### 14 JUN 1983 

# N

One Source. One Search. One Solution.

U.S. Department of Commerce 

### National Technical Information**s~** 

# . - OTS0545948 111111111111111111111111111111111111111111111111111111111111



# INITIAL SUBMISSION: ONE-MONTH INHALATION TOXICITY OF METHYL IODIDE TO MALE AND FEMALE SPRAGUE-DAWLEY RATS WITH COVER LETTER DATED 080792Microfiche No.

.' 8ECP 8EHQ-Q892-9501 OTS0545948

08127/92 88-920007803

MONSANTO CO 06114/83

METIIYL IODIDE CODING FORMS FOR SRC INDEXING

Chemical Category 

### INITIAL SUBMiSSION: ONE-MONTH INHALATION TOXICITY OF 

### METHYL

IODIDE TO MALE AND FEMALE SPRAGUE-DAWLEY RATS WTI1I COVER

DATED 080792COpy 

### I 1 PUBLIC FILE

COpy # 2 JIM DARR/Vivian 

# COMPANY SANrnzeo

. ORIGINAL PUBLIC FILE TDAS (BLAn:)

CBIC (Vera)



## .. ORIGINAL (COMPLIANCE AUDIT PROGRAM) 

### sce)

COpy 

### I 1

COpy I 2



# TSCA 

# CONfIDENTIAL ·BUSINESS 

# INFORMAnON

NOTE: Peter provi.des data entry in OIl'S for the See) CAP Documents.The information included herein is characterized as follows:

'. 

# I 

# I 

# I ',<**i,.i_-,,::~:i** T**,~.;** "

.. :**~;** ':

88928887883 IHIT 88/27--92 

# 1I1111111111 

# Illllllll**6tJh-o~9}--** 

# 9su/

DCcntains 

### NO CBI"



# , Sine:erely,

# ~~ J. R. Condray Director, Regulatory Management (314) 694-8883 Information/Study Type

- II.B,2,b/Subcbronic: Toxicity Study

Information/Study Identification

- ONE-MONTH INHAlATION TOXICITY OF METHYL IODIDE TO MALE AND FEMALE SPRAGUE-DAWLEY RATS ML-81-Q84**Pr~ous** TSCA. 8(e) or PMN submissions, if any, for the referencc c:bemical can be fOUlld in AppcndixA Chemical Identity

- 

### IOoo METHANE; methyl iodide; CP 10340

Chemical CAS No.

- 000074884

Identification of Reportable Endpoint; SIGNS OF NEUROTOXICITY Registered Mail Return Receipt Requested

Attention: Section 8(e) a>ordinator (CAP Agreement) 

# Monsanto

Llonsatto Company
8CIO N. Lindbergh Ilo.JIevard Sl. Louis, Mi5:ID.lri 63167 Phone: (314) 694-1000 August 7,1992

Document ProccssiDg Center (TS-790) Office of Toxic: Substances Euvironmenta1 Protection Agency 401 M Street. SW Washington, DC 20460

It should be noted that this summary is not all inclusive. Therefore, it may not higbligbt aD adverse effects that EPA may judge to meet TSCA 8(e) reportability. This submission/report does
not contain confidential business information. This submission is pursuant to the TSCA Secrion 8(e) Compliance Audit Program and CAP Agreement #8ECAP-00'36. Triplicate Copies Enclosed

### JUN 141983

C0TfcQra tjfEPS IOMEH fF:HT. COJDIV EPTJLOCAnONI

___**-=~F~IN~AL~..""",..._---REPORT** rTYPe OF REPORTl



# , ABSTRACT: Four groups of 10 male and lO female SpragueDawley rats per group were each exposed to 0, 0.l42, O.42l or O.BlO mg methyl iodide per liter of air in lO m 3 inhalation chambers six hours per workday over an approximate four-week period (21 exposure days). Rypoactivity, hyperactivity, irritation of the eyes and/or nose, breathing difficulties, and tremors, twitches and/or convulsions were observed during exposure. Irritation of the eyes, hypoactivity, nasal discharge, respiratory difficulties, abnormal appearance of the skin and fur and a singular occurxence of trem::lrs

were observed in the non-exposure periods. These gross signs of toxicity were concentration-related in that they were observed primarily in the high exposure group and to a lesser extent in the midexposure group. Compound and concentration-related decreases in mean body weight were noted in the midand high exposure groups. Five test material-related deaths occurred in the high exposure group: 1 spontaneous death (1 female) and 4 sacr:i:ficed in extremis (2 

