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Effects of 1,1-dimethylhydrazine on corynebacterium parvum-induced immuno-suppression
controls. The effect of multiple concentrations of UDMH on the induction of PITSinduced SC and the effector function of SC induced by the PITS factor are being examined. The results from these experiments will provide further information regarding the effect of UDMH on SC circuits. This work is supported in part by Grant No. 86-0129 from the Air Force Office of Scientific Research.
E F F E C T S OF 1 , 1 - D I M E T H Y L H Y D R A Z I N E ON C O R Y N E B A C T E R I U M PARVUM-|NDUCED IMMUNO-SUPPRESSION
Melinda J. Tarr,* Richard M. Bauer, and Richard G. Olsen The Ohio State University, Department of Veterinary Pathobiology, Columbus, Ohio 43210
Previous experiments have indicated that 1,1-dimethylhydrazine (UDMH) causes enhancement of certain immune functions upon in vitro or in vivo exposure. The experiments reported here as well as other experiments suggest t h a t one possible mechanism of this immunoenhancement is interference with the "normal" suppressive immunoregulatory activity ofmacrophages, particularly activated macrophages. In one e x p e r i m e n t , mice were injected with C o r y n e b a c t e r i u m parvurn (Cp) to induce macrophage activation, and four groups of mice were treated daily with 0, 25, 50, or 100 mg/kg UDMH during the seven days following Cp administration. All mice were then sacrificed, and t h e i r s p l e n o c y t e s were e v a l u a t e d for l y m p h o c y t e b l a s t transformation (LBT) response to concanavalin A. Splenocytes from mice treated with Cp alone showed a marked decrease in LBT response compared to the response of untreated normal (control) mice (89% suppression and 97% suppression in 24- and 48-h LBT assays, respectively). UDMH treatment at all doses tested caused significant reversal of the Cp-induced suppression; the 24-h LBT response was restored to nearly normal, while the 48-h response was partially restored. In the second experiment, splenocytes from Cp-treated mice were assayed for LBT response in the presence of varying concentrations of UDMH. This in vitro U D M H exposure partially reversed the LBT suppression resulting from Cp t r e a t m e n t at concentrations of 25 and 50 pg/ml, when added at the beginning of a 72-h LBT assay. These results indicate that the abrogation of Cp-induced immunosuppression observed with in vivo UDMH treatment is at least partly due to direct effects of UDMH on the splenocytes involved in the LBT response, and not to effects on other organ systems. Further experiments are under way to determine if UDMH is specifically interfering
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with the suppressor activity of activated macrophages, or if some other cell type (e.g., lymphocyte) is affected. This work is supported in part by Grant No. 86-0129 from the Air Force Office of Scientific Research. C O M P A R I S O N OF M U L T I P L E ASSAYS F O R S K I N I R R I T A T I O N Wally E. Dalbey,* George Cruzan, M.L. Barth, C.J. D'Aleo, and Edward J. Singer Toxicology Division, Mobil Oil Corporation, Princeton, New Jersey 08540
A composite model for skin irritation was developed for simultaneous evaluation of the influence of abrasion, occlusion, and duration of treatment on irritation and for fulfillment of requirements for labeling considerations under DOT, CPSC, OSHA, and EEC. Thus, the number of animals required to address submissions under multiple agencies is greatly reduced compared to performing each test separately. In the composite test, test materials were placed on six sites on the same rabbits: an intact and an abraded site each of which was occluded for 4 h, occluded for 24 hours, or left unoccluded for 24 h. Results are presented from 88 composite tests with 80 petroleumrelated materials. For the materials tested, abrasion of the skin had no effect on the irritation response. Occlusion of the test site generally did not result in dramatic increases in response, except for petroleum refinery streams with a boiling point range below 500°F. Exposure for 4 h rather than 24 h generally resulted in less irritation; however, for individual compounds, the irritation from the 4-h exposure could not be predicted from the response to the 24-h exposure. Of the 80 materials tested, 12 would be labeled as skin irritants under FHSA guidelines, three under OSHA, and 20 under EEC. Of the 20 that would be labeled under EEC criteria, only seven would be labeled under CPSC criteria. Results from skin irritation studies performed under one set of conditions cannot be used to predict the degree of irritation that would be produced under a different set of exposure conditions.
P E R C U T A N E O U S A B S O R P T I O N AND P H A R M A C O K I N E T I C S OF P E R M E T H R I N IN Y O U N G AND A D U L T R A T S P.V. Shah,l* Henry L. Fisher, 2 Martha R. Sumler,l and Larry L. Hall 2 I Northrop Services, Inc. - Environmental Sciences, Research Triangle Park, North Carolina 27709 and 2 U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Percutaneous absorption of permethrin was determined in young (33 days) and adult (82 days) female Fischer-344 rats by employing in vivo and in vitro methods. Carbon-14-
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E F F E C T S OF 1 , 1 - D I M E T H Y L H Y D R A Z I N E ON C O R Y N E B A C T E R I U M PARVUM-|NDUCED IMMUNO-SUPPRESSION
Melinda J. Tarr,* Richard M. Bauer, and Richard G. Olsen The Ohio State University, Department of Veterinary Pathobiology, Columbus, Ohio 43210
Previous experiments have indicated that 1,1-dimethylhydrazine (UDMH) causes enhancement of certain immune functions upon in vitro or in vivo exposure. The experiments reported here as well as other experiments suggest t h a t one possible mechanism of this immunoenhancement is interference with the "normal" suppressive immunoregulatory activity ofmacrophages, particularly activated macrophages. In one e x p e r i m e n t , mice were injected with C o r y n e b a c t e r i u m parvurn (Cp) to induce macrophage activation, and four groups of mice were treated daily with 0, 25, 50, or 100 mg/kg UDMH during the seven days following Cp administration. All mice were then sacrificed, and t h e i r s p l e n o c y t e s were e v a l u a t e d for l y m p h o c y t e b l a s t transformation (LBT) response to concanavalin A. Splenocytes from mice treated with Cp alone showed a marked decrease in LBT response compared to the response of untreated normal (control) mice (89% suppression and 97% suppression in 24- and 48-h LBT assays, respectively). UDMH treatment at all doses tested caused significant reversal of the Cp-induced suppression; the 24-h LBT response was restored to nearly normal, while the 48-h response was partially restored. In the second experiment, splenocytes from Cp-treated mice were assayed for LBT response in the presence of varying concentrations of UDMH. This in vitro U D M H exposure partially reversed the LBT suppression resulting from Cp t r e a t m e n t at concentrations of 25 and 50 pg/ml, when added at the beginning of a 72-h LBT assay. These results indicate that the abrogation of Cp-induced immunosuppression observed with in vivo UDMH treatment is at least partly due to direct effects of UDMH on the splenocytes involved in the LBT response, and not to effects on other organ systems. Further experiments are under way to determine if UDMH is specifically interfering
229
with the suppressor activity of activated macrophages, or if some other cell type (e.g., lymphocyte) is affected. This work is supported in part by Grant No. 86-0129 from the Air Force Office of Scientific Research. C O M P A R I S O N OF M U L T I P L E ASSAYS F O R S K I N I R R I T A T I O N Wally E. Dalbey,* George Cruzan, M.L. Barth, C.J. D'Aleo, and Edward J. Singer Toxicology Division, Mobil Oil Corporation, Princeton, New Jersey 08540
A composite model for skin irritation was developed for simultaneous evaluation of the influence of abrasion, occlusion, and duration of treatment on irritation and for fulfillment of requirements for labeling considerations under DOT, CPSC, OSHA, and EEC. Thus, the number of animals required to address submissions under multiple agencies is greatly reduced compared to performing each test separately. In the composite test, test materials were placed on six sites on the same rabbits: an intact and an abraded site each of which was occluded for 4 h, occluded for 24 hours, or left unoccluded for 24 h. Results are presented from 88 composite tests with 80 petroleumrelated materials. For the materials tested, abrasion of the skin had no effect on the irritation response. Occlusion of the test site generally did not result in dramatic increases in response, except for petroleum refinery streams with a boiling point range below 500°F. Exposure for 4 h rather than 24 h generally resulted in less irritation; however, for individual compounds, the irritation from the 4-h exposure could not be predicted from the response to the 24-h exposure. Of the 80 materials tested, 12 would be labeled as skin irritants under FHSA guidelines, three under OSHA, and 20 under EEC. Of the 20 that would be labeled under EEC criteria, only seven would be labeled under CPSC criteria. Results from skin irritation studies performed under one set of conditions cannot be used to predict the degree of irritation that would be produced under a different set of exposure conditions.
P E R C U T A N E O U S A B S O R P T I O N AND P H A R M A C O K I N E T I C S OF P E R M E T H R I N IN Y O U N G AND A D U L T R A T S P.V. Shah,l* Henry L. Fisher, 2 Martha R. Sumler,l and Larry L. Hall 2 I Northrop Services, Inc. - Environmental Sciences, Research Triangle Park, North Carolina 27709 and 2 U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Percutaneous absorption of permethrin was determined in young (33 days) and adult (82 days) female Fischer-344 rats by employing in vivo and in vitro methods. Carbon-14-
230