## 14 MAY 1987 

# e 

# NTIS One Source. One Search. One Solution.



# u.s. Department of Commerce 

## National Technical Information Service 

## OTS0555281 111111111111111/1111/1111111111111111111111/1111111111111111 

# INITIAL SUBMISSION: ACUTE INHALATION TOXICITY OF METHYL IODIDE IN THE RAT WITH COVER LETTER DATED 

# 08/26/92

# --'.

8ECP**8E}{<2~992-10675**



### 09/02192 OTS0555281

88-920008964

EASTMAN KODAK. CO 05/14/87 

### Microfiche No.

METHYL IODIDE CODING FORMS FOR SRC INDEXING



### Chemical Category INITIAL SUBMISSION: ACUTE INHALATION TOXICITY OFMETHYL IODIDE IN 

### THE RAT WlTII COVER 

### LETI'ER DATED 08126192

# /f61s-' COMPANYSANmzeD

. ORXGINAL PlrBLIC FILE 

### COpy '1 PUBLIC 

### FILE COpy '2 JIM DAIR/Viv:1au 

## see)

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### .:( 

### .' :' "**.:~.,'(**



# ....

# ~,:,:~d::L"cJ):~>**,;;i~E~;;~~i'ii..d** (COMPL:IANCE AUDIT PROGRAM.)



# CONTAINSNO

# cal ORIGINAL
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### Copy 

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i.. ORIGINAL COpy 

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### COPY, 2



# TSCACONFIDENTIAL BUS1NESS 

# lNFORWtT1OM

NOn:: Peter provides data eutry :in 

### CBI'rS for 'the BCe) 

### CAP DOCUllleDU.

## ., -0- .-'

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## 92$E? -2 AliII: l;

## I "Conta3nSJO**~!** • J 

# £1-1 Q
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# 10l?75'

Reportsubmittedby: Eastman Kodak

### Company 343 StaleStreet Rochester, 

### NY 14650 (716) 724-4000 CAP 

### AgreementIdeutifica.:ion

### NumbeI:**(8ECAP~9)** 

### ThereportpenaiDs to 

### iodometbane (synonym: methyl iodide) 

### [CAS #

### 74-88-4] aad

### is being 

### submittedbecauseofhistopathologic 

### effectS observed 

### in anacuteinhalation

### study in raIS. The

### title ofthereportbeing submitted is: 

### -AcuteInhalationToxicityof

### MedlylIodide 

### in the

### Rat-. 

### 11Ie latter report is

### being identified

### as astudy involvingotherthanhuman

### effectS (UDit

### B.B.2.bofCAP Agreement). Groups of5 male aDd 

### 5 female rats

### were exposed to 

### 1280, 1600, or2000 ppm 

### of

### methyl iodidefor 

### one. one hour

### exposure. All deaths occurred within

### 48 bouts 

### after

### exposure. lbeonehoar

# I.e. was 1347

### ppmand 

### 976

### ppmformales aDd

### females, respectively. Gross 

### abDomIali&ies in

### aDimals " dying

### beforestudy

### terminationincludedlunghemon:bages, eD1aIged

### livers, aod

### palekidDey cortices. Bistopalhologic changes 

### inthese

### animals included: irrltation, 

### hemoal1ages, aod

### fDcal necrosisoftheorespirarorytract; 

### hydropic degeaeraliOD, 

### focal aec:rosis, aDd. hemoabage

### oftheliver; 

### hydropicdegenerationand focal 

### necrosis ofthe

### reaal tubules; and 

### spleaiclympbal:icfollicle atrophy. Except

### for

### minimal focal iDfIaminariml ofthelungs in ODe

### female, DO 

### gross

### pathologic cbaDges wereobserved in 

### animals survivingto 

### studyteaDiDaIion. This 

### miterial is used 

### as an int.emlediateand 

### soldas a pure

### chemical. "-=-:;.- .... 0',_.**,~**



### Subject: Reportsubmitted in accordancewith 

### guidelinesestablishedbythe

### U. S. 

### EnviroDmeDtal ProtectionAgency Registrationand AgreementfortheTSCA 8(e) CompliaDc:eAudit 

### Program DearSiror Madam: 

### August26, 1992

# ~=in~=n~~~cs 

# 1IIIIIImllili u. S. Enviroameatal ProtectionAgency 

# I 401 M Street, SW 89928888964 

### Washington, DC 20460 Attn: 

### section 8(e) CoordiDator (CAP

### Agreement)

EAS1lwtAN KODAKCOMPANY • 343 S'DO'E STREET • ROCHESTER. NEW

### "19fIJC "14150

### 230960D 'Ct-86-267

Acut.e Inhalation Toxicity of Ketbyl :Iodide i:l t.he Rat.