### males, 2 females). No exposure-reIi'ted

C.CONTINtI'ED ON m:vERSE SIDE) AUTHORS: Thomas L. Blank TITLE: One-Month :I.nhaJ.ation Toxicity of Methyl Iodide to Male and Female Sprague-Dawley Rats REPORT NO.: MSL-3012

JOBIPROJECT NO.: 810006/MI.-8l-084

DATE: June 7, 1983 0 

## '*'

III 'C ..,oj 'tl 0



### ....

.-l >. .c

III aI**~~** IU 1401= 0 >. >'Ill**~.-l ..,oj~**  o IU

.... Q XI o III**Eo4~** C' s:: III**O~**

.... 0. ./.Jtn IU

.... al c: Ill

.... III**'2~** .-l a:I Hill tz. .c ..:l ./.J'C c: 

# = CII o ca III E 1 41 0 Ill

.... .c C III Ero 0:&



### en a: 0 

## ::w**I-~** :ll- <i=

N .-l 0 M I ..:l It)

ci ci 

### z z
> a. w a::

R·loealAl

### Number of pages: 78 

## S//1/X"3 Date

-, .:',':"

... ;:'.**-~-** .. "\ ."-:.:. ,":..;.::.i

# "",,~;,:;:'~i:;;~:.kc.

- I 

# I EBL 810006 PAGE 1

'(' .

. -;- .. \.' ,.:::;',"

" 

# '.

June 7, 

### 1983 

# 1f\ \\1J. 

# e**~A** 2'-\ M_

### ,qK~**M~q. RoTc5'm\\-G""'r-o-u-p-""'Le-a-d~e-r-----=-;L..:..~-D~!...a** **t~e'** Inhalation Toxicology MONSANTO COMPANY ENVIRONMENTAL BEALTB LABORATORY 645 s. NEWSTEAD ST. LOUIS,**~ISSOORI** 

### 63110

# ~~d~ Thomas L.**B~nk,** 

### Study Director Study Number: 810006 DMEB Project Number: ML-8l-084 One-Month Inhalation Toxicity of Methyl Iodide to Male and Female sprague-Dawley Rats

Report Issued: Author and Study Director: Thomas L. Blank Submitted to:**~onsanto** 

### Industrial Chemicals (Sponsor) Through: R. 

## s. Nair, staff ToxicologistSOMMARY



### Four groups of 10 male and 10 female Sprague-Dawley rats per group were each exposed to 0, 0.142, 0.421 or 0.810 mg methyl iodide per liter of air in 10 m3 inhalation chambers six hours per workday over an approximate four-week period (21 exposure days). Hypoactivity, hyperactivity, irritation of the eyes and/or nose, breathing difficulties, and tremors, twitches and/or convulsions were observed during exposure. Irritation of the eyes, hypoactivity, nasal discharge, respiratory difficulties, abnormal appearance of the skin and fur and a singular occurrence of tremors were observed in the non-exposure periods. These gross signs of toxicity were concentration-related in that they were observed primarily in the high exposure group and to a lesser extent in the mid-exposure group. Compound and concentration-related decreases ir. mean body weight were noted in the mid- and high exposure groups. Five test material-related deaths occurred in the high exposure group: 1 spontaneous death (1 female) and 4 sacrificed in extremis (2 males, 2 females). No exposure-related gross pathological lesions were observed in either the test material-related deaths or terminal sacrifice animals. A -no-effect- exposure level for male and female rats receiving 21 six-hour exposures of methyl iodide over an approximate one-month period was 0.142 mg/l of air.



