Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 5 No. 5 November 06, 2018 p.167-170
Original Article
Derivation of acceptable daily exposure value for alanine, N,N-bis(carboxymethyl)-, trisodium salt
  • Masayuki Mishima (Research Division, Chugai Pharmaceutical Co., Ltd. /
Masayuki Mishima 1) , Dana Hoffmann 2) , Gaku Ichihara 3) , Satoshi Kitajima 4) , Makoto Shibutani 5) , Satoshi Furukawa 6) , Akihiko Hirose 7)
1) Research Division, Chugai Pharmaceutical Co., Ltd. , 2) Group Safety, Security, Health and Environmental Protection, F. Hoffmann - La Roche Ltd., Switzerland , 3) Department of Occupational and Environmental Health, Tokyo University of Science , 4) Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences , 5) Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology , 6) Biological Research Laboratories, Nissan Chemical Corporation , 7) Division of Risk Assessment, Center for Bioligical Safety and Research, National Institute of Health Sciences
Keywords: Alanine,N,N-bis(carboxymethyl), Detergent builder, Chelate, Cleaning agent, ADE

Use of a non-phosphate detergent builder, alanine, N,N-bis(carboxymethyl)-trisodium salt (ABCT), has been expanded to wide range of washing and cleaning products for consumer uses and industrial applications including cleaning agents in food or pharmaceutical factories. Therefore, determination of acceptable daily exposure (ADE) of ABCT by oral, parenteral or inhalation route based on updated toxicity database could provide valuable information on the risk management for protection of consumers, patients and workers. Here, we proposed the ADEs based on the toxicological information of various in vivo and in vitro non-human studies. Because the full report of each toxicity study was not disclosed, derivation of the ADE was done based on available information mainly from ECHA database. ABCT exhibited renal toxicity as a main effect; however, ABCT did not exhibit carcinogenicity, genotoxicity, reproductive toxicity, irritation, and sensitization. Applying modification factors to the NOAEL of the animal study of longest treatment period, oral ADE was determined as 260 mg/person/day. Taking the oral bioavailability into the consideration of conversion to other routes, parenteral and inhalation ADEs were determined as 50 mg/person/day.