Report prepared by: 

### Eagene R. 

### Kenner. Jr•• B.A.
Toxicological Sciences Sect.iOD Healt:h and Environment. 

### Laboratories Eastman 

### ltodak company 2ochest.er••ft 14650

Date of Study COIIIplet.iOD: Kay 14. 1987 

### ..

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

# :" 'J' 

## ......

# .-,

... 230960D %%-86-267



### Acute 'Inhalation 'roxieity of 1!ethyl 'Iodide in 1:he Bat.



### ••========-,••_..,_......... 

# -,.-_.==.....= ..... Abstract. Groups of S male aDd 

### 5 f_le rats 

### were exposed to 

### a t:arzet. concent.rations of 1280. 1600. 

### or 2000 ppm 

### _thyl iodide 

### un) for one. OIle hour exposure. III 

### caused Saspins. excessive teariD&. and letharzy in animals 

### exposed to 1280 ppm. ad 

### S8SPiD&. excessive 

### t.eariD&. usal discurse. cd a sait. disturbance 111 

### animals exposed to 1600 

### or 2000 

### ppm. Bo deaths 

### were detect.ed durins t.'ba one hour exp08Ure. .&11 deaths 

### occurred wit.bin 48 

### hours after tbe 

### exposure. IIOrtality vas 0.**~o.** 

### and 

## 8en. of t.be males and 

## "0. 80. 

### aDd**1~** 

### of the 

### females for 1280. 1600, 

### cd 2000 ppm. 

### respectivel,... Clinical sips 

### of toxicity disappeared wit.bin one weele. 

### Body weisbt pin 

### appeared nomal. except for depressed veiSbt. sain in tbe one 

### female survivins exposure t.o 1600 

### ppm. 'rbe probable cau8e of death for 

### rats dyi.D& after exposure t.o III 

### vas not. det.erained. Compound-relat.ed sross patholou found in animals dyins before the scheduled terminat.iOll of t.be study included IUDS 

### hemorrhases, enlarsed livers. md pale cortex 

### of the 1cidneJ's. Bo compound-related sross patholozy vas 

### found in ani.Jllals 

### survivins to 

### the scbeduled termination of the st.udy, except for 

### one female at 1280 ppm 

### which 

### shoVed minimal focal infl...t.iOll of the l1Jtl&S.**Histopathol~ical** 

### expmtnatiOll of animals 

### which died before the 

### acbeduled necropsy revealed 

### respirat.ory t.ract irritation. focal necrosis. ed_a aDd 

### sero-cellular exudate in tbe 

### nasal p".asea. beIIIorrha&e in the 

### lUl\&s. cd sero-cellular exudate in the trachea. Alao. III 

### produeed hydropic dese:aeratiOll.focal necroais. _d· beIIIOrrbaSe of the liver; b1'dropic deseneratiOll aDd 

### focal llecrcMtia of the 

### renal tubules. cd splenic lymphatic follicle atropbT. 'fbe 

### nasal passaSes. trachea, 

### IUIIIS, liver. 

### m4 1cidDe7S·are aites of toxicit.y at. the concentratioaa 

### tested. 

## .a. no-observed-4ffect. eonc.entration for e1i1dcal sips aDd 

### patholOS7' ... not. determined. IIOrtalitJ' vas seea. at all CODCeDt.ratioaa t.estad. 'rile ODe hour LC10 was 1347 ppIIl 

### _d 976 ppm 

### for mal.. 

## aDd f_l88.**~ct.i.ve1Y.** ODe hour LC],0 

### for .-les aa4 females COIIIbined ...**107~** ppID 

### with a 9S'fa 

### cODf'idenee 

### iDtet'ft.1 from 

### 56S t.o 1266 ppm.

, 

# .-. 

# . .

ore
oroBAu
'th 

### io 

### si (E '.re Ee 

### In

lie' La' (91**de~ at~** --- :: . 

### ..**.-~**

. ' :: (12-1-81) 

### ..thyl iodide IodOlMthane 

# 7.-8a-. C1U 

### 90016. 86-0102 860102:I1 Clt3l: 

### 142 

### U.S 2.3 

### at 20120·C 

### 4.9 330 - II: IISDS 

### 8beet. Chemical ftaIe 

### Alternate ftaIe CAS ReI. 

### Bo. 

### S2ID Bo. Acc. Bo: HAEL 80: Experiment. 

### 80: 8111pirical fo=-ala 1Io1ecu1&r nisht 

### BoiliD& point. (·C) 

### Specific Invit.y 

### (H20 • 1) Vapor deasit.y (Air
- 1) 

### Vapor pre88Ure (torr 

### at a·C)

" '. ''":. 

### Test ProcecSures Tennessee Eastm:m COlIIPany. 

### tiUS8port.• "Dl 

### Sponsor Purpose

Auzgst. 26. 19S6. 