# '.

EHL 810006 

### PAGE 2

"

-

.. -3

# ~~;,.:~L~~t~~~~~. 

# I I I 

# I-**'~'.-:4**

. . .. ,'.:.,:.;-:-,: "_".

_ _

# :.·:".{{_~~ __ :1,·_:

..

# ,.~-:;_·-~.~~,~:~.·~.~~.>·~~,~.~~;~.£.&l~_

.

_**·'J...r]~::1.·'·~:_.'·.::.** _ . -**--~,-** -**-..=-:-~~** 

# -- TABLE OF CONTENTS

TITLE PAGE

SUMMARY

TABLE OF CONTENTS

INTRODUCTION

MATERIALS AND METHODS



### ·Test Material .Test System: Animals and Husbandry .Exposure System .Procedures for Monitoring Methyl Iodide in the Inhalation Chamber ·Animal Observations and Body Weights -Gross Pathology -Statistical Procedures -Comments on Study Conduct Versus Protocol

RESULTS



### -Chamber Atmosphere Analysis and Environmental Data -Animal Observations and Body Weights -Gross Pathology

DISCUSSION AND CONCLUSIONS

REFERENCES

SUPPLEMENTAL STODY INFORMATION
QUALITY ASSURANCE STATEMENT


### Figure 1 - 

### Chronic Inhalation Chamber
Figure 2 - Control Panel and Metering System
Figure 3 - 

### Control Panel and Metering System for sODic Jet

Em. 810006 PAGE 3 

### Report Page

1

2

3-5

6

6-9

6 6-7 7 7-8

8 8 8 9

9-10

9

10 10

11

12

13

14

15



### 16

17

### Appendix II

- In-Life Animal Observations

39-48 35-36 24-27



### 37-36 32-67



### 33-34 23

31 

### 30 23-31

28-29 18-31

19-22 

### Report Page

Mean Daily Nominal Methyl Iodide Chamber Concentrations

EHL 810006 PAGE 4 Occurrence of Specific Gross signs of Toxicity in Rats Observed During Exposure to Methyl Iodide by Exception
Weekly Summary of Occurrences of Gross Signs of Toxicity Oeserved Before and After Exposure to Methyl Iodide by Exception

Individual Animals Exhibiting Gross Signs of Toxicity Before and After Exposure to Methyl Iodide by Exception

Individual Clinical Signs Summary of Chamber Environmental Measurements Daily Analytical Concentrations of Methyl Iodide
Daily Miran Check (O.D) for the Determination of Methyl Iodide

Distribution of Methyl Iodide in the Test Chambers

Table 1 -



### Table 3 -



### Table 4 - 

### Appendices
Appendix I - Chamber Atmosphere Analysis and Environmental Data

Exhibit II

- Determination of Methyl Iodide Concentrations in Air, Distribution and Environmental Data Exhibit I - Procedure for Analysis of Methyl Iodide Determination Using a Miran e Infrared Detector

Table 4 - 

### Table 3 -



### Table 2

- 

### Table 5 - 

### Table 1 -



### Table 2

-Appendix III

- Gross Pathology

Text Table 5 -

Table 6 -

Table 7 -

TCi.ble 8 -

Table 1 -

Table 2 - Summary of Body Weight Data

Individual Body Weight Data
Change in Mean Animal Body Weights Post-Exposure Relative to Pre-Exposure

Animal Termination History

Summary Incidence of Individual Gross Necropsy Alterations

- Unscheduled Deaths
Summary Incidence of Individual Gross Necropsy Alterations

- Terminal sacrifices



# ..

Em. 810006 PAGE 5



# I I

Report page

49-50

51-58

59

60-67

68-78

69-70

71-74

75-78

.. , :

... -", ._f)

# ·······I·"·';;;i"c!i"-.~

# - I NTROD tlC"l'ION

The purpose of this study was to determine tbe inbalation toxicity of metbyl iodide vapor-aerosol in Sprague-Dawley male and female rats exposed over an**approxi~ate** 

