Castor oil, ethoxylated

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Data source

Reference

Reference Type:

publication

Title:

Assessment of the allergenic potential of althesin and its constituents

Author:

P. TACHON, J. DESCOTES, A. LASCHI-LOQUERIE, J. P. GUILLOT AND J. C. EVREUX

Year:

1983

Bibliographic source:

Br. J. Anaesth. (1983), 55, 715

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Guinea pig maximization test

Principles of method if other than guideline:

Guinea pig maximization test was performed to evaluate the dermal sensitization potential of the test chemical

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Currently no LLNA study is available for assessment. The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.

Test material

Test material information

Constituent 1

Reference substance name:

Castor oil, ethoxylated

EC Number:

500-151-7

EC Name:

Castor oil, ethoxylated

Cas Number:

61791-12-6

Molecular formula:

C57H104O9(CH2CH2O)n

IUPAC Name:

Castor oil, ethoxylated

Test material form:

liquid

Details on test material:

- IUPAC Name: Castor Oil, ethoxylated
- Smiles: CCCCCCC(CC=CCCCCCCCC(=O)OCC(C(=O)OCCCCCCCC=CCC(O)CCCCCC)OC(=O)CCCCCCC=CCC(O)CCCCCC)OCCOCCOCCOCCOCCO
- Molecular formula:C65H120O14
- Substance type:Organic
- Physical state:Liquid

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: IffaCredo, l'Arbresle, France
- Weight at study initiation: 300 to 400 g
The guinea pigs were maintained under standard test conditions

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

unchanged (no vehicle)

Concentration / amount:

two intradermal injections of Freund's complete adjuvant
10 repeated intradermal applications of the substance (0.5 ml per animal)

Day(s)/duration:

no data available

Adequacy of induction:

not specified

Induction 2

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.5 ml

Day(s)/duration:

48 h

Adequacy of induction:

not specified

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.5ml

Day(s)/duration:

48 hours

Adequacy of challenge:

other: guineapigs were challenged on the abdomen, using the maximum dose which had not caused any orthoergic skin reaction in preliminary studies

No. of animals per dose:

Groups of 10 male and female guinea pigs.

Details on study design:

RANGE FINDING TESTS: no data available

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal exposure
- No. of exposures: 10
- Exposure period: no data available
- Test groups: 10
- Control group: no data available
- Site: back
- Frequency of applications: 2 intradermal injections of FCA, 10 repeated intradermal applications of the substance (0.5 ml per animal)
- Duration: 48 hours
- Concentrations: 2 intradermal injections of FCA, 10 repeated intradermal applications of the substance (0.5 ml per animal)

Epicutaneous, Occlusive exposure
- No. of exposures: single
- Exposure period: no data available
- Test groups: 10
- Control group: no data available
- Site: back
- Frequency of applications: single
- Duration: 48 hours
- Concentrations: 0.5 ml


B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge:
- Exposure period: no data available
- Test groups: 10
- Control group:
- Site: abdomen
- Concentrations: Guineapigs were challenged on the abdomen, using the maximum dose which had not caused any orthoergic skin reaction in preliminary studies, 0.5 ml
- Evaluation (hr after challenge): 48 hours

OTHER: The macroscopic cutaneous response was evaluated, according to a classical scale for erythematous and oedematous lesions (Draize, Woodgard and Calvery, 1944). The macroscopic
examination was negative (no allergy) when the score was equal to or less than the score obtained following the first intradermal application. Otherwise, the examination was considered doubtful and a histological examination was undertaken to obtain specific evidence of an allergic reaction, such as skin infiltration with lymphocytes and plasmocytes.

Challenge controls:

no data available

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5 ml

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

The test chemical was found to be deviod of sensitizing capacity

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

Table: Skin-sensitizing potential of Althesin and its constituents in guinea pigs. Doses per animal used for challenge were 0.5 ml for the test chemical.

This dose was the maxima which did not cause any orthoergic response in preliminary studies

Substance	Macroscopic examination (% doubtful)	Histological examination (% positive)	Conclusion
Test chemical
Female	50	0	Not sensitizing
Male	60	0	Not sensitizing

Applicant's summary and conclusion

Interpretation of results:

other: not sensitizing

Conclusions:

The test chemical was found to be deviod of sensitizing capacity 48 hours after challenge exposure.
Hence, the test chemical was considered to be not sensitizing to skin.

Executive summary:

Guinea pig maximization test was performed to evaluate the dermal sensitization potential of the test chemical.

Groups of 10 male and female young adult Dunkin Hartley guinea pigs were used for the study.All animals were submitted to an intradermal sensitization test, performed with two intradermal injections of Freund's complete adjuvant.

During the induction period, 10 repeated intradermal applications of the substance (0.5 ml per animal) were performed on the skin on the back of the guineapigs. An occlusive bandage was applied for 48 h. After a 12-day rest period, guineapigs were challenged on the abdomen, using the maximum dose which had not caused any orthoergic skin reaction in preliminary studies. Doses per animal used for challenge were 0.5 ml for the test chemical. This dose was the maxima which did not cause any orthoergic response in preliminary studies.

Fortyeight hours later, the macroscopic cutaneous response was evaluated according to a classical scale for erythematous and oidematous lesions.The macroscopic examination was negative (no allergy) when the score was equal to or less than the score obtained following the first intradermal application, otherwise the score was considered as doubtful and a histological examination was performed to obtain the specific evidence of skin sensitization.

The test chemical was found to be deviod of sensitizing capacity 48 hours after challenge exposure.

Hence, the test chemical was considered to be not sensitizing to skin.