2-isopropyl-5-methyl-cyclohexanone

Endpoint summary

Description of key information

Skin irritation / corrosion: Reaction mass of isomenthone and trans-menthone is deemed to be irritating to skin.
Eye irritation: Reaction mass of isomenthone and trans-menthone is deemed to be not irritating to the eyes.

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:

other: GLP study according to OECD TG 439

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

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:

other: other: Relative Absorbance

Value:

10.4

Remarks on result:

other:

Remarks:

Basis: other: Test item on EpiSkin. Max. score: 100.0. Reversibility: no data. Remarks: % of negative control. (migrated information)

Results after treatment with 620103 Menthone / Iso Menthone Racemic 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 [% 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	0.106	0.145	0.086	0112	9.8 13.5 7.9	2.8	10.4

*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:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The mean relative absorbance value of the test item, corresponding to the cell viability, decreased to 10.4% (threshold for irritancy: ≤ 50%), consequently the test item was irritant to skin.

Executive summary:

This in vitro study was performed to assess the irritation potential of 620103 Menthone / Iso Menthone Racemic 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 620103 Menthone / Iso Menthone Racemic the mean relative absorbance value decreased to 10.4%. This value is below the threshold for irritancy of ≤ 50%. Therefore, the test item is 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 620103 Menthone / Iso Menthone Racemic is irritant to skin according to UN GHS and EU CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

from 1999-07-30 to1999-09-17

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was performed under GLP according to OECD TG 405. Read across from Isomenthone.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

other: SPF

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kisslegg
- Age at study initiation: no data
- Weight at study initiation: 2.3-2.4 kg
- Housing: individually in PPO cages (floor area: 2576 cm^2) with perforated floor
- Diet (e.g. ad libitum): pelleted complete rabbit diet "Altromin 2123" from Altromin, D-32791 Lage, Lippe, ad libitum.
- Water (e.g. ad libitum): domestic water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth, ad libitum.
- Acclimation period: at least one week

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

IN-LIFE DATES: From: 1999-08-23 To: 1999-08-31

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

once

Observation period (in vivo):

1, 24, 48 and 72 hours as well as day 7 after the treatment.

Number of animals or in vitro replicates:

4

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with 20 mL 0.9 % sodium chloride solution
- Time after start of exposure: 24 h

SCORING SYSTEM:
Cornea: opacity degree of density from 0 to 4; Area of cornea involved from 1 to 4
Iris: from 0 to 2
Conjunctiva: redness from 0 to 3; chemosis from 0 to 4; discharge from 0 to 3

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Remarks:

degree

Basis:

animal #1

Time point:

other: readings after 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Remarks:

degree

Basis:

animal #2

Time point:

other: readings after 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Remarks:

degree

Basis:

animal #3

Time point:

other: readings after 24, 48 and 72 h

Score:

0.2

Max. score:

4

Irritation parameter:

cornea opacity score

Remarks:

degree

Basis:

animal #4

Time point:

other: readings after 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: readings after 24, 48 and 72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: readings after 24, 48 and 72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: readings after 24, 48 and 72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #4

Time point:

other: readings after 24, 48 and 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: readings after 24, 48 and 72 h

Score:

1.33

Max. score:

3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: readings after 24, 48 and 72 h

Score:

1

Max. score:

3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

other: readings after 24, 48 and 72 h

Score:

0.67

Max. score:

3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #4

Time point:

other: readings after 24, 48 and 72 h

Score:

1

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: readings after 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: readings after 24, 48 and 72 h

Score:

0.33

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: readings after 24, 48 and 72 h

Score:

0.33

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

other: readings after 24, 48 and 72 h

Score:

0.33

Max. score:

4

Irritant / corrosive response data:

On day 7 all animals were free of any signs of eye irritation.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Isomenthone shall not be classified as eye irritating.

Executive summary:

The eye irritant effect of Isomenthone was investigated according to the method recommended in the OECD TG 405, "Acute Eye Irritation/Corrosion", Feb. 1987, and EEC Guideline B.5 "Acute Toxicity (Eye Irritation)", Jan. 1997. Four female albino rabbits were exposed to 0.1 mL of the test article in the left eye. The eyes were examined and the changes were graded according to a numerical scale one hour, 24, 48 and 72 hours as well as day 7 after dosing. Slight to well-defined signs of irritation were observed an the treated eyes. No significant eye irritation according to CLP Regulation was observed in the tested animals from mean scores following their grading at 24, 48 and 72 hours after installation of the test material. On day 7 all animals were free of any signs of eye irritation. Therefore Isomenthone shall not be classified as eye irritating.

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

Reaction mass of isomenthone and trans-menthone is considered to be irritating to skin. The reliable study in vitro (three tissues of human skin model EpiSkin) conducted according to OECD TG 439 and GLP showed decrease of mean relative absorbance value to 10.4 % (Heppenheimer 2012). This value is well below the threshold for irritancy of ≤ 50 %. Therefore the test item is considered to possess skin irritating potential.

Eye irritation / corrosion

Key study

The reliable in vivo study with rabbits (Schreiter 1999) conducted with Isomenthone according to OECD TG 405 is considered as valid for read across to Reaction mass of isomenthone and trans-menthone. In this study Isomenthone is not irritating to the eyes. Therefore it is concluded that the reaction mass of isomenthone and trans-menthone is not irritating to eye as well.

Justification for selection of skin irritation / corrosion endpoint:
GLP study performed according to OECD TG 439 (In vitro Skin Irritation: Reconstructed Human Epidermis Test Method).
This in vitro study was selected as the key study since the registration item is a 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, no additional in-vivo study shall be performed. In addition, according to ECHA Chapter R.7a (Version 2.0, November 2012, page 174), it is expected that the EPISKIN test will be validated and endorsed as a full replacement of the in vivo test. The available in vitro study is therefore considered acceptable to serve as the key study.

Justification for selection of eye irritation endpoint:
GLP study performed according to OECD TG 405. Read across from Isomenthone.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

- skin irritation / corrosion:

The results of the skin irritation / corrosion test of Reaction mass of isomenthone and trans-menthone show that the test item is a skin irritant. Accordingly Reaction mass of isomenthone and trans-menthone need to be classified as "R38 Irritating to skin" according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and as Category 2, "Warning - H315: Causes skin irritation" according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

- eye irritation/corrosion:

Based on the above stated assessment of the irritating properties of Reaction mass of isomenthone and trans-menthone, the results from a reliable study show that the substance is not corrosive or irritating to the eye. Accordingly the substance does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN GHS in the EU.