### study 

### Start Date 

### Toxicolo&ical Scieftces sectiorl. Health and 

### EnvirOfl2lll!ll'1t. Laboratories. B-320 

### Xodalt Park. East.mlm 

### XocSalt Company. 

### Rochest.er. B.Y. 1.650. 

### Testins Facility 230960D '1%-86-267



### fte purpose of this Rudy 

### was to determine acute toxicity and the LelO 

### value of methyl io4icSe in t.he rat. 

### folloriD& a _iDele 0Ile 

### hour vapor . 

### exposure.**Acu~e** 

### 11Ihalaticm Toxicity of Methyl :Iodide in t.be 

### I1at

This study 

### vas desironed**~o** 

### determine the or1e 

### bour LelO 

### valose of 

### methyl io4ide. :In all**o~ber** 

### respects. this 

### study 

### was**Cor1cSuc~ecS** 

### by procedures similar t.o the Toxic SUbstances Control Act. Test. Cuidelines (Environmental Prot.ect.iorl qency. September 21. 1985). 

### Guidelines for**Tes~inl** 

### of Chemicals:**~03.** 

### Acut.e l:nbalatiOl1 Toxicit.,. (orzanizat.icm 

### for Economic Cooperation and Development..

# Ita,.. 1981). 

### mut Annex 

### V.B.2. 

### Acute Inbalatiorl Toxicity (Burop8all 

### BCorlO'llliC Coaamity. hptaber. 19&6). 

### Test Article Characterization

..thyl iodide (1I:I). 

### identified as 

## sam 80. C14&. 

### was obtained 

### froll 

### XocSalt Laboratory 

## 81:ut Specialty CbtaIIicals.**~ter.** 1Ir. 

### ..thyl iodide purit.y**(98.~** - ria las 

### c.broIIIatosrapby/f1alDe icmizatiOll cS-.ctiaa 

### anaiJsia) .... det.el:'llliuecS 1>1 Chemical8 

### QualUy senices DivbiOll (CQSD). DcSak Part. JIG 

### attempt vas _de 

### to identify the 

### t.race COIIIPODeDu 1A 

### ample.**~"** 

## "

# ..".. ". 

# I ._'

cbaDI week. 

### this reed cerU 

### were avail was t expec outcc Ident All 'I: All 'I: usilll 

## £lim Body init.i ehaml a.1Il. from t.oxic t.he 1 

## ADm. neere cmD; sevel necre duodl killnl

. . sl_1 1IIlI1Tt over: 

### Oqm pasSI pat.ht**~lel** stoml



### ..**~.~** Stat.:

":£.


### • 1Iort: it.. ' CClIIIpl 

### Inst 230960D D-86-267 

### -2-**E!posu~** Ccrndit.ions



### 1l.ats were chosen for t.his s1:udy. bec.ause they are a COIIIIIIOIl repreasentative species for t.oxicity studies. 3:went.y-one male cd twenty-one female weanliq 

### rats [CRL:coe(SI»Blt] were received from 

### Cbarles tiver Laboratories. Inc•• 

### Wilmi.Dst.on. ltA.. 

### on Ausust. 20. 1986. 

### 1l.ats 

### ware selectee! by clinical ex-m;lW.tion. and 

### accordin& to body weisht 

### usiDs the Auto1llat.ed Animal 'roxicolosy system 

### CULL prosnm. Fifteen 1IIIlle aDd fifteen female 

### rats weishins from 185-208. and 173-1.93 

### S1:'IIZIIS respectively. were select.ed for tbis stud,.. Rousins fte test. material vapor distribut.ion was measured for 18 case positions wit.hin inhalation cbamber B-02. and compared t.o a fixed reference position (Appendix I - Fisure 3). SUbsequently. chamber vapor concentration was measured from the fixed reference position. C'bmIlber vapor ccmcentraticrns were determined four**t.~** per hour by a IA infrared analyzer equipped for autQlllated 8ampLiUS and analysis (Appendix I - PiSUre 2). Cbalber t.empera1:ure and relative 'bumidity was recorded t.wice per hour. and nominal vapor ccrncent.ratioDS were calculat.ed. 'rWice durins eaeb exposure. the eoncent.rat.ion of t.he nonsaseous baeql"OU'ft4 material was 1IIe8SUre4 in the exposw:e cbamlnr. and compared t.o a ncmexposure ebmllber. t.o ccrnfirm that the inhalat.ion exposures were t.o a vapor. and not an aerosol.



### DuriD& the isolation period (five d.,..>. .u.-ls weN srouped 

### boued in su.,eDded stainless 

### steel c:qes in 

### room 1056. On Allpat 25. 1986. 1:ba _imals 

### were released to the stud,. 

### in sooc! bea1tb. 

### Du1:'i.1Is lIonexpo.ure 

### periods. cimals were 

### siDal,. boa.ed 

### in ..

### ltiCOllParimeD'ted stainless steel 1Ile8h cases in room 1.056. The telllperature cd relative bI.idit,. of room 1056 raused 

### frolll 66 to 73-F. &Cd 56 to 6"'-. reqectivelJ'. Bale _d female 

### rat.s ware bousec! on 

### the ... 

### rack. A 12 bow:" (6 ..... to , p •••) p'botoperi04 

### was maintained.**~orbeAt** 

### paper UDder 

### t:bec:qes was Test. Ani1ll8ls A complete description of test. mat.erial vapor seneration. samplins. and maalysis is presented in Appendix I. llet.hyl iodide :,;.apors were produced by meterins t.he test. material dropwise into a Slass bead-packed distillins col\llllD supplied 

