1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl)-benzene

Endpoint summary

Description of key information

The test item is not a skin sensitiser under the conditions of the LLNA.

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

Study period:

May 03 - Jul 24, 2007

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:

2002-04-24

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands B.V., Postbus 6174 NL, 5960 AD Horst
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 18.5 +/- 1.0
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-88
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: day 1 To: day 5

Vehicle:

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

Concentration:

pre test for signs of irritation: 2.5, 5, 10 and 25 % (v/v)
main test: 5, 10 and 25 % (v/v)

No. of animals per dose:

pre test: 2
main test: 5 (f) per group (3 test groups, 1 control group) total 20 (f)

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: solubility in vehicle was demonstrated
- Irritation: pre test performed
- Lymph node proliferation response: no data
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: OECD TG 429
- Criteria used to consider a positive response: 3-fold greater response at one concentration in SI than control animals
TREATMENT PREPARATION AND ADMINISTRATION:
a) Topical application of 25 µL test item preparation (test group) or vehicle (control group)
b) five days after topical application: iv application of 3H-methyl thymidin
c) prior each treatment (a and b) ear thickness measurement
d) five hours after treatment (b) necropsy and analysis of the 3H thymidin incorporation in draining lymph nodes
e) method: pooled per animal

Positive control substance(s):

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

Statistics:

Dunnets Test

Positive control results:

Conc. SI
5 %: 2.43
10 % 4.07
25 % 4.88

Key result

Parameter:

SI

Value:

1.83

Test group / Remarks:

5 % test item

Key result

Parameter:

SI

Value:

1.69

Test group / Remarks:

10 % test item

Key result

Parameter:

SI

Value:

1.04

Test group / Remarks:

25 % test item

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA
Control: 508.3 DPM/lymph node
5 % test item: 930.0 DPM/lymph node
10 % test item: 858.1 DPM/lymph node
25 % test item: 530.4 DPM/lymph node

EC3 CALCULATION
The EC3 value could not be calculated since all SI's are below 3.

CLINICAL OBSERVATIONS:
No deaths occured. No symptoms of local toxicity at the ears of the animals and no systemic findings were observed.

BODY WEIGHTS
The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is not a skin sensitiser under the conditions of the LLNA.

Executive summary:

In the study the test item was dissolved in acetone:olive oil (4+1) was assessed for its possible contact allergenic potential. For this purpose a local lymph node assay was performed using test item concentrations of 5, 10, and 25 %. The GLP study was performed according to OECD 429.

The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. A relevant increase in ear thickness gain could not be observed after treatment with the test item. In this study Stimulation Indices (S.I.) of 1.83, 1.69, and 1.04 were determined with the test item at concentrations of 5, 10, and 25 % in acetone:olive oil (4+1), respectively. Since the S.I. was not increased above 3 at any test group, no EC3 could be determined.

From the data it can be concluded that the test item is not a skin sensitiser under the conditions of this assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In the study the test item was dissolved in acetone:olive oil (4+1) was assessed for its possible contact allergenic potential. For this purpose a local lymph node assay was performed using test item concentrations of 5, 10, and 25 %. The GLP study was performed according to OECD 429.

The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. A relevant increase in ear thickness gain could not be observed after treatment with the test item. In this study Stimulation Indices (S.I.) of 1.83, 1.69, and 1.04 were determined with the test item at concentrations of 5, 10, and 25 % in acetone:olive oil (4+1), respectively. Since the S.I. was not increased above 3 at any test group, no EC3 could be determined.

From the data it can be concluded that the test item is not a skin sensitiser under the conditions of this assay.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin sensitisation, the test item does not require classification for skin sensitisation according to Regulation (EC) No 1272/2008 (CLP).