Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1971
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only short abstract available
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
Skin irritation was assessed in an acute dermal toxicity study.
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.2 to 3.3 kg bw
Type of coverage:
semiocclusive
Preparation of test site:
other: one site clipped and one site abraded per animal
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
4 (2 males and 2 females)
Details on study design:
Animals were observed for mortality, clinical signs of toxicity and dermal reactions for 14 days.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other:
Remarks:
abraded skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48 h
Score:
3
Max. score:
4
Reversibility:
other: Animal died on day 4
Remarks on result:
other:
Remarks:
abraded skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
other:
Remarks:
Induration and sloughing were observed up to 14 days
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
other:
Remarks:
Induration and sloughing were observed up to 14 days
Remarks on result:
other:
Remarks:
intact skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
other:
Remarks:
Induration and sloughing were observed up to 14 days
Remarks on result:
other:
Remarks:
abraded skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48 h
Score:
2
Max. score:
4
Reversibility:
other: animal died on day 4
Remarks on result:
other:
Remarks:
abraded skin
Irritant / corrosive response data:
Skin responses consisted of very slight to well-defined erythema and slight to very slight edema at 24 hours to moderate erythema and induration with skin sloughing by 14 days.
Other effects:
None

None

Interpretation of results:
other: irritating
Remarks:
in accordance with EU CLP (EC 1272/2008 and its updates)
Conclusions:
Overall skin responses consisted of very slight to well-defined erythema and slight to very slight edema at 24 hours to moderate erythema and induration with skin sloughing by 14 days. More specific, in the two rabbits with intact skin the average (24/48/72h) erythema and edema score was 1 in both rabbits. However the skin irritating effects in these two rabbits increased to slight and moderate effects during the 14 days. Under the conditions of the test the substance is considered to be a skin irritant.
Executive summary:

Rosemary oil was tested in an acute dermal toxicity study similar to OECD TG 402. Four New Zealand White rabbits were exposed to the test substance via dermal application. 2 males and 2 females were exposed to 10 mL/kg bw undiluted test substance under occlusive conditions for 24 hours. The substance was applied on the back and flanks of the rabbits. The skin was clipped and intact in two rabbits (one male and one female) and clipped and abraded in the other two animals. After an observation period of 14 days animals were necropsied. Gross signs of dermal irritation were determined and scored by the method of draize. Overall skin responses consisted of very slight to well-defined erythema and slight to very slight edema at 24 hours to moderate erythema and induration with skin sloughing by 14 days. More specific, in the two rabbits with intact skin the average (24/48/72h) erythema and edema score was 1 in both rabbits. However the skin irritating effects in these two rabbits increased to slight and moderate effects during the 14 days. Under the conditions of the test the substance is considered to be a skin irritant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1971
Report date:
1971

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

1
Reference substance name:
Rosemary, ext.
EC Number:
283-291-9
EC Name:
Rosemary, ext.
Cas Number:
84604-14-8
Molecular formula:
Not applicable for UVCB substance
IUPAC Name:
1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane; 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one; 2,2-dimethyl-3-methylidenebicyclo[2.2.1]heptane; 2,6,6-trimethylbicyclo[3.1.1]hept-2-ene
Test material form:
liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation:
females: 2.95 and 2.73 kg
males: 2.19 and 3.33 kg
- Housing: Animals were confined to a specially designed restrainer during exposure.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: The substance was applied on the back and flanks of the rabbits. The skin was clipped and intact (n=2) or clipped and abraded (n=2).
- Type of wrap if used: dental dam

REMOVAL OF TEST SUBSTANCE
- Washing (if done): sponged with warm tap water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 10 mL/kg
- Concentration: Undiluted

VEHICLE
not aplicable
Duration of exposure:
24 hours
Doses:
10 mL/kg
No. of animals per sex per dose:
2
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observation of gross signs of systemic toxicity of percutaneous absorption of the test material was made during the day following application and daily and thereafter for 14 days. Gross signs of dermal irritation were determined and scored following removal of the binders at 24 hours and thereafter for a total of 14 days. Individual body weights were recorded initially and at termination of the study.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 mL/kg bw
Based on:
test mat.
Mortality:
One death occured (day 4).
Clinical signs:
other: Ataxia was noted in one rabbit for three days. On day 4 this rabbit died. No toxic symptoms were observed in the remaining rabbits.
Gross pathology:
No gross pathological findings were noted in any of the animals.
Other findings:
- Other observations:
Very slight erythema was noted in Rabbit No. 21 at 24 hours and became well defined at day seven and moderate by day 10 through day 14. Very slight edema noted at 24 hours. !nduration at the application site occurred on day seven followed by sloughing. Similarly, very slight erythema noted in rabbit no. 22 at 24 hours became well-defined on day seven followed by sloughing. Well defined erythema and slight edema noted at 24 hours in the abraded rabbits became moderate by two to six days with moderate edema noted in Rabbit No. 23 at five days. By day eight the skin became indurated followed by sloughing in Rabbit No. 23.

Applicant's summary and conclusion

Interpretation of results:
other: not acute toxic
Remarks:
in accordance with EU CLP (EC 1272/2008 and its updates)
Conclusions:
The acute dermal toxicity test showed an LD50 of > 10 mL/kg bw corresponding to ca. 8000 mg/kg bw. Based on this result, the substance is considered to be not acute toxic via the dermal route.
Executive summary:

Rosemary oil was tested in an acute dermal toxicity study similar to OECD TG 402. Four New Zealand White rabbits were exposed to the test substance via dermal application. 2 males and 2 females were exposed to 10 mL/kg bw undiluted test substance under occlusive conditions for 24 hours. The substance was applied on the back and flanks of the rabbits. The skin was clipped and intact in two rabbits (one male and one female) and clipped and abraded in the other two animals. Skin responses consisted of very slight to welldefined erythema and slight to very slight edema at 24 hours to moderate erythema and induration with skin sloughing by 14 days. After an observation period of 14 days animals were necropsied. Ataxia was noted in one rabbit for three days (animal with abraded skin). On day 4 this rabbit died. No toxic symptoms were observed in the remaining rabbits. Body weight gain of the three surviving animals averaged 0.3 kg. No gross pathological findings were noted in any of the animals. The LD50 was determined to be higher than 10 mL/kg bw corresponding with ca. 8000 mg/kg bw.