Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD guidelines No. 402 “Acute Dermal Toxicity” 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:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Guideline followed.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report)
- Physical state: White powder
- Analytical purity: 99.5%
- Storage condition of test material: Room temperature in the dark.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Oxon, UK.
- Age at study initiation: 8-12 weeks (All the females were nulliparous and non-pregnant)
- Weight at study initiation: Atleast 200g
- Fasting period before study: overnight fasting immediately before dosing.
- Housing: The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

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

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and Flanks
- % coverage: 10% (approximately)
- Type of wrap if used: A piece of surgical guaze was placed over thetreatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Wiped with cotton wool moistened with arachis oil.
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): Test item was moistened with arachis oil.
Duration of exposure:
24 h
Doses:
2000 mg/kg bodyweight.
No. of animals per sex per dose:
5 male and 5 female rats were exposed to 2000 mg/kg bodyweight.
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for death or overt signs of toxicity 30 min, 1, 2 and 4 hour after dosing and subsequently once daily for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
None

Results and discussion

Preliminary study:
No mortality or evident toxicity observed at a dose level of 2000 mg/kg bodyweight.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality related to test item dermal toxicity.

However one animal was killed for humane reasons due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK HomeOffice Project Licence.
Clinical Observations: Signs of systemic toxicity confined to the animal that was humanely killed were prostration, ptosis and increased respiratory rate.
Necropsy: Abnormalities noted at necropsy of the animal that was humanely killed were haemorrhagic lungs, dark liver, dark spleen, small testes, enlarged prostate and fluid filled and reddened bladder.
Clinical signs:
There were no signs of systemic toxicity noted in the surviving animals.

Signs of systemic toxicity confined to the animal that was humanely killed were prostration, ptosis and increased respiratory rate.
Body weight:
Surviving animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Abnormalities noted at necropsy of the animal that was humanely killed were haemorrhagic lungs, dark liver, dark spleen, small testes, enlarged prostate and fluid filled and reddened bladder.
Other findings:
Dermal Irritation: Very slight erythema was noted at the test sites of three females. No ther signs of dermal irritation were noted.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000mg/kg bodyweight.
Executive summary:

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat following OECD TG No. 402 A group of 10 animals (5 males and 5 females) was given a single, 24 h, semi-occluded dermal application of the test item to intact skin at a dose level of 2000mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy at the end of study period.

Mortality: One animal was killed for humane reasons due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence.

Clinical Observations: Signs of systemic toxicity confined to the animal that was humanely killed were prostration, ptosis and increased respiratory rate. There were no signs of systemic toxicity noted in the surviving animals.

Dermal Irritation: Very slight erythema was noted at the test sites of three females. No signs of dermal irritation were noted. Bodyweight: Surviving animals showed expected gains in bodyweight over the study period.

Necropsy: Abnormalities noted at necropsy of the animal that was humanely killed were haemorrhagic lungs, dark liver, dark spleen, small testes, enlarged prostate and fluid filled and reddened bladder. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

CONCLUSION: The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000mg/kg bodyweight.