4'-trans-propyl-1,1'-bicyclohexyl-4-trans-carboxaldehyde

Endpoint summary

Description of key information

Key, skin sensitisation, LLNA, mouse, OECD 429, GLP: positive

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:

2 JUL 2007 - 26 SEP 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study performed according to OECD TG 429

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

24 April 2002

Deviations:

yes

Remarks:

The relative humidity in the animal room was increased above the recommended upper limit of 70 % for eight time intervals of 1 to 4 hours during the course of the study. This deviation, however, did not affect the validity of the study.

GLP compliance:

yes (incl. QA statement)

Remarks:

Hess. Ministerium für Umwelt, ländlichen Raum und Verbraucherschutz, Mainzer Str. 80, 65189 Wiesbaden

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Remarks:

CaOlaHsd

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands B.V. Postbus 6174 NL - 5960 AD Horst
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 18.7 - 22.0 g
- Housing: single
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days
- Indication of any skin lesions: Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30 - 85%
- 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:

2.5, 5, and 10% (w/v)

No. of animals per dose:

5

Details on study design:

PRE-SCREEN TESTS:
no details provided

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response:
A test item is regarded as a sensitiser in the LLNA if the following criteria are fulfilled:
- First, that exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the stimulation index.
- Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.

TREATMENT PREPARATION AND ADMINISTRATION:
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with different test item concentrations of 2.5, 5, and 10% (w/v) in acetone:olive oil (4+1). The application volume, 25 µL, was spread over the entire dorsal surface (Ø ~ 8 mm) of each ear lobe once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals).

Positive control substance(s):

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

Statistics:

The ANOVA (Dunnett-test) was conducted to assess whether the difference is statistically significant between test item groups and negative control (vehicle) group. Statistical significance was at the five per cent level (p < 0.05). However, both biological and statistical significance were considered together.

Positive control results:

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

Parameter:

SI

Value:

1

Test group / Remarks:

vehicle control group

Key result

Parameter:

SI

Value:

4.94

Test group / Remarks:

test concentration 2.5 % (w/v)

Parameter:

SI

Value:

7.35

Test group / Remarks:

test concentration 5 % (w/v)

Parameter:

SI

Value:

7.92

Test group / Remarks:

test concentration 10 % (w/v)

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA
control group: 793.6 DPM/lymph node
2.5 % group: 3923.0 DPM/lymph node
5 % group: 5833.7 DPM/lymph node
10 % group: 6283.9 DPM/lymph node

DETAILS ON STIMULATION INDEX CALCULATION
The mean of the background DPM values was subtracted from the test group value. DPM/lymph node was determined by dividing the sum of the measured values from all lymph nodes within a group by the number of lymph nodes taken from that group. Stimulation Index = (DPM/lymph note of test group) ÷ (DPM/lymph node of control group).

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

CLINICAL OBSERVATIONS:
No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period.
The measured ear thickness of all animals treated was recorded prior to the 1st application and prior to treatment with ³HTdR. A relevant increase in ear thickness gain was not observed after treatment with the test item.

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:

other: Category 1 (skin sensitising) based on EU GHS criteria

Conclusions:

It can be concluded that the test item is a skin sensitiser under the conditions of this assay.

Executive summary:

Study Design

In this study the test item was assessed for its possible contact allergenic potential in a local lymph node assay. The GLP study was performed according to OECD TG 429. The test item concentrations of 2.5, 5, and 10% (w/v) in acetone:olive oil (4+1) were applied.

Results

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 4.94, 7.35, and 7.92 were determined with the test item at concentrations of 2.5, 5, and 10% in acetone:olive oil (4+1), respectively. Since the S.I. was increased above 3 even at the lowest tested concentration, an EC3 value could not be derived.

Conclusion

From the data it can be concluded that the test item is a skin sensitiser under the conditions of this assay.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Skin sensitisation-LLNA

Study Design

In this study the test item was assessed for its possible contact allergenic potential in a local lymph node assay. The GLP study was performed according to OECD TG 429. The test item concentrations of 2.5, 5, and 10% (w/v) in acetone:olive oil (4+1) were applied.

Results

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 4.94, 7.35, and 7.92 were determined with the test item at concentrations of 2.5, 5, and 10% in acetone:olive oil (4+1), respectively. Since the S.I. was increased above 3 even at the lowest tested concentration, an EC3 value could not be derived.

Conclusion

From the data it can be concluded that the test item is a skin sensitiser under the conditions of this assay.

Justification for classification or non-classification

Based on the result of the LLNA the registered substance is classified as Skin Sens Cat. 1 (H317: May cause an allergic skin reaction.) in accordance with Regulation (EC) No 1272/2008.