TOXICOLOGY AND HUMORAL IMMUNITY ASSESSMENT OF DECAMETHYLCYCLOPENTASILOXANE (D-5) FOLLOWING A 1-MONTH WHOLE-BODY INHALATION EXPOSURE IN FISCHER-344 RATS

D-5 is a low-molecular-weight cyclic siloxane used for industrial and consumer product applications. The objective of the present study was to assess potential toxic and immunomodulatory consequences of inhalat ion exposure to D-5. Male and female Fischer 344 rats (25/group) were exposed by whole body inhalation to 0, 10, 25, 75, or 160 ppm D-5 6 h/ day, 7 days/week for 28 days. Clinical signs, body weights, and food c onsumption were recorded. On the day following the final exposure, 10 rats/group/sex were euthanized and a complete necropsy performed. Foll owing a 14-day nonexposure recovery period, the remaining 5 rats/sex/g roup were necropsied. Body and organ weights were obtained and a compl ete set of tissues was taken for histopathology. Samples were also col lected for serum chemistry, hematology, and urinalysis. Immunotoxicolo gy-designated rats (10/sex/group) were immunized with sheep erythrocyt es (sRBC) 4 days prior to euthanasia and cyclophosphamide (CYP) was ad ministered i.p. to positive controls on days 24 through 28. The anti-s RBC antibody-forming cell (AFC) response was evaluated in a standard p laque assay. Blood was also collected for examination in the anti-sRBC enzyme-linked immunosorbant assay (ELISA). D-5 exposure did not modul ate humoral immunity, while the internal control, CYP, produced the ex pected suppression of the AFC response. D-5 exposure caused no adverse effects on body weight, food consumption, or urinalysis parameters. S erum alkaline phosphatase (SAP) was significantly decreased in females at terminal (12%, 160 ppm) and recovery sacrifice. A significant incr ease in the liver-to-body weight ratio was observed in female animals at the end of exposures (13%, 160 ppm), but was not noted in recovery animals from the same exposure group. In males, significant increases in liver-to-body weight (5%) and thymus-to-body weight (14%) ratios we re also noted at the high dose at terminal sacrifice and were not pres ent at recovery. At recovery only, a significant increase in spleen-to -body weight ratios (14 and 17%; 25 and 160 ppm, respectively) was not ed. At the end of exposure, histopathological analysis indicated an in creased incidence and severity of nasal (Level 1) goblet cell prolifer ation. Focal macrophage accumulation in the lung was also observed to be increased in incidence in both sexes at 160 ppm. At the end of the recovery period, the effects in both of these organs appeared to be re versible. In summary, D-5 inhalation exposure did not alter humoral im munity and caused only minor, transient changes in hematological, seru m chemistry, and organ weight values. Histopathological changes were c onfined to the respiratory tract and appeared to be reversible. The no observed effect level for systemic toxicity, based primarily on the l iver weight changes, was 75 ppm. (C) 1998 society of Toxicology.