Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-06-03 to 2008-06-17
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): LCE08086
- Physical state: Liquid
- Analytical purity: 31% (dry extract)
- Purity test date: 2008-03-29
- Lot/batch No.: 0807000020
- Expiration date of the lot/batch: 2001-03-10
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Sprague Dawley rats (SPF Caw) originated from Elevage JANVIER (F-53940 Le Genest St Isle), were used after an acclimatation period of at least five
days. At the beginning of the study, the animals of the treated group weighed between 211g and 257g (males) and between 202g and 220g
(females) and were 7-8 weeks old.
Housing:
During treatment, the animals were kept in individual cage. At D3, the animals were put into their cage by 2 or 3. The rats were kept in
solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventionnal air conditionned animal husbandry; the environmental conditions were:
- Temperature: between 41% and 69%
- Relative humidity: between 41% and 69%
- Lighting time: 12 hours daily
- Rate of air exchange: at least ten changes per hour

Food and drink:
Drinking water (tap-water from public distribution system) and foodstuff were supplied freely.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Animals received by topical application, under porous gauze dressing, an effective dose of 2000 mg/kg body weight of LCE08086, administrated
under a volume of 1.83 mL/kg body weight, during 24 hours. After 24-hour exposure period, the gauze dressing were removed.
Animals from control group received in the same experimental conditions the control Item (Liquid paraffin) under a volume of 2.32 mL/kg body body weight
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight (1.83 mL/kg body weight)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
Systemic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 5 days after administration of the test item.
This examination focuses particularly on a list of symptoms, recorded as "present" or "absent" on the examination sheet.
These observation were compared to control data.
Observations and mortality report were then carried out every day for 14 days.

The animals were weighed on day D0 (just before administrating the test item) then on D2, D7 and D14.

On D14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels. Macroscopic observations were entered on individual autopsy sheets.
Only those organs likely to be modified in cases of acute toxicity were examined. Those presenting macroscopic anomalies can be removed and preserved in view to microscopic examinations.
Statistics:
no data

Results and discussion

Preliminary study:
no preliminary study performed
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study
Clinical signs:
No systemic clinical signs related to the administration of the test item were observed.
A slight to well defined erythema was noted, on the treated area, 24 hours after the test item administration in four treated female rats (4/5). The
treated areas have recovered a normal aspect between D2 and D4.
Body weight:
The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals.
Gross pathology:
No gross pathology

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of the test item LCE0806 is 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 the E.E.C. Directives 67/548, 2001/59 and 99/45, the test item LCE08086 must not be classified. No symbol and risk phrase are required.
In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must not be classified in category 4. No signal word and hazard statement are required.
Executive summary:

The test item LCE08086 was applied onto the intact skin of 10 sprague Dawley rats (5 males and 5 femalles) at the single dose of 2000 mg/kg body weight. The experimental protocol was established on the basis of the official method as defined in the OECD guideline n° 402 dated February 24th, 1987 and the test method B.3 of the directive n°92/69/EEC.

No mortality occured during the study.

No systemic clinical signs related to the administration of the test item were observed.

A slight to well defined erythema was noted, on the treated area, 24 hours after the test item administration in four treated female rats (4/5). The treated areas have recovered a normal aspect between D2 and D4.

The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals.

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

In conclusion, the LD50 of the test item LCE0806 is 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 the E.E.C. Directives 67/548, 2001/59 and 99/45, the test item LCE08086 must not be classified. No symbol and risk phrase are required. In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must not be classified in category 4. No signal word and hazard statement are required.