# reoc

**~DINOtF'OAM** 

## FORIRCINDEXING Cl ( Ci

# +e.. v?l 

### C.; JJ

### ,·15 i



## ~_·•·\l'jl\{ct{

**liiiCII'JIIC~ICICITY** IITaDID IN .... ITB AND IIATIII WITH 

# ......-....:mI'JIIflNI 11M! WITH.IiliT'MCIIIIINTB 

## +vzr-b REVISED 1011SIU


### •I



## 8'8~--7fOoO

# bS'" ,-... I -":' .. :"·-- " •••-"' **·--,~•••:-:--•••:** -:.;- •,7:-:"7"'·::---;• t _ ... ,1: ,:(..
**_~ ··~**  •

**~** •
**-~-·.** I . . - . ..• . ·: • .tt!.. ':... ..+ ·_

**~:.** I 

### fSH61-0~'11

## ....fJ{)#jJ

•• ·---·:-· wo" '-·, 

### VaL.a:u:c::u.. C:HaM•tCAL ICICIRIICIIIIIA'I"I•CIN

**.,~--** 

# •• • Decembt'UI:' 

## 19, 1977 

# ••

. ' 

### \

### '' 

## .' Dire.ctor.of 

### the Office of



### :~·,;.~ :· ··



### '!;.~

## /. 

# =· • • 

# • •••• · 7-\lxt., silb•t8naa• · **clfB~ss7>** 

## . **,~>··**

# · Rtwvf.fi ·

**"<.~~**

## ... g;.s.. 

### :Bnv.iroDIDeJltal 

### P.rotao:l:tcn .AgenDy" ..:; , .· ·F .. · ·. .•

**~()J;,Jl**..

### St%ft8t S.W. . . . t ·•! ,.
**~** 

## £8 1918 · .';



## W...IJili~gton, **D~C**•.· 20460 ;.:;:- . ·.J·. ..&J..· .·.·..a. 

# t: Bel **IJ.,xabU..,cyciLt>'~decllllll** . ( 

# J \'\.... llfl 

## ji:. Also called JriJ:emaste: 100 ' .. ,.:··-

**~~-** 

### . . •. 

## · .....

**~·**

## ····o:.:-

**~ ~-...--:-** 

## :\·. : ·**~-st::** 

## .. ·.)· ·, ,:..' · · •

.....··.·.··•·· 'l'ha•attaoha4.dooumer1t.ill·aul;attte!l for 

### you:.f:Llea •&Dd··lD.

# c1· ·.:plillJ:lce. 

### with 'lSCA 

### INICtion B·(e)

**.t:f.,·~** 

### ... 

### la:tteris.naaaasary••
. ·.. .. . .In DUJIIIIIU'y,. 

### th.ta c!oCWIIIInt. 

### :eporta 

## t:ha :raault of 

### a toxicology 

# ••:t.:uelY· "c:tr the 

### ri!JIQCrd, 

### this doatiiii8Dt 

### .is ideJ),tified. u 

### follona nAOute. 

### 'l'oxicit.y .Studies. in
**~b:Lta** .and 

### Rata" I 

### IRDC 163 ..



## 499, J)eaemJ:aar 7,.1977•.

. 11'& 

### lllak• 

### no jUiigiii8Jlt 

### that 

### t:hill 4!)0\IIIIIUlt
**cc:m~ina** 

### in:foriDation

**C:OJICI~n:4lg** 

### a aubat.antial rillk• 

### We ,resuva 

### .ou: right to **~teat** 

### · **-thlll~propr:Lety** 

### .of 'l'SCA .eect:LQn 

### .8 (e).. . · · · ·

·'l'BL:eh

Bncloaure 

### Sincerely, \'BI;BICQL .CBBMICAL **ccmPO~IOH**



# /~·~fl~~ 'l'homa• 

## a. ·.Loy

**~gar,** 

### . ·..
**~gul,at.ory** 

### Activitias · 

### Bnvi:rQmaental Bc:lenaea and **~latoi:yActt:Lv.tt:Lea**

# ~**~--** "l.Joco46" 

# 1~1+9~'18~**6;,•i.f;~** ·. 

# .,. . . 

## lnternationllll(eseQI!ch

# cu'ld..Dt!J!elopmentCoqJora#on· ;··.

**-~**

.SPOIIISOR.: 

# msx !fA'lB_II.t.AI;: 

### BTUDf !111!mBJlt B1111JBcr1 

### ·' 

# ,t..'., ....·.. ""::...

**Va~:l.col** c:lwliCal eorporat:l.on 

### ftzaaatazlOO Lot 53

**71~902** 163-499 

### Acut:a ToxicitY>St\lOI:I.u :111
.labb:i.ta. aDd Rata• 

# ... •.'

. 