### four-week period, 6 bours per day, 5 days per week for a total of 21 exposure days. Groups of equal numbers of male and female rats were each exposed during the study to target concentrations of 0 (Control, Group N), 0.140 (Low, Group 1), 0.420 (Mid, Group 2)

or 0.840 (High, Group 3) mg methyl iodide per liter of air. Exposure concentrations were**ba~ed** 

### on a previous investigation (1). This study was conducted from March 11, 1981 to April 9, 1981, at the Environmental Health Laboratory**(Ea~),** 

### 645 S. Newstead Ave., St. Louis, Mo. 63110.

MATERIALS AND METHODS

Test Material
Methyl Iodide (Mel) is a clear to yellow liquid with a vapor pressure of 6.6 psia at 70 0 

### p, boiling point of 42.4oC and

a molecular weight of 142. The test compound was received from the Texas City Plant with unique identification, 500-201(2/9/81). The EHL substance identification code is TalOOl3. It was reported to be 86.8\ Mel.

Test System: Animals and Husbandry
Eighty (40 males, 40 females) Sprague-Dawley rats (Crl:CD- (SD)BR) were obtained from the Charles River Breeding Laboratories (Portage, Michigan). Test animals were beld and observed in quarantine for 7 days prior to release for study. Pive days prior to the start of the study animals weigbed 192-204 grams for males and 159-169 grams for females. On tbe first day of stUdy, males were 48 days old and females were 53 days old. Eacb rat was uniquely identified by an eartag and bar-coded cage card. Animals were randomly selected by the computer and allocated on the basis of body weight into 4 groups of 10 animals/sex/group. This randomization precluded'

eaegistered Trademark of Charles River Breeding Laboratory,

Wilmington, Massachusetts.



# '.

EHL 810006 PAGE 6

.**,,~.**

. .. ...**,:~;.** .



## . ,-:,,-,:

.. >,,>

# ,\/:,;;i>2:.~~~~,.'~-~.:/-:>;g~~



# III 

# Isignificant differences among group mean body weights and variability of individual body weights Within the groups.

Animals were individually housed in suspended stainless steel wire mesh cages and given Purina Laboratory Certified Rodent Chowe (5002) and tap water (St. Louis City, MO) ad libitum except during the exposure period. Animal rooms-Were routinely maintained at 70-740? and 35-60\ relative humidity with a l2-hou: light/12-hour dark cycle.

Exposure System

Feur lO-m3 Rochester-type stainless steel chambers with pyramidal tops and bottoms (Figure 1) were used for the exposures. The rats were placed individually in wire mesh cages suspended in an inhalation cage rack positioned on the left side of the exposure chamber. Males were placed on**o~e** side of the rack and females on the other. Rats were positioned on the middle two tiers on the cage rack. The low and mid-exposure atmospheres were generated by passing air through MeI in a glass bubbler (Figure 2). MeI concentrations

were varied by altering the rate of airflow through the bubbler. The high exposure atmosphere was generated by metering pressurized MeI from a steel tank through a stainless steel capillary tube into a Laskin-style nebulizer (2) located at the top inlet of the exposure chamber. Test material concentrations were varied by changing the flow rate of material to the nebulizer. This was accomplished by changing the pressure in the tank headspace above the test material (Figure 3). Airflow in the chambers was maintained at a constant flow of 1699 liters/min.

procedures for Monitoring Me! in the Inhalation Chamber

Nominal atmospheric concantration measurements were determined daily for the low and mid- chambers following exposure. This concentration was determined by dividing the amount of test compound delivered to the chamber over the six-hour exposure time by the total airflow through the chamber during the same six-hour period. The amount of test material delivered to the chamber was determined by calculating the difference between the pre- and post-exposure weights of the bubbler. Nominal

-Registered Trademark of Ralston purina Company, St. Louis, MO.

EHL 810006 PAGE 7

".

" ...



