Benzenamine, N-phenyl-, reaction products with 2,4,4-trimethylpentene

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From March 18, 1994 to June 29, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according toOECD guideline and according to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

Buehler Test

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

When this study was performed, the LLNA had not yet been adopted as an OECD method.

Species:

guinea pig

Strain:

other: Hartley-Albino

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley, Houston, Texas, USA
- Weight at study initiation: males: 364-456g, females: 359-468g
- Housing: 3-5 per cage (males separate from females) in suspended, wire bottom, stainless steel cages
- Diet (e.g. ad libitum): Purina Guinea Pig Chow, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: at least 5 days
- Cage Type: Suspended, wire bottom, stainless steel
- Transfer to Clean Cages: Weekly
- Litter Pan Lining: Paper
- Litter Pan Lining Change: Three times weekly
- Water System: Water bowls

Route:

intradermal and epicutaneous

Vehicle:

cotton seed oil

Concentration / amount:

Intradermal injections; 5% (v/v) of test mateirla in cottonseed oil vehicle with and without adjuvant (50:50 v/v)
Epicutaneous application: 100% test material

Route:

epicutaneous, occlusive

Vehicle:

cotton seed oil

Concentration / amount:

Intradermal injections; 5% (v/v) of test mateirla in cottonseed oil vehicle with and without adjuvant (50:50 v/v)
Epicutaneous application: 100% test material

No. of animals per dose:

Screening test: 3 males and 3 females
Test group: 10 males and 10 females
Control group: 5 males and 5 females

Details on study design:

RANGE FINDING TESTS:
- No. of animals: 3 males and 3 females
Selection of 5% v/v for intradermal injection was based on the fact that 5% is the maximum concentration suggested by Magnusson and Kligman (1969), and it was not irritating in the screening test.
Undiluted test material was selected for the topical insult because it was requested by Ciba and it was not irritating in the screening test. The undiluted test material was also selected for the challenge because although slight irritation was seen with undiluted test material in pretest screening, no irritation was present after the topical treatment with undiluted test material.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: day 0: 3 pairs of intradermal injections, Day 6: Sodiumlauryl sulfate in pertolatum gently massaged into the skin, Day 7: epicutaneous exposure for 48 hours, Day 21: challenge epicutaneous exposure for 24 hours
- Test groups: First insult:
with 1) adjuvant diluted 50% v/v in an injectable isotonic saline solution, 2) a 5% v/v solution of the test material in cottonseed oil, and 3) a 50:50 mixture of adjuvant (diluted 50% v/v in an injectable isotonic saline solution) and the 5% v/v solution of the test material
Second insult:
the exposure sites of the test group animals were treated with the undiluted test material
- Control group: First insult:
with 1) adjuvant diluted 50% v/v in an injectable isotonic saline solution, 2) vehicle alone (cottonseed oil), and 3) a 50:50 mixture of adjuvant (diluted 50% v/v in an injectable isotonic saline solution) and the vehicle
Second insult:
the exposure sites of the control group animals were covered with a dry patch of filter paper
- Site: the upper back of each animal within a 4 x 6 cm exposure area running laterally across the shoulders (within a 2 x 4 cm area)
First pair of injections was made at the anterior edge of the exposure area
Second pair of injections :was made approximately 0.5 cm behind the first pair
Third pair of injections was made approximately 0.5 cm behind the second pair of injections.
- Concentrations:
First pair of injections consistes of Freund's Complete Adjuvant diluted to 50% v/v in 0.9% saline
Second pair of injections, consisting of a 5% v/v solution of the test material in cottonseed oil
Third pair of injections, consisting of a 50:50 mixture of Freund's Complete Adjuvant (diluted to 50% v/v in 0.9% saline) and a 5% /v solution of the test material in cottonseed oil


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Exposure period: 24 hours
- Test groups: A 2 x 2 cm patch of filter paper saturated with 0.5 ml of the undiluted test material
- Control group: in a manner identical to the Day 7 treatment (A patch of dry filter paper was placed over the exposure areas)
- Site: applied topically to the right flank of each test
- Concentrations: 100%
- Evaluation (hr after challenge): 48 hours

Grading of sensitization was based on Magnusson and Kligman (J. Invest. Dermat. 52: 268-276 (1969))

Challenge controls:

Control animals were treated at the same time periods and locations as the test group but with the vehicle used in place of the diluted test material for the intradermal mjections. The control animals received a topical application of dry filter paper only. Two weeks after the topical application, all animals were challenged with a topical application of the undiluted test material at a virgin test site.

Positive control substance(s):

yes

Remarks:

DNCB C-3762 Lot 98F03521

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5 mL undiluted

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

2 animals found dead on day 9, but not related to the administration of test material

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 mL undiluted. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: 2 animals found dead on day 9, but not related to the administration of test material.

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.5 mL undiluted

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.5 mL undiluted. No with. + reactions: 0.0. Total no. in groups: 20.0.

None of the test animals or control animals exhibited skin reactions after the challenge treatment.

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

EC 270-128-1 is considered to be non skin sensitizing in this Maximization Test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

EC 270-128-1 was evaluated for its sensitizing potential in Guinea Pigs. It was found to be non-sensitizing.

The studies were found to be adequate to fulfil the purposes of this endpoint.

Migrated from Short description of key information:
not skin-sensitizing to guinea gigs

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

There are conclusive but not sufficient data for classification of EC 270 -128 -1 with regard to skin sensitization.

EC 270 -128 -1 is not classified for this endpoint in accordance to Directive 67/548/EEC or the CLP Regulation (EC) No 1272/2008.

 

No data are available for respiratory sensitization.

EC 270 -128 -1 is therefore not classifiable for this endpoint in accordance to the CLP Regulation (EC) No 1272/2008.