### with metered. dried. oil-free compressed air (Appendix 1 - Pi,sure 1). Betbyl iodide exposures vere conducted in a ..20 L stainless steel and slasa; inhalat.icm c1ullDber at. tarset. concentratiODS of 2000. 1600. end USO ppIII.. '.the chamber was maintained at. a lIesat.ive pressure of 0.1 incb water (sause) relat.ive 

### to t'OOIIl air. and at 6 air chaD&es per bour. For eacb Srcrup. male and female rats were exposed si.2Dult&neously in the 8l1li8 inhalation cbamber for Ofte hour. Additional animals were exposed 

## to 1600. USO. and on t.he followins day. 800 ppm methyl iodide. for evaluat.ion of pulmonary function (Experiment 860102P2).Stat;istical Procedures 230960D D:-86-267 

### -3-



### Orzans collected at. necropsy for bist.opatbolosic ........

### inatioa. tnU:'e DUal passases. tracbea, 

### 1Im&s. aDd abnormal 

### oqaus desipate4 

### b1' the pat.bololist.. Abnormal oqaDS 

### collected ineluded 

### eD1ar&ed liven aDd spleens, kidneys wit.b a pale 

### cortex, aDd bemorrbazic areas of tbe
- stomacb. jejUDUlll.. aDd ileum. Identification

Clinical Observations 

## 804)" weiSht. vas measured on Days O. 7, aud 14, and cOlllPared 

### to t.beir initial (Da)" 0) weiSht 

### as a measure of Srovtb. Rats visible t.brouSb clwDber windows were observed for 'IDOrt.alit.)' 

### cSurins exposure. At. about. 8 a.m. and 3 p.m. on eacb workd8)" during the stud)'. each rat was removed 

### from its case by a trained technician and observed for clinical 

### -izm; of toxicity. Observations included. but were not. limit.ed t.o, ex83IIinat.ion of t.he hair, skin. eyes. mot.or act.ivit.y, feces, and urine. All randomization and cullin& was achieved b)" computer-senerated list.s usin& t.he Automated 

### Animal 'toxicology S)"st.em. Jlandqmizat.ion

Pat.holosy Examinat.ions Animals d)"in& before t.be scbeduled necro;>8Y dat.e 

### were iJiIDediately necropsied. SUrvivors were fasted for about 16 hours prior 

### to necropsy 

### an Day 15. Animals ...re anesthet.ized with CO2 aDd ex:sa:nr;uinated by severini t.he post.erior vena cava. 'lbe followinz tissues 

### were examined at. necropsy in all animals: tracbea, l'UD&s, beart. esopbqus. 

### stomach. duodeDUlll, jejunum. ileum, cecum. 

### colon. paDcreas. 

### liver••ali98%'7 SlaDds. kidneys, urinary bladder. pituitary Iland. adrenal s1ands, tbJroid Ilands. parathyroid slands. t.b,..us. spl... _enteric lympb'DOdes. bone 1IIarrOV (femora1.). braiD, t.estes. epidicS)'IIlides. male accesory 11aDds. ovaries. wlina. 

### uterus. and Fallopian 

### tubes. certified feed (.I&va)" Prolab Animal Diet mDi-3000. pelleted) and water. 

### _re available libitUlll only duriD& nonexposure periods. Water 

### vas available throuSh 

### an IlUtomatic vateriD& system. 'lbe source of the water was the Ilonroe Count)" wat.er Authorit.y. 

# .0 known contaminants W8re expect.ed t.o be present in feed or water. which would int.erfere with t.he outcome of this study.
All rat.s 

### were icSentified by a unique JDel;.al ear t,q. cbaD&ed tbree times per week. caees and racks were washed once per week. An;,..ls fram Experiment 860102P2 ...re 'boused in**~e** 

### same room with this study. 

### reed and Water 

# I

..

### "

### 'tbis bee&1: (200, detel BodY Body resp4 prese in 'rl**cont~** weiS): fema] diSt' exhi't Clini lIortli founl!



### - mit (mine (mine Two 'II eXhi't discI 

### remai aft.el rest

### 1 (mine expo! '1'bret ppm 1! One e rat e t.he • of t.l One t (1Din3 fema] 

### senez (mini hour! necre 

### -.- wit.hi whicl Or;! stud] ., 

# •

230960D D-86-267

G. 