# . "

..**;'-::c<2~-** 

# :.;.'

. .**~i:~~** 

# • 

# •

### atmospheric concentration Ir·"'c,- 

### ·'.::t:ments were obtained at least four times during each**his~-~ev~l** 

### exposure. This nominal concentration was determined by dividing the net amount of test compound delivered to the chamber per unit time by the airflow per unit time. Analytical samples were obLained four times per**cha~ber** 

### per day at a port in**approximat~ly** 

### the center of the exposure chamber door. The analytical concentration of test material was determined by a Miran. Infrared Analyzer. The analytical method is given in Appendix I, Exhibit I. Quality control samples were injected into the closed loop system of the Miran Infrared Analyzer. The results of these injections were in relatively good agreement with the expected (Appendix I, Exhibit II, Table 3). Distribution of the test matarial was determined three times in each chamber during the study.

Animal Observations and Body weights

Animals were observed between the second and fifth hour of each exposure, and a percentage estimate of animals eXhibiting hypoactivity, hyperactivity, tremors and/or convulsions, irritation of the eyes and/or nose or breathing difficulties

was recorded. All animals were also individually examined for gross signs of toxicity prior to and following each exposure and at comparable times on non-exposure days. Weekly, each animal was weighed and given a thorough examination for gross signs of toxicity.

Gross Pathology

A maximum of ten fasted animals/sex/group were thoroughly**ex~ined** 

### following four weeks of exposure, euthanized and necropsied. A maximum of five animals/sex/group were selected**fo~** 

### necropsy for each necropsy day. Animals that were found dead and/or sacrificed in extremis were also given a detailed necropsy examination. Necropsy included examinations of all external areas and orifices, the cranial cavity, the external surface of the brain, thoracic and abdominal cavities and the subcutaneous cervical tissues and organs.

Statistical Procedures
Body weight data for animals of each group/sex were evaluated by Dunnett's (two-tailed) Test (3) to detect significant differences between means of treated groups and those of the respective control group. Differences in tbe frequency of lesions were determined using Kolmorogov-Smirnov one-tailed test (4).**~Registered** 

### Trademark of the Foxboro Company, Norwalk, CT. EBL 810006 PAGE 8



# ,1.076 (0.097)

0.810 (0.049)

1.33 0.612 (0.076)

0.421 (0.030)

1.45 0.186 (0.031)

0.142 (0.012)

1.31 Low (0.14) Mid (0.42) High (0.84)

Nominal (+ S.D.) Analytical (+ S.D.) Nominal/Analytical Comments on Study Conduct versus Protocol
Analytical concentrations of MeI in the high exposure level

were 0.810 mg/l and nct C.840 mg/l as specified. The nature**~f** the generation system and the test material did not allow the consistent**ge~eration** of 0.840 mg/l. Three males and 2 females in the high exposure group were necropsied the second**necrop~y** day. A**~aximum** of 5 animals/group/sex/day are usually l:ecropsied tcot' equal numbers/group/day although due to animal deaths in the high exposure groups, these numbers were reduced the second day (Sections 2.2.2 and 2.5.6). purina Certified Rocent Chow**~nstead** of Standard ChOW, is used exclusively ac this**f~cility** and meets reqUirements for nutrition and**~est~ictions** for toxic contaminants (Section 2.5.5). Control chamber analysis was inadvertently not measured the**f~rst** week of exposure (Section 2.8). It is the opinion of the study director that these deviations did not adversely affect the course of this stUdy.



### -- EHt 810006 PAGE 9 Chamber Atmosphe:e Analysis and Environmental Data

Mean nominal and analytical values fot' the three exposure levels of Mel were as follows:

