Iodomethane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 December 2000 to 04 January 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: JMAFF, 12 NouSan No. 8147

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Iodomethane

EC Number:

200-819-5

EC Name:

Iodomethane

Cas Number:

74-88-4

Molecular formula:

CH3I

IUPAC Name:

iodomethane

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Iodomethane
- Physical state: liquid
- Analytical purity: 99.7%
- Impurities (identity and concentrations): 0.2 % water and <0.1 % methanol
- Composition of test material, percentage of components: not stated
- Isomers composition: not stated

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl:CD®(SD)IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 to 12 weeks of age
- Weight at study initiation: 222 to 292 g
- Fasting period before study: Food and water were witheld during the exposure
- Housing: Individual suspended wire-mesh cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum of 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 22 °C
- Humidity: 54 to 61 %
- Photoperiod: 12 hours light/ 12 hours dark

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass and stainless steel whole body exposure chamber
- Exposure chamber volume: 130 L
- Method of holding animals in test chamber: The animals were caged individually during exposure
- Temperature, humidity, pressure in air chamber: Exposure atmosphere conditions were recorded four times during the exposure.
- Vapour atmospheres of the test material were generated using the following system: The test material was held in a glass gas washing bottle. Compressed air (generation air) was delivered to the washing bottle to create a vapour of the test material. The resulting vapour was carried to the chamber with the appropriate flow of dilution air. Humidified purge air was also supplied to the chamber to help maintain the protocol-specified humidity range. Exhaust vapour from the chamber was filtered (charcoal) prior to entering the facility exhaust system.
- Generation airflow; 581 ppm: 41 to 49 mL/min, 710 ppm: 51 to 60 mL/min, 797 ppm: 65 to 68 mL/min and 1189 ppm: 110 to 128 mL/min.
- Dilution airflow: 11 L/min for all test concentrations
- Purge airflow rate: 11 L/min for all test concentrations

TEST ATMOSPHERE
- The nominal exposure concentration was calculated as the total amount of test material used during each exposure divided by the total volume of air that passed through the system during that exposure.
- Actual exposure concentrations were measured using gas chromatography. Samples of the exposure atmospheres were manually collected from the chamber using a sampling valve and sample loop. The gas chromatograph (GC) conditions were:
- Instrument: Hewlett Packard 5890A with a 3396A integrator
- Detector: Flame ionisation
- Column: DB-W AX/0.25 µm 30 m x 0.25 mm
- Gases: Carrier-Helium: 53 psig (8 L/min), Fuel hydrogen: 18 psig (31 mL/min) and Air: 35 psig (300 mL/min) .
- Temperatures (°C): Detector: 250, Column: 45 and Injector: 250
- Injection volume: 0.25 mL
- Retention time: Approximately 1.1 minutes
- Samples taken from breathing zone: yes/no
- The GC was standardised using known concentrations of the test material prepared in Tedlar® gas bags. The bags were prepared by injecting known volumes of test material into a glass vaporisation bulb. A continuous flow of air through the bulb carried the vaporised test material to a 40 L bag. The volume of air was measured by a dry test meter. Concentrations of the gas phase standards were calculated as follows:
Concentration (ppm) = (VOL x R x T x D x 10^-3 x 10^6 ) / (L x GMA x P)
Where VOL = volume of the test article (µL), R = universal gas constant (62.36 L mmHg/mol K), T = nominal laboratory temperature (294 K), D = density of test article (2.28), L = volume of air used to make bag (32 L), GMW = molecular weight of test material (141.94), P = laboratory barometric pressure (730 mmHg), 10^-3 = µL to mL conversion, 10^6 = ppm conversion
- Standards were prepared that bracketed the target concentration for each exposure. Each standard bag was prepared and analysed on the GC. An instrument response for each standard was recorded to produce a calibration curve. On the day of exposure, one standard was analysed to confirm GC calibration. Then for each exposure, the instrument response was converted to concentration from the calibration curve for each sample.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

581, 710, 797, 1189 ppm

Duration of exposure:

ca. 4 h

Concentrations:

Target concentrations of 600, 700, 800 and 1200 ppm (concentrations confirmed at 581, 710, 797 and 1189 ppm respectively)

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rat was observed immediately following exposure on day 0 and once daily thereafter for 14 days. Due to the limited visibility of the animals in the exposure chamber, observations during exposure were limited to an evaluation for mortality.
- Body weights were obtained prior to exposure on day 0 and on post-exposure days 3, 7 and 14. A final body weight was recorded for all animals found dead.
- Necropsy of survivors performed: yes, all animals found dead or euthanised after the 14-day observation period underwent a gross necropsy. Animals at the scheduled necropsy were euthanised by an intravenous injection of sodium pentobarbital. The major organ systems of the cranial, thoracic and abdominal cavities were examined for all animals.

Statistics:

The data did not warrant statistical analysis, however the LD50 and 95 % confidence intervals were calculated separately for each sex using a computer adaptation of the method of Litchfield and Wilcoxon.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 691 ppm

Based on:

test mat.

Exp. duration:

4 h

Mortality:

- For the 710 ppm group, one male died during exposure, one male and one female died following exposure on day 0 and two males and three females died on day 1. For the 797 ppm group, one male died following exposure on day 0, three males and three females died on day 1 and one female died on day 2. Four males and five females in the 1189 ppm group died during exposure and the one remaining male in the 1189 ppm group died within one hour of the end of the exposure on day 0.
- Mortalities can be seen in Table 1.

Clinical signs:

other: - Clinical signs can be seen in Table 2 and Table 3. - All animals in the 581 ppm group were considered normal by day 7. The surviving animals in the 710 and 797 ppm groups were considered normal by day 4.

