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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:
31 October to 24 November 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Reference substance name:
Alcohols, C6-12
EC Number:
271-642-9
EC Name:
Alcohols, C6-12
Cas Number:
68603-15-6
IUPAC Name:
octan-1-ol
Details on test material:
- Name of test material (as cited in study report): Linevol 79, C6-12 alcohols Type C
- Substance type: technical product
- Physical state: clear, colourless liquid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: 1% C9
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: AL63995F
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: < 15 oC in dark

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall, Darley Oaks, Staffordshire UK
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 344-418 g
- Housing: 5 animals of the same sex per cage in stainless steel cages with grid floors
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-23
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 31-Oct-1995 To: 24-Nov-1995

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
1st application: Induction 50 % intradermal
2nd application: Induction 50 % occlusive epicutaneous
3rd application: Challenge 5 % and 30% occlusive epicutaneous
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
1st application: Induction 50 % intradermal
2nd application: Induction 50 % occlusive epicutaneous
3rd application: Challenge 5 % and 30% occlusive epicutaneous
No. of animals per dose:
10/sex test groups
5/sex control groups
Details on study design:
RANGE FINDING TESTS:
Primary irritation screens were carried out to determine the concentrations for the main test. To assess the reactions after intradermal injection, two animals were administered 0.1 ml at 10, 30 and 50% in vehicle and the same doses in Freund's Complete Adjuvant (6 injections/animal) and two animals were administered 1, 3 and 5%. Irritation after occluded topical application was assessed in two animals administered 0.25 ml at 10, 30, 50 and 100% (4 test sites/animal). Skin reactions were assessed 1, 2 and 7 days after removal of the dressings. Irritation after topical challenge was assessed by occluded application of 0.03 ml of 5, 10, 30 and 50% to the skin of three animals (4 test sites/animal) and reactions examined at 24 and 48 hr.

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal injection:
- No. of exposures: 1
- Test groups: 3 pairs of injections (0.1 ml) - test substance in Freund's Complete Adjuvant; test substance in vehicle; Freund's Complete Adjuvant
- Control group: vehicle in Freund's Complete Adjuvant; vehicle; Freund's Complete Adjuvant
- Site: dorsal region
- Frequency of applications: once
- Duration: day 1
- Concentrations: 50%

Occluded topical application:
- No. of exposures: 1
- Exposure period: 48 hr
- Test groups: 0.6 ml test substance in vehicle
- Control group: 0.6 ml vehicle
- Site: dorsal region overlying scapulae
- Frequency of applications: once
- Duration: day 8-10
- Concentrations: 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 22
- Exposure period: 24 hr
- Test groups: one flank treated with 0.03 ml test substance at each of 2 concentrations, the other flank was treated with 0.03 ml vehicle
- Control group: one flank treated with 0.03 ml test substance at each of 2 concentrations, the other flank was treated with 0.03 ml vehicle
- Site: right flank (left flank treated with vehicle)
- Concentrations: 5 and 30%
- Evaluation (hr after challenge): 24 and 48 hr

Challenge controls:
The control group (5/sex) were not induced but were challenged with 5 and 30% of the test substance
Positive control substance(s):
not required

Study design: in vivo (LLNA)

Statistics:
none

Results and discussion

Positive control results:
not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
30%
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
either slight erythema or eschar formation
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30%. No with. + reactions: 12.0. Total no. in groups: 20.0. Clinical observations: either slight erythema or eschar formation.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
30%
No. with + reactions:
19
Total no. in group:
20
Clinical observations:
either slight erythema or eschar formation
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30%. No with. + reactions: 19.0. Total no. in groups: 20.0. Clinical observations: either slight erythema or eschar formation.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
slight erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: slight erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
eschar formation
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: eschar formation .
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
30%
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
either slight erythema or eschar formation
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 30%. No with. + reactions: 5.0. Total no. in groups: 10.0. Clinical observations: either slight erythema or eschar formation.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
30%
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
either slight erythema or eschar formation
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 30%. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: either slight erythema or eschar formation.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no irritation reactions
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no irritation reactions.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no irritation reactions
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no irritation reactions.

Any other information on results incl. tables

RESULTS OF THE RANGE-FINDING STUDY: 

Intradermal administration resulted in slight erythema which had regressed by day 7.

Some animals developed eschar by day 7 and pallor, skin discoloration was also reported. There was no obvious dose relationship although concentrations from 1 to 50% were tested. Following topical induction eschar was observed at sites receiving undiluted Linevol 79, concentrations of 10 -30% resulted in exfoliation only, erythema was not observed. The topical challenge resulted only in discoloration in one animal and exfoliation in several.

 

RESULTS OF THE MAIN TEST:

After the intradermal induction phase, Freund's Complete Adjuvant either alone or with the test substance caused moderate erythema in the majority of animals.

 

After topical induction one male and one female had slight erythema and all 20 animals showed exfoliation on removal of the occlusive dressing. No reactions were observed in the ten control animals.

 

- Sensitization reaction: Challenge application of 30% v/v Linevol 79 in propylene glycol gave rise to eschar in 9 test and 3 control animals. A further 10 test and 5 controls showed slight erythema. Exfoliation was present in 2 test animals. Challenge application of 5% Linevol 79 resulted in eschar formation in 1 test animal and slight erythema in 1 test animal, exfoliation was observed in 3 test animals. No dermal reaction was evident following challenge application of propylene glycol alone. Irritation in the main test was obviously more marked than in the pilot study. While there was a slight increase in the incidence of significant responses in the test group this was attributed to primary irritation. Total significant responses in the test group were 19/20 for the 30% challenge and 8/10 for controls. Following challenge with 5% Linevol 79 in propylene glycol 2/20 test and 0/10 controls showed a significant response.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
In a reliable study, conducted according to OECD guideline 406 (Magnusson and Kligman method) Linevol 79 was not a skin sensitiser in the guinea pig maximisation test. A slight increase in significant reactions in the test group was attributed to primary irritation. The study was performed in compliance with GLP.

Classification: not sensitizing

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