Iodomethane

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 May 2000 to 29 May 2000

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:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: JMAFF, 59 NouSan No. 4200

Version / remarks:

1985

Deviations:

no

GLP compliance:

yes

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:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: males: 11 to 12 weeks of age and females: 12 weeks
- Weight at study initiation: males 2.2 to 2.7 kg and females: 2.5 to 2.6 kg
- Fasting period before study: no
- Housing: The animals were housed individually in suspended stainless steel cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: a minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 to 22 °C
- Humidity: 46 to 82 %
- Air changes: 10-15 air changes/hour
- Photoperiod: Light timers were set to maintain a 12-hour light/12-hour dark cycle

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: 100 %

Duration of treatment / exposure:

Single application for 3 minutes, 1 and 4 hours

Observation period:

Examined either immediately (3 and 1 hour exposures only) or at 1 hour after patch removal (4 hour exposure period) and at approximately 24, 48 and 72 hours and up to 28 days after patch removal.

Number of animals:

4 males and 2 females per dose.

Details on study design:

TEST SITE
- Area of exposure: dorsal area of the trunk
- area of coverage: approximately 1 x 1 inch
- For the 3-minute, 1- and 4-hour dosing procedures, the test material was administered under the gauze patch. For the initial animal dosed, the 1" x 1" 4-ply gauze was held in contact with the skin at the cut edges with tape for the 3 minute and 1 hour exposure periods. This tape apparently produced an interaction. Therefore, for the 4-hour exposure period and for the remaining animals, a 2" x 2" single ply gauze was used to cover the 4-ply 1"x1" gauze patch. The gauze patch was held in contact with the skin at the cut edges with a non-irritating tape except on the bottom side, which was left un-taped. Additional gauze was used to catch any potential leakage from the test site rather than the tape.
- Removal and ingestion of the test material was prevented by placing an elastic wrap over the trunk and test area (semi-occlusive binding). The elastic wrap was then further secured with adhesive tape around the trunk at the cranial and caudal ends. Using an indelible marker, a dot was placed on the elastic wrap over the area where the 1-hour exposure test site was located in order to facilitate removal of the patch at the appropriate exposure time interval.
- After dosing, collars were placed on each animal and remained in place until removal on day 3.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the residual test material was removed using gauze moistened with deionised water, followed by dry gauze.
- Time after start of exposure: 3 minutes, 1 hour or 4 hours.
- Following completion of the 3-minute and 1 hour exposure periods, an approximate 2" x 2" window was cut into the elastic wrap over the first test site and the gauze patch and tape were removed. The comers of the test site were delineated using a marker and the residual test article was removed using gauze moistened with deionized water, followed by dry gauze. Following patch removal for the exposure, the elastic wrap was taped down with nonirritating tape around the cut window in order to insure that the test site remained nonoccluded during the remainder of the study.

OBSERVATION TIME POINTS
- Animals were examined for signs of erythema and oedema and the responses scored immediately after patch removal (for the 3-minute and 1-hour exposure periods) or at 1 hour after patch removal (4-hour exposure period) and at approximately 24, 48 and 72 hours and up to 28 days after patch application according to the Macroscopic Dermal Grading System based on Draize. The dermal sites were re-clipped as necessary to allow clear visualisation of the skin.
- Any unusual observations and/or mortality were recorded. A general health/mortality check was performed twice daily (in the morning and in the afternoon).
- Individual body weights were obtained for each animal prior to dosing on day 0.
- Each animal was euthanised by an intravenous injection of sodium pentobarbital following its final scoring interval. Gross necropsy examinations were not required for these animals.

ANALYSIS OF DATA
- Each exposure period was evaluated independently. Corrosion was considered to have resulted if the substance in contact with rabbit skin had caused destruction or irreversible alteration of the tissue on at least two of the rabbits tested. Tissue destruction was considered to have occurred if, at any of the readings, there was ulceration or necrosis. Tissue destruction does not include merely sloughing of the epidermis, or erythema, oedema or fissuring.
- In the event that any exposure period was non-corrosive, the data from that exposure period was classified as indicated below:
The 1 (or initial observation), 24, 48 and 72 hour erythema and oedema scores for all animals were added and the total divided by the number of test sites x 4. The calculated Primary Irritation Index (P.1.1.) was classified according to the Dermal Evaluation Criteria.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 3 minutes

Score:

3.58

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 1 hour

Score:

4.25

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4 hours

Score:

4.88

Reversibility:

not reversible

Remarks:

persisted through to study day 28

Results 4

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

R2464/M

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 10 days

Remarks on result:

other: After 3 minute exposure

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

R2467/M

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: After 3 minute exposure

Results 6

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

R2466/M

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: After 3 minute exposure

Results 7

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

R2476/M

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: After 3 minute exposure

Results 8

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

R2509/F

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 10 days

Remarks on result:

other: After 3 minute exposure

Results 9

Irritation parameter:

erythema score

Basis:

animal #6

Remarks:

R2513/F

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 10 days

Remarks on result:

other: After 3 minute exposure

Results 10

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

R2464/M

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: After 3 minute exposure

Results 11

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

R2467/M

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: After 3 minute exposure

Results 12

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

R2466/M

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

other: After 3 minute exposure

Results 13

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

R2476/M

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: After 3 minute exposure

Results 14

Irritation parameter:

edema score

Basis:

animal #5

Remarks:

R2509/F

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: After 3 minute exposure

Results 15

Irritation parameter:

edema score

Basis:

animal #6

Remarks:

R2513/F

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: After 3 minute exposure

Irritant / corrosive response data:

- Exposure to the test material for a 3-minute exposure period produced very slight to well-defined erythema and very slight oedema on 6/6 and 4/6 test sites, respectively, immediately following patch removal. The dermal irritation resolved completely on all test sites by study day 14. Additional dermal findings included superficial lightening and desquamation; and erythema extends beyond the test site, which were noted on 6/6 and 3/6 test sites, respectively.
- Exposure to the test material for a 1-hour exposure period produced very slight to well-defined erythema and very slight to slight oedema on 6/6 test sites immediately following patch removal. The dermal irritation resolved completely on all test sites by study day 14. Additional dermal findings included superficial lightening, desquamation and erythema extends beyond the test site; and blanching which were noted on 6/6 and 1/6 test sites, respectively.
- Exposure to the test material for a 4-hour exposure period produced well-defined erythema to notable dermal lesions (blanching) and very slight to severe oedema on 6/6 test sites at the 1-hour scoring interval. In one animal, the dermal irritation progressed to notable dermal lesions (blanching} by the 24-hour scoring interval. The dermal irritation resolved completely on 5/6 test sites by study day 14 and persisted in the remaining test site through study day 28. Additional dermal findings included superficial lightening, erythema extends beyond the test site and desquamation; and focal areas of purple within test site, which were noted on 6/6 and 3/6 test sites, respectively.

Any other information on results incl. tables

Table 1: Summary of scoring

	Erythema						Oedema
Animal No.	2464/M	2467/M	2466/M	2476/M	2509/F	2513/F (3 min and 1 hour) 2463/M(4hour)	2464/M	2467/M	2466/M	2476/M	2509/F	2513/F (3 min and 1 hour) 2463/M(4hour)
	3 Minute exposure
24 h	2	2	2	2	2	2	4	3	4	3	4	3
48 h	2	2	2	2	2	2	4	2	2	1	2	2
72 h	1	2	2	1	1	2	1	1	2	1	1	1
24/48/72h	1.7	2	2	1.7	1.7	2	3	2	2.7	1.7	2.3	2
Reversible within	10 days	7 days	14 days	7 days	10 days	10 days	7 days	7 days	10 days	7 days	7 days	7 days
	1 hour exposure
24 h	2	2	2	M4	2	2	4	4	4	4	4	4
48 h	2	2	2	M4	2	2	4	3	2	2	2	3
72 h	2	2	1	2	1	2	1	2	1	2	1	3
24/48/72h	2	2	1.7	3.3	1.7	2	3	3	2.3	2.7	2.3	3.3
Reversible within	14 days	10 days	14 days	14 days	10 days	10 days	7 days	10 days	10 days	10 days	10 days	10 days
	4 hour exposure
24 h	2	M4	2	2	2	M4	4	4	4	4	4	2
48 h	2	2	2	2	2	M4	4	3	2	2	2	2
72 h	1	2	2	1	2	M4	1	1	2	1	1	1
24/48/72h	1.7	2.7	2	1.7	2	4	3	2.7	2.7	2.3	2.3	1.7
Reversible within	14 days	14 days	14 days	10 days	10 days	not in 28 days	7 days	10 days	10 days	7 days	10 days	28 days

 

Applicant's summary and conclusion

Interpretation of results:

other: EU crieria category 2: irritant

Remarks:

Migrated information

Conclusions:

Under the conditions of this study, the test material was not considered a dermal corrosive following a 3 minute, 1 or 4 hour exposure periods. The test material was considered to be a Category 2: irritant in accordance with EU criteria.

Executive summary:

The skin irritation potential of the test material was investigated in accordance with the standardised guidelines OECD 404, OPPTS 870.2500 and JMAFF 59 NohSan No. 4200, under GLP conditions.

The potential irritant and/or corrosive effects were evaluated on the skin of New Zealand White rabbits. Six rabbits received 0.5 mL doses of the test material at 3 minute, 1 hour and 4 hour intervals. Patches were removed at specified time intervals and any remaining test material was wiped from the skin using gauze moistened with deionized water followed by dry gauze. Test sites were subsequently examined and scored for dermal irritation for up to 28 days following patch removal. 3-Minute Exposure: Exposure to the test material for the 3-minute exposure period produced very slight to well-defined erythema and very slight oedema on 6/6 and 4/6 test sites, respectively, immediately following patch removal. The dermal irritation resolved completely on all test sites by study day 14. Additional dermal findings included superficial lightening and desquamation; and erythema extending beyond the test site, which were noted on 6/6 and 3/6 test sites, respectively.

1-Hour Exposure: Exposure to the test material for the 1-hour exposure period produced very slight to well-defined erythema and very slight to slight oedema on 6/6 test sites immediately following patch removal. The dermal irritation resolved completely on all test sites by study day 14. Additional dermal findings included superficial lightening, desquamation and erythema extending beyond the test site; and blanching which were noted on 6/6 and 1/6 test sites, respectively.

4-Hour Exposure: Exposure to the test material for the 4-hour exposure period produced well-defined erythema to notable dermal lesions (blanching) and very slight to severe oedema on 6/6 test sites at the 1-hour scoring interval. In one animal, the dermal irritation progressed to notable dermal lesions (blanching) by the 24-hour scoring interval. The dermal irritation resolved completely on 5/6 test sites by study day 14 and persisted in the remaining test site through study day 28. Additional dermal findings included superficial lightening (6/6 test sites), erythema extending beyond the test site (5/6 test sites) and desquamation (6/6 test sites); focal areas of purple within the test site (3/6 test sites), and blanching (3/6 test sites).

Under the conditions of this study, the test material was not considered a dermal corrosive following a 3 minute, 1 or 4 hour exposure periods. The test material was considered to be a Category 2: irritant in accordance with EU criteria.