BUTYLBENZYLPHTHALATE: HAZARD CHARACTERIZATION AND EXPOSURE–RESPONSE ANALYSIS

Abstract

Butylbenzylphthalate (BBP) has been assessed as a Priority Substance under the Canadian Environmental Protection Act. Effects that occur at lowest concentrations in rats are increases in organ to body weight ratios, primarily for the liver and kidney, and histological effects on the pancreas and kidney. In studies with protocols specific for investigating reproductive toxicity, adverse effects on testes have been reported, although at dose levels higher than those that had effects on other organs, such as liver and kidney. Although results of available studies do not support the conclusion that BBP is estrogenic, the potential for other endocrine-mediated effects cannot be precluded at this time. A tolerable daily intake of 1300 μg/kg body weight per day has been derived, based upon the lower 95% confidence limit for the benchmark dose associated with a 5% increase in the incidence of pancreatic lesions in male rats in an oral subchronic assay.

ACKNOWLEDGMENTS

To ensure transparency and defensibility of the health assessments, a cut-off date for consideration of new data is specified so as not to compromise the integrity of several stages of internal and external review. Data obtained after April 1998 were not considered for inclusion in this assessment.

Sections of the supporting documentation and Assessment Report that served as the basis for preparation of this paper were reviewed by D. Blakey (genotoxicity) and W. Foster (reproductive and developmental toxicity) of the Environmental and Occupational Toxicology Division of Health Canada. Sections of the supporting documentation pertaining to human health were reviewed externally by R. Nair, Solutia Inc., primarily to address adequacy of coverage. Accuracy of reporting, adequacy of coverage and defensibility of conclusions with respect to hazard characterization and exposure–response analysis were considered in written review by staff of the Information Department of BIBRA International and at a panel meeting of the following members, convened by Toxicology Excellence for Risk Assessment (TERA) on April 27, 1998, in Cincinnati, Ohio: M. Abdel-Rahman, University of Medicine & Dentistry of New Jersey; J. Christopher, California Environmental Protection Agency; G. Datson, The Procter & Gamble Company; J. Donohue, U.S. Environmental Protection Agency; M. Dourson, TERA; D. Proctor, ChemRisk; R. Rudel, Silent Spring Institute (submitted written comments; not able to attend panel meeting); and A. Stern, New Jersey Department of Environmental Protection.

A Concise International Chemical Assessment Document (CICAD), which was prepared on the basis of the content of the Assessment Report, was also externally reviewed by R.A. Andersen, Norwegian University of Science and Technology, Norway; T. Berzins, National Chemicals Inspectorate, Sweden; R. Cary, Health and Safety Executive, United Kingdom; R. Chapin, National Institute of Environmental Health Sciences, USA; R.S. Chhabra, National Institute of Environmental Health Sciences, USA; J. DeFouw, RIVM, The Netherlands; R.J. Fielder, Department of Health, United Kingdom; P. Foster, Chemical Industry Institute of Toxicology, USA; S. Jordan, Food Directorate, Health Canada; P. Lundberg, National Institute for Working Life, Sweden; C. Nilsson, Institute of Environmental Medicine, Sweden; P. Ridgeway, Health and Safety Executive, United Kingdom; E. Soderlund, National Institute of Public Health, Norway; F.M. Sullivan, consultant toxicologist, United Kingdom; K. Svensson, National Food Administration, Sweden; S. Tarkowski, Nofer Institute of Occupational Medicine, Poland; J. Taylor, Agency for Toxic Substances and Disease Registry, USA; G. Ungvary, Jozsef Fodor National Centre of Public Health, Hungary; and A. Wibbertmann, Fraunhofer Institute for Toxicology and Aerosol Research, Germany. Subsequently, a revised version of the CICAD was approved at a meeting in Tokyo on June 30 - July 2, 1998, by a Final Review Board composed of R. Benson, Environmental Protection Agency, USA; T. Berzins, National Chemicals Inspectorate, Sweden; R. Cary, Health and Safety Executive, United Kingdom; C. DeRosa, Agency for Toxic Substances and Disease Registry, USA; S. Dobson, Institute of Terrestrial Ecology, United Kingdom; H. Gibb, Environmental Protection Agency, USA; R.F. Hertel, Federal Institute for Health Protection of Consumers and Veterinary Medicine, Germany; I. Mangelsdorf, Fraunhofer Institute for Toxicology and Aerosol Research, Germany; M.E. Meek, Health Canada, Canada; J. Sekizawa, National Institute of Health Sciences, Japan; S.A. Soliman, Alexandria University, Egypt; D. Willcocks, Worksafe Australia, Australia; and P. Yao, Chinese Academy of Preventative Medicine, People's Republic of China.