# •• 

# .. ·-··.. 

# •• 

# :a



# -

D:l:r:actoz.

**;o~·** 111balat:ton 

### To:x:lcblo&Y .Appxoyd byl D. CW;ffoxcl 

### Juaup. Ph•D· . .Uaociata.Dbactoz of .Raaeali:Ch 

### Date: DQca.ber 

### 7, 1?77 ·' I..


### .. I.I.· I.II.. 

# v. lnterllational·

## ReseOI'ch lJnd

## .DevelopmentCor]ldratton

**Bj'llopl~·** 

### .II • • • • • • • I a • • 

### -,.'.rUt--Kat:ea:liil • • • • • • • • •CON.TBRTS • • • • • • • • • 

### • • • • • • • Pd.Jaary Bye I.J:ritllt:!,on Study :I.D ll&bb:l.ta , • • , A· 

### *l:bCu;J· • • • • • • • • • • • • • • • • • • • • • • 

### • • • ., 

# ..

# ..

# . • • • 

### • • • •• • • • • B• Raalll:;t;a • • • • • • • • • • • • • • • • • • • • • • • • Pr:l.aary Sllo:I.D..I:r:r:l.t:at:l.oD.Study ill llabll:l.tll • , , , , • • • • • <A-! ·Hatb.Cd. • • • • • • • • • • • • • • • • • • • • • 

### • • • •

**~-·** . .,._U:lta • • • • • • • • • • • • • • • • • • • • • • • • .Acute.,DaJ:Ul .'toxtctty. S.tudy 

### ill labb:Lta , , , , • • , • • 

### • 

### • A·

**Ha~d._** • • • • • • • • • • • -• • • • • • • • • • • • 

### •• RUulta •• 

### 1. Kcn:.tality• 

### • • • • 

### • • • 

### • • • • • • • • • 

### • • • 

### • • • • • 

### • • • • • • • • 

### • 

### • • • • 

### • • • 

### • • 

# . ,

# .. l. 2 3 :3 :6 

### 16 16 16 20 20

**~0** 20 2, ·**l'ha~otoxic** S:I.IPUI • • • • • • • • • • • • • • • • 

## 2:L 3. Bo41-:_,Waiahte -• • • • • • • • -. • • • • • • • • • • • 23 VI.. . .M,ut:a Oral 'J:ox:l.c:l.t:v (LD50) Stwl:v :I.D 

### !lata • • • • • , • .• • • 24

**A~-** llathod -• ,. • • • • • • • • • • • , • • • • • • • • • • • 24 -beU.ltl 0 I I 0 0 0 0 • 0 0 0 0 I 0 0 e 0 0 1. 

### Koi:.ti.lit,. • • • • • • • • • • • • • • • • • • • 

### • • • 

### • • • • 

### • 1·.

**Pba~otox:i.~** ·Sips • • • • • !' • • • • , • • • • • 24 24 

### 24 3, 

### lodJ. -Weilhta • -• • • • • • • • • • " • • • • • • " • 26 'VZ.I. .&cut& ZIJhslat:l.on Toz:Lc:tty.ficwly :I.D ll&ta • • • • , • • • • • 27 

### • 

### • Hac:hocl • • • • 

### 1. AD1Nl8 • 

### • • • • 

## • • • 

### • • 

### • • • • 

### • • 

### • • 

### • • 

### • 

### • • 

### • • • • 

### • • 

### • 

### • 

# . " 

# . .

# .

# ..

# ... 27 27 2,

**4dm1n'l•t~&t10D** ' • • • • • • • • • • • • • • ' • • • 27 

### 3. Duat.··Gtaeration • • • • • • • • • • • • • • • • • • 

### 27 4. 

## on.n-atiou • • • • • • • • • • • • • • • • • • • • 28 .B• -lleau:Lta • -• • • • • , • • • • • • , • • • • • • • • • • 28 1.