Body weight:

- All animals in the 581 ppm group lost weight (6 to 22 g) from days 0 to 3. All animals in the 581 ppm group surpassed their initial day 0 body weight by day 7.
- In the 710 ppm group, body weight losses of 63 and 31 grams were noted from days 0 to 3 for the surviving male and female, respectively. Both of these animals surpassed their initial body weight by day 14.
- Similarly, the surviving male and female in the 797 ppm group lost 49 and 18 grams, respectively, from days 0 to 3 and surpassed their initial weight by day 14.

Gross pathology:

- A distended, gas-filled stomach was noted macroscopically for eight (four males, four females) of the 10 animals in the 1189 ppm group that died during exposure.
- For the animals in the 797 ppm group that died early, a distended intestine (parts or entire length) was observed for three males and one female, dark red adrenal glands and a haemorrhagic thymus gland were each observed for two females.
- Dark red lungs were observed for two males and a reddened pituitary gland was observed for one male in the 710 ppm group that died early. In addition, a distended, gas-filled stomach was observed for one male and a reddened glandular portion of the stomach was observed for two females in the 710 ppm group that died.
- There were no other toxicologically significant internal findings in the animals found dead.
- There were no internal macroscopic findings at the scheduled necropsies .

Other findings:

- At the nominal concentrations of 1046, 1369, 1542 and 2388 ppm the actual concentrations were 581, 710, 797 and 1189 ppm.

Any other information on results incl. tables

Table 1: Mortalities

Concentration (ppm)	Number dead/Number treated
	Males	Females	Males and Females combined
581	0/5	0/5	0/10
710	4/5	4/5	8/10
797	4/5	4/5	8/10
1189	5/5	5/5	10/10

Table 2: Clinical signs observed immediately after exposure

Concentration (ppm)	Clinical sign	No. of animals
		Males	Females
581	Hypoactivity	5	5
	Clear material around the mouth, nose and/or eyes	5	5
	Clear nasal discharge	4	4
	Rales	4	3
	Laboured respiration	5	1
	Gasping	3	1
	Red material around the nose	1	0
	Ataxia	1	0
710	Hypoactivity	4	5
	Clear material around the mouth, nose and/or eyes	4	5
	Laboured respiration	3	3
	Gasping	1	1
797	Hypoactivity	5	4
	Clear material around the mouth, nose and/or eyes	5	5
	Laboured respiration	4	3
1189	Hypoactivity	1	0
	Clear material around the mouth, nose and/or eyes	1	0
	Laboured respiration	1	0

Table 3:Clinical signs observed during the 14 day observation period

Concentration (ppm)	Clinical sign	No. of animals
		Males	Females
581	Hypoactivity	5	5
	Red material on various body surfaces	3	3
	Rales	2	0
	Decreased defecation/ urination	0	1
710	Hypoactivity	1	1
	Rales	1	0
	Laboured respiration	1	1
	Gasping	1	0
	Red material on various body surfaces	1	1
	Decreased defecation/ urination	1	1
	Mucoid faeces	0	1
	Unkempt appearance	1	0
797	Hypoactivity	1	2
	Red material on various body surfaces	1	2

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of this study, the acute inhalation LC50 was 691 ppm in both male and female rats.

Executive summary:

The acute inhalation toxicity of the test material was investigated in accordance with the standardised guidelines EPA OPPTS 870.1300 and JMAFF 8147 under GLP conditions.

The acute inhalation toxicity was evaluated in a four hour, single-exposure study in rats. The test material was administered to four groups of five male and five female albino rats each via whole-body exposure as a vapour atmosphere at concentrations of 581, 710, 797 and 1189 ppm. Following each exposure, all surviving animals were maintained for a 14-day observation period. Parameters evaluated were mortality, clinical observations, body weights and gross necropsy.

Eight animals in each of the 710 and 797 ppm groups and all 10 animals in the 1189 ppm group died within two days of exposure as a result of test article administration. There were no deaths in the 581 ppm group.

Ataxia, clear nasal discharge, gasping, hypoactivity, laboured respiration, rales and red material around the nose were observed immediately following exposure in the 581 ppm group. Gasping, hypoactivity and/or laboured respiration were observed for the surviving animals in 710, 797 and 1189 ppm groups immediately following exposure. During the 14-day observation period, decreased defecation/urination, hypoactivity, red material on various body surfaces and rales were noted in the 581 ppm group. In addition to these clinical findings, gasping, mucoid faeces, laboured respiration and unkempt appearance were also observed for the surviving animals in the 710 ppm group. For the surviving animals in the 797 ppm group, hypoactivity and red material on various body surfaces were noted. All surviving animals were considered clinically normal by day 4 for the 710 and 797 ppm groups and by day 7 for the 581 ppm group.

Body weight losses were observed for all animals in the 581, 710 and 797 ppm groups from days 0 to 3. All surviving animals surpassed their initial day 0 body weight by day 14.

Macroscopic findings were limited to the animals that died early. In the 1189 ppm group, a distended, gas-filled stomach was noted for eight animals. For animals found dead in the 797 ppm group, a distended intestine (parts or entire length) was observed for three males and one female and dark red adrenal glands and a haemorrhagic thymus gland were each observed for two females. Dark red lungs were observed for two males and a reddened pituitary gland was observed for one male in the 710 ppm group. In addition, a distended, gas-filled stomach was observed for one male and a reddened glandular portion of the stomach was observed for two females in the 710 ppm group.

Under the conditions of this study, the acute inhalation LC50 was 691 ppm in both male and female rats.