Allyl 3-cyclohexylpropionate

Endpoint summary

Description of key information

Allyl 3-cyclohexylpropionate is deemed to be not irritating to skin according to the key study of in vitro testing with human skin model EpiSkin. Additionaly, it is deemed to be not corrosive or irritating to eyes according to a reliable study in the rabbit.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2012-05-14 to 2012-08-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Details on test animals or test system and environmental conditions:

not relevant

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 µL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

15 min treatment + 42 h incubation

Number of animals:

not relevant

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with PBS
- Time after start of exposure: 15 min

SCORING SYSTEM:
In vitro result: In vivo prediction:
mean tissue viability ≤ 50 % → irritant (I), H315 (category 2)
mean tissue viability > 50 % → non-irritant (NI)

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

mean of 3 runs

Value:

93.9

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

 Results after treatment with the test item and controls

Dose group	Treat-ment interval	Absor-bance 540 nm Tissue 1*	Absor-bance 540 nm Tissue 2*	Absor-bance 540 nm Tissue 3*	Mean Absorbance of 3 Tissue	Relative absor-bance [%] Tissue 1, 2+3**	Stan-dard De-viation [%]	Rel. Absor-bance / Tissue Viability [% of negative control]***
Negative Control	15 min	1.154	1.047	1.032	1.077	107.1 97.2 95.8	6.2	100.0
Positive Control	15 min	0.175	0.142	0.154	0.157	16.3 13.2 14.3	1.6	14.6
Test Item	15 min	1.157	0.941	0.938	1.012	107.3 87.3 87.1	11.6	93.9

*Mean of two replicate after blank correction

**Relative absorbance per tissue [rounded values]: 100xabsorbance (tissue)/mean absorbance (negative control)

***Relative absorbance per treatment group [rounded values]: 100xmean absorbance (test item)/mean anbsorbance (negative control)

 

Interpretation of results:

GHS criteria not met

Conclusions:

It can be stated that in this study and under the experimental conditions reported, the test item is non irritant to skin according to UN GHS and EU CLP regulation.

Executive summary:

This in vitro study was performed to assess the irritation potential of the test item by means of the Human Skin Model Test according to OECD TG 439. Three tissues of the human skin model EpiSkin™ were treated with the test item, the negative or the positive control for 15 minutes. 10 μL of the liquid test item were applied to each tissue, spread to match the tissue size. 10 μL of either the negative control (deionised water) or the positive control (5% Sodium lauryl sulfate) were applied to each tissue. After treatment with the negative control the absorbance values were well within the required acceptability criterion of mean OD ≥ 0.6 till ≤ 1.5 for the 15 minutes treatment interval thus showing the quality of the tissues. Treatment with the positive control induced a sufficient decrease in the relative absorbance as compared to the negative control for the 15 minutes treatment interval thus ensuring the validity of the test system. Compared to the value of the negative control, after exposure of the test item the test item the mean relative absorbance value decreased to 93.9%. This value is well above the threshold for irritancy of ≤ 50%. Therefore, the test item is not considered to possess an irritant potential. In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item the test item is non irritant to skin according to UN GHS and EU CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-05-17 to 1999-05-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: Mol:Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Four female SPF albino rabbits of the stock Mol:Russian
- Source: Möllegaard Breeding and Reasearch Centre A/S, Ejby, Lille-Skensved, Denmark
- Age at study initiation: not reported
- Weight at study initiation: 2.3 to 2.7
- Housing: individually in PPO cages (floor area 2580 cm2) with perforated floor in animal room no. 3
- Diet (e.g. ad libitum): pelleted complete rabbit diet Altromin 2123 from Altromin, Lage/Lippe, Germany ad libitum
- Water (e.g. ad libitum): domestic quality drinking water acidified with hydrochloric acid to pH 2.5 ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 mL of neat test substance

Duration of treatment / exposure:

single administration; after 24 hour reading Fluorescein was instilled and treated eye was washed with 20 mL 0.9% sodium chloride solution

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

4

Details on study design:

REMOVAL OF TEST SUBSTANCE
- substance was not removed from the treated eye

SCORING SYSTEM:
see section "Any other information on materials and methods"

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
Fluorescein was instilled after 24 hours, eyes were rinsed with 20 mL 0.9% sodium chloride solution and were examined using UV light

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.8

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.8

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

Some light response to exposure of the eyes to the substance was observed in all animals at the early timepoints of observation at 1 hour, 24 and 48 hours after instillation. After 72 hours three out of four animals were free of any signs of eye irritation while one animal stilled exhibited light signs of irritation. These had disappeared at the observation made 7 days after exposure.

Other effects:

No other effects were reported.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is non-irritating to the rabbit eye and does not need classification.