**Cbu~** ,J)uat

**C'~DCentJ:at:Lon** • , • • • • , • • • • • • 28 2. . AD:lllal Obaarv&t:l.one • • • • • • • • • • • • • • • • 28 3. B047 Wdahta • • • • • • ,. • • • • • • • • • • • • • 28 4. .::.:.tal:l.ty • • • • • • • • • • • • • • • • • • • • • 28 ""' 

### 16l-499 

## .· 

# 3 

# .... 

# - • 

# - - :

# . 

# •• 

# • • 

### ·

# ... ':, 

# lnternational.Jiesearch.and

# [)evelopnre1Jt.Co1!poration·.

- <

. ' 

## or COH'riH'rS 

### (Continued) 

## ·c. .CQilclua:ton:. • • • • • • • • • • • • • • • • • • • • 

### • • 

### •
. .Tabla 

### llo. 1. Pdmary lye Irritat:Loa - G:roup Obaanatioaa • • • • • • 2. Pl'1mary 

### 1Je Irr:itattaa. ... GJ:Oup Avaraaa Scoru ••• , • 

### 3. Prilllry 

## EJ'a Irr:itat:l.on - Illcl1ndua1 Scorea ••••••• 4. Pr:lllar:v 8k:l.n Irritation.... IM:I.vidual i&bb:Lt

**Sco~.aa** and·- ..score. :calcUlation: · • • • • •

**~** • • . • • • • • • • • • .5. .A.cuta...IDhalatiaa..!oz:Lc:Lty- Hun.Bocly Wa:l.pta of R.ata llcpall.cl· :.to·:.Jl·z:illluuiltet..

### 100. ·• •.••• ·•

**--~** 

### •••••••



### 163-499 

## '!!a 29 

# • 

# • 

# • 

# • • ·8 

# ::-1 9 . ....

# 1·.··· 10-lS


### ..... 19 30•• 4 • 

# lnternatlonalll.esearch and

# DevelopmentCorporatfon Pale 24i1: 

# ,. VI.. .6CIJTB :OW. fODCI'ft' CLD50) S'mDY 

### Dl' ltA!S 

# = A. .MB'rllODt . ll'ive male and 5 f8111111e rata of t:ha C!uu:laa B:f:var CD strain (ob

### tab,ad. from ctllu:lu Jliver Laboraton.u. Portap. Htcb:l.pn) 

### veisbJ.og··&aa. .20tl 

### to 2ll.Sftlllllo were Ulled fo:r 

### tbie stud)'. nMl.·· rata

# waH b.oUIIacl by 

# I

au in



## a:r~:~upa<of 5 rata.per c:aaa. 

### :1.11 .haua;tns vir ....... 

## h ·capa· ..

## :lu·~· : paratun 

### .and bn•1cl1ty. 

### controlled .quartan, Tlwy 

### va1v ..tnt•fnod

**~** 

# 1· ac:cordalu:a vitb.·•the recQIWIIIlat:l.ou ·conta:l.rutd.·in·

### B .•1.w. Pllblicadon · . 

### Ho. 74-23

**(I~.I.B.)** 

### entitled "Guiu 

### for the 

## cu. IJld.U.e of 

### Laboratozy Mful•''• Water amt···P.w:ina...LIIboratory .Chow wera.av.u.,ie·ad 11h:U:IIII, exetl}lt f!'I'E' Ill OV'IIll:llipt .per:l.od 

