Ethyl 3-phenyloxirane-2-carboxylate

Endpoint summary

Description of key information

Skin corrosion: Not corrosive in absence of skin and eye irritation

Skin irritation: Not irritating, based on read across from Ethyl 3-methylphenylglycidate (tested according to OECD TG 439)

Eye irritation: Not irritating, based on read across from Ethyl 3-methylphenylglycidate (tested according to OECD TG 405)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 January 2012 - 23 January 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The information is used for read across to Ethylphenylglycidate

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

22 July 2010

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

other: epidermal keratinocytes

Cell source:

other: SkinEthic Laboratories, Lyon, France.

Source strain:

other: Not applicable

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN Small ModelTM, 0.38 cm^2
- Ten μL of the undiluted test substance was added into 12-well plates on top of the skin tissues.
- The test item was applied topically to the corresponding tissues ensuring uniform covering.

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: approximately 37.0°C

PRE-TEST PROCEDURE:
Assessment of Direct Test Item Reduction of MTT
MTT Salt Metabolism, Cell Viability Assay
The MTT assay, a colourimetric method of determining cell viability, is based on reduction of the yellow tetrazolium salt (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) to a blue formazan dye by mitochondrial succinate dehydrogenase in viable cells.
One limitation of the assay is possible interference of the test item with MTT. A test item may directly reduce MTT, thus mimicking dehydrogenase activity of the cellular mitochondria. This property of the test item is only a problem, if at the time of the MTT test (after rinsing) there are still sufficient amounts of the test item present on or in the tissues. In this case, the true metabolic MTT reduction and the false direct MTT reduction can be differentiated and quantified.
Test for Direct MTT Reduction + colour interference:
10 μL of the test item was added to 2 mL of a 0.3 mg/ml MTT solution freshly prepared in assay medium. The solution was incubated in the dark at 37ºC, 5% CO2 in air for 3 hours. Untreated MTT solution was used as a control.
If the MTT solution containing the test item turns blue, the test item is presumed to have reduced the MTT.

PRE-INCUBATION:
2 mL of maintenance medium, warmed to approximately 37°C, was pipetted into the first column of 3 wells of a pre-labelled 12-well plate. Each epidermis unit was transferred into the maintenance medium filled wells (3 units per plate). A different 12-well plate was used for the test item and each control item. The tissues were incubated at 37°C, 5% CO2 in air overnight.

APPLICATION/TREATMENT OF TEST SUBSTANCE:
2 mL of maintenance medium, warmed to approximately 37°C, was pipetted into the second column of 3 wells of the 12-well plate.
Triplicate tissues were treated with the test item for an exposure period of 15 minutes. The test item was applied topically to the corresponding tissues ensuring uniform covering. 10 μL of the test item was applied to the epidermis surface. Triplicate tissues treated with 10 μL of DPBS served as the negative controls and triplicate tissues treated with 10 μL of SDS 5% w/v served as the positive controls. To ensure satisfactory contact with the positive control item the SDS solution was spread over the entire surface of the epidermis using a pipette tip (taking particular care to cover the centre). After 7 minutes contact time the SDS solution was re-spread with a pipette tip to maintain the distribution of the SDS for the remainder of the contact period. The plate(s) were kept in the biological safety cabinet at room temperature for 15 minutes.
At the end of the exposure period, each tissue was removed from the well using forceps and rinsed using a wash bottle containing DPBS with Ca++ and Mg++. Rinsing was achieved by filling and emptying each tissue insert for approximately 40 seconds using a constant soft stream of DPBS to gently remove any residual test item. The rinsed tissues were transferred to the second column of 3 wells containing 2 ml of maintenance medium in each well. The rinsed tissues were incubated at 37ºC, 5% CO2 in air for 42 hours.

