Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Equivalent or similar to OECD 402. There is no GLP compliance statement in the report but it is indicated that the study was designed to ensure compliance with the Code of GLP published in the Federal Register, December 1978.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1979

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

Constituent 1
Chemical structure
Reference substance name:
[3R-(3α,3aβ,7β,8aα)]-1-(2,3,4,7,8,8a-hexahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl)ethan-1-one
EC Number:
251-020-3
EC Name:
[3R-(3α,3aβ,7β,8aα)]-1-(2,3,4,7,8,8a-hexahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl)ethan-1-one
Cas Number:
32388-55-9
Molecular formula:
C17H26O
IUPAC Name:
1-((3R,3aR,7R,8aS)-3,6,8,8-tetramethyl-2,3,4,7,8,8a-hexahydro-1H-3a,7-methanoazulen-5-yl)ethanone
Test material form:
other: clear liquid
Details on test material:
- Name of test material (as cited in study report): IFF #78-060-04 , which is confirmed as Methyl Cedryl Ketone by data holder IFF
- Physical state: clear liquid
- Storage condition of test material: Amber bottle

Test animals

Species:
rabbit
Strain:
other: albino New Zealand type
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: C.S.E. Colony located in Branchville, N.J. USA.
- Age at study initiation: young adult
- Weight at study initiation: 2.34 to 3.09 kg at the start of dosing
- Housing: Standard laboratory conditions
- Diet (e.g. ad libitum): Purina rabbit chow
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 7 days

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal surface of the trunk
- % coverage: approximately 20%
- Type of wrap if used: Open plastic sleeves ("baggies") placed over trunk and the anterior end was taped against the rabbit. The substance was applied and then the posterior end of the sleeve ws taped against the rabbit, allowing the central portion to balloon.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Excess material cleansed from skin using disposable napkin moistened with saline
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Dose - 5 mL/kg bw
- Constant volume or concentration used: Variable volume (11.70 mL - 15.45 mL) based on body weight


Duration of exposure:
24 hrs
Doses:
5 mL/kg bw
No. of animals per sex per dose:
6 animals (3 male, 3 female)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations - Twice daily (weekdays) and once daily (weekends). Weighing - Before dosing and all survivors weighed before necropsy
- Necropsy of survivors performed: yes (gross necropsy)
- Other examinations performed: clinical signs, body weight, qualitative estimate of dermal irritation.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: Given as mL/kg bw in report; converted to mg/kg bw using density: 1.001 g/mL
Mortality:
There were no deaths (Appendix 1).
Clinical signs:
Application of the test article to the skin appeared to be tolerated well by the rabbits and slight to moderate erthema only was observed during the first 24 hours after application. Treated skin lost pliability and became thickened and dry by Day 6. By Day 14, the texture of the skin was reverting to normal in all animals. No signs of overt systemic toxicity were observed (Appendix I).



Body weight:
Bodyweights are presented in Appendix II.

Gross pathology:
Positive findings were restricted to the treated skin. In all rabbits the skin was scaled and the surface dry and the underlying fascia appeared sparse. (Appendix III)

Any other information on results incl. tables

Study report attachments:

Appendix I (Clincial signs) & II (Body weight) (CSE 0056)

Appendix III Gross Necropsy Findings (CSE 0056)

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to CLP
Conclusions:
A dose of >5000 mg/kg bw/day of the test substance maintained in contact with the skin for 24 hrs did not cause any mortalities, so the substance is considered non-toxic.
Executive summary:

In an acute dermal toxicity study (CSE 0056), groups of young adult albino New Zealand rabbits (3 males and 3 females) were dermally exposed to methyl cedryl ketone for 24 hours (approximately 20% body surface area) at doses of 5 mL/kg bw. Animals were then observed for 14 days.

Dermal LD50 Males/Females = >5000 mg/kg bw (limit test)

(LD50 values given as mL/kg bw in study report; LD50 values were converted to mg/kg bw using density: 1.001 g/mL)

No mortalities or signs of overt systemic toxicity were observed. The only treatment related clinical signs and necropsy findings related to the skin. Application of the test article to the skin caused transient moderate erythema and drying and scaliness by Day 8, which persisted through termination. Gross necropsy of each individual animal revealed effects were restricted to the skin. In all rabbits the skin was scaled and the surface dry and the underlying fascia appeared sparse.

This acute dermal study is classified as acceptable. It does satisfy the guideline requirement for an acute dermal study (OECD 402) in the rabbit.