Document EdyyN9kZEQRb1z6GG1Eo7vDVR

r ... .......... ............ - ,H 4 f7 ce: J. M itchell, J r ., P la stics J . A. Zapp/G. J . Stopp s, H a sk e ll Lab J. F. Morgan, H a sk e ll Lab. C. F. Reinhardt, H askell Lab. H. Sherman, H a s k e ll Lab. In tu rn , H a sk e ll Lab May 8, 1970 7 . S . HILTON FLUOROCARBONS DIVISION WASHINGTON WORKS PARKERSBURG, W. VA. TOXICOLOGICAL INFORMATION ON Cg APTC I'm s o r r y f o r th e d e la y in r e p ly in g to you r re ce n t re q u e s t f o r an e v a lu a tio n o f em ployee h a za rd from CgAPFC in y o u r p o ly m e r iz a tio n o p e r a t io n s . I hope t h i s l e t t e r w i l l s u f f i c i e n t l y a m p lify my te le p h o n e .comments o f A p r i l 1 6 . As I u n d erstan d i t , you c u r r e n t l y a r e u s in g C-APFC, b u t a r e p h a sin g i t ou t and w i l l be u s in g CgAPFC f o r c a . 80 p e r c e n t o f the.T eflon! p o ly m e r iz in g and c h lo r e n d ic a c id f o r the o t h e r 20 p e r c e n t . AHT i s n o t u se d . I have summarized th e a v a i l a b l e t o x i c i t y in fo r m a tio n on CgAPFC and c h lo r e n d ic a c id In th e a t ta c h e d t a b l e . We have even l e a s in fo r m a tio n on CGAPFC and some o f i t i s i n t e r n a l l y c o n f l i c t i n g . The In fo rm a tio n i s in a d e q u a te f o r a complete e v a lu a tio n o f the t o x i c i t y o f th e se m a te r ia ls . Your p r in c ip a l exposure i s b y s k in a b s o r p tio n . We h ave no s k in a b s o r p tio n t o x i c i t y in fo r m a tio n on any o f th e t h r e e . CgAPFC and CGAPFC ca u se l i v e r e n la rg em e n t, b u t we d o n 't know what i s the lo w e s t re p e a te d o r a l d o sa g e t h a t w i l l cau se i t . We have no re p e a te d o r a l d osage s tu d y t o i n d ic a t e i f CgAPFC o r CgAPFC a ccu m u la tes i n th e body t o t o x i c l e v e l s . We do n o t know th e e y e o r s k in i r r i t a t i o n p o t e n t ia l, f o r CgAPFC o r CgAPFC and we do n o t know w h e th e r th e l i v e r en largem en t e f f e c t o c c u rs o n ly in r a ts or in o th er sp e cie s as w e ll. Except fo r the knowledge th a t ch lo ren d ic acid does not cause li v e r enlargem ent, our data fo r th is m a te ria l are s im ila r ly s k e tc h y . We have no in fo r m a tio n on th e t o x i c i t y o f d i s u c c i n i c a c i d p e r o x id e . To answ er th e i n i t i a l t o x i c i t y q u e s tio n s on CgAPFC, I s u g g e s t th e fo llo w in g tests: I . Determ ination o f le t h a l co n cen tra tio n by s in g le o r a l doses and determ ination o f low est o r a l dosage causing li v e r enlargem ent in rats (histopathology o f liv e r o n ly ). ` 600 EID072196 w. E. Hilton Page 2 May 8 , 1970 I I . Accumulation in the r a t to cause li v e r enlargement--- (two-week subacute, o ra l d osin g). I I I . Accumulation in the r a t to le t h a l le v e ls (w ith h is t o p ath o logic exam ination o f tis s u e s , o ra l d o sin g). IV. Recovery stu dy fo r regressio n o f li v e r enlargem ent in the ra t a fte r o ra l dosing. V. Single ad m in istration sk in absorption t o x ic it y ( th is is done in the ra b b it and can be done w ith enough ra b b its to measure l i v e r enlargem ent). VI. Repeated a p p lica tio n sk in absorption study w ithout h i ato pathology but w ith exam ination o f liv e r s . VII. Prim ary sk in I r r it a t io n and s e n s itiz a tio n ( th is i s done in the guinea p ig and can be done w ith enough guinea p ig s to determ ine i f there is s ig n ific a n t liv e r enlargem ent). V III. Eye i r r i t a t i o n . IX. Repeated (two-week^ in h a la tio n a d m in istra tio n w ith h ls t o pathology. X. C oord in ation o f the above program, in terim re p o rts and fin a l evaluation. & 750 *ikoo *1000 * 800 1500 .1200 ` 300 2000 +15* The l i v e r en largem en t e v a lu a t io n i n th e above s t u d ie s has n o t added m a t e r i a l l y t o th e c o s t . In a d d it io n , v e re c cronend a 90- d a y fe e d in g s tu d y in r a ts and dogs in clu d in g a o n e-gen eration rep ro d u ctio n -terato gen stu d y in r a ts . T h is w ould c o s t c a . .*30, 000. T h is s tu d y i s r e companded b e cau se we have no c h r o n ic stu d ie s on any o f th e se su rfa c ta n ts and no adequate stu d ie s in non-rodent s p e c ie s . Depending on th e r e s u lts o f t h is 90-d ay stu dy, a p ro tra c te d stu d y in dogs o r dogs and r a t s , m ight be In d ica te d . None o f th e above s t u d ie s would a llo w us t o s e t an a tm o sp h e ric l e v e l o f Cq'VPEC t h a t w ould be h y g i e n i c a l l y a c c e p ta b le on a c h ro n ic b a s i s . T h is w ould re q u ire a ch ro n ic in h a la tio n stu d y . The e x a c t c o s t would depend on f i n a l t e s t d esign , but i t would be in excess o f *100,000. 000087 EID072197 DWS 10313534 W. E. H ilton Page J May 8, 1970 I f you can e lim in a t e co n tin u ou s expoao re t o CgAPPC b y i n h a la t i o n , none o f the repeated in h a la tio n stu d ie s would be n ecessary. S im ila r ly , e lim in a tio n o f repeated exposure b y sk in absorption would elim in a te the need fo r a repeated sk in absorption t o x ic it y study. I suggest a v i s i t by our in d u s tr ia l h y g ie n is t, Mr. Morgan, as the most b e n e f ic ia l n ext s te p to determ ine the e x ten t o f the t o x ic it y te s tin g program. This would a ls o g iv e us b e tte r in s ig h t in to developin g th e n ecessary t o x ic it y te s tin g program fo r chlorendic a cid . RSW: ljm Attachment RICHARD S. WARITZ RESEARCH MANAGER, BIO-SCIENCES GROUP 000088 EID072198 $1.036535 SUMMARY OF TOXICITY nATA$OH CqAFFC AHD CHLOHENDIC ACID Teat O ral Approximate L e th a l Dose O ral li v e r enlargement O ral Subacute CgAFFC 670 mg/kg 60-90 mg/kg ND Approximate L eth al Dose 0 .8 mg/L (caused liv e r enlargem ent) Chlorendlc* Acid 5000 mg/kg** No 8 x 1000 mg/kg caused seven deaths (10 ra ts used) HD C h loren dlc* Anhydride 1000 mg/kg not le t h a l Ho 8 x 1000 mg/kg caused s ix deaths (10 ra ts used). HD (R espiratory ir r ita n t in ra ts). ND - Not determ inad * - Data from Hooker Chem ical ** - Iajporatory found 2250 mg/kg t - / O 1 KJKJ i EID072199 000089 Q W 5 1038536 *