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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 12 Sep 2007 to 29 Nov 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to an international test guideline and to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, Wölferstrasse 4, 4414 Füllinsdorf, Switzerland
- Age at study initiation: 8 weeks for males and 11 weeks for females
- Weight at study initiation: approximately 250 g for males and 200 for females
- Fasting period before study: No
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz) during treatment and observation.
- Diet (e.g. ad libitum):Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst/ Switzerland) ad libitum. Results of analyses for contaminants will be archived at RCC Ltd.
- Water (e.g. ad libitum):Community tap-water, from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses will be archived at RCC Ltd.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 (music during the daytime light period)

IN-LIFE DATES: From 20 sep 2007 to 04 Oct 2007

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back of the animals
- % coverage: 10% of the total body surface
- Type of wrap if used: The semi-occlusive dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.90 mL/kg bw
- Concentration (if solution): 1.0553 g/mL
- Constant volume or concentration used: yes
- For solids, paste formed: not applicable
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Daily during the acclimatization period, at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
- Frequency of weighing:On test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs: Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded. Local signs: Once daily during days 2-15. All abnormalities were recorded.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occured during the study.
Clinical signs:
No clinical signs were observed during the observation period.
Body weight:
All animals gained weight during the study period. The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
Effects on organs: No macroscopic findings were recorded at the scheduled necropsy.
Other findings:
Signs of toxicity (local):
At removal of the patch, no local signs were observed in any animal. However, on test day 5, one female exhibited a slight local erythema. Additionally, slight scaling was recorded at the same observation time point up to day 8 (in the same female). Otherwise, no local reactions were observed in any other animal up to the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material is not harmul by the dermal route.
Executive summary:

In an acute dermal toxicity study ((RCC 2007 study n° B31195), 5 male and 5 female Wistar rats were dermally exposed to undiluted Dimethyl 2-methyl glutarate for 24 hours to 10% of body surface area at the dose of 2000 mg/kg bw.  Animals were then observed for 14 days.

 

Dermal Combined LD50> 2000  mg/kg bw.

Dimethyl 2-methyl glutarate is not classified based on the LD50.

 

No mortality and no clinical signs were noted during the study. No local signs were observed in any animal except for one female which exhibited a slight local erythema on day 5 and a slight scaling from days 5 to 8. There was no effect on body weight gain.

 

This acute dermal study is classified as acceptable.  It does satisfy the guideline requirement for an acute dermal study (OECD402) in the rat.