Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 November 1991 to 20 December 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guidelines and the study was conducted under GLP conditions.

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test

Test material

Constituent 1
Reference substance name:
9-Octadecenoic acid (Z)-, isooctyl ester, reaction products with glycerol trioleate and sulfur
EC Number:
306-111-3
EC Name:
9-Octadecenoic acid (Z)-, isooctyl ester, reaction products with glycerol trioleate and sulfur
Cas Number:
96152-40-8
IUPAC Name:
9-Octadecenoic acid (Z)-, isooctyl ester, reaction products with glycerol trioleate and sulfur
Test material form:
not specified
Details on test material:
- Physical state: liquid
- Purity: 100%
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Murphy Breeding Laboratories, Plainfield, IN, USA
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: 286 - 382 g
- Housing: individually in stainless steel cages
- Diet: Guinea Pig Chow 5025, Ralston Purina Co., St Louis, MO, USA ad libitum
- Water: purified water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ºC (average)
- Humidity (%): 37 % (average)
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: epicutaneous (unspecified)
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.3 mL test material was applied undiluted
Challengeopen allclose all
Route:
other: epicutaneous (unspecified)
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.3 mL test material was applied undiluted
No. of animals per dose:
10 males were treated with test material and 10 males served as untreated controls
Details on study design:
RANGE FINDING TESTS:
Preliminary testing was conducted to help inform on the concentration of test material to dose during definitive testing. Concentrations of 0.5, 1, 5, 10, 25, 50, 75 and 100% test material in mineral oil were applied to the skin before being scored for erythema. Based on the results of the preliminary tests it was decided to use the test material undiluted in the skin sensitisation assay.

MAIN STUDY
A. INDUCTION EXPOSURE
The backs of all guinea pigs were clipped free of fur. Using a Hill Top Chamber, 0.3 mL of undiluted test material was applied to the upper left quadrant of ten guinea pigs once a week for a period of 3 weeks. An elastic adhesive bandage was wrapped around the midsection of each guinea pig to keep the Hill Top Chamber in place. All wrapping materials were removed 6 hours after each application. Ten control guinea pigs were handled in the same manner, but were not dosed with test material during the induction phase of the study.

B. CHALLENGE EXPOSURE
Two weeks following the application of the last induction dose, 0.3 mL of the undiluted test material was applied to the lower left quadrant of the backs of the ten treated and ten control guinea pigs. The test material was applied as described above. All wrapping materials were removed 6 hours after test material application.

- Skin Examination: Approximately 24 and 48 hours after administration of the first induction dose and the challenge dose, the test sites were scored for erythema according to the method of Draize (see "Any other information on materials and methods incl. tables" for further information). To facilitate scoring, the guinea pigs were depilated with Neet® Hair Remover approximately 2 hours prior to the 24 hour scoring during the challenge phase.

- Observations: All animals were observed daily for mortality and morbidity

- Bodyweights: Bodyweights were measured weekly

- Animal disposition: After the final observation all animals were sacrificed without necropsy
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene

Results and discussion

Any other information on results incl. tables

Mortality

None of the animals died during the study.

Bodyweights

The bodyweights of the treated animals was comparable to those of the controls.

Skin effects

Erythema reactions with Draize scores of 2 were observed in five treated and four control guinea pigs 24 hours after challenge. Based on the results of the preliminary testing and erythema scores seen in the treated animals following the first induction dose and in the control animals at challenge, the erythema present in the treated animals following the challenge dose was considered to have been caused by test material irritation rather than by a sensitisation response. Only one animal had an erythema score of 3, which in this study would have been considered to be a positive response, indicative of a sensitisation reaction.

Table 2: Summation of Individual Erythema Scores Following Challenge

Group

Time of scoring after challenge dose

24 hours

48 hours

0

1

2

3

4

0

1

2

3

4

Treated

0

4

5

1

0

0

7

3

0

0

Control

0

6

4

0

0

0

8

2

0

0

Positive Control Results

Positive erythema reactions were observed in all treated animals following challenge compared to only one animal in the control group. A strong positive sensitisation reaction was observed thereby confirming the validity of the test method.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Test material-induced skin irritation prevented the assessment of a weak sensitisation response in this study. However, the presence of moderate to severe erythema in only one treated animal following challenge indicated that repeated dermal exposure to the test material did not induce a moderate to strong dermal sensitisation reaction. Under the conditions of the study, the test material was determined to be not sensitising.
Executive summary:

The skin sensitisation potential of the test material was determined following a methodology equivalent to that in the standardised guideline OECD 406 using the Buehler Method. During the study, 0.3 mL test material was applied, unchanged, to the shaved backs of ten male guinea pigs once a week for three weeks. Ten control guinea pigs were handled in the same manner but were not treated with the test material. Two weeks following the induction period, the treated and control animals received a challenge dose of 0.3 mL of undiluted test material. All animals were scored for erythema 24 and 48 hours following the first application of induction dose and of the challenge dose.

 

Erythema scores of 2 were observed in five treated and four control animals 24 hours after the challenge dose. An erythema score of two is usually considered a positive indication of a sensitisation response, however, since an erythema score of 2 was seen in approximately the same number of control animals as treated animals following challenge, the erythema was considered to have been caused by test material irritation, rather than indicating a true sensitisation response. The presence of test material-related dermal irritation therefore prevented the assessment of a weak sensitisation response, however, since moderate to severe erythema was seen in only one of the treated animals, the test material did no appear to induce a moderate or strong dermal sensitisation response during the study. Therefore, the test material is considered to be unlikely to be a skin sensitiser.

Categories Display