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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:
2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD guideline 402 and in accordance with GLP.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Principles of method if other than guideline:
Guideline followed
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Bioban TMCS-1246
- Molecular formula (if other than submission substance): C7H13NO2
- Molecular weight (if other than submission substance): 143.09
- Physical state: Clear Liquid
- Analytical purity: 98.7% ± 0.01%
- Lot/batch No.: TC1031LAH3
- Stability under test conditions: Not reported, assumed to be stable under normal storage conditions
- Storage condition of test material: +18 to +36 Deg. C

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Inhouse Bred
- Age at study initiation: 12 weeks
- Weight at study initiation: Males: 277.44 to 287.10 g
Female: 209.97 to 227.95 g
- Fasting period before study:
- Housing: Housed individually in standard polysulfone cages, with stainless steel top grill having facilities for pelleted food and drinking water.
- Diet (e.g. ad libitum): Mice pellet food ad libitum
- Water (e.g. ad libitum): Deep bore-well purified water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 23 deg.C
- Humidity (%): 65 to 67 %
- Air changes (per hr): 12 to 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsolateral thoracic surface
- % coverage: 10%
- Type of wrap if used: cotton gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Wiped with water using clean towels
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg body weight (1.85ml/kg body weight)
- Concentration (if solution): Undiluted test substance


VEHICLE
- Amount(s) applied (volume or weight with unit): Undiluted test substance used (No vehicle used)
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight (1.85 ml/kg body weigh)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

The acute dermal toxicity of Bioban TMCS-1246 was tested in male and female Wistar rats. The test was conducted using 10 rats, 5 males and 5 females. Approximately 24 hours prior to treatment, the hair on the dorso lateral thoracic surface of the skin was clipped (approximately 8 x 10 cm). Doses were calculated based on individual body weight, the undiluted test substance at the dose of 2000 mg/kg body weight (A volume of 1.85 mL/kg body weight) was applied directly to the prepared skin of the animal and covered with a cotton gauze and secured in position by non-allergenic surgical tape wound around torso. The test substance contact period with the skin was for 24 hours.

After the 24-hour contact period, the patches were removed and the application site was wiped with water using clean towels to remove any residual test substance.

Clinical observations, body weights and local skin reactions were recorded. At the end of the 14 day observation period, all rats were euthanised by using isoflurane anaesthesia. External surface of the body, all orifices, tissues and organs of the thoracic and abdominal cavities of all animals were examined. All findings were recorded.
Statistics:
None

Results and discussion

Preliminary study:
An initial dose of 2000mg/kg body weight (1.85 ml/kg body weight) was applied to 5 female rats. There was no test substance related mortality observed.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no test substance related mortality observed.
Clinical signs:
The clinical / toxic signs observed were hypersensitive response to handling in five female rats at 30 minutes after application, and at 1
hour and 2 hours in both male and female rats and it persisted in two female rats (Rb8503 and Rb8505) at 3'* hour post application. All the
male rats were normal from 3rd hour and all the female rats were normal from 4th hour post application period onwards.
Body weight:
All rats gained body weight through the observation period.
Gross pathology:
There was no abnormality detected at necropsy.
Other findings:
There were no local skin reactions observed at the site of application.

Any other information on results incl. tables

Refer attachment: Table1. Body weight, body weight Changes and Pre-Treatment deaths

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results, it can concluded that the acute dermal LD50 of Bioban TMCS-1246 is greater than the limit dose of 2000 mg/kg body weight in male and female rats.
Executive summary:

The acute dermal toxicity of BiobanTMCS-1246 was tested in male and female Wistar rats following OECD Guideline for Testing of Chemicals, No. 402; OPPTS 870.1200 (1 998) and European Communities. Methods for theDetermination of Toxicity, Part B.3.

The test was conducted using 10 rats, 5 males and 5 females. Approximately 24 hours prior to treatment, the hair on the dorso lateral thoracic surface of the skin was clipped (approximately 8 x 10 cm). Doses were calculated based on individual body weight, the undiluted test substance at the dose of 2000mg/kg body weight (A volume of 1.85 mL/kg body weight) was applied directly to the prepared skin of the animal and covered with a cotton gauze and secured in position by non-allergenic surgical tape wound around torso. The test substance contact period with the skin was for 24 hours.

 

After the 24-hour contact period, the patches were removed and the application site was wiped with water using clean towels to remove any residual test substance.

 

Clinical observations, body weights and local skin reactions were recorded. At the end of the 14 day observation period, all rats were euthanised by using isoflurane anaesthesia. External surface of the body, all orifices, tissues and organs of the thoracic and abdominal cavities of all animals were examined. All findings were recorded.

The toxic signs observed were hypersensitive response to handling at 30 minutes to 3 hours in female rats, and at 1stand 2nd hour in male rats and all the male rats were normal from 3rdhour and all the female rats were normal from 4thhour post application period onwards. There were no local skin reactions observed and no pre-terminal deaths. All rats gained body weight through the observation period. There were no abnormalities detected at necropsy.

Based on the above results, it is concluded that the acute dermal LD50 of BiobanTMCS-1246 is greater than the limit dose of 2000 mg/kg body weight in male and female rats.