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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 May 2000 to 24 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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF, 59 NouSan No. 4200
Version / remarks:
1985
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
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
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: males: 14-16 weeks of age and females: 11-18 weeks
- Weight at study initiation: males 3.0 to 3.3 kg and females: 2.4 to 3. 7 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 to 15 air changes/hour
- Photoperiod: Light timers were set to maintain a 12-hour light/12-hour dark cycle

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: The dorsal trunk area. The region included the scapula (shoulder) to the wing of the ilium (hipbone) and half way down the flank on each side of the animal.
- % coverage: approximately 10 %
- Type of wrap if used: a 4-ply porous gauze dressing backed with a plastic wrap. Removal and ingestion of the test material was prevented by placing an elastic wrap over the trunk and test area. The elastic wrap was further secured with adhesive tape around the trunk at the cranial and caudal ends.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test material was removed using gauze moistened with deionised water followed by dry gauze.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 500 mg/kg dose group: 0.23 mL/kg and 2000 mg/kg dose group: 0.90 mL/kg
- Concentration: The test material was administered as received. The density of the test material was determined twice to confirm the volatile nature of the test material. The average of the two density measurements resulted in 2.22 g/mL.

- After dosing, collars were placed on the animals and remained in place until removal on study day 3 for the 500 mg/kg dose level and on study day 14 for the 2000 mg/kg dose level.
Duration of exposure:
24 hrs
Doses:
500 and 2000 mg/kg
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
- The test animals were examined for erythema and oedema and the responses scored following patch removal on study day 1 and daily thereafter (days 2 to 14) according to the Macroscopic Dermal Grading System which is based on Draize. The dermal test sites were re-clipped as necessary to allow clear visualisation of the skin.
- The test animals were observed for clinical abnormalities two times on study day 0 (post-dose) and daily thereafter (days 1 to 14). A mortality check was performed twice daily, in the morning and afternoon.
- Individual body weights were obtained for the test animals prior to dosing on day 0 and on days 7 and 14.
- Necropsy of survivors performed: yes, all animals were euthanised by an intravenous injection of sodium pentobarbital at study termination (day 14) and were necropsied. Body cavities (cranial, thoracic, abdominal and pelvic) were opened and examined. Treated skins samples were retained for one male and one female for possible future histopathological examination.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during this study.
Clinical signs:
- Clinical abnormalities observed during the study included decreased defecation, soft stools, faeces small in size, decreased food consumption, breathing abnormalities and dark material around the facial area.
- Dermal irritation was noted at the site of test material application for every animal. The dermal irritation for the 2000 mg/kg dose level was severe and included apparent haemorrhaging at the test site. The severity of findings at the 2000 mg/kg dose level precluded dosing higher levels
Body weight:
- A slight body weight loss was noted in two males in the 500 mg/kg dose group and in two males and two females in the 2000 mg/kg dose group during the day 0 to 7 body weight period.
- Body weight gain was noted for all other animals during the test period.
Gross pathology:
- Thickened skin at the treated test site was observed externally at the 2000 mg/kg dose level (in addition to the in-life scores).
- Four incidences of cyst(s) on the oviduct(s) were observed; however, these findings were not considered to be significant since they are commonly found in rabbits of this strain.
- No significant treatment-related gross internal findings were observed at necropsy on study day 14.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of this study the percutaneous LD50 was found to be in excess of 2000 mg/kg for both male and female rabbits.
Executive summary:

The acute dermal toxicity of the test material was investigated in accordance with the standardised guidelines OECD 402, OPPTS 870.1200 and JMAFF 59 NohSan No. 4200, under GLP conditions.

The single-dose dermal toxicity of the test material was evaluated in New Zealand White rabbits. Initially, a limit test was performed in which one group of five male and five female rabbits received a single dermal administration of the test material at 500 mg/kg body weight. A second limit test was then performed in which one group of five male and five female rabbits received a single dermal administration of the test material at a dose of 2000 mg/kg body weight. Due to the severity of the dermal responses/clinical observations, for humane reasons no additional higher levels were attempted.

Following dosing, the limit test rabbits were observed daily and weighed weekly. A gross necropsy examination was performed an all animals at the time of scheduled euthanasia (day 14). Clinical abnormalities observed during the study included decreased defecation, soft stools, faeces small in size, decreased food consumption, breathing abnormalities and dark material around the facial area. Severe dermal irritation was noted at the site of test material application. Severe dermal irritation was noted for the 2000 mg/kg dose level including apparent haemorrhaging at the test site. A slight body weight loss was noted in two males in the 500 mg/kg dose group and in two males and two females in the 2000 mg/kg dose group during the day 0 to 7 body weight period. Body weight gain was noted for all other animals during the test period. No significant gross internal findings were observed at necropsy on study day 14.

Under the conditions of this study the percutaneous LD50 was found to be in excess of 2000 mg/kg for both male and female rabbits.