### pracecl1taa O'E'al.

### edw1n1atrat:lolltdu1'il\g

**~ch** 

### food, but not vatar wu 

### v:Lthbeld. 

## 'l!ha teat .. teriel. trU auapallllacl ::l.n cor:a 

### oil auc1 acbw!

### idatencl 

### ol:'ally byaavaaa

**a~** .a cloaap 

### .laval. of 10000 1111/ka• A.vollllllll,of..

**~o** 111/kaof.body we:l.aht vu adafnict.racl. All rata van obaezved fo)l aortlll:l.t:)' and ph&macotoZ:I.c 

## •:Lau clur:tq 

### the f:Lrst foiiZ' houn aftel:' cloa:I.Da. at 24 boUZ'e ad clally thar.-
.. ' . ' 

# . aftel:',

### foz:o a total 

### of 14 daJ•. Body 

### 1Jdahte .. n ncorcled :l.ll:l.tially 

### 111111 at 

### 7. and 

### 14 clap. 

### B.. JlBSPLTSr l• Mortality:

**~~** of 

### the 10 l:'&ta clied duriu& 

### the 14-daJ obaanation par:l.od. 'lba 

# mi""•"' lathal doee vu foUDd. to 

### be 

### arutu tbllll10000 

### q/q. 2. Pbarmacoto#c 

### B1&• 'lhe fo1l.owig pba'CIII&COtodc ei&IUI wen DbllllrV&d 

### diiZ'ina tba l4-c1&y 

### obaenat:l.on

**par:l.od~** 

### See tha follov:l.ng 

### paaa.
163-499 •.··. . J!'irelllolat:ar 100.1 

### lOOOOg/y
l.hour 

## ·211**~oura** <J)ap 1'"5
.. 

### D&ya·6-7 oaY-8


## .0&1• g.,;l4**1~** 

### 21J houra

4 

## haul:.• J)aya 

### kl4 

## li' Tf 

# !**~-** 

## ! 0 

# e: • = 5/5 2/5 3/5 

### S/S 2/5 2/5 2/5

5/5 

### 4/5 1/5 

### SIS Pap25



# . ·lt II 

## 11 88' 

## B II< 

### 3/5 3/5 3/5 

### 2/5 3/5 

## 11$

1/5 

## . '**.::.:~** 

# • a ;

# .. 

# - - - • 

# - - • 

# •••

• ••



# =**··~·.** t



# .lnternatiolllllResearch..

# and:DeVcelopment.Corporatlon 3. Bocly :Wdlbtac 'rha feillOid.:As bod:y 

### 1nl:isht• were obt•h•cl cJUdns the 14-cla7 obsenat:LC)Q..pu:locJ: 

# »o••

**~t~:ol** 

### 7..,Dtl.y 

### 14-Daf 

### La vet .IIIAi:l.v.l;clual

**W~t:.** 

### Wa:LP.t WUaltt: wtlsa 

### Ia£ ;Jmlb4n: 

### Su: (pau) 

### (E ... ) 

## <'!"'> .. .. 

### 10000 62406 Hale 

### 200 260 268 62407 Hale 

### 201 259 266 62408 Mala 

### 204 274 271' 62409 Mala 

### 202 259 269 62410 Mala 

### 200 253 

### 254 62411 irellale 

### 211 253 256 62412· l'ellale · 

### 203 240 

### 251 62413 l!'eJUJ.e 

### 208 242

**~60** 

### 62414 l!'eu.l.e 

### 201 226 234 

### 62415 I' 

### aula 2115 

### 225 230



# ..

:1.63-499 

# - ... 

# - - : •• : I 

# • I 

# ... ."•: ..... -: 

### .. . .

### ...



# ..• ": " ,·..:.. ···::"., •.,. ' 

## . "'

**~**:· ' '." 

## Jntematlonalkaefll'.ch 

## andDevelopment.·Col!]Joratl()n 

# ·•· 

# -.

...,. 

# LYxt• 'ACII'liLDIJW.l!riCILTOXICIT! STIID!. IH .!AT@ A. MB'DIODt Pap 27 

# .I 

# - 1. ·.

## tn•m·'J.•:; Jiva.•ula and S faal.a. Cb&rlu 

### 11.:1.va.r CD, 

### rata., 

## ••:L&hiDs f:roa 

### 231 to 258

**~1118**•

# vera uead 

### ·111

**~** atudJ. of 

### the CllapOUDd• . 

### .'J:be t:ata vera.houaacl..in41v:l:clual1Y· 111 win"''llllal1

# =-a•• IIDd 

### WJ:e ll&inta:l.uell m a
.. t...,.ratura &r&d hull:lcl1ty.. CODtrolled E'OCllll tbrouahout 

### tJ1a •pra-upoaura .. 

### &114 pciat 

### upoaura pam.:oda. Purll:la 'Laboratory Cblll!IJ •awl 

### wat:er ware auppliacl:.Y,.,lJ:bit1111, 

### ucrapt· dllJ:illl upoaura ill 

### the challlllar. 2,. Admin:f•atrat:ln: 'IIua 

### J:&tll 

### Wlin capcl.1D groupe of. 

### 2. or

**~** by 

### au. 

### 1114 1fira-111Uh upoaura•cqaa. 'lila 

### capa

# •r•p1ac84 :f.lla 160..litar cubica1·•.ta:f.ll

## 1u• ateal. 

## al;all• dwlbar. A. conatant

**chab~r** a:trflav of 7 litera par

# - ·:

· .lllinuta ,.. .uillta:iri.'l4 b)' llltl&ll.l of ·& l:Otat)' CIIAtrifuaal a:l:r:.

