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Description of key information

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Berolamine AA15. pre-guideline, pre-GLP. No data on positive control or reliability check is given.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Remarks:
Pre-GLP; signed authentication form present
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Porcellus Animals Ltd
- Age at study initiation: Not indicated
- Weight at study initiation: 300-400 g
- Housing: 5 per cage
- Diet (e.g. ad libitum): BP Nutrition FDI diet, at lib.
- Water (e.g. ad libitum): Source not specied; ad lib.
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS: Not indicated
IN-LIFE DATES: From: 4 april 1979 To: 27 April 1979
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal: 1% (w/w) testsubstance in water
Topical induction: 5% (w/w) in water (slightly irritant)
Topical challenge: 2% (w/w) in water (non-irritant)
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal: 1% (w/w) testsubstance in water
Topical induction: 5% (w/w) in water (slightly irritant)
Topical challenge: 2% (w/w) in water (non-irritant)
No. of animals per dose:
10 animals with test substance in treatment group, 7 animals in control group.
Details on study design:
RANGE FINDING TESTS:
Determination of maximum non-irritant concentration in two guinea pigs that were pretreated as the induction phase. Material was tested under occlusive patch system used for topical induction in concentrations of 10%, 5%, 2% and 1.0% (w/w) in water.
Test substance was slightly irritating at 5%. A concentration of 2% in water was selected for th challenge of the test group.

MAIN STUDY
A. INDUCTION EXPOSURE
- Test group: 10 animals
1. intradermal: Two rows of three intra dermal injections on each side of the midline across the shaved scapular region.
0.1 ml Freund's Complete Adjuvant (FCA) alone
0.1 ml test agent (1% w/w) alone
0.05 ml test agent (1% w/w) emulsified with 0.05 ml FCA.
2. One topical application 6 days later:
Injection side shaved and treated with 10% lauryl sulphate for mild inflammatory response. Solution was massaged into the backs, kept unbandaged for 24 hours. Then a 2x2 cm patch (Whatman no. 3 MM filter) saturated with 5% w/w test substance, and covered by impermeable plastic adhesive tape (Blenderm). The whole area was then firmly bound by Sleek acclusive tape and dressing was left in place for 48 hours.

- Control group: 5 animals
1. intradermal: Two intra dermal injections of FCA only on each side of the midline across the shaved scapular region.
2. No topical induction

B. CHALLENGE EXPOSURE
Test group and control group:
Two weeks after topical induction, a 2% test substance solution was applied to the shave right flank of the animals using the same method as for topical induction. The patch was removed after 24 hours. The response was determined 24 hours after removal of the challenge patch.

C. RESPONSE
Any animal showing erythema at the site of challenge would be considered to have shown a positive response.
Challenge controls:
Control group consisted of 7 animals similar to treatment group.
Controls only received FCA injections. Two animals were used for determining teh maximum test substance concentrations to be used for induction and challenge.
Positive control substance(s):
no
Positive control results:
No positive control or information on reliability is given.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2% w/w in water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2% w/w in water. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
2% w/w in water
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 2% w/w in water. No with. + reactions: 0.0. Total no. in groups: 5.0.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Substance was not senstisiting in the Guinea pig maximisation test
Executive summary:
Berolamine AA15 was tested according the Magnusson-Kligman Guinea pig maximisation test (similar to OECD 406). Berolamine AA15 did not elicit positive responses in the test group after challenge of the 10 guinea pigs by topical application with 2% aq. solution. From these results it is concluded that this product is a non-sensitiser in guinea pigs.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:
Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-productswas not senstisiting in the Guinea pig maximisation test.

 

All skin sensitisation studies performed on other AAI substances all indicate them to be sensitising.

As the substances within the AAI group show the same reactive groups, show similar composition inherent reactivity and toxicity is not expected to differ much between these substances.

However, Tall oil + ammonia-ethanolamine reaction by-products differs from other substances in the AAI group that are based on fatty acids with polyamines, in that it contains a high amount of hydroxylated polyethylene amines, causing it to display more neutral OH groups rather than basic primary amine groups. As toxicity is much related to the presence of free primary amine groups, it can be expected that specifically in aspects of sensitisation which is related to direct chemical interactions (protein binding required for haptenisation), this substance shows less effects compared to other AAI substances.


Migrated from Short description of key information:
Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-products was not sensitising to skin in a GPMT test.

Justification for selection of skin sensitisation endpoint:
Only study available

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There is no information on respiratory sensitisation, however, Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-products was not sensitising in a GPMT.Additionally, the likelihood for exposure via inhalation and thus becoming sensitised to AAI, is very low, based on the high boiling point (> 300 °C) and very low vapour pressure (of 8.4 x 10-8Pa at 25°C).


Migrated from Short description of key information:
No study available

Justification for selection of respiratory sensitisation endpoint:
At present, recognised and validated animal models for the testing of respiratory hypersensitivity are not available.

Justification for classification or non-classification

Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-products was not sensitising to skin in a GPMT test.

 

The actual risk of sensitisation is probably low, as AAI are corrosive to skin and consequently exposure will be low due to necessary protective measures to limit dermal exposure.

 

There is no data available with respect to respiratory sensitization byAAI-AEA. However, followinga very low vp pressure of 8.4 x 10-8Pa at 25°C anduse that does not involve the forming of aerosols, particles or droplets of an inhalable size, exposure of humans via the inhalation route will be unlikely.