# )\lyp~\**concent}~t{;~~** (mg/l }·\AC.> RESOLTS

Nominal exposure concentration values are shown in Appendix I, Exhibit II, Table 1. Individual and mean analytical values for samples obtained for each chamber/day are given in Appendix I, Exhibit II, Table 2. There was good agreement between target and analytical levels. The distribution of the exposure atmosphere was determined to be uniform (> 94%) at each of the exposure levels (AppendiX I, Exhibit II, Table 4). The ratios of nominal to analytical concentrations were slightly higher than those of a true vapor (a true vapor would have a value of 1). The daily means of environmental measurements, such as temperature, relative humidity and airflow were maintained throughout the study at 20.S-24.0 o c, 21-58% and 1699 l/min, respectively**(A~pendix** I, Exhibit II, Table 5).Animal Observations and Body Weights Hypoactivity, hyperactivity, irritation of the eyes and/or nose, breathing difficulties and tremors, twitches and/or convulsions were observed in animals during the period of animal exposure (Appendix II, Table 1). This was most prevalent in the high and to a lesser extent in the mid-exposure level animals. Irritation of the eyes, hypoactivity, nasal discharge, respiratory difficulties, abnormal pppearance of the skin and fur and a singular occurrence of tremors were observed in the pre- and post-exposure observation periods (Appendix II, Tables 2 and 3) in the high exposure group and to a lesser extent in some of the categories in the mid-exposure group. Similar observations were made at the weekly weigh periods (Appendix II, Table 4). Significant decreases (p < O.Oll in mean body weight compared to those of the controls were observed throughout the study in high exposure male and female rats. Significant decreases (p < 0.01) were also observed in the mid-level male and female rats from Day 15 through the end of the study. Summary and individual body weight data for each exposure group versus those of the controls are given in Appendix II, Tables 5 and 6. The mean body weights of the high exposure animals were actually less at -Exposure Day 28 than Day 22. Animals of themidand high exposure groups were not gaining weight at the same rate as comparable controls (Appendix II, Table 7). Five test material-related deaths (1 female was found dead, 2 males and 2 females were sacrificed in extremis) of the high exposure group also occurred the

**~ast** week of exposure. The animals sacrificed in extremis suffered large losses of body weight and were in 

### generally poor physiological condition. Animal termination histories are shown in Appendix II, Table 8.

Gross pathology

The most consistent finding in the necropsies of four of the five unscheduled deaths was the gaseous distension of the gastro-intestinal tract (Appendix III, Table 1). One female was found dead and the carcass was destroyed before a necropsy could be performed. No compound referrable abnormalities were detected at the terminal sacrifice of the remaining animals with the exception of the presence of a granular reddish/brown material on the backs of the high exposure group animals (5/8 males, 1/7 females) and a single 10,1{ exposure male and a suggestion of gastric difficulties (single C3se in each sex) in high exposure animals (Appendix III, Table 2). The suggestion of gastric difficulties may be an

**early~ndication** of stress but due to the low incidence, its relationship to compound toxicity cannot be determined.

EHL 810006

PAGE 10

-";.=.-':',

. 

# I

"

# I DISCUSSION AND CONCLUSIONS

Irritation of the eyes and/or Dose, hypoactivity and breathing difficulties observed during exposure and**non-e~posure** periods indicate that methyl iodide may be an irritant. The poor physical appearance of the animals, as evidenced by the skin and fur abnormalities, decreased weight gain or weight loss, and death observed in the high exposure group animals are indicative of the compromised physiologic condition of the animals. These effects, excluding death, were seen to a lesser extent in the mid-level animals, thus demonstrating a concentration related phenomenon. The decrease in body weight and the deaths observed late in the study suggest there may be

a cumulative toxic effect from repeated exposure to the compound.

In conclusion, the results of this study indicate that the highest -no-effect- exposure level for male and female rats receiving six-hour exposures of methyl iodide during a four-week period was 0.142 mg/l.



# ..

EHt 810006

PAGE 11

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


### - 

## . REFERENCES

EHL 810006 PAGE 12 1. Blank, T. L. Inhalation Toxicity of Methyl Iodide (MeI) to Sprague-Dawley Rats. MSL-26S0, 

### EHL StUdy S10005. ML-SI-OIS. 19S2.

2. Drew, R. T., Bernstein, D. M., and Laskin S. The Laskin Generator. J. Tox. Environ. Health 

### i 661-70 (197S).

3. Dunnett, C. W. MUltiple Comparison Procedure for Comparing Several Treatments with a Control. Jour. 

### Am. Stats. Assoc. 1096-1121 (1955).

4. Siegel, 

## s. Nonparametric Statistics for the Behavioral Sciences. McGraw 

### Hill Co. NY (1956).

dmo/4711A-12Appendix I, Exhibit II

Table 1

Mean Daily Nominal Methyl Iodide Chamber Concentrations

Exposure Concentration (mg/I) Day Low (0.14) Mid (0.42) High (0.a4)

