Toxicity value for 3-monochloropropane-1,2-diol using a benchmark dose methodology. 2009

Myungsil Hwang, and Eunkyung Yoon, and Jayoung Kim, and Dong Deuk Jang, and Tae Moo Yoo
Division of Risk Assessment, Department of Risk Assessment Research, National Institute of Toxicological Research, Korea FDA, 5 Nokbun-dong, Eunpyung-ku, Seoul 122-704, Republic of Korea.

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.

UI MeSH Term Description Entries
D006965 Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells. Hyperplasias
D007684 Kidney Tubules Long convoluted tubules in the nephrons. They collect filtrate from blood passing through the KIDNEY GLOMERULUS and process this filtrate into URINE. Each renal tubule consists of a BOWMAN CAPSULE; PROXIMAL KIDNEY TUBULE; LOOP OF HENLE; DISTAL KIDNEY TUBULE; and KIDNEY COLLECTING DUCT leading to the central cavity of the kidney (KIDNEY PELVIS) that connects to the URETER. Kidney Tubule,Tubule, Kidney,Tubules, Kidney
D008297 Male Males
D008452 Maximum Allowable Concentration The maximum exposure to a biologically active physical or chemical agent that is allowed during an 8-hour period (a workday) in a population of workers, or during a 24-hour period in the general population, which does not appear to cause appreciable harm, whether immediate or delayed for any period, in the target population. (From Lewis Dictionary of Toxicology, 1st ed) Maximum Permissible Exposure Level,MPEL,Maximum Permissible Exposure Concentration,Allowable Concentration, Maximum,Allowable Concentrations, Maximum,Concentration, Maximum Allowable,Concentrations, Maximum Allowable,MPELs,Maximum Allowable Concentrations
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D005506 Food Contamination The presence in food of harmful, unpalatable, or otherwise objectionable foreign substances, e.g. chemicals, microorganisms or diluents, before, during, or after processing or storage. Food Adulteration,Adulteration, Food,Adulterations, Food,Contamination, Food,Contaminations, Food,Food Adulterations,Food Contaminations

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