Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 Nov - 3 Dec 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 24 Feb 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Commission Directive 92/69/EEC
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD®BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Ltd, Margate, UK
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 209 - 227 g (males) and 204 - 214 g (females)
- Housing: individually during 24 h exposure period and in groups of 5 by sex for the remainder of the study in polypropylene cages, woodflake bedding
- Diet: Rat and Mouse Expanded Diet No.1 (Special Diets Services Limited, Witham, Essex, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 21, On one occasion the temperature was below the limit specified in the protocol (19 °C). This deviation was considered not to affect the purpose or integrity of the study.
- Humidity (%): 50 - 56
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
moistened with distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped area on back and flanks
- % coverage: approx. 10%
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semioccluded with a piece of self-adhesive bandage. The bandage was further secured with a piece of BLENDERM wrapped around each end.

REMOVAL OF TEST SUBSTANCE
- Washing: Treated skin and surrounding hair was wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- Concentration: 100%
- Constant volume or concentration used: yes
- For solids, paste formed: yes, moinstened with distilled water

Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 h after dosing and subsequently once daily for 14 days. After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidente of primary irritation and scored according to Draize Score. Individual body weights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

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 the study period.

Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
All animals showed expected gain in body weight during the whole study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
- Other observations: No signs of skin irritation were noted during the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this acute dermal toxicity study in rats an LD50 value of > 2000 mg/kg bw was found.
Executive summary:

A group of ten animals (five males and five females) was given a single oral dose of test material as a solution in dimethyl sulphoxide at a dose level of 2000 mg/kg bodyweight. The study was performed according to OECD guideline 402 and GLP. The animals were observed for fourteen days and were then killed and subjected to gross pathological examination. 2/5 males were found dead. Signs of systemic toxicity noted were ataxia, hunched posture, lethargy, decreased respiratory rate and laboured respiration with additional signs or incidents of pilo-erection, ptosis, gasping and noisy respiration, loss of righting reflex, increased salivation, red/brown stains around the mouth or snout and splayed gait. Surviving animals recovered three to six days alter dosing. Abnormalities noted at necropsy of the males that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study. The LD50 >2000 mg/kg.