N-(5-chloro-2-isopropylbenzyl)cyclopropanamine

Skin sensitisation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2010

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

N-{[5-chloro-2-(propan-2-yl)phenyl]methyl}cyclopropanamine

EC Number:

941-682-8

Cas Number:

1476113-93-5

Molecular formula:

C13 H18 Cl N

IUPAC Name:

N-{[5-chloro-2-(propan-2-yl)phenyl]methyl}cyclopropanamine

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Remarks:

OlaHsd

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Remarks:

(AOO)

Concentration:

2.5, 5, 10 and 25%

No. of animals per dose:

5

Positive control substance(s):

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

Results and discussion

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

0.5

Test group / Remarks:

test material (2.5% w/v)

Results 2

Key result

Parameter:

SI

Value:

0.9

Test group / Remarks:

test material (5% w/v)

Results 3

Key result

Parameter:

SI

Value:

2.3

Test group / Remarks:

test material (10% w/v)

Results 4

Parameter:

SI

Value:

5.6

Test group / Remarks:

test material (25% w/v)

Remarks on result:

other:

Remarks:

strong symptoms of systemic toxicity excludes this group from conclusion

Results 5

Parameter:

SI

Value:

3.9

Test group / Remarks:

Positive control (25% HCA)

Applicant's summary and conclusion

Interpretation of results:

other: not sensitising

Conclusions:

Based on the results of the range finding test (excessive toxicity at 50 and 100% dose), the top dose of the test material in the main test was selected to be 25%. 25 μL of the different concentrations were applied to the ear of the mice once daily for 3 consecutive days. On day 6, the animals were euthanised and the lymph nodes prepared for the analysis. The calculated SI values for the treated mice were below 3 (0.5, 0.9 and 2.3 at 2.5, 5 and 10% of the test material respectively), the threshold for skin sensitisation. At 25% of the test material a SI value of 5.6 was obtained. As at this concentration morbidity and/or systemic toxicity was observed in 2/5 animals, this dose was not accepted for the conclusion. There were no confounding effects of irritation or systemic toxicity in the other 3 animals of this dose group and at the 2.5, 5 and 10% (w/v) concentrations. Slightly enlarged lymph nodes were observed in the 10% (w/v) group while enlarged lymph nodes were observed in the 25% (w/v) group for the four survived animals and in the positive control group.
The resulted stimulation index values were under the threshold limit of 3 observed at the three examined concentrations indicating that the test material is not a skin sensitizer according to EU classification criteria.