Adipic acid, compound with hexane-1,6-diamine (1:1)

Endpoint summary

Description of key information

LLNA: not sensitizing; BASF 2010, OECD Guideline Study

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

April 24, 2002

GLP compliance:

yes (incl. QA statement)

Remarks:

Experimental Toxicology and Ecology BASF SE 67056 Ludwigshafen, Germany

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

- Analytical purity: > 99.9%
- Lot/batch No.: Charge: 49501856P0

Species:

mouse

Strain:

other: CBA/J

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld
- Age at study initiation: 7 - 12 weeks
- Weight at study initiation: 18.3 g – 20.0 g
- Housing: single
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

other: 1% aqueous Pluronic

Concentration:

20%

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: 20% was highest possible concentration
- Irritation: At 20% the animal did not show any signs of local irritation as confirmed by the ear weight and lymph node weight measurements

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: The increase SI of cell count by a factor of ≥ 1.5 and/or of 3H-thymidine incorporation by a factor of ≥ 3 as compared to the concurrent vehicle control group is generally considered as indicating a sensitizing potential of a test substance. If a test substance does not elicit a biological relevant increase in cell count, 3H-thymidine incorporation but shows a clear concentration related increase in response, further investigation of the sensitization potential at higher concentrations should be considered.

TREATMENT PREPARATION AND ADMINISTRATION: Epicutaneous application is simulating dermal contact with the compound which is possible to occur under practical use conditions. Application volume: 25 μL per ear; Site of application: Dorsal part of both ears; Frequency of application: 3 consecutive applications (day 0 – day 2) to the same application site. On study day five (about 66 to 72 hours after the last application of test substance to the ears) the mice were injected intravenously with 20 μCi of 3H-thymidine in 250 μl of sterile saline into a tail vein.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Parameter:

SI

Remarks on result:

other: Cell counts: control group: 1.00; test group: 1.21 3H-Thymidine incorporation: Control group: 1.00; test group: 0.92 Lymph Node Weight: control group: 1.00; test group: 1.0 Ear weight: control group: 1.00; test group: 1.03

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: 3H-Thymidine incorporation: Control group: 1081.1 DPM/Lymph node pair Test group: 998.4 DPM/Lymph node pair

Interpretation of results:

GHS criteria not met

Conclusions:

Thus it is concluded that AH-Salt (Adipic acid, compound with hexane-1,6-diamine (1:1)) does not show a skin sensitizing effect in the Murine Local Lymph Node Assay under the test conditions chosen.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a dermal sensitization study (BASF 2010) with 20% AH-Salt (Adipic acid, compound with hexane-1,6-diamine (1:1)) in 1% aqueous Pluronic, 5 young female CBA/J mice were tested using the method of OECD 429 (Local Lymph Node Assay). The study was carried out as a limit test, using 1 test group and 1 control group. Three days after the last application the mice were injected intravenously with 20 μCi of³H-thymidine into a tail vein. About 5 hours after the³H-thymidine injection, the mice were sacrificed and the auricular lymph nodes were removed. No signs of systemic toxicity were noticed. When applied as 20% preparation in 1% aqueous Pluronic®, the test substance did not induce a biologically relevant response (no increase to 1.5 fold or above of control value = stimulation index (SI) ≥ 1.5) in the auricular lymph node cell counts. Concomitantly, the increase of³H-thymidine incorporation into the cells was not biologically relevant (no increase above the cut off stimulation index of 3). There was no increase in lymph node weights and ear weights, as well. Thus it is concluded that AH-Salt (Adipic acid, compound with hexane-1,6-diamine (1:1)) does not show a skin sensitizing effect in the Murine Local Lymph Node Assay under the test conditions chosen (20% AH salt).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the data available for a 20% AH-Salt in solution, there is no need to classify AH-Salt for skin sensitisation according to the Directive 67/548/EC or EU GHS criteria (Regulation (EC) N° 1907/2006).