Document KRqRgJ0JNK0L8pM3pKKvY06jw

R & D REPORT REV BfflMP* KE) DOW CHEMICAL U.S.A. RESTRICTED: for use within The Dow Chemical Company only. Tnvimlnqy ResparcbJ-ahoEalfli^i- LABORATORY RRRORT COOK 4HET K-1715-07) * February 8 , 1980 cxrmr- KOtCCM NO* hhL 010 |0 i 010 i 81 6 A THIRTEEN WEEK REPEATED INHALATION STUDY ON ETHYLENE DIBROMIDE (EDB) 56 IN MALE AND FEMALE RATS 0E Uai kUTNOR|>] E K. D. Nitschke, R. J. Kociba, D. G. Keyes, R. C. Childs, and M. J. McKenna PAGES IN FULL REPORT GOC w'i Ll: L J DATA REFERENCES (book and p**>? 78-87 (R*f*r tl*o to wllr nlnd rapon* and publication*.) PATENT STATUS: I i dndotura tubmittad I DESCRIPTIVE SUMMARY WITH CONCLUSIONS: I cam filad i I no patent action raquiiod , | Male and female CDF (F-344) rats were exposed to 0, 3, 10 or 40 ppm pthylene dibromide, 6 hours/day, 5 days/week for 13 weeks for a total of 67-68 exposures in 95-96 days. Scheduled sacrifices occured after 1, 6, and 13 weeks of exposure. Addition al rats were held for a recovery period of 88-89 days and subsequently necropsied. Body weight data was obtained throughout the study and the animals were observed daily for signs of toxicity. Hematology, urinalysis and clinical chemistry parameters were measured. Gross and microscopic pathological examinations were conducted on selected tissues of all animals. Weights of various organs were recorded and organ/body weight ratios were calculated. Rats exposed to 3 ppm EDB showed no consistent effect in any parameter measured. At 10 ppm, EDB caused slight epithelial hyperplasia of the nasal turbinates in animals necropsied after 1, 6 or 13 weeks of exposure; however, 88 days after the last exposure to EDB, no morphological difference from control animals was observed. Rats exposed to 40 ppm EDB showed a definite adverse response characterized by a decrease in body weight gain throughout the 13-week exposure period, an increase in liver and kidney weights after 6 and 13 weeks of exposure, and pathologic effects in the nasal epithelium. At this concentration the nasal turbinates of rats progressed from very slight hyperplasia of the epithelium after 1 week of exposure to EDB to hyperplasia and nonkeratizing squamous metaplasia of the epithelium after 13 weeks of exposure to EDB. After a recovery period of at least 88 days, only a single focus of hyperplasia of the nasal epithelium in one rat and increased relative liver weights were apparent as residual effects from the subchronic exposure. It is believed that these observations would have returned to control limits if allowed a longer recovery period. Therefore, while this study has shown that repeated subchronic exposure of rats to 10 or 40 ppm EDB induces pathologic changes in the respiratory epithelium of the nasal turbinates, a subsequent post-exposure phase revealed a lack of progression of the lesions, with almost complete reversion toward normal histologic appearance of the nasal turbinates. In view of these findings, and the lack of any lesion subsequent to repeated exposure to 3 ppm EDB, short-term repeated exposure to DISTRIBUTION: Sm Sack Pr D0 130639 FONF TDFNT IAI roM e-4<49 these concentrations of EDB would not be expected to result in any long term irreversible effects upon the nasal turbinates or other tissues of the body. f) 130^0 C0NFTDFNTTA1 RESTRICTED: THIS PAGE SHOULD FOLLOW THE DOW SUMMARY PAGE AND BE ATTACHED ONLY TO THE REPORT MAINTAINED IN THE TOXICOLOGY RESEARCH ARCHIVES. pyv LOCATER SHEET TOXICOLOGY RESEARCH LABORATORY HEALTH & ENVIRONMENTAL SCIENCES, USA DOW CHEMICAL U.S.A. MIDLAND, MICHIGAN 48640 FILE NO. K1715-17 DEAD STORAGE NO. 1634 TITLE OF REPORT: A Thirteen Week Repeated Inhalation Study on Ethylene Dibromide (EDB) in Male and Female Rats DATE REPORT ISSUED: February 11,1980 AUTHOR(S): K. D. Nitschke, R. J. Kociba, D. G. Keyes, R. C. Childs, and M. J. McKenna NOTEBOOK(S) - Number and Page(s): 1) 78-87 2) 3) 4) 5) 6) SPECIMENS: 1) 2) 3) 4) ADDITIONAL DOCUMENTS: 1) 2) PATHOLOGY NUMBERS: Control 79-37-79-76 79-197-79-216 Tppm 79-157-79-196, ________ 79-257-79-276 10 ppm-79-117-79-156, ________ 79-237-79-256 40 ppm 79-77-79-116, ________ 79-217--79-236 Slides & Blocks pathology archives LOCATION: ALL DATA ARE SIGNED, DATED, IDENTIFIED BY PROJECT FILE NUMBER, LOGICALLY ORGANIZED, AND ADEQUATELY BOUND IN COMPLIANCE WITH GOOD LABORATORY PRACTICES PROCEDURES. * STUDY DIRECTOR: 'MeywJtA.DATE: $JTZtLsuUfe 27 February 1979 DO 130031 OONF TDFNT TAI DOW CHEMICAL U-S.A. biochemical research lab. TQUEST FOR TOXICOLOGICAL STUDIES NAME OF MATERIAL TO BE TESTED " 1 MIDLAHO, MICHICAH 4S640 1803 BLDG. " "tox. HO. k / 7tr- / 7 riLc nv. .t tfSlL K-I1IS-G7) SUBMITTED BY SUPERVISOR X if)UZ^cAAjL- ESTIMATED COST #81 ?r I(Dt* *nd Byiltfiftp) l(Bvildmf) 1 76f l(Phor*) PROJECT SAFETY COORDINATOR (Date) ACCOUNT number LOCATION GROUP SECTION LEDGER FUNCTION SUB. FUNC SUFFIX PROBLEM NO. LAB. TO BE USED BY <7 /TOXICOLOGY PROBLEM 1NDI. "0-________________ 30BLEM 7 0 o o\o g\c SAMPLE INFORMATION MOLECULAR FORMULA Cj___________ ______ MOLECULAR weight *--------------------------------------------------- i /??. ** structural forhulajor composition ^^ TaIiPlE ftEFEkEHd, SOURCE AND/OR IDENTIFICATION i' " ___1 PROTOCOL COMPLETED 1 ANIMALS ORDERED ^ ANIMALS STARTED ON TEST 1 NECROPSY DONE DATE 1___ | STATISTICS DONE 1 1 CLINICAL TESTS REPORTED 1 1 HEMATOLOGY TESTS 1___ 1 REPORTED 1 1 SLIDES STARTED Date 1___ 1 SLIDES TO BE READY 1 | SLIDES READ 1 1 HISTOPATH reported 1----- 1 WORK ALL DONE, READY I 1 TO WRITE OATE HO 1 30633 OONFTDFNTTAI