Phenol, 4-nonyl-, branched

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-07-14 to 1986-08-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study OECD 406

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The in vivo study data were obtained in studies performed before any in vitro sensitization tests had been validated and accepted for regulatory purposes’

Test material

Test material information

Constituent 1

Reference substance name:

Isononylphenol

EC Number:

234-284-4

EC Name:

Isononylphenol

Cas Number:

11066-49-2

IUPAC Name:

3-nonylphenol

Details on test material:

- Name of test material (as cited in study report): Nonylphenol
- Substance type: pure active substance
- Physical state: liquid
- Analytical purity: >= 98% iso-Nonylphenol
- Impurities (identity and concentrations): 90% p-Nonylphenol; 10% o-Nonylphenol; <= 2% Dinonylphenol; <=0,2% Phenol

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Bor: DHPW

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Age at study initiation: not mentioned
- Weight at study initiation: 342.8 g (mean weight of the test animals); 359.0 g (mean weight of the control animals)
- Housing: 1 - 5 animals in Makrolon cages type IV
- Diet (e.g. ad libitum): G4 complete feed for guinea pigs ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 4 - 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per h): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1986-07-15 To: 1986-08-15

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Induction 2

Concentration / amount:

- Concentrations used for induction: intradermal injection: 0.1 ml 0.9 %; dermal treatment: 50 % (2x4 cm)
- Concentration in Freunds Complete Adjuvant (FCA): 0.9 % test substance in a mixture of FCA and corn oil (1:1)
- Concentrations used for challenge: 1st challenge: 10 % and 30 %; 2nd challenge: 45 %

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Challenge 2

Concentration / amount:

- Concentrations used for induction: intradermal injection: 0.1 ml 0.9 %; dermal treatment: 50 % (2x4 cm)
- Concentration in Freunds Complete Adjuvant (FCA): 0.9 % test substance in a mixture of FCA and corn oil (1:1)
- Concentrations used for challenge: 1st challenge: 10 % and 30 %; 2nd challenge: 45 %

No. of animals per dose:

test group: 20 animals
control group: 10 animals

Details on study design:

RANGE FINDING TESTS: 50% dilution tested in 4 animals, no further details mentioned

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 1st exposure: intracutaneous injections (0.1 mL); 2nd exposure: epicutaneous for 48 h; evaluation 24 and 48 h after patch removal
- Concentration in Freunds Complete Adjuvants (FCA): 0.9% test substance in a mixture of FCA and corn oil (1:1)
- Test group: dermal: 50% test substance in corn oil (2 x 4 cm patch)
- Control group: corn oil (2 x 4 cm patch)
- Frequency of applications: day 0: intradermal treatment, day 7: dermal treatment
- Duration: 3 weeks


B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: on day 21 and 28
- Exposure period: dermal application for 24 h
- Test groups: 1st challenge: 10 and 30% test substance in corn oil (2 x 2 cm patch); 2nd challenge: 45% test substance in corn oil (2 x 2 cm patch)
- Control group: same treatment as test group animals
- Site: 1st challenge: left flanks (front: 30%; rear: 10% test substance in corn oil); 2nd challenge: right rear flanks
- Evaluation (hr after challenge): 48 and 72 h

Challenge controls:

see above B. Challenge exposure

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

10, 30 and 45 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10, 30 and 45 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 2

Reading:

2nd reading

Hours after challenge:

72

Group:

negative control

Dose level:

10, 30 and 45 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 10, 30 and 45 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 3

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10, 30 and 45 %

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10, 30 and 45 %. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 4

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

10, 30 and 45 %

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 10, 30 and 45 %. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

RESULTS OF PILOT STUDY: The preliminary test of a 50% dilution had caused skin irritation in 1 of 4 animals.

 

RESULTS OF TEST

- Sensitization reaction: No sensitising effects were noted.

- Clinical signs:

General reactions during the investigation: The changes in body weight did not differ between the treated animals and controls.

Local reactions during the test:

After the intracutaneous administration there was distinct erythema and oedema and the formation of necrosis at all FCA injection sites. There was slight erythema and oedema after injection of the test substance 0.9%. There was also slight erythema after the injection of corn oil.

After the patch test with contact for 48 h, the test animals had moderate to severe inflammation at the FCA injection sites, and the control animals likewise had slight inflammation and incrustation of these injection sites.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Iso-nonylphenol has no sensitizing potential in a guinea pig maximization test according OECD 406.

Executive summary:

In a dermal sensitization study with iso-nonylphenol (>= 98%) 20 female guinea pigs (Bor:DHPW) were tested using the method of Magnusson-Klingman (OECD 406). No clinical signs or substance related changes of body weight were observed. No sensitising effects were noted after intradermal induction with 0.9% and challenge with 10% to 50% after 7 and 14 days.

In this study, iso-nonylphenol is not a dermal sensitizer. The sensitization study in guinea pigs is classified acceptable and satisfies the guideline requirement.