• Sex Factors
• alpha-Chlorohydrin