1 0.144 0.711 0.892 + 0.017 2 0.162 0.533 0.989 

### +' 0.072 3 0.163 0.595 1.025 

## '+ 0.017 4 0.167 0.628 1.032 

### +' 0.009 5 0.177 0.567 1. 040 

### +' 0.000 6 0.163 0.490 1.040 

### +' 0.000 7 0.154 0.656 1.010 

### +' 0.000 8 0.154 0.570 1.018 

### +' 0.025 9 0.136 0.644 1.066 

## +' 0.010 10 0.149 0.623 1.040 

## + 0.000 11 0.206 0.453 1.031 

## +' 0.004 12 0.188 0.580 1.029 

## +' 0.014 13 0.203 0.602 1. 074 

## '+ O. 0.10 14 0.204 0.665 l.072 + 0.000 15 0.239 0.544 1.185 

## +' 0.076 16 0.216 0.541 1.246+0.080 17 0.217 0.675 1.143 + 0.016 18 0.212 0.763 1.108 

## +' 0.004 19 0.216 0.664 1.050 

## +' 0.050 20 0.209 0.687 1.350 

## + 0.228 21 0.232 0.670 1.148 

## +' 0.197

lC j: S.D. 0.186 + 0.031 0.612 + 0.076 1.076 

### .:!: 0.097

EHL 810006

PAGE 23



# I '.**~.** 

# II**:.~~. ~;::** 



# ,

# 'L}:!:2:il~**.~,**B B B B C E B B Females

B C**,:.~**



# .**,>":.;'2~~**

... ...

# .;,L;z,2id~~y;ij,~~~_· I, 

# I

, I Exposure Levels

.J"-'. " B B

C E B B

,.".;,.
.. "



## .. ' Males

B B B B B B B B B B B B B B C C C D D D E E 

# '. B C

EHL 810006

PAGE 33 1 2 3 4-8 9-18 19 20 21 Occurrence(a) of Specific Gross Signs of Toxicity in Rats Observed During Exposure to Methyl Iodide by Exception Appendix II

Table 1

Breathing Difficulty 1-17 18-19 20 21 Bypoactivity Exposure No.

1-4 5-13 14 15-17 18-19 20 21
Tremors, Twitches and Convulsions 1-18 19-20 21 Hyperactivity

### Females



# '. Exposure Levels Males

iXL 

### 810006

PAGE 34 

### Appendix II

Table 1 (Continued)**,,'~**

. .... _.' ,,.



# ... ...

# '~,·>~,,{&i~;t_,:,~t'i~,/'~~fJ2~illi!k.\!i/l-

. 

# ...**~.** 

# I

Occurrence(a) of Specific Gross signs of Toxicity in Rats Observed During Exposure to Methyl Iodide by Exception

