Dental Pulp Infarction in Female Rats Following Inhalation Exposure to 2-Butoxyethanol

Abstract

Female Fischer 344 (F344)/N rats (10 per exposure group) were exposed to 2-butoxyethanol (BE) vapors (0, 31, 62.5, 125, 250, or 500 ppm 6 h/d, 5 d/wk, for 13 weeks) to characterize its prechronic toxicity. Dental lesions consisting of bilateral multifocal dental pulp thrombosis, pulp infarction, and odontoblast infarction were noted in the maxillary incisors of 3 of 4 rats from the 500-ppm group that were sacrificed when moribund during the first week of exposure. In addition, 1 rat from the 500-ppm group that was sacrificed on day 32 had similar unilateral incisor lesions but with additional findings consistent with a unilateral maxillary incisor fracture. In contrast, rats sacrificed after 13 weeks of exposure lacked dental lesions. In conclusion, BE has the potential to cause pulp thrombosis and odontoblast infarction in female rats. The apparent variability in response to BE noted in moribund sacrificed vs terminally sacrificed rats was attributed to development of tolerance to BE-induced hemolysis and subsequent incisor regeneration.

Histopathologic changes in dental and oral soft tissues in 2‐butoxyethanol‐induced hemolysis and thrombosis in rats*

“…Consequently, that thrombus formation led to capillary occlusion resulting in segmental sections of the necrotic odontoblastic layer is suggested. The thrombotic effect of 2-BE on incisor pulp in rats was previously described, although the administration of the material was via inhalation compared with gavage in this study (11). Thus, the mode of exposure to 2-BE does not change the organ affected or the severity of the cellular and tissue injuries (29).…”

“…The 2‐BE‐related hemolysis in rats is preceded by massive swelling, change in shape of the erythrocyte, and increased hematocrit, suggesting that 2‐BE targets the membrane of these cells (7, 8). The disseminated thrombosis involves associated infarction of the coccygeal vertebrae, femur, nasal cavity, cardiac atrium, lungs, liver, and eyes and odontoblasts and pulp of the incisors (9–12). Thrombosis was always preceded by change in the erythrocytic shape 30 min post‐exposure, followed by severe hemolysis 4 h later (13, 14).…”

A chemically induced rat model of hemolysis with disseminated thrombosis

“…This cellular swelling leads to an increase in mean cell volume (MCV) and increased hematocrit (7,8). Thrombosis, first evidenced after 2 d of exposure, was associated with infarctions in bone, tooth, eye, and liver (10)(11)(12)(13). Thrombosis formation was always preceded by change in erythrocytic shape at 30 min postexposure, followed by severe hemolysis after only 4 h of exposure (9).…”

2-Butoxyethanol Female-Rat Model of Hemolysis and Disseminated Thrombosis: X-Ray Characterization of Osteonecrosis and Growth-Plate Suppression

“…It has been shown to cause acute hemolytic anemia in Fischer 344 rats upon metabolic activation to 2-butoxyacetic acid (BAA), with the hemolysis occurring more rapidly and severely in female rats (Ghanayem et al, 2000;Ezov et al, 2002). After 3 to 4 days of exposure to the chemical, thrombosis becomes apparent in several organs in the female rats, including the cardiac atrium, lungs, brain, submucosa of the anterior nasal septum, pulp of the incisor teeth, liver, coccygeal vertebrae, and femur (Nyska et al, 1999a(Nyska et al, , 1999bLong et al, 2000;Ezov et al, 2002;Redlich et al, 2004). In addition, acute infarction occurs in the coccygeal vertebrae of the affected females, including that of the growth plate, and necrosis is seen grossly in the distal third of the tail (Nyska et al, 1999b;Shabat et al, 2004).…”