Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 26 June to 10 July 2012
Reliability:
1 (reliable without restriction)

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:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
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: orange fluid gel
Details on test material:
Lot/Batch: No.1645
Purity: 100%
Test item was considered to be stable in test conditions

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
5 males and 5 females
Age: 7 and 8 weeks for males and females, respectively
Weight at dosing: 220 - 238 g (males) and 188 - 205 g (females)
Acclimation period: at least 5 days

Diet: M2-rat/mouse maintenance
Water: tap-water from public distribution system (Microbiological and chemical analyses of the water were carried out once every six months by IPL, Santé, Environnement Durables - Atlantique, Bordeaux)
Housing: Individually during treatment (24 hours), then 5 rats / cage (clear polycarbonate cages with stainless steel)

Temperature: 19-25°C
Humidity: 30 - 70%
Air changes: fifteen changes per hour
Photoperiod: 12 hours continous light (07:00 to 19:00) and 12 hours darkness

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 hours before the treatment, fur was removed from the dorsal area of the trunk of the test animals by clipping. At least 10 per cent of the body surface area was clear for the application of the test item.
Then, rats received the test item by topical application, under porous gauze dressing.
Duration of exposure:
After 24-hours exposure period, the gauze dressings were removed and the treated area was rinsed with distilled water.
Doses:
An effective dose of 2000 mg/kg body weight of CAE administered under a volume of 2.19 mL/kg body weight (corresponding to 2 g/kg b.w. according to the calculated density).
No. of animals per sex per dose:
Limit-test: 10 rats treated with a single dose of 2000 mg/kg b.w.
Control animals:
other: control historical data
Details on study design:
Mortality, clinical signs and skin examination were recorded daily for the duration of the study (14 days).
Individual body weights were measured and recorded on days 0 (dosing), 2, 7 and 14. On day 14, all surviving animals were sacrificed and all animals were necropsied for gross pathological changes.
Statistics:
None.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred during the study.
Clinical signs:
No systemic clinical signs related to the administration of the test item were observed. Erythema was noted from 48 hours post-dose in three females and was totally reversible on day 4. Dryness was noted from day 3 in three females and was totally reversible on day 6.
Body weight:
The body weight evolution of the animals remained normal throughout the study.
Gross pathology:
The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
In conclusion, the LD50 of the test item CAE was higher than 2000 mg/kg body weight by dermal route in the rat.
According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with EEC Directives 67/548, 2001/59 and 99/45, the test item CAE must not be classified. No symbol or risk phrase is required.
In accordance with Regulation EC No.1272/2008 on classification, labelling and packaging of substances and mixtures, the test item must not be classified. No signal word or hazard statement is required.
Executive summary:

In an acute dermal toxicity study, the test item CAE was applied onto the intact skin of 10 Sprague Dawley rats (5 males and 5 females) at the single dose of 2000 mg/kg body weight (limit test) under an occlusive patch, according to the official method as defined in O.E.C.D. guideline No.402 and in test method B.3 of Council Regulation No.440/2008.

All animals were observed for 14 days. Then surviving animals were sacrificed and a necropsy was conducted. Body weights were recorded on days 0 (dosing), 2, 7, 14.

No mortality occurred during the study. No systemic clinical signs related to the administration of the test item were observed. Erythema was noted from 48 hours post-dose in three females and was totally reversible on day 4. Dryness was noted from day 3 in three females and was totally reversible on day 6.

The body weight evolution of the animals remained comparable between treated and control animals throughout the study.

The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

In conclusion, the LD50of the test item CAE was higher than 2000 mg/kg body weight by dermal route in the rat.

According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with EEC Directives 67/548, 2001/59 and 99/45, the test item CAE must not be classified. No symbol or risk phrase is required.

In accordance with Regulation EC No.1272/2008 on classification, labelling and packaging of substances and mixtures, the test item must not be classified. No signal word or hazard statement is required.