**.p~ l.c!ce.~ad**  ll.t the ubauatpailla of the chamber. The cbll!lbar nb•uat 'lfU

**f:l.l~:racl** v:Lth. u.act:lY.. 

### tad~charCII&l. filter



### ·.~~Ad a Cabr.l.\:laa AllaoluC.. f:lltar be- ·fora ba:lua U.cbaraad outa:lda of the lll.boratory. · 3. l?!!!t Gaarattaru The. duat.at:aiiJaphara of the

**co~~pouad** 

### wu •p1uu:atacl 

### .'bJ cl.iapar:a:f.lla 

## the pavclar at a' calculated rata with a. apau:Lall:y

**oout::nu~t:ed** c!.uat

## :a_. arator located 

### nur the 

### c:hamlNar air 

### iDl.at at

**~** top 

### of tha llllpOIIura 

### ch"'*'-1:• .Thia 

### duat<aeurator conaiated of 

### a ravolriq plata with

**~­**

**:l,b~ated.** ''cupa'' for 

### ueupo:o:ot1Da a kllDVD qUIIlt:lty of

**p~** par UD:lt 

### of.t:i.lla 

### f:rcm 

### a :rua:rvo:lr to 

### a ''bl.owhola"• A.t

**~ ''b1avhola** 

**~** the powcle:ra :l.n a i•cup" vera .d.tapa:raed :lnto the clualber by a jet of air blow.lq at tha rate 

### of 2. 

### litaz:a par llinute. The actual. quut:Lty of powder -J:leawnated vu llatarminacl by ·niah:llll the .qUIIlt:li:,o of povdar 111 the ruawoir before and

**~tar** the



### u:pe:rt.ut. The 

### CODcmtratioD. of .the duata :ln ·the chamllar atmosphere vu. calc:ulatad 

### fNil the rat::Lo of the ratu of povda:r. d:l.ealllll:lnat:l.on.to · the .total chuibar airflow (the vol- of air ajactad froa the d.111t aen

### arato:r plua the vol'Ulll of lUke-up air)• 

### 163·499' 

## . ...



## n-n--~

# ··•<.r Pap 4. Observations: Obaan'lltiou for oculU IIDii Dallal :l.ftitat:f:CIIl, :r:up:iratozy cU.atrua .&Dd.martll:l.t:J ware made 

### 4urt_na IDd f!'.. n ll!at:aly•fol.lOir:I.Da; . the 

### 4 how: .axpoma pu:l.odiiDd cW.ly 1:harufta:r: for 14 daya•. IuUV1dual. ·body. n1aht:a:vara racOI'dad. p'l::l.or to the 4 1J,gw: IIXPOIII!I1'e 

### &1111 padod• . •-



### :i.ca.l.ly .thuuftB. :l.u order to detact 

### any tra.aiat:effecta follovira& ••.. .,



## the~~· ··- B

.•. BBSUL'ma 

# !!. .

·. 1. Ol.abar Dult Cllllcentrat:I.CIIl: . ;; A total of 339•65 arolllll of••the

**~** vaa disseminated durins 

## · tAla 4 hour .upoaw:.1 .pe:r:iocl. rhe rata of powder diaatllllf.llatecl

## W.. caJ.-

. culatecl to be



### 1.4~ S'l:olllll .par lllinuta. "rha total 

### challbes: !li'ifl.ov ,..

7 l:l.i:era per 11d.nuta.acl tha>challlbar duat CODCent:r:et:l.cm 

## vae ul.culatad 

## tel be 202.14.q/La "rha chubu etliiDapha:r:a wu atr-.l:y 

### clual:f. 2. .Artt•al:.Obaervat:I.Onll 1 rha 1•-d:tata;:r:upoua of 1:ha rata to •t'llll uped.Mntalai:IIOa-

.pha:r:a 

### wu 1111:acr.... of act:I.'Vtt:y :I.D p:r:auiaa• Aft111: 10 llf.uutu of

.azpoaw:a1 the. rata:aettlad dow. r:r:oa 1 hour -.cl.30 lli1lut:as afta:r: t:Ji.."'•:I.D:Ltiat:I.CIIl of upoaw:a to the ad of 1:ha 4. bow: pa:r:1ocl 1 

