Inhalation toxicity of cyclododecatriene in rats

Cyclododecatriene (CDDT, CAS No. 4904-61-4) was tested for its inhalation t oxicity in rats following repeated exposures. Male rats were exposed nose-o nly to CDDT for 6 hr/day, 5 days/wk for a total of 9 exposures over 2 weeks . Particular attention was paid to neurotoxicologic endpoints. Concentratio ns of 0 (control), 5, 50 and 260 ppm were studied. The 260 ppm chamber cont ained both vapor and aerosol while the 5 and 50 ppm chambers were vapor onl y. Four groups of 10 rats each were used to measure standard clinical signs and growth, clinical pathology (including hematology, biochemistries, and urine analysis), and tissue pathology. Another 4 groups of similar size wer e used for neurotoxicity testing. In the standard toxicity groups, 1/2 of t he rats were sacrificed 1 day following the 9th exposure; the other half un derwent a 2-week recovery period prior to being sacrificed (recovery group) . During the exposures rats inhaling 260 ppm had a diminished or absent res ponse to an alerting stimulus. Irregular respiration and lethargy were obse rved in these rats immediately following exposure. These signs were rapidly reversible and were not seen prior to the subsequent exposure. Body weight s in rats exposed to either 50 or 260 ppm were significantly lower than the corresponding controls. No compound-related clinical pathology changes wer e seen in any of the test groups and tissue pathology effects only occurred in the nasal tissue. In rats exposed to 260 ppm, minimal degeneration/necr osis of nasal olfactory epithelium was observed in rats examined immediatel y following the exposure period. This change was not seen in the recovery r ats. Functional observational battery (FOB) assessments and motor activity (MA) evaluations conducted after the 4th and 9th exposures on rats from all test groups, and specific neuropathologic evaluation on perfused brain, sp inal cord, and skeletal muscle from rats exposed to 260 ppm failed to demon strate any specific neurotoxicity. Outward signs of sedation were seen at t he top level tested. Under the conditions of this test the no-observed-adve rse-effect level (NOAEL) was determined to be 5 ppm based upon a reduced ra te of body weight gain in the 50 ppm group. No specific neurotoxicity was d etected and the histopathologic response was limited to reversible changes in the nasal epithelia in rats exposed to 260 ppm.