Aspartic acid

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:

2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

Principles of method if other than guideline:

The "maximisation test" of B. Magnusson and A. M. Kligman modified according to Maurer & Hess was performed to reveal a possible sensitising potential of "L-Asparaginsäure". Investigations performed were in conformance with the EC-directive 96/54, 8.6., "Skin Sensitisation" and the OECD-guideline 406, "Skin Sensitisation". As the test substance was insoluble in a variety of solvents, the protocol according to Maurer and Hess was followed (Th. Maurer and R. Hess (1989). The Maximization test for skin sensitization potential - updating the standard protocol and validation of a modified protocol. Fd. Chem. Toxic. Vol. 27, No. 12, p. 807-811).

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

Supplier: Harlan Winkelmann, Gartenstrasse 27, D-33178 Borchen.
Species, strain: Supplier: Guinea pigs, Dunkin Hartley, HsdPoc:DH.
Sex, specification: Female healthy young adult and non pregnant animals
Age of the animals: Approx. 4 - 7 weeks at the first application.
Weight range of the animals at the first application: 211 g to 389 g.

Room temperature: Average of 22 °C, continuous control and recording
Relative humidity: Average of 50.8 % in step 1, of 63.2 % in step 2; continuous control and recording.
Air exchange: Approx. 12/h.
Light: Only artificial light from 6.00 a.m. to 6.00 p.m.
Cages: Until Day 0: Makrolon cages type III (23 cm x 39 cm bottom area, 18 cm height) with wire mesh lids, single caging. From Day 0: group caging in plastic containers (46 cm x 105 cm x 36 cm), partly shaded, 1 group per container.
Feed: Altromin Maintenance Diet No. 3122, rich in crude fibers, ad libitum, offered in stainless steel containers.
Bedding material: Wood chips (aspen). Reduction of microorganisms by autoclaving.
Water: Tap water offered in Makrolon bottles with stainless steel canules ad libitum.
Acclimatisation: 4 days.

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

50 % (w/w) in white petrolatum for the first epicutaneous induction,
50 % (w/w) in white petrolatum for the second epicutaneous induction and
50% (w/w) in white petrolatum for the challenge exposure.
A test substance concentration of 50 % (w/w) in white petrolatum was the highest technically feasible concentration.

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

50 % (w/w) in white petrolatum for the first epicutaneous induction,
50 % (w/w) in white petrolatum for the second epicutaneous induction and
50% (w/w) in white petrolatum for the challenge exposure.
A test substance concentration of 50 % (w/w) in white petrolatum was the highest technically feasible concentration.

No. of animals per dose:

2 x 10 animals for the test substance group; 2 x 5 animals for the control group.

Details on study design:

The study was performed in two consecutive steps: In the first step 10 control and 5 test substance animals were used and as negative results were obtained, additional 10 + 5 animals were used.
As the test substance was insufficiently or not at all soluble in water, acetone, DMSO and ethanol, white petrolatum (ÖAB9) was used as a vehicle and as a reference substance for the epicutaneous induction exposures and for the challenge exposure.

First induction exposure on Day 0: intradermal injections of FCA (to enhance a possible sensitisation) and immediately afterwards epicutaneous application of the test substance to the sites of the intradermal injections. Application site was an area of approx. 2 cm x 4 cm in the interscapular region. The exposure time was 24 hours.
Second induction exposure on Day 8: epicutaneous application of the test substance to the sites of the intradermal injections. The exposure time was 48 hours.
Challenge exposure on Day 22: epicutaneous application of the test substance to the left flanks and application of the vehicle to the right flanks of all animals. Exposure for 24 hours.

Challenge controls:

Epicutaneous application of the test substance to the left flanks and application of the vehicle to the right flanks of all animals, including the control animals.

Positive control substance(s):

yes

Remarks:

periodic check with hexylcinnamic aldehyde

Positive control results:

80 % of the positive control animals were sensitized.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the results of this study, L-aspartic acid needs not to be labelled with "R43 May cause sensitisation by skin contact".

Executive summary:

The "maximisation test" of B. Magnusson and A. M. Kligman modified according to Maurer & Hess was performed to reveal a possible sensitising potential of "L-Asparaginsäure". Investigations performed were in conformance with the EC-method B.6., "Skin Sensitisation" and the OECD-guideline 406, "Skin Sensitisation". As the test substance was insoluble in a variety of solvents, the protocol according to Maurer and Hess was followed.

The study was performed in two consecutive steps: In each step 10 female guinea pigs were used as a test substance group and another 5 females were used as a negative control group. Immediately after the injection of Freund's complete adjuvant the test substance was administered epicutaneously on the same area. One week later a second epicutaneous induction exposure followed and two weeks afterwards the epicutaneous challenge exposure. Test substance concentrations were:

50 % (w/w) in white petrolatum for the first epicutaneous induction,

50 % (w/w) in white petrolatum for the second epicutaneous induction and

50% (w/w) in white petrolatum for the challenge exposure.

Results:

Skin reactions after the challenge exposures:

The control sites of all animals of both groups were normal at each reading time.

After the challenge exposures, no animal of the test substance group had positive skin reactions at the test substance treated sites 24 hours and/or 48 hours after the end of the exposure. No adverse skin reactions were observed in the control animals. Therefore no animal of the test substance group was regarded to be sensitised.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Migrated from Short description of key information:
No sensitisation was observed in a guinea pig maximisation test.

Justification for selection of skin sensitisation endpoint:
the key study is selected.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

There is no indication to justify a classification.