Glycerides, castor-oil mono-, di- and tri-

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1964

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1964

Report date:

1964

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

In an intracutaneous test in albino guinea pigs, the control or test compound, dissolved in physiological saline, was injected every other day, three times each week until a total of 10 doses has been given. The injection sites were read and scored for diameter and intensity of erythema and height of edema at 24 and 48 hours following each injection. Two weeks after the administration of the tenth sensitization dose, a challenge dose was given by injection. Reactions were read and scored at 24 and 48 hours.

GLP compliance:

no

Type of study:

intracutaneous test

Justification for non-LLNA method:

No LLNA study performed with the substance is available for assessment. The test has been performed before the LLNA assay became the standard.

Test material

Test material information

Constituent 1

Reference substance name:

Castor oil

EC Number:

232-293-8

EC Name:

Castor oil

Cas Number:

8001-79-4

IUPAC Name:

Castor Oil

Specific details on test material used for the study:

- Name as cited in study report: Wyandotte Surfactant (Ethylene oxide adduct)
- Lot: 0-21848-C
- Purity: considered to be free of impurities
- Appearance: yellow viscous liquid

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Albino

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 383 to 548 grams
- Housing: The animals were group housed according to the respective test group in metal cages suspended above the droppings in an air-conditioned room.
- Diet: The diet consisted of Purina Laboratory Chow supplemented with fresh cabbage three times weekly, ad libitum
- Water: ad libitum

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal

Vehicle:

physiological saline

Remarks:

0.9 %

Concentration / amount:

0.1 % / First application: 0.05 mL, remaining nine doses: 0.1 mL

Day(s)/duration:

every other day (3 times a week) / 10 applications

Adequacy of induction:

not specified

Challenge

No.:

#1

Route:

intradermal

Vehicle:

physiological saline

Remarks:

0.9 %

Concentration / amount:

0.1 % / 0.05 mL

Day(s)/duration:

14 days after last induction

Adequacy of challenge:

not specified

No. of animals per dose:

8 animals in the treatment group, 4 animals in the positive control group.

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures:10
- Exposure period: every other day, three times each week, until a total of ten such sensitizing doses had been given.
- Site: A prepared area on the back and flanks of the respective guinea pigs. The backs were prepared by shaving with electric clippers and throughout the study were further shaved as necessary. In no case was the same injection site used more then once (each site was identified with a marking pen, directly below the site of injection). The test and control compounds were injected on the right flank of each animal and an identical volume of the vehicle was injected on the left side of each animal.
- Concentrations: 0.1 %
- Evaluation: The injection sites were read and scored for diameter and intensity of erythema and height of edema at 24 and 48 hours following each injection.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Two weeks following the administration of the tenth sensitizing dose
- Concentrations: 0.1 %
- Evaluation (hr after challenge): 24 and 48 hours

EVALUATION CRITERIA
In the event that the score for a challenge dose was greater then the average score of the ten sensitizing doses, the control or test compound was considered to have produced dermal sensitization in the guinea pig.

Challenge controls:

- Physiological saline was the control vehicle and was administered to the left flank of all the animals in this study.

Positive control substance(s):

yes

Remarks:

0.1 % dinitro-1-Chlorobenzene in 0.9 % physiological saline

Results and discussion

Positive control results:

Two sensitizing injections were made before skin reactions became apparent to 2,4-dinitro-l-chlorobenzene. From the third sensitizing dose on, a reaction was observed in all of the guinea pigs after each injection. Scarring and alopecia were observed at several of the injection sites. Reactions to the challenge dose were severe in all of the guinea pigs. Within 48 hours the center of the wheal appeared necrotic and was followed by formation of a scab and scar. The mean score for each of the four animals responding to the challenge dose of 2,4-dinitro- 1-chlorobenzene was 100 % greater than the mean values obtained from the sensitizing doses. Based upon the results obtained all of the guinea pigs in this positive control group were considered to have been dermally sensitized to 2,4-dinitro-1-chlorobenzene.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1%

No. with + reactions:

2

Total no. in group:

8

Clinical observations:

wheal and flare score of a greater magnitude then those observed during the sensitizing doses

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1%

No. with + reactions:

0

Total no. in group:

8

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.1%

No. with + reactions:

4

Total no. in group:

4

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.1%

No. with + reactions:

4

Total no. in group:

4

Any other information on results incl. tables

- All of the guinea pigs used in this study appeared essentially normal at all times.

- Mild to moderate reactions to the sensitizing doses of the test compound were observed. This could be considered as a reflection of drug irritancy. It will also be noted that on several occasions similiar but somewhat less pronounced reactions were observed following the injection of the control vehicle in the same animal.

- Four-of-eight guinea pigs responded to the challenge dose. Two of those responding produced a wheal and flare score of a greater magnitude then those observed during the sensitizing doses. These observed reactions however were not of the magnitude of any of those observed in the positive control group represented by 2,4-dinitro-1-chlorobenzene.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met