Nonylphenol, branched, 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:

other: Study was conducted similar to the OECD guidance 406 and the EU method B.6

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

; observations made only at single time point (i.e. 48 h after challenge) and not at 72 h

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

yes

Remarks:

; observations made only at single time point (i.e. 48 h after challenge) and not at 72 h

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study was conducted before LLNA method implementation

Test material

Test material information

Constituent 1

Reference substance name:

Nonylphenol, branched, ethoxylated

EC Number:

500-209-1

EC Name:

Nonylphenol, branched, ethoxylated

Cas Number:

68412-54-4

Molecular formula:

not available for this UVCB

IUPAC Name:

Nonylphenol, branched, ethoxylated (> 1 < 2.5 mol EO)

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 300-400 g
- Housing: groups of 5 animals in cage
- Diet: ad libitum (standard diet for guinea pigs)
- Water: ad libitum (a supplement of ascorbic acid was dissolved in the drinking water)

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

Injection: 1.0%
Topical: 5.0%
Challenge: 0.25%

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

Injection: 1.0%
Topical: 5.0%
Challenge: 0.25%

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS: The maximum sub-irritant concentration to be used in the main test was determined in preliminary experiments in which a series of concentrations of the test agents were applied.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Intradermal injections - three; topical application - single
- Exposure period: 48 h (topical application)
- Test group: Intradermal injections - Two rows of 3 intradermal injections were given on each side of the midline.
i) 0.1 mL Freunds adjuvent alone
ii) 0.1 mL test agent alone
iii) 0.1 mL test agent emulsified with Freunds adjuvent
Topical application - 6 d later the injection sites were shaved and treated with 10% sodium lauryl sulphate. The sites were left unbandaged for 24 h and after that a patch of test substance was applied occlusively for 48 h.
- Control groups: During the induction period the control animals were treated similarly to the test animals with the exception that the test compound was replaced with positive (p-phenylenediamine) and negative control (SLS), respectively.
- Concentrations: the test group: 1% (injection) and 5% (topical); the positive control group: 2.0% (injection and topical); the negative control group: 1% (injection) and 5% (topical)
- Frequency of applications: Topical application was made 1 wk after intradermal injections

B. CHALLENGE EXPOSURE
- No. of exposures: Single
- Day(s) of challenge: 1 d
- Exposure period: 24 h
- Test groups: The animals were challenged with test material topically 2 wks after the induction period. The challenge patch were removed after 24 h
- Control group: The control animals were treated similarly to the test animals with the exception that the test compound was replaced with positive (p-phenylenediamine) and negative control (SLS), respectively.
- Site: Flank
- Concentrations: the test group: 0.25%; the positive control group: 2.0%; the negative control group 0.5%
- Evaluation (h after start of challenge): 48 h

Challenge controls:

No data

Positive control substance(s):

yes

Remarks:

(2% p-phenylenediamine)

Results and discussion

Positive control results:

The group treated with p-phenylenediamine showed a positive reaction of 80%, which classifies it as a strong sensitiser.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

-

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.5%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: -.

Results 2

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.25%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

-

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.25%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: -.

Results 3

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

Dose level:

2%

No. with + reactions:

8

Total no. in group:

10

Clinical observations:

-

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 2%. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: -.

Any other information on results incl. tables

No reactions were observed on the guinea pigs treated with the test substance.

Applicant's summary and conclusion

Conclusions:

The substance did not induce skin sensitisation in guinea pig maximisation test.

Executive summary:

A study was conducted to evaluate if the substance induces sensitisation in guinea pigs. The test was conducted equivalent or similar to OECD Guideline 406 and the EU Method B.6. Ten female Dunkin-Hartley guinea pigs per group were used in the test. The procedure consisted of two parts: induction and challenge exposures. Doses were determined on the basis of preliminary investigations. The following test concentrations and protocol were used:

(i) Induction injection: 1.0% [two rows of 3 intradermal injections (Freunds adjuvent alone; test agent alone; test agent emulsified with Freunds adjuvant) were given on each side of the midline]

(ii) Induction topical application: 5.0% (a patch was applied occlusively for 48 h after 1 wk of injections)

(iii) Challenge: 0.25% (a patch was applied occlusively for 24 h after 2 weeks of induction)

The degree of response was determined 24 h after removal of the challenge patch. A positive control group was treated with p-phenylenediamine and a negative control group was treated with sodium lauryl sulphate. The positive control group showed a positive reaction of 80%, which classifies it as a strong sensitiser. None of the negative control or test animals showed sensitization reactions. In conclusion, the test substance did not induce skin sensitisation in guinea pig maximisation test (Cuthbert JA, 1975).