Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27.May.2008-10.June.2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Test material form:
liquid
Details on test material:
• Sponsor’s identification: LCA08009 • Date received : 14 May 2008
• Container : plastic flask (n=1) • Form : liquid
• Quantity : 142.44 g (container + contents) • Colour : brown
• Batch n° : LCA08009 • Storage : room temperature
• Production date: - • Expiry date: -
• CAS No: - • Purity: 30% It was identified under the code number: PH-08/0227.

The test item was considered as 100% for the study.
Informations concerning the identity, purity and stability of the test item are the responsibility of the Sponsor. A safety data sheet and an information data sheet concerning the test item were provided by the study monitor.
Specific details on test material used for the study:
• Sponsor’s identification: LCA08009 • Date received : 14 May 2008
• Container : plastic flask (n=1) • Form : liquid
• Quantity : 142.44 g (container + contents) • Colour : brown
• Batch n° : LCA08009 • Storage : room temperature
• Production date: - • Expiry date: -
• CAS No: - • Purity: 30% It was identified under the code number: PH-08/0227.

The test item was considered as 100% for the study.
Informations concerning the identity, purity and stability of the test item are the responsibility of the Sponsor. A safety data sheet and an information data sheet concerning the test item were provided by the study monitor.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals:
Twenty Sprague Dawley rats (SPF Caw) originated from Elevage JANVIER (53940 Le Genest St Isle – France), were used after an acclimatisation period of at least five days. At the beginning of the study, the animals of the treated group weighed between 226 g and 248 g (males) and between 185 g and 222 g (females) and were 7-8 weeks old.
Group 1 (control): 5 male rats Rm0722 to Rm0726 and 5 female rats Rf0727 to Rf0731
Group 2 (treated): 5 male rats Rm0752 to Rm0756 and 5 female rats Rf0757 to Rf0761

Housing:
During the 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 conventional air conditioned animal husbandry; the environmental conditions were:
- temperature : between 19°C and 21°C - relative humidity : between 39% and 55% - 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. Microbiological and chemical analyses of the water were carried out once every six months by the Institut Européen de l'Environnement de Bordeaux (I.E.E.B.).

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Dose and administration mode
Animals from Group 2 received by topical application, under porous gauze dressing, an effective dose of 2000 mg/kg body weight of LCA08009, administered under a volume of 2.05 mL/kg body weight, during 24 hours. After 24-hour exposure period, the gauze dressings were removed and the treated area was rinsed with distilled water.
Animals from Group 1 received in the same experimental conditions the control item (liquid paraffin) under a volume of 2 mL/kg body weight.
Duration of exposure:
24 hours
Doses:
Group 1: control item (liquid paraffin) under a volume of 2mL/kg body weight
Group 2: 2000 mg/kg body weight under a volume of 2.05 mL/kg body weight
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
Examinations of the animals

Daily examination
Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 5 days after administration of the test solution. This examination focuses particularly on a list of symptoms, recorded as "present" or "absent" on the observation sheet. These observations were compared to control data. Observations and a mortality report were then carried out every day for 14 days.

Periodical examinations
The animals were weighed on day D0 (just before administering the test item) then on D2, D7, and D14. Weight changes were calculated and recorded.

Examination at the end of the test
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
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.
Clinical signs:

No systemic clinical signs related to the administration of the test item were observed. It was noted a slight to moderate erythema, on the treated area, 24 hours after the test item administration in all treated animals. The treated areas have recovered a normal aspect between D3 (male) and D11 (female).
Body weight:
The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals.
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:
GHS criteria not met
Conclusions:
The LD50 of the test item LCA08009 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 LCA08009 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 LCA08009 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. The experimental protocol was established on the basis of the official method as defined in the O.E.C.D. guideline. n° 402 dated February 24th, 1987 and the test method B.3 of the directive. n° 92/69/EEC.

No mortality occurred during the study.

No systemic clinical signs related to the administration of the test item were observed. It was noted a slight to moderate erythema, on the treated area, 24 hours after the test item administration in all treated animals. The treated areas have recovered a normal aspect between D3 (male) and D11 (female). The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals.

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

In conclusion, the LD50 of the test item LCA08009 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 LCA08009 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.


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