MTT LOADING/FORMAZAN EXTRACTION:
Following the 42-Hour post-exposure incubation period each 12-well plate was placed onto a plate shaker for 15 minutes to homogenise the released mediators in the maintenance medium. 1.6 mL of the maintenance medium from beneath each tissue was transferred to pre-labelled micro tubes and stored in a freezer at -14 to -30ºC for possible inflammatory mediator determination.
2 mL of a 0.3 mg/mL MTT solution, freshly prepared in assay medium, was pipetted into the third column of 3 wells of the 12 well plate(s). The tissues were transferred to the MTT filled wells, being careful to remove any excess maintenance medium from the bottom of the tissue insert by blotting on absorbent paper. The tissues were incubated for 3 hours at 37°C, 5% CO2 in air. At the end of the 3-Hour incubation period each tissue was placed onto absorbent paper to dry. A total biopsy of the epidermis was made using the EPISKINTM biopsy punch. The epidermis was carefully separated from the collagen matrix using forceps and both parts (epidermis and collagen matrix) placed into labelled 1.5 mL micro tubes containing 500 μL of acidified isopropanol, ensuring that both the epidermis and collagen matrix were fully immersed. Each tube was plugged to prevent evaporation and mixed thoroughly on a vortex mixer. The tubes were refrigerated at 1 to 10°C until Day 6 of the experiment, allowing the extraction of formazan crystals out of the MTT-loaded tissues.

CELL VIABILITY MEASUREMENT:
At the end of the formazan extraction period each tube was mixed thoroughly on a vortex mixer to produce a homogenous coloured solution.
For each tissue, duplicate 200 μL samples were transferred to the appropriate wells of a pre-labelled 96-well plate. 200 μL of acidified isopropanol alone was added to the two wells designated as ‘blanks’. The optical density was measured (quantitative viability analysis) at 540 nm (without a reference filter) using the Anthos 2001 microplate reader.

DECISION CRITERIA:
- A test substance is considered irritant in the skin irritation test if: The relative mean tissue viability of three individual tissues after 15 minutes of exposure to the test substance and 42 hours of post incubation is ≤ 50% of the mean viability of the negative controls.
- A test substance is considered non-irritant in the in vitro skin irritation test if: The relative mean tissue viability of three individual tissues after 15 minutes of exposure to the test substance and 42 hours of post incubation is > 50% of the mean viability of the negative controls.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

Test material
- Amount applied: 10 μL

Duration of treatment / exposure:

15-Minute exposure period and 42 hours post-exposure incubation period.

Number of replicates:

A total of 9 tissues were used: Triplicate tissues were treated with: test substance, positive control or negative control.

Amount / concentration applied:

- Concentration (if solution): undiluted

Positive control and details on concentration and application

Irritation / corrosion parameter:

% tissue viability

Value:

115.8

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: The relative mean tissue viability compared to the negative control tissues (100%).

Other effects / acceptance of results:

Direct MTT Reduction:
The MTT solution containing the test item did not turn blue which indicated that the test item did not directly reduce MTT.

Quality Criteria:
The relative mean tissue viability for the positive control treated tissues was 7.7% relative to the negative control treated tissues and the standard deviation value of the percentage viability was 0.7%. The positive control acceptance criterion was therefore satisfied.
The mean OD540 for the negative control treated tissues was 0.834 and the standard deviation value of the percentage viability was 4.4%. The negative control acceptance criterion was therefore satisfied.
The standard deviation calculated from individual percentage tissue viabilities of the three identically treated tissues was 4.5%. The test item acceptance criterion was therefore satisfied.

Mean OD540 Values and Percentage Viabilities for the Negative Control Item, Positive Control Item and Test Item

Item	OD540 of tissues	Mean OD540 of triplicate tissues	± SD of OD540	Relative individual tissue viability (%)	Relative mean viability (%)	± SD of Relative mean viability (%)
Negative Control Item	0.860	0.834	0.037	103.1	100	4.4
	0.792			95.0
	0.851			102.0
Positive Control Item	0.063	0.064	0.006	7.6	7.7	0.7
	0.059			7.1
	0.070			8.4
Test Item	0.929	0.965	0.037	111.4	115.8	4.5
	0.964			115.6
	1.003			120.3

SD = Standard deviation

*The mean viability of the negative control tissues is set at 100 %

Interpretation of results:

other: Not a skin irritant.

Remarks:

According to EU CLP Regulation (EC) No. 1272/2008 and its amendments

Conclusions:

The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with the substance compared to the negative control tissues was 115.8%. Since the mean relative tissue viability for the substance was above 50% the substance is considered to be non-irritant.

Executive summary:

The possible skin irritation potential of the substance was tested in vitro using a human skin model through topical application for 15 minutes. The study procedures described in this report were according to OECD TG 439 guideline and GLP principles. Skin tissue was treated by topical application of 10 μL test substance. After 42 hours post incubation period, determination of the cytotoxic (irritancy) effect was performed. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) MTT at the end of treatment. Skin irritation is expressed as the remaining cell viability after exposure to the test substance. Reliable negative and positive controls were included.

