Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-08-20 to 1986-02-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because the study closely followed OECD 406.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test

Test material

Constituent 1
Reference substance name:
Unrefined light paraffinic distillate (CAS # 64741-50-0)
IUPAC Name:
Unrefined light paraffinic distillate (CAS # 64741-50-0)
Details on test material:
- Name of test material (as cited in study report): 84-01 Light Paraffinic Distillate
- Test substance: Unrefined light paraffinic oil
- Physical state: Yellow liquid
- CAS number: 64741-50-0

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Dutchland Inc., Denver, Pennsylvania
- Age at study initiation: 5 to 6 weeks of age
- Weight at study initiation: Between 435 and 595 grams
- Housing: Individual cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 24 degrees Celsius
- Humidity (%): 37% to 62% relative humidity
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Paraffin oil
Concentration / amount:
A 25% volume/volume mixture of the in paraffin oil was used for the induction applications.
1% volume/volume mixture was used for the challenge dose.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Paraffin oil
Concentration / amount:
A 25% volume/volume mixture of the in paraffin oil was used for the induction applications.
1% volume/volume mixture was used for the challenge dose.
No. of animals per dose:
10 animals were exposed per dose application.
Details on study design:
RANGE FINDING TESTS:
6 guinea pigs received two concentrations of undiluted test concentrations of 25%, 50% and 75% volume/volume in paraffin oil. Additional testing at 10% and 1% volume/volume were needed due to the irritation seen at the 25% volume/volume test.

Results from range finding test:
1% - no dermal irritation
10% - slight dermal irritation and no response
25% - slight dermal irritation
50% - well defined dermal irritation
undiluted test material applications - well defined dermal irritation

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: One application per week for three weeks, for a total of three applications
- Exposure period: 6 hours
- Test groups: Six groups consisting of 10 guinea pigs each group. Dose range group tested 6 animals.
- Control group: The positive control group tested 20 guinea pigs
- Site: Back of each animal. Hair was removed.
- Frequency of applications: One application per week for three weeks
- Duration: Three weeks
- Concentrations: 25%

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: One
- Exposure period: 21 hours
- Test groups:
- Control group: Vehicle control group dosed with 0.4 mL of undiluted paraffin oil. Positive and naive control group: 0.4 mL of a 0.1% w/v suspension of 2,4- dinitrochlorobenzene in acetone.
- Site: Previously untreated test sites were used for the challenge application
- Concentrations: 0.4 mL of 1% v/v mixture of test material in paraffin oil.
- Evaluation (hr after challenge): 24 and 48 hours
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene 0.3% w/c in 80% aqueous ethanol.

Study design: in vivo (LLNA)

Positive control substance(s):
other: 2, 4-dinitrochlorobenzene

Results and discussion

Positive control results:
Slight to severe irritation was exhibited by all twenty animals. The reactions of all 20 animals equaled or exceeded the highest reaction observed in the naive positive control animals.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: sensitisation phase
Group:
test chemical
Dose level:
0.4 mL at 25%
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
slight erythema
Remarks on result:
other: Reading: other: sensitisation phase. Group: test group. Dose level: 0.4 mL at 25%. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: slight erythema .
Reading:
other: challenge phase
Group:
test chemical
Dose level:
0.4 mL at 1%
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
slight erythema
Remarks on result:
other: Reading: other: challenge phase. Group: test group. Dose level: 0.4 mL at 1%. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: slight erythema .
Reading:
other: sensitising phase
Group:
negative control
Dose level:
undiluted Paraffin oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no signs of erythema or oedema
Remarks on result:
other: Reading: other: sensitising phase. Group: negative control. Dose level: undiluted Paraffin oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no signs of erythema or oedema.
Reading:
other: challenge phase
Group:
negative control
Dose level:
undiluted Paraffin oil
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
slight erythema, no oedema
Remarks on result:
other: Reading: other: challenge phase. Group: negative control. Dose level: undiluted Paraffin oil. No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: slight erythema, no oedema.
Reading:
other: sensitisation phase
Group:
positive control
Dose level:
0.4 mL at 0.3%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
slight to severe irritation
Remarks on result:
other: Reading: other: sensitisation phase. Group: positive control. Dose level: 0.4 mL at 0.3%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: slight to severe irritation.
Reading:
other: challenge phase
Group:
positive control
Dose level:
0.4 mL at 0.1%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
slight to severe irritation
Remarks on result:
other: Reading: other: challenge phase. Group: positive control. Dose level: 0.4 mL at 0.1%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: slight to severe irritation.

Any other information on results incl. tables

The criteria used to evaluate the responses are described in the report as follows:
Determination of sensitization was based upon reactions to the challenge dose. Grades of 1 or greater in the test animals indicate evidence of sensitization, provided grades of less than 1 are seen in the naive controls. If grades of 1 or greater are noted in the naive control animals, then the reactions of test animals that exceed the most severe naive control reaction are considered sensitization reactions.

Using these criteria, none of the test animals became sensitized following treatment with API 84-01. In contrast, all the positive control animals were sensitized by their treatment.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
84-01 was not considered to be a skin sensitizer in guinea pigs when tested by the closed patch technique.
Executive summary:

In a dermal sensitization study using 84 -01 in paraffin oil, 10 young Hartley guinea pigs were tested using the method of Buehler.

Slight erythema reaction was exhibited by six animals but did not exceed the highest reaction of the naive control animals. The other four animals tested did not exhibit a reaction. In this study, 84 -01 is not considered to be a dermal sensitizer.

This study received a Klimisch score of 1 and is classified as reliable without restriction because the study closely followed OECD 406.