4-(1,1-dimethylethyl)cyclohexyl methacrylate

Endpoint summary

Description of key information

The substance is considered to be a skin sensitizer Cat 1 based on QSAR analysis and read across from analogous substance, 101-43-9

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

For the assessment of the registered substance, QSAR results were used for skin sensitization. The criteria listed in Annex XI of Regulation (EC) No. 1907/2006 are considered to be adequately fulfilled and therefore the endpoint sufficiently covered and suitable for risk assessment.

Principles of method if other than guideline:

QSAR

Justification for non-LLNA method:

based on animal welfare considerations, the endpoint is being fulfilled via QSAR and read across

Remarks on result:

positive indication of skin sensitisation

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Based on QSAR analysis, the substance is considered to be a skin sensitizer, Cat 1

Executive summary:

Based on QSAR analysis, the substance is considered to be a skin sensitizer, Cat 1

Reference 2

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

see attached Read Across rationale

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

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 Winkelmann GmbH, Borchen, FRG
- Age at study initiation: about 8 weeks
- Weight at study initiation: 16.9 g - 20.9 g
- Housing: single housed
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 29 days before the first test substance application

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

Vehicle:

other: acetone

Concentration:

3, 10, 30 %

No. of animals per dose:

6

Details on study design:

The study comprised three treatment groups and a vehicle control group.
Each group consisted of 6 mice. A check for dead or moribund animals was made twice each workday and once on Saturdays, Sundays and on public holidays.
No detailed clinical examination of the individual animals was performed but any obvious signs of systemic toxicity and/or local inflammation at the application sites were noted in the raw data.
Body weights of the individual animals were determined on study day 0 prior to the first application and on day 5 prior to the sacrifice of the animal.
Percutaneous 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

The animals were sacrificedon study day 5 by cervical dislocation.

Immediately after the death of each animal a circular piece of tissue (diameter 0.8 cm) was punched out of the apical part of each ear. The weight of the pooled punches wasdetermined for each animal.

Immediately after removal of the ear punches the left and right auricular lymph nodes were dissected. The weight of the pooled lymph nodes from both sides was determined for each animal.


A concurrent positive control (reliability check) with a known sensitizer was not included into this study.
Studies using the positive control substance Alpha-Hexylcinnamaldehyde,techn. 85% are performed twice a year in the laboratory in order to show that the test system is able to detect sensitizing compounds under the test conditions chosen.

Parameter:

other: Lymph node Weight Index

Value:

1.29

Test group / Remarks:

3 % in acetone

Parameter:

other: Cell count Index

Value:

1.48

Test group / Remarks:

3 % in acetone

Parameter:

other: Ear Weight Index

Value:

0.95

Test group / Remarks:

3 % in acetone

Parameter:

other: Lymph node Weight Index

Value:

1.47

Test group / Remarks:

10 % in acetone

Parameter:

other: Cell count Index

Value:

1.68

Test group / Remarks:

10 % in acetone

Parameter:

other: Ear Weight Index

Value:

1.05

Test group / Remarks:

10 % in acetone

Parameter:

other: Lymph node Weight Index

Value:

1.78

Test group / Remarks:

30 % in acetone

Parameter:

other: Cell count Index

Value:

1.93

Test group / Remarks:

30 % in acetone

Parameter:

other: Ear Weight Index

Value:

1.18

Test group / Remarks:

30 % in acetone

No signs of systemic toxicity were noticed. The test substance induced a statistically significant and biologically relevant response of the auricular lymph nodes when applied as 3%, 10% or 30% preparations in acetone. The concentration dependent statistically significant increases in ear weights induced by the test substance when applied as 10% and 30% preparation indicate some irritation of the ear skins.

In conclusion, Cyclohexylmethacrylat has a skin sensitizing effect in the Murine Local Lymph Node Assay. The threshold concentration for sensitization induction was < 3% under the test conditions chosen.

Based on the available data, Cyclohexylmethacrylate is a skin sensitizer of strong potency. However, taking into account the observed irritating effects on the ears, and the missing dose-dependency of the lymph node proliferation, the sensitising effect cannot be clearly discriminated from at least partly possible lymph node proliferation based on skin irritancy.

Test group	Treatment	Lymph node Weight Index	Cell count Index	Ear Weight Index
1	Vehicle acetone	1.00	1.00	1.00
2	3 % in acetone	1.29 ##	1.48 ##	0.95
3	10 % in acetone	1.47 ##	1.68 ##	1.05 ##
4	30 % in acetone	1.78 ##	1.93 ##	1.18 ##

The statistical evaluations were performed using the WILCOXON-test (# for p<= 0.05, ## for p<= 0.01

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Classification: sensitising

Executive summary:

Classification: sensitising

Reference 3

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The substance is considered to be a skin sensitizer Cat 1 based on QSAR analysis and a read across from analogous substance, 101-43-9.