1-3 C C
4-5 B B 6-16 C C
17-18 C C C C
19-21 

### C E C E



### cal B = 25% 

### of the observable animals have this effect.
C 50% 

### of the observable**a~imals** 

### have this effect.

D = 75\ 

### of the observable animals have this effect. E

... 100\ 

### of the observable animals have this effect. Exposure No.

Irritation of the Eyes and/or NoseTHISREPORTUASOENERATEDfROHDATALOCKEDTHROUGII5-AUG-82Table5STUDYSTART[lATEI11-HAR-81Of&ODYUEIOHTDATA(OH)SPECIESIRATSPRAGUE-DAULEYSEXIHALEDATE(198illPRE-18-HAR25-HARl-AF'R7-APRDROUPTARGETDOSEDAYOFBTUDYITEST8152228------------------------------------------------------------------------------------._.--------------------------------HH"EAN199.0287.8328.6364.3387,1HEDATIVECONTROLBTD.nEV.3.2314.3415.64IB.4520.19SAHPLESIZE10101010 10STUDYHUH&ERI810006DHEHNUHBERIRTEOFAD"IHIINHALATION"- - -LEGEND- - -•__DUNNETT'STEST(TWO-TAILED)INDICATESSTATISTICALLYSIGNIfICANTDIFfERENCEIP!.05)••__DUNNETT'STEST(TWO-TAILED)INDICATESSTATISTICALLYSIGNIFICANTDIFfERENCEPT--BARTLETT'STESTINDICATESSTATISTICALLYSIGNIFICANTDIFfERENCEAHONOVARIANCESOFTHEDIFFERENTGROUPSIP!.OI)NA--DUHNETT'STESTHOTAPPROPRIATEFORTHISGROUP/SEX/DATESTUDYHUHBERt810006MONSANTOENVIRONHENTALHEALTHLA&oRATORYPAOE11H0.14HG/LITERHEAN199.1286.2322.6357.8376.7TESTGROUPBTD,DEV,3.1817.3027.6735.7338.73HETHYLIODIDESAHPLEBIlE1010101010i!2M0.42HO/LITERHEAN199.2275.1298.1U313.4U321.1UTE¥TDRoUPSTD.DEli.3.339.9312.1917.2917.06HEHYLIODIDESAMPLEBIZE1010101010.....0\DO3M0.84HG/LITERHEAN198.9257.9**276.4**284.8U265.0U0enTESTGROUP8TD.DEV.J.8417.2116.1217.3041.99HETHYLIODIDESAHPLESIZE1010101010"I.!!IIi';-,.'\.-i-:';',tM",>··I.1I:;f,,;,·,...:jI'·::':",1,.;,.<"/····f··.":..--:1;,:..:.•,...,•"·""";'iV'.'1\""('".:'l1.\;C:"."_,......j','-,1..'"THISREPORTWASGENERATEDFROHDATAlOCKEIJTHROUGII5-AUO-B2STUDYSTARTDhTEIII-HAR-BlSTUDYHUHBERI810006DKEHNUHBERIRTEOFADHINIINHALATIONTable5(Continued)SUHHARYOFWEIGHTDATACGH)SPECIESIRATSTRAIN/BREEDISPRAGUE-DAWLEYSEXIFEHALEDATE(1981)1PRE-IS-HAR25-HARl-ArR7-APRGROUPTAROETDOSEDAYOF8TUDYITEST8152228---------------------------------------------------------------------.._------------------------------------------------HfHEAN164.3205.1220.4234.0242.68TNEDATIVECONTROLBTD.DEV.3.406.649.1712.16SAHPLESIZE1010101010IFO.14HO/LITERHEAN164.5208.4224.6241.1249.7TESTDROUPSTD.DEV.3.277.937.739.0413.18"ETHYLIODIDESAHPLESIZE10101010 102FO.42HO/LITERMEAN164.5198.5206.7n217.2**221.2**DEV.2.955.988.425.81SPLESIZE1010 1010...iLnO003FO.84HD/LITERliEAN164.2186.4**191.2**196.4**188.0n0)aITESTGROUPSTD.DEV.3.198.2110.839.5622.03.1,,'-HETHYLIDIlIDESAHPLESIZE10 1010108,II';".':'I#:':i",!11';"':,:/.r'i,I,,,'.tD,,;·,j;-,:J.-:,'t,,:":j;r!l,:;:f.\.I•.J:';:"':'Itij';,:>;.,I,•ItI"I'.,:.,'.;'.,;',...,,'.__..'- - -LEOEND---*--DUNNETT'STEST(TWO-TAILED)INDICATESSTATISTICALLYSIGNIFICANTDIFFERENCEIP!.05)••--DUNNETT'STEST(TWO-TAILED)INDICATESSTATISTICALLYSIGNIFICANTDIFFERENCEBT--BARTLETT'STESTINDICATESSTATISTICALLYSIGNIFICANTDIFFERENCEAKDNDVARIANCESOFTHEDIFFERENTDROUPSIP,.OI)NA--DUNNETT'STESTNOTAPPROPRIATEfORTHIBOROUP/SEX/DATESTUDYNUH8ERI810006HONSANTOENVIRONMENTALHEALTHPAOE2-