Disseminated thrombosis and bone infarction in female rats following inhalation exposure to 2-butoxyethanol

Groups of 10 male and 10 female F344/N rats were exposed to 0, 31, 62.5, 12 5, 2501 and 500 ppm of 2-butoxyethanol (BE) by inhalation, 6 hr/day, 5 days /wk, for 13 wk. Four moribund female rats from the 500 ppm group were sacri ficed during the first 4 days of exposure, and 1 moribund female from the s ame group was sacrificed during week 5. Dark irregular mottling and/or loss of the distal rail were noted in sacrificed moribund rats. Similar gross l esions were noted in the terminally sacrificed females exposed to 500 ppm B E. Histologic changes noted in the day 4 sacrificed moribund rats included disseminated thrombosis involving the coccygeal, vertebrae, cardiac atrium, lungs, liver, pulp of the incisor teeth, and the submucosa of the anterior section of the nasal cavity. Alterations noted in coccygeal vertebrae from the 500 ppm sacrificed moribund rats included ischemic necrosis and/or deg eneration of bone marrow cells, bone-lining cells, osteocytes (within corti cal and trabecular bone), and chondrocytes (both articular and growth plate ), changes that are consistent with an infarction process. The moribund fem ale rat that was sacrificed during week 5 and those female rats treated wit h 500 ppm and sacrificed following 13 wk of treatment lacked thrombi, but t hey had coccygeal vertebral changes consistent with prior infarction and tr ansient or complete bone growth arrest. No bone lesions or thrombi were not ed in the male rats treated with the same doses of BE. In conclusion, expos ure to 500 ppm BE vapors caused acute disseminated thrombosis and bone infa rction in female rats. Possible pathogenic mechanisms are discussed.