### btz. Ph.D. E. Renner• .Jr•• B.A. R. IIau1.ton H•. Vlaovic.**D.V~H** •• 1'b.D. G. .J. Henkinson. D.V.K•• H.S. 2. Scbumacher. H.S. -4-

Basalts Patholosist Laboratory Animal 1!Iedicitae Analytic Chemist Study Director StueSy 'recllnicians

Exposure COftdiUons The low temperature of tbe animal bousiUC 

### room ransed fro:n 66 to 72-F. exceecSins tolerances specified in t.he protocol (73 % 3-F) for the duration of the study. GLP Statement

Tbechamber flovrate vas 43 liters per miDute. yieldins 6 air chan&es per hour not 11 as specified in the protocol. because the air baDcUins system vas modifieeS by addins a vapor scrubbin& system. The followiD& deviat.ions were observed duriuc the study. but. did not affect. its 

### outcome: '1'be final 

### report. data sbeets. aDd all taon-peri.sbable rav dau are stored in the HAEL archives.

SOP aneS Protocol Deviations



### Project Participants

IIe8I1 vapor concentratiODS**(~)** of t.he 

### tat. ut.erial 

### wre U9M71.**1SS4~162.** aDd**1973~4S4** 

### ppm. Exposure CGI:lCeDtratiODS 

### wra comparable 

### to the tarset 

### CODC8Dtrations. BD4 DOID1Dal CcmCea.t:ratiODS 

### wue 19. 17, cd 2SS biaher tba t.he auJ.yzed 

### vapor CODceDtraUcms.**rupect.i~.** Overall -.an ebamber telllperature aDd relative bullidi'ty 

### varied 

### frcra 22 

### to 

# n-c BD4 63 t.o 7BT.. 

### respectively. Particle COUD't 

### data iD4ica'te4 

### that

_ aertJaol of the test material 

### Was tao't preseDt. A lIu.ar7 of c"embar espo8UE'8 conditions is presented in'ra1»le 1. Prior to the study 

### start, c10alLber vapor dist.ribuUon .... det.eal1De4 'by

...surin& the vapo:: CODceIl'traUon at 18 differallt posiUoDa 

### wi'tJain·. iDhalation cb8lll1Msr 8-02. 'l'be

__ 

### CODCeDtratiOll 

### was 394 ppm with.**:.>\j~** coefficient of variation of 2S ('fable 'X af 

### -,-"ix 'X). ." . ........"li



# .

# .;,,;~,;,**~~¥;,,~E;~;::~~4:~>3t~~;l;,;~[.**
-- I**.~** nu study vas conducted**.~cordi~** to: 1) Good Laboratory Practice for Icmclinical Laboratory Studies as prcmulzat.ed by the Food aDd DruS . Administration. 2:' 

### en Part :58. trecember:' 22. 1978. 2) EIlvironmental Prot.ection Acency Good Laborat.ory Practice Staftdards "0 CF]l Part. 792. Iavelllber 29. 1983. except. stability vas not detend.ned. reserve sB1llPles 

### were not collected. and the desree of absorption 

### vas not determined because it 

### vas not applicable. 

# IClinical Sisns 230960D '.1:1:-86-267 

# I

..... 

### :.; ::.:. 

### ;'.:-. -5-

'..t.;.... -'.-

### :'.:-:;;i;' 1600 P2!l
- Durior. exposure. all anblals exhibited sail. disturbauce (minor). s&SPins (minor). and excessive teariq (1D04erate). After exposure. two male rats and t.wo female rats were found dead. 2000 ppm - Durin& exposure. all ani1IIals exhibited saito disturbauce (millor). letbaru (mocSerate). pspiUS (1Ilinor). and excessive 

### t.eari.n& (millor). After exposure. t.hree male and five female rats were found dead. 

### 'this cODcentration level was cbDsen 

### durins earl,. t.ecbDical development. because it was COIIIParable to levels orisinaUy selected for the study (200. '-00. and 800 pPm). SubsequenUy. these levels were increased 

### to determine the LC],0 concentration.**~y** 'Weisht Body weiSbt.s are illustrated in FiSUres 1 

### and 2 for 1II&1es and females. respectivel,.. 'Individual body weiSbts for Days O. 7. and 1.- are presented ill -rable XI. Hean body weishts for Da,.s O. 7. and 1'- are sbowD in 'rable XII. All males surviviD& to the ..d of the auady sbawec! continued veisbt pins t.brouSh the 14 da,. observation periocS.**~ese** veiSht sains 

### were cOlllParable lIIZIIOD& t.he tbree exposure Sroups. only female exposed to 1600 pPm survi.viUS t.o the eDc! of t.he auady. exhibUed 

### a slisht veisht loss on Da,. 

### 7. but subsequently paralleled the weiSht. pin exhibited by survivors in the 1280 pPm srouP. IIortality of rats exposed t.o l!I is presented in 'lable 1:V. 110 deat.bs 

### were found durillS exposure. (Clinical siSns were rat.ed 

### on a four level scale

- mini1llal. millar. 1IIOderat.e. and severe).

'two IDales survived the one bour exposure t.o 2000 

### ppmKI. One 1II&1e exhibited poor seneral body**con~:'tiOD** (minor). S-spiUS (1IliDor). IlAsal discharse (minor). and die4 within 24 bours followiJl& the exposure. remainins 'III8le survived to llecropsy. and showed uasal dischar&e (mi'D.imal) after exposure. but recovered within 2-' bours anc! allPeare!! UOl:'m8l for t.he rest. of t.he study.

