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Toxicological information

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
Study period:
22 Apr - 04 June 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP guideline study. Reliability check data were not reported in details, but a report number was mentioned referring to these data. Since the study was GLP and guideline conform, the non-reporting of the reliability check data was not considered to affect the validity and reliability of the present study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The test was performed in 1992 when the OECD Guideline 406 adopted in 1992 was the current version. According to this guideline "the Guinea Pig Maximisation Test (GPMT) [...] and the non-adjuvant Buehler Test are given preference over other methods".

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): methyl hexanoate
- Batch No.: 1291191
- Physical state: colourless liquid
- Purity: > 98%
- Stability: stable for at least 3 years
- Expiration date: June 24, 1994
- Storage: at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain as given in study report: Dunkin-Hartley; Crl: (HA)BR
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: approx. 335 g
- Housing: 2-3 animals in Makrolon Type IV cages with standard softwood bedding
- Diet: Pelleted Altromin Maintenance Diet 3022 (Altromin, Lage, Germany), ad libitum, and carrots offered regularly
- Water: tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 45 - 70
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
Induction: 90% test substance in olive oil
Challenge: 50% test substance in olive oil
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
Induction: 90% test substance in olive oil
Challenge: 50% test substance in olive oil
No. of animals per dose:
3 (preliminary test), 10 (main test, both control and treatment)
Details on study design:
RANGE FINDING TESTS:
In a preliminary study a 90% dilution of the test substance in olive oil was detected as minimal irritating and a 50% dilution as a maximally non-irritating concentration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 (once a week)
- Exposure period: 6 h
- Test groups: 10 animals treated with the test substance
- Control group: 10 animals treated with olive oil alone
- Site: left cranial flank
- Frequency of applications: once a week
- Duration: 3 weeks
- Concentrations: 90% solution in olive oil

A patch test chamber (1 cm², van der Bend, INTERDERM bv) was used. The application dose was 0.08 mL/chamber

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after the 3rd induction
- Exposure period: 6 h
- Test groups: 10 animals treated with the test substance
- Control group: 10 animals treated with the test substance
- Site: bilaterally to caudal sheared flanks
- Concentrations: 50% solution in olive oil
- Evaluation (hr after challenge):24 and 48 h

SCORING OF SKIN REACTION
Grades of skin reaction:
0 = no reaction;
1 = weak erythema and/or edema;
2 = moderate and diffuse erythema and/or edema;
3 = strong erythema and/or edema.

EVALUATION CRITERIA
At least 15 % of treated animals with dermal effects.
Positive control substance(s):
yes
Remarks:
it was stated that last reliability check in the testing facility was done in May 1990 (Rep. Nr. given as TBD 900384)

Results and discussion

Positive control results:
Reliability check data not reported in present study report.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50% solution
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
weak dermal effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% solution. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: weak dermal effects.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% solution
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
weak dermal effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50% solution. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: weak dermal effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50% solution
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
weak dermal effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% solution. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: weak dermal effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% solution
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
weak dermal effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% solution. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: weak dermal effects.

Any other information on results incl. tables

In the tabulation above only results from the right flank are given, as the right flank was not used for induction.

According to OECD guideline 406, challenge should be performed on the untreated flank of the animals.

Table 1: Skin reactions 24 and 48 h after challenge with 50% solution of methyl hexanoate in olive oil:

 

24 h

48 h

test

group

control

(10)

treatment

(10)

control

(10)

treatment

(10)

flank

left

right

left

right

left

right

left

right

no skin reaction

1

7

4

9

3

7

6

7

weak

9

3

6

1

7

3

4

3

moderate

0

0

0

0

0

0

0

0

strong

0

0

0

0

0

0

0

0

 

No deaths occurred. No significant differences in body weight gain were noticed between treatment and control group.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified