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Carcinogenic Activity of the Flame Retardant, 2,2-Bis(bromomethyl)-1,3-Propanediol in Rodents, and Comparison with the Carcinogenicity of Other NTP Brominated Chemicals
June K. Dunnick
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
James E. Heath
Southern Research Institute, Birmingham, Alabama 35255
Daniel R. Farnell
Southern Research Institute, Birmingham, Alabama 35255
J. David Prejean
Southern Research Institute, Birmingham, Alabama 35255
Joseph K. Haseman
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Michael R. Elwell
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Several brominated chemicals have been shown to be multisite-multispecies carcinogens in laboratory animals, and in this paper we report that the flame retardant, 2,2-bis(bromomethyl)-1,3-propanediol (BMP) is also a multisite carcinogen in both sexes of Fischer 344 rats and B6C3F, mice. BMP was administered continuously in the diet for up to 2 yr to rats at doses of 0, 2,500, 5,000, or 10,000 ppm and to mice at doses of 0, 312, 625, or 1,250 ppm. Interim groups of rats were examined at 15 mo. An additional recovery group of male rats received the chemical for 3 mo at 20,000 ppm in the feed, and then the control diet for the remainder of the study. Chemical exposure caused neoplasms of the skin, subcutaneous tissue, mammary gland, Zymbal's gland, oral cavity, esophagus, forestomach, small intestine, large intestine, mesothelium, kidney, urinary bladder, lung, thyroid gland, seminal vesicle, hematopoietic system, and pancreas in the male rat; mammary gland, oral cavity, esophagus, and thyroid gland in the female rat; lung, kidney, and Harderian gland in male mice; and subcutaneous tissue, lung, and Harderian gland in the female mouse. The recovery group of male rats presented with the same spectrum of treatment-related neoplasms as in the core study. In this recovery group, BMP (at 20,000 ppm) caused irreversible effects at numerous sites after 90 days of exposure that was not detectable by histologic examination, but without further exposure resulted in carcinogenic responses at 2 yr. BMP is mutagenic in the salmonella test, but it was not determined if the BMP-induced effects that eventually lead to development of neoplasms at multiple sites are the same in both species and in all organ systems affected.
Key Words: Brominated chemicals • 2,2-bis(bromomethyl)-1,3-propanediol • carcinogenesis
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Toxicologic Pathology, Vol. 25, No. 6,
541-548 (1997)
DOI: 10.1177/019262339702500602
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