'rbree male and three female rats survived the ODe hour exposure to 1600 ppm 

### KI. 'tWO 1IlBle rats exhibited porphyrin uasal discbaqe (mini1D8l). ODe of t.hese 1IlBles also shoved sialorrbea ('JIIinor). %be 

### NIIIIlixW:l& 1II8le rat ex'bibited poor seneral body ccmdiUOD ('JIIinor). 

### All ..lea wrviri.D& the exposure recovered wit.biJl 

### 24 hourS 8DC! appeared 1lOaaal for t.be rest. of t.he study. One female rat exhibited nasal c!iacbar&e (1IIIinor). 

### exc...ive 

### tearinc (:II';n;-l). and died within**2~** hours followiDs the exposure. 

### bother f...le rat showed porphyrin DUal diacbaqe (1D04erate). deUriorat.iD& Senera1 'body CDDdiUou (1IIoinor prosressiD& to ••vue). excessive 

### t.eacin& (miniJllal). hypothermia (moderate). C)'aQosis (mi:nor). cad died 

### wltId:D 24 

### hours followiD& the 

### exposure. 'lbe ODlT female rat. 

### 1lUrri.rin& UIlt1l 'Decropsy sbowd poor seneral body ccmditiOD (mini_]). 'but ncOYM'8d wit.hiu 

### 24 

### hours followiD& 

### the exposure. Except for ••

### Upt. Deck 

### WOUDd. which healed in ODe week. the female 

### was 1lOrmal for 

### the**~C'** of 1:be study. "."

### PatholoST Examinat.ions

":,.'.i 230960D T.t-86-267 -6-



### Gross Patholop;,r
-**Tr~.atment-related** 

### changes were observed in t.he l\J1\&s and livers of male and female rats from tbe 2000 and 1600 ppm 

### exposure sroups. These chan&es were characterized as beJllOrrhaseof t.he 

### lunss, ancS enlar&ed livers. The i'robable cause of deat.h for rats dying aft.er exposure t.o met.byl iodide was not det.ermined. The pat.hologist.'sreport., includin& summary gross and**hiE~opat.holo&y,** 

### and individual animal incidence tables, is 

### presented i':1 Appendix V.

Also seen in males and females of the 2000 ppm 

### exposure &rOUP, 

### was a t.reatment.-related change t.o the kidneys, described as a pale cortex. 80 

### t.reatment-relat.ed changes were seen in males of t.he 1280 

### ppm exposure &roup. 

### Rist.opat.bolosy
- 'treatment.-related 

### ebanses were seen 

### in usal passases, lunss, and livers of males and females 

# of the 2000 and 1600 ppm 

### exposure sroups, and females 

### only from t.he 1280 ppm 

### exposure sroup. These cban&es were described as the 

### presence of exudate. edema, focal necrosis. and erosion of t.he nasal passases i 

### hemorrba&e 

### in the 

### lunss i 

### and hydropic degeneration and focal necrosis iu 

### the liver. Clinical signs are summarized in Tables V and VI for males and females, respectively. Probit analysis of the data is presented in Appendices II, 111. and IV for males. females, and combined sexes, respect.ively. "rhe calculated one hour LC10 was 1347 ppm (95'1. confidence interval 

### = 286 to 1562 ppm) 

### for males and 976 ppm (upper 95'1. confidenee interval 

# =1206 ppm) for females. The lower limit of the confidence int.erval can nat. be calculated for females. because the variance was too hi&b. The one hour LC10 value for the sexes combined was 1074 ppm (95'1. confidenee interval 

### = 565 to 1266 ppm). 

### The probability of mortality at. other concentrations can be estimated from Table I in each of Appendices II, 111. and IV. After the exposure, all female rats exhibited poor &eneral body condition (minimal). One female rat died within 24 hours following the exposure. Another female rat showed deterioratiD& body condition (minimal progressing to moderate). hypothermia (minor), cyanosis (minor), and died within 48 hours following the exposure. "rhe remaining female rats recoverecS within 24 hours and appeared normal for the rest of the study. 1.280 

### ppm - During exposure, all animals exhibit.ed let.bargy (minor), &aspiD& (mnor). and excessive t.earing (minimal). AJ.l animals survived to tbe end of t.he exposure. Five male and five female rats survived tbe one hour exposure t.o 1280 ppm I!I. 

### After the exposure, all of the male rat.s exhibited poor general body condition (minimal). one of tbese males also showed excessive tearin& (minor) . All male rats recovered within 24 bours following t.be exposure and appeared normal for tbe rest of the study.



# ---

### Discussion

'J:he LelO 

### value for males and females combined is 1074 ppm 

### with a 951. confidence interval of 

### 565 to 1266 

### ppm. 2309600 D-86-267

- .. OJ 

# :::..;..j 

# ,'.:

# .<_:~L.,,!**it.;:,;~~i** 

# ---**,~,.** ..... 

# I -7-



### A no-observed-effect level for toxicity 

### was not seen at tbe concentration levels tested. Localized toxic effects were seen as irritation t.o t.he respiratory tract (nasal passages, trachea. and lunss). Systemic effects were observed in liver. kidneys. and spleen. Ifethyl iodide is a strong skin irritant whicb is abscrbed t.hrough the skin (lISDS: 12-1-81.). 