The relative mean tissue viability for the positive control treated tissues was 7.7% relative to the negative control treated tissues and the standard deviation value of the percentage viability was 0.7%. The positive control acceptance criterion was therefore satisfied. The mean OD540 for the negative control treated tissues was 0.834 and the standard deviation value of the percentage viability was 4.4%. The negative control acceptance criterion was therefore satisfied. The standard deviation calculated from individual percentage tissue viabilities of the three identically treated tissues was 4.5%. The test item acceptance criterion was therefore satisfied. The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with the substance compared to the negative control tissues was 115.8%. Since the mean relative tissue viability for the substance was above 50% the substance is considered to be non-irritant.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

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

Adequacy of study:

key study

Study period:

2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: read-across information

Justification for type of information:

The read across justification is presented in the Endpoint summary on irritation. The accompanying files are also attached there.

Reason / purpose for cross-reference:

read-across source

Irritation / corrosion parameter:

% tissue viability

Value:

115.8

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: The relative mean tissue viability compared to the negative control tissues (100%).

Other effects / acceptance of results:

Direct MTT Reduction:
The MTT solution containing the test item did not turn blue which indicated that the test item did not directly reduce MTT.
Quality Criteria:
The relative mean tissue viability for the positive control treated tissues was 7.7% relative to the negative control treated tissues and the standard deviation value of the percentage viability was 0.7%. The positive control acceptance criterion was therefore satisfied.
The mean OD540 for the negative control treated tissues was 0.834 and the standard deviation value of the percentage viability was 4.4%. The negative control acceptance criterion was therefore satisfied.
The standard deviation calculated from individual percentage tissue viabilities of the three identically treated tissues was 4.5%. The test item acceptance criterion was therefore satisfied.

Interpretation of results:

other: Not a skin irritant.

Remarks:

According to EU CLP Regulation (EC) No. 1272/2008 and its amendments

Conclusions:

Ethylphenylglycidate is not irritating to skin.

Reference 3

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 March 2000 - 01 April 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Information is used for read across to Ethylphenylglycidate

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

February 1987

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: Chbb:HM(SPF)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Littlerussian from BI Pharma KG, 88397 Biberach
- Age at study initiation: No data.
- Weight at study initiation: 2.3 - 2.6 kg
- Housing: Individually in PPO cages with perforated floor.
- Diet: Free access to pelleted complete rabbit diet (Altromin 2123" from Altromin, D-32791 Lage, Lippe)
- Water: Free access to quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth.
- Acclimation period: No data.

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

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye remained untreated and served as control.

Amount / concentration applied:

Amount applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Single instillation on Day 1

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

4 females

Details on study design:

STUDY DESIGN
The test material was applied undiluted in 4 animals.

TREATMENT
In accordance with OECD 405. The test substance is placed in the conjunctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids are then gently held together for about one second. The other eye serves at control.

REMOVAL OF TEST SUBSTANCE
-Washing: Yes, 24 hours after instillation of the test substance.

OBSERVATIONS
- Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.

SCORING SYSTEM:
The irritation scores and a description of all other (local) effects were recorded. The irritation was assessed according to OECD 405.

TOOL USED TO ASSESS SCORE: After the first 24 hour reading Fluorescein was instilled. After rinsing with 20 mL 0.9% sodium chloride solution the eyes were examined again using UV-light to detect possible corneal damage.

Irritation parameter:

cornea opacity score

Basis:

other: animal #1, #2, #3 and #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

other: animal #1, #2, #3 and #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

other: animal #1, #2, #3 and #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

other: animal #1, #2 and #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One hour after application of the test article animal #1 showed a diffuse, crimson red conjunctiva with individual vessels not easily discernible, a swelling above normal and a discharge different from normal. In animal #2 were observed some conjunctival vessels definitely injected, a swelling above normal and a discharge with moistening of the lids and hairs just adjacent to lids. The animal #3 showed some conjunctival vessels definitely injected, a swelling above normal and a discharge different from normal. In animal #4 were observed a diffuse, crimson red conjunctiva with individual vessels not easily discernible, a swelling above normal and a discharge with moistening of the lids and hairs just adjacent to lids.
24 hours after application of the test article in animals #1, #2 and #4 were observed some conjunctival vessels definitely injected and