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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01-02-2012 to 15-02-2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Justification for type of information:
Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
inspected: July 2011; signature: August 2011
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methoxy-4-methylphenyl methyl carbonate
EC Number:
700-673-7
Cas Number:
132638-45-0
Molecular formula:
C10H12O4
IUPAC Name:
2-methoxy-4-methylphenyl methyl carbonate
Test material form:
solid
Details on test material:
- Physical state: Extremely pale yellow crystalline solid
- Storage condition of test material: Approximately 4°C in the dark, under nitrogen

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan: WIST
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised Supplier
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: Female: 213 - 230 g; Male: 272 – 300 g; The weight variation did not exceed ±20% of the mean weight per sex at the start of treatment.
- Fasting period before study: Not applicable.
- Housing: suspended solid floor polypropylene cages furnished with woodflakes; the animals were housed individually during the 24 hour exposure period. Then in groups of five by sex, for the remainder of the study.
- Diet (ad libitum): 2014C Teklad Global Rodent Diet (Recognised Supplier); provided ad libitum
- Water (ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: 01-02-2012 To: 15-02-2012

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
TEST SITE
- Area of exposure: the day before treatment the back and flanks were clipped free of hair. Dorsal area application.
- % coverage: Approximately 10% of total body surface
- Type of wrap if used: The area of application was covered piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- Constant volume or concentration used: Not applicable.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 per sex per dose (5 male/5 female); treated sequentially following application to 1 sentinel per sex per dose .
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality checks were conducted at approximately 0.5, 1, 2, and 4 hours and subsequently once daily for 14 days. Local effects were examined once daily for 14 days after the completion of the 24-hour exposure period. Full details on the scoring and criteria (consistent with Draize) are given in the full study report. Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
other: - Clinical observations: No signs of systemic toxicity were noted during the observation period. - Dermal reactions: Very slight erythema was noted at the test site of four females (maximum score = 1; in 5 females and 5 males at days 1 to 2 only). Test si
Gross pathology:
No abnormalities were noted at necropsy

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the dermal LD50 was established to exceed 2000 mg/kg bw in male/female Wistar (RccHan: WIST) strain rat. Applicant assessment indicates, under the conditions of this study, and according to the GHS criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.
Executive summary:

The study was performed according to OECD TG 402 and EU Method B.3 Acute Toxicity (Dermal) and in accordance with GLP to assess the acute dermal toxicity of the test substance in the Wistar (RccHan: WIST) strain rat. A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There was no mortality during the study. There were no signs of system toxicity or abnormalities on necropsy. All males and females showed expected gains in body weight during the study, except for two females which showed no gain or a slight loss (1 gram) in body weight during the first week with expected gain in body weight during the second week. However, this was still considered to be within the historical range for this strain. Very slight erythema was noted at the test site of four females (maximum score = 1; in 5 females and 5 males at days 1 to 2 only). Test sites appeared normal two or three days after dosing. No other signs of dermal irritation were noted. Under the conditions of this study, the dermal LD50 was established to exceed 2000 mg/kg bw in male/female Wistar (RccHan: WIST) strain rat. Applicant assessment indicates, under the conditions of this study, and according to the GHS criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.

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