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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from publication .

Data source

Reference
Reference Type:
publication
Title:
THE SENSITIZATION POTENTIAL OF SOME PERFUME INGREDIENTS TESTED USING A MODIFIED DRAIZE PROCEDURE
Author:
D.W. SHARP
Year:
1978
Bibliographic source:
Toxicology, 9 (1978) 261-271

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Modified Draize test method.
Principles of method if other than guideline:
Modified Draize Technique was employed to determine the concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the test chemical
GLP compliance:
not specified
Type of study:
Draize test
Justification for non-LLNA method:
not specified.

Test material

Constituent 1
Chemical structure
Reference substance name:
Octan-2-one
EC Number:
203-837-1
EC Name:
Octan-2-one
Cas Number:
111-13-7
Molecular formula:
C8H16O
IUPAC Name:
octan-2-one
Test material form:
liquid
Details on test material:
- Name of test material: Octan-2-one
- Molecular formula: C8H16O
- Molecular weight: 128.21 g/mol
- Substance type: Organic
- Physical state: Liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 350 g
- Housing: Housed in wire mesh cages in pairs of the same sex
- Diet (e.g. ad libitum): Pelleted guinea pig diet, cabbage and hay ad libitum
- Water (e.g. ad libitum): water ad libitum

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
other: yes (no details mentioned)
Concentration / amount:
Induction concentration: 0.1 mL at 2.5 X 1%(ICC) : 10 guinea pigs
Day(s)/duration:
3 weeks
Adequacy of induction:
other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC).
Challenge
No.:
#1
Route:
intradermal and epicutaneous
Vehicle:
other: yes (no details mentioned)
Concentration / amount:
Challenge concentration: 0.1 mL at 1% (ICC) and 20% (ACC): 10 guinea pigs
Re- challenge concentration: 0.1 mL at 1%(ICC) and 20% (ACC): 10 guinea pigs
Day(s)/duration:
24 hours
Adequacy of challenge:
other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC). The highest concentration which caused no irritation was selected as the application challenge concentration (ACC)
No. of animals per dose:
10 animals (4male and 6 female)
Details on study design:

RANGE FINDING TESTS: For each test material preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing.

MAIN STUDY
A. INDUCTION EXPOSURE: Intradermal
- No. of exposures:4
- Exposure period: No Data Available
- Test groups:10 guinea pigs
- Control group: No Data Available
- Site: 4 sites, 2 auxillary and 2 inguinal lymph nodes
- Frequency of applications:1
- Duration: No Data Available
- Concentrations: 0.1 mL at 2.5 X 1% (ICC)

B. CHALLENGE EXPOSURE: Intradermal and Epicutaneous
- No. of exposures:1
- Day(s) of challenge: Fourteen days later, challenge test was performed
- Exposure period:24 hours
- Test groups:10 guinea pigs
- Control group: No Data Available
- Site: onto the shaved flank in a small circular area
- Concentrations: 0.1 mL at 1% (ICC) and 20%(ACC).
- Evaluation (hr after challenge):24 hours

C. RECHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge: 7 Days Later , rechalleange test was performed.
- Exposure period: No Data Available
- Test groups:10 animal
- Control group: 4 animal (same sex)
- Site: Intradermally and topically on opposite flanks
- Concentrations: 0.1 mL at 1% (ICC) and 20% (ACC).
- Evaluation (hr after challenge): No Data Available

-Other:

Observations and scoring –
Each injection reaction was given a total score based on size (2 largest diameters), erythema and oedema. Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale. Reactions were examined under a Philips colour-matching unit with 3 Philips 40 W Actinic Blue 05 fluorescent tubes and 3 Philips 40 W White 35 fluorescent tubes.
Challenge controls:
At each challenge with controls, 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively.
Positive control substance(s):
not specified

Results and discussion

Positive control results:
No data

In vivo (non-LLNA)

Results
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 ml at 1%[ICC] and 20%[ACC]
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin sensitization reactions was observed at the tested concentrations
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

SENSITIZATION POTENTIAL OF SYNTHETIC PERFUME INGREDIENTS

Non-sensitizer = no evidence of sensitization

Test chemical

ICC(%)

ACC(%)

Results

111 -13 -7

1

20

Not sensitizer

 

Applicant's summary and conclusion

Interpretation of results:
other: not sensitising
Conclusions:
No signs of contact sensitization were observed at 1% ICC and 20% ACC concentrations. Hence, the test chemical was considered to be non-sensitizing to the skin of albino Hartley guinea pigs..

Executive summary:

Modified Draize Technique was employed to determine the concentrations suitable\ for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the test chemical

Hartley strain albino guinea pigs bred were used for the study. Four guinea pigs of same sex were used for the preliminary irritation study and 10 guinea pigs were used for the main sensitization studyand 4 previously untreated animals of the same sexwere used as challenge controls.

The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration(ACC) ]

The ICC and ACC for the test chemical was determined to be 1% and 20% respectively

In the induction phase, 0.1 ml aliquots of test substance at 2.5 times the ICC were injected intradermally at 4 sites which overlie the 2 auxillary and 2 inguinal lymph nodes. After a rest period of 14 days, each animal was challenged

intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC: the topical application was made by spreading 0.1 ml of the test substance onto the shaved flank in a small circular area which was not covered. Twenty-four hours later the reactions were scored and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included.At each challenge with controls, 4 previously untreated animals of the same sex were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively.

 

Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale and individual reactions were considered positive if (a) they were + or greater and (b) there were no erythema reactions in controls.

 

No signs of contact sensitization were observed at 1% ICC and 20% ACC concentrations. Hence, the test chemical ewas considered to be non-sensitizingto the skin of albino Hartley guinea pigs.