## the rata uldob:l.tad .al.:l.aht !l:yapua.. DuriDI the

**l~a:y** Obae:r:vatiOD par:f.o4 IID:Ll.tllla.."PPII&r•d 11.0mal. 

### 3. BO!ty Wlli!lhtaa AUrata CODt:I.Duad to &aiD bo4T vaipt aftar the upoaw:a. "rhe :l.ncli'VtduaJ. bo!l:y va:lpta are prucmtad :l.u Tabla 5. 

### 4. Hortal:l.tJ.a Ro dal.t:h occurracl dul'iDS or dtar the 4 bow: upoaw:a to the uper:l-tal atmoapluara. 

### 163-499 

## !t ..

### ••



### Int~rnational.Research

# ··tllid])evelop1'fl.ellt·Carporatlon· C. CIJIICLUSIOH.a

**~ati011** 

### upoeure of zoat:a to t:he . clwat.at:aoapluazoa of !':I.I:IIIIIUt:er 100 ;t:uUlted ill 

### aliaht

**dyep~~aa** 

### .dU'riDa.expoeUZ'e. Bowawzo, no latsnt advuaellffec:t..wu·. obntvad poatexpoaure• :Busd .upon 

### t:ha 

### :Upar1.aa.tal

**.r~Ul;e,**

### •• 

### tt :I.e c:011c:lwllacl t:hat 

### a aiD&le 4 b9.ur :1nh•Jeti011 u:poeure to t:he duata 1101ild •IIOt likely be bamful. 

### Ill ac:cordance wtt:h the BPA (IDYtrODIIISilt:al Protection



### .~.geuey)

### , teet::f.lls p;daUDaa 162;10.(h)(1)(:L)(ci),·



### l':l.r~ter 100. duat:a would 

# ·I . be · clue:l.ftsd .. a .Cataaory

## .tv

**~o.UDAl••b)r.·**.bh•1•t:i011.. . . · .


### ~

ID 

### accor:Unca wtth t:ha 

### raqutrii!Milt of the J)Cit, 

### .;lfuarcloua Hatari, llaa1ilat::1.0111, 

### 49 .CD Part

**173.34~**

**0** l':l.r.... 

### ter 100 .duata

**~** 

### nOt be · • clau:LUed u •• Clue B Pots011 

### bJ Jnb•let:I.Oil. In 

### accordanca wtth thll 

### requir81111Ult of tba JIISA 

### (!eder:al. B.uar:doua Subetances Ac:t)., Sectioa. 191.1 (f)(2), Pirllluter: 100 ciuat voul.cl not liiiUit the apeeificati0118 for ·a toxic aubatanea bll" :l.llhalat:l.cn1o



### 163-499 "" . / :···

# .. **::I~~I:**

# ..
.. -::,

**~:·** ' 

### ..... . 

## . 

# InternationalResearch and

# Di!velopmentC011p0ralion 

# ·•·' •••• ·:

**Do~ap** Laval. 

### .(!a/ka) 

### 202.1428 p/1

163-499 

# •• • : •••• IncliW:4ua1 Body.Weipte of Bats bpoaecl to

## l':Ln~~Uter: 100•••

**~t'l'Ol** 7-Day 14-,.Da:v Incliv:ldu.el Wetallt . Wuaht Weiaht Bat.Humber Sa: . (E&lllll) (pqa) (&CII)

. ' 

### 68690 Male 2.52 310 360 

# I 

# •• 68692 Male 242 269 301 

# • 6,6!16 Male 246 260 280 

# • . . 

### 68698 Hale 

### 251 259 261 686!19 Hale 242 280 310 68691 !'-1• 2.$8 321 362 .68693 I' 

### tamale 2.54 aD3 

### 350 61695 !'elllllle. 239 251 272 6869.7 !'tamale 238 240 243 68699 !'elllllle 232 244 

### 2.55 . :' 

### .