Executive summary:

The potential for eye irritation of allyl cyclohexyl propionate was tested in a GLP study according to OECD guideline No. 405. Four healthy SPF albino rabbits (Mol:Russian) weighing 2.3 to 2.7 kg were used in the study. The day before testing both eyes of the animals were examined before and after the instillation of Fluorescein to ensure there were no defects or irritation. The next day an aliquot of 0.1 mL of the neat substance was placed in the left eyes of the animals by gently pulling the lower lid away from the eyeball. The lids were then gently hold together for one second. The right eye remained untreated and served as control. The eyes were examined and the grade of ocular reaction was recorded 1 and 24 hours later. After a first reading at 24 hours Fluorescein was instilled and the treated eye was rinsed with 20 mL 0.9% sodium chloride solution. Then the eye was examined again using UV-light to detect possible corneal damage. Further gradings were done after 48 and 72 hours after treatment. All animals showed slight conjunctival effects at the examinations occurring 1, 24 and 48 hours after treatment. Three out of four animals did no show any signs of eye irritation at the 72 hours observation timepoint, while one animal exhibited some conjunctival vessels definitely injected and swelling above normal. All these effects were transient and no reactions in the treated eyes of all four animals were seen in the examinations after 7 days. On the basis of these observations it was concluded that the substance is non-irritating to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

Key study

The test item is considered to be not irritating to skin. The result from fully reliable study conducted according to OECD TG 439 a GLP in vitro (three tissues of the human skin model EpiSkin) showed decrease of the mean relative absorbance value to 93.9 % (Heppenheimer 2012). This value is well above the threshold for irritancy of ≤ 50 %. Therefore, the test item is not considered to possess an irritant potential.

 

Supporting information

In one supporting study (Politano 2006), the test item showed a non-irritating potential when test item was applied as semiocclusive coverage during 24 h to the back of the volunteers. The maximal concentration of the test item was 2 % in different vehicles (diethyl phthalate, 3:1 diethyl phthalate:ethanol and 1:3 diethyl phthalate:ethanol). Despite the low concentration of the test item on the applied patches, this study supports the classification of the substance as not irritating.

In the second supporting study (Smith 2000), allyl 3-cyclohexylpropionate showed an irritating potential in 8 from 10 selected subjects when 20 µg test item was applied as occlusive coverage during 24 h to the upper backs. Irritation was measured however only 50 min after patch removal. Observation on irritation reversibility was no longer performed. Therefore, this data may be not relevant for the classification and could be considered as supporting information.

 

Eye irritation / corrosion

Key study

The test item is considered to be not irritating to eye based on the results from a fully reliable study (Schreiter 1999, according to OECD TG 405 and GLP). Some light response to exposure of the eyes to the substance was observed in all animals at the early time points of observation at 1 hour, 24 and 48 hours after instillation. After 72 hours three out of four animals were free of any signs of eye irritation while one animal stilled exhibited light signs of irritation. These had disappeared at the observation made 7 days after exposure. The substance is non-irritating to the rabbit eye and does not need classification.

Justification for selection of skin irritation / corrosion endpoint:
GLP study according to OECD TG 439 (In vitro Skin Irritation: Reconstructed Human Epidermis Test Method). This in vitro study was selected as key study since the test item is going to be registered as cosmetic raw material and starting from March 11th, 2009, it was enacted to ban the tests of cosmetic raw materials on animals in the EU. Therefore, the conduct of the new guideline conform in vivo study shall be waived.
In addition, according to ECHA Chapter R.7a (Version 2.0, November 2012, page 174), it is expected that the EPISKIN text will be validated and endorsed as a full replacement of the in vivo test. In this case the test should be used for Annex VII and for Annex VIII to avoid in vivo testing for skin irritation.

Justification for selection of eye irritation endpoint:
Only one valid and reliable study is available.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available studies are considered reliable for this assessment.

 

Skin irritation/corrosion:

Based on the above stated assessment of the irritating properties of the test item, the results from reliable studies show that the substance is not irritating to the skin. Accordingly, the test item does not need to be classified according to Regulation (EC) No 1272/2008 of the European Parliament and of the Council, as amended for the 17th time in Regulation (EU) 2021/849) as implementation of UN-GHS in the EU.

 

Eye irritation/corrosion:

Based on the above stated assessment of the irritating properties of the test item, the results from a reliable study shows that the substance is not corrosive or irritating to the eye. Accordingly, the test item does not need to be classified according to Regulation (EC) No 1272/2008 of the European Parliament and of the Council, as amended for the 17th time in Regulation (EU) 2021/849) as implementation of UN GHS in the EU.