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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose:
read-across: supporting information

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

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
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Type:
impurity
Test material form:
liquid
Details on test material:
Batch No. : FAB-29062016
Purity : 96.2% (sum of the two main constituents)
Name of test material (as cited in study report): alpha-pinene multiconstituent
Physical state: colourless liquid
Storage Conditions: +2°C to +8°C, under nitrogen and protected from light
Expiry Date: 28 June 2017

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 7 weeks old (male) and 8 weeks old (female)
- Weight at study initiation: from 253g to 286 g (male) and from 195g to 217g (female)
- Housing: Animals were housed in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid; During the treatment, the animals were kept in individual cages and after the removal of the patch on Day 1, the animals were put into their cage by group of 5.
- Diet: Foodstuff (SAFE, A04), ad libitum
- Water: Drinking water (tap water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: At least 10 changes/h
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 h before the treatment, fur was removed from the dorsal area of the trunk of the test animals by clipping.

TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: Approximately 10 % of the body surface area
- Type of wrap if used: Test material was applied by topical application, under porous gauze dressing.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Dose volume: mL/kg bw (corresponding to 2000 mg/kg bw according to the density of the test item)
- Constant volume or concentration used: Yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Animals were observed for any behavioural or toxic effects on the major physiological functions at 1, 3 and 5 h 24 hours and 48 hours after administration of the test item and continued on the following days if necessary. Clinical observations and mortality were recorded every day for 14 days.
- The integrity of the skin on the application site was noted.
Bodyweight was recorded on Days 0 (just before administering test item), 2, 7 and 14.
- Necropsy of survivors performed: Yes; On Day 14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels and macroscopic examination was performed.
Statistics:
None

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No systemic clinical signs related to the administration of the test item were observed.
Cutaneous reactions (erythema and dryness) were noted in all animals (10/10) at 24 h post-dose and were totally reversible on day 13.
Body weight:
Body weight evolution of the animals remained normal throughout the study compared to the historical control group.
Gross pathology:
No macroscopic abnormalities were observed at necropsy.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 of alpha-pinene multiconstituent is higher than 2000 mg/kg bw in rats therefore it is not classified according to CLP Regulation (EC) n° 1272/2008 and UN GHS.
Executive summary:

In an acute dermal toxicity study performed according to OECD Guideline 402 and in compliance with GLP, a group of Sprague Dawley rats (5/sex/dose) was given a single dermal application of alpha-pinene multiconstituent at 2000 mg/kg bw. The test item was applied on dorsal area of the trunk representing approximately 10% of the total body surface area of the animals. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

No mortality occurred during the study. No systemic clinical signs related to the administration of the test item were observed. Cutaneous reactions (erythema and dryness) were noted in all animals (10/10) at 24-hour post-dose and were totally reversible on day 13. Body weight gain of the animals remained normal throughout the study. The macroscopic examination of the animals at the end of the study did not reveal any treatment-related changes.

In conclusion, the LD50 of test item alpha-pinene multiconstituent is higher than 2000 mg/kg body weight by dermal route in the rat. Test item alpha-pinene multiconstituent does not have to be classified in accordance with Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures and UN GHS.