Document xgDDpOR1wXgqmY5gJX9qQXy1

m April,.19, 1265 i-lr. Kcttult L. H&taSsr', . Pharmaceutical 'Division Nordsn Laboratories, Inc. Lincoln, Uebras-ka 63591 ' . "* - * ; Dear Mr. Mouror: =' Your letter of April 14, .1966. concerning .toxicity data for Arocior 5^60 since 1957 has been referred to me for reply. The only toxicity .data, that-we-have .'accumulated since 1957 is- as .follows: . . . --' . ' , The abutoral^-LD^ for nixed .se:c;Tats v;as 19,203 . (16,300-22,500) ng/icg when Arocior 5460 was administered . as'-a 33*3vp-ercant-'.soiuti'on>in- corn oil. The survival . time was 3 to 5 clays 1 The toxic sighs observed were . severe diarrhea, loss:of appetite, lethargy and. eventual ' collapse. Gross, autopsy revealed inflammation of the hJ gastric mucosa with liver-and.renal congestion. - By . this route of administration Arocior. .5460 was classed . as practically non-toxic.;. . . ..... The application of >a 33*33; Percent :solution :in corn oil of Arocior "5460 to;.-the clipped, intact 'skin of female . rabbits indicated, that., tho minimal, lefciial do.se wap , -. . ' greater. than* 7940-1 close- v?a- applied* over*'a-- ' 3 day period'so as to prevent run-off of the sample. . -The only untoward signs observed from this dose were reduced appetite' and moderate lethargy. By this route / of administration Aroclo'r. 5ii60 ;V;ae...c];assed. as..practically non-r toxic. ' ' .. EX P-2388 Page 1 of 2 PCB-ARCH-EXT0375633 Mr'.-KeraifccrL. Mourer"" -2? April, 19, 19.66 /In;,a.-subacut2*derrnal ctudy;,,v;hen>a 50vpercent (w/v) corn -oil solution ol*:'Ar:oe:i,or^5^6^ .was^applied to the... clipped lnta3ct/-^icin^of;,ra^blito'`''at:^os;asi--o-f*'100.i:. . 500 arid 1000 rgArg.XdSy for "20 days, fchsw dose of MOO- ^SA'S fail ad- to, adversely affect the body' weight. ""The weights were comparable to the controls. However*- - the 500 and 1000 ng/kg doses produced slight to moderately adverse effects, respectively, upon . . . body weight. . > ~ '1. V" ' .A - \ The 20 day subacute dermal, LD50 v;as :250 mgArg*: There was generalised inactivity, ..weakness, lassitude and- loss of appetite from the 500--and-1000 mg/Jcg/day doses. These: signs were not observed in animals which received, the 100 mg/kg/day dose. Erythema progressing5to sutdermal hemorrhages wa3 noted among-animals, of'all test doses. The severity of reaction was related;to the magnitude . of the' dose:. During ..the*: 14 day observation period . following the dosing the application site of the animals which received the -100 mg/ieg/day' dose became necrotic. . By the end of this period the necrotic areas began to . . slough off revealing new?skin. ' The hematologic data and the results ofsurine analysis ; for the test groups in this subacute -study, compared well, with those of trie, treated.-control graupianinals. .. V Therewere no. significant gross 'or"*microscopic pathologic .. tissue alt crati0ns ..no bed among:.; the surviving, test .-. animals sacrificed at the conclusion of the test which wore attributed to .absorption of the test material. ... Findings' for"the tost animals were comparable to,those seen iu the treated control animals. . I trust , the. above.-will b.e helpful and if we may, be. o further - service >please"':contact me -directly . . -. . . * - ` ` . -- . Sincerely, - ' . Wlpiara^H. Hunt,, Ph.D. Toxicologist . Medical Department. . bcc.: . Depress*;,,. EX . P-2388 Page 2 of 2 PCB-ARCH-EXT0375634