### produci,ns gross edema and skin burns with blist.er formation. The t.oxic responses observed for methyl iodide would be expected of a sttong skin irritant. %he mechanism of _tbyl iodide's toxic action was not determined. 'J:reatment-related changes in kidneys were oberved 

### in two males and 

### one female of the 2000 ppm 

### group, and described as dilatation. by4ropic degeneration, and 

### casts in the renal tubule. III the spleen of one 2000 

### ppm male rat, splenic lymphoid follicles were at.rophied. . Exposure of rats to vapor concentrations of 1.280. 1600. 

### or 2000 ppm 

### methyl iodide. produced concentration-dependent clinical signs of lethargy. gait disturbance. gaspins, excessive tearins. and death. Also seen were t.reatment-relat.ed cbanses to the tracbeas of males and 

### females from the 2000 ppm 

### exposure r;roup. and females only in 

### the 1600 ppm 

### exposure r;roup. %bese chan.Zes were seen as sero-cellular exudate in 

### the trachea.230960D n-86-267



# /7/,.,t**,,~/??** 

## 7! Date Dat.e



# 5.../1-87 Dat.e Dat.e -8-**.~**
. . 'n:


### . "

### ..

# ,

....,d



# ..

# ...,~'(".;",:' ...".:.,',.

# _.;~?ii;'f.::::iVif:ifi2il. 

# ,;-I' - Sipature Page 

# 4 mL

# YR4?rmM

## .Q**2Ui~** R. Renner 

## J:C. 

# s.l Inhalation 'tee'hnieian

## 1 eli 

### I 

# .. I 

# • 

# - I ,,; 

# - I .; 

# - 1 

# !liz



# i 1 111



### .. 15

tI'I 

# i 1 

# .. ,',

........ 2309601) U-a6-267 nGDBE 1

.'ISZ • 

### -.z .'112 "**.'~** . Cs.MI:!) 'sueJU!' o\IlIlI .'ga • '8IOZ Body Veiz,ht of Bal.. Jxpo_ed t:o wet-btl 'Iodide

.'l1t 

# - % 

### I! 

### ;:


# .. - i iii III 

# .. • 

# - z 

## ! a: 

# ... S •••

### I lit;



# ! 

# ; I W 

# .e

III 

# i I 

# • I N


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### I

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### .... 

# - I 

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# -

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## .·zzz 

# · 

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### .'**,;:j~** 

### ....... ",'

# ,.,. - • "lIZ 

### .....,. -,- "

BodY Weicht; of .....1811 '!!posed 

### too ..thy! Xodi4• 23096(1) 'U-86-267 nGUU 2



# ......

•••


# i


# .. I 

# .. ft)

### !~~ 

### is ......**a::ft)**



# ...... >u UTABLE 'I .. -...

.-"**-.~** 4 1

2 1

2 

### 22.2:1:0.0 2641 2000



### 6S.0±0.O 1973:1:454 Study Bo: 

### 86010211 Accession Bo: 

### 900164 Compound 80: 86-0102

2

2 1


### 22.2:1:0.0 1



### 1874 1600



### 63.0±2.8 1554:1:162

2 2 1 1



### 1472 1280



### 22.5:1:0.4

77.5:1:0.7 1190±71 1094-1258 

### 1336-1702 1336-2316

lparticle count. data indicat.e4 tbat. an aerosol 

### was 1lOt pnseD.t.. 2calculat.ed from daily chemical cOllSUlllPt.iOll an4 

### total airflow. STUDY StnD!ARY OF EJPOSUBE COllDI'rIOlllS 

### 230960D D-86-267



# • Extremes of Daily !leans



# • lIean:l: 

### SD

!leaD: 

### ± SD Compound: lletbyl 

### iodide

Bumber of Exposures Analyzed**Coneent.ra~ion** (ppm) 

### !lean1

### ± SD**Tat"&e~ COncen~rat.ion**  (ppm)



### blat.ive**HumicSit.~ (~)**  

### Temperature (-C) 80111inal 

### Concent.rat.ion (ppm) lIean ZFemales



### 10 16 18

· -{ ·**-~**



### ·**'~** b

b b b 

### 10 202 b 

### 182 b

b b 2309600 1%-86-267



### 26 27 27 29 

### 30 16 17 18 19 20

207 212 

### 233 195 192 220 b b

21 22 

### 23 24 2S 

### 177 187 183 197 176 189 :'83 198 184181

186 188 197 

### 192 180 'tABLE II Individual Animal BodY weigbts and Percent. Weilbt. Gain

b

a Wei&bt. 

### in &rams b All 

### animals died 

### wit.hin 48 

### hours aft.ef' exposure. c CWeil,bt. on Dar 14
- Weilht. on Dar 0) x 100 (we1&ht 

### on Day 0)230960D D-86-267 WLEnY Ani'llllll Bean Body lleil'ht.s8
1211._ 1...... 

# ......

PPM 

# .... 

# .... GRCU'-II liIQP-tI GfIIClUJ-II IIEEX , 1 

### DAY I 1tt.1 33.2 33.1 4.2 11.5 5._

5 5 5 

### DAY 7 2M•• 222.7 b 12.4 15.3 5 3 

## wmc. , 2 

### DAY 14 2IS.3 2112•• 12•• 11.4 5 3

1218.... 1....... 2118....



# .... .... ..... GRCU'-F CRCUI-F GIIa.P-F WEEK , 1 

### DAY 

# • 117.2 1U._ 1••1 I .• 

## a.1 1.4

5 5 5 

### DAY 7 212.2 

### e d 15.7 3 WEEK , 2 

### DAY 1. .217.3 

### 13.1 3



### • WeiSht. iD &r'8II8. 

### b ODe male IlUrvived 

### unU1 the 

### .cheduled Decropq. 

### ca DOt: 

### cslcu1ate 

## -.c. e ODe fema1. 8Urvived UDtil the 8Cheduled DeCrOpq. CIIQ 

### DOt calculate 

### -.n. IS All animals died at tbe IQd 

### of exp08Un. ·-.**:~**



## .. ".

,

# , .:;

### tABLE 

### 1Y

5/5 4/5 2/5 215



### .,5 0/5 . Day 14

5/5 4/5 2/5 2/5 0/5 

### Day 2

2000 pp!!! 

### 1600 pp!!! 

### 1280 pp!!!

SIS illS 2/5 illS 1/S 

### OIS Day 1

5/5 2/5 2/5 

### o/s 0/5 

### Post Exposure 

### Day 0 

### Darin& Exposure

;,-; 

## .....-

;4**:.::;.~~**

# "L"~b;,.~;.,i.ii~;~fii!il;L;;!'j;tiL~~;~FtI I I 230960D '%%-86-267

cumulat.ive 1I0rtalit.y of Bat.s Exposed to lIet.lwl Iodide fot" ODe Hour

'1otal ..........••..•..•.••....•....•.••.••...••.•.••••••••••.••••.•• 9110 

### Females 0/5 Bales 0/5 4f'ot.a.l •••••••••••••••••••• .,.......................................... 6/10 Bales 0/5 

### Females 0/5 total ••••.••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 2/10 

### BAles 0/5 

### Females O/STABLE V
2000



### 11 11-15 11-15 11-15 11-15

11. 12 11. 13-

15 9 8 ].600



### 6-10 6-10 6-10



### 8. 10 6. 7 23096011 D-B6-267 SU:amary of Clinical Sims
- Bales& Location Clinical 

### Sips 1280 b Bervous System letbarU 

### 1-5c sait disturbance Lunss 

### Supins 1-5 Eyes 

### excessive teariDs 

### 1-5 Body 

### as a

Whole seneral conditiou poor 

### 1-5 IIoutb sialorrhea Bose porphyrin discharse dischaqe BaS 

### deatbd
a·S rats/sroup b Tarset concentratiou in ppm. 

### c llulllber assisned to 

### tbe affected rat. d 110 animal.$ died dUri..ns 

### exposure. Animal 

### Bos. 6. 7. 

### 11. 

### 13-15 died after exposure. Lethaqy. 

### sait disturbance. excessive tear1ns. saapias. sialorrhea. aad' 

### nasal discharse were seec. eiUler 

### durl.ns or just after exposure. 'rbe 

### severity of 'the 

### clinical sisns vas concentration dependeDt. Abnormal clinical sips resolved within 48 hours. end did not reappear 

### durinc**~e** 

### obaervation period.

### 26-30 26-30 26-30 2000 26-30 26-30



### 23 22 24 22


### 21. 22.**2~.** 2S 

### 22.23

22 

### 21-25 21-25 21-25 1600



### 19
19. 20 16-20 16-20



### 19 19 16-20 summary of Clinical SilmS
- Femalesa



### discoloration. blue exeessi

### ve tearins letbar&Y sait. 4isturb8Dce Clinieal Sims


### sasping

porpbyrin 4iscbarse discbarse JIIOS 

### ceneral condition poor hypothermia unkempt haireoat Body 

### as a Whole 2309600 

### D-86-267 .,**.~~** ...

Locat.ion

. '_:':**~'1** ....." 

# ;J

, . ol' .. 

### Tail Bose
Skin of 

### Beck wound



### Letbarzy. cait disturbance, excessive teari.Ds. caspius. and DeSal discbaqe vere seen either 

### darius or just. after 

### exposure. %be 

### "verit.y of**~e** 

### clinical 

### sisns was 

### coneentration dependent. Abnormal clinical 

### sisDs resolved rit.biu .8 hours. 

### and di4 not reappear duriDs the 

### observat.ion period. a 

### S rats/croup b 

### Tarset eoncentration in ppm. C 

### Bumber assisned to t.he**affec~** rat.. 

### d 50 animals 

### died duriUS exposure. Animal Bos. 19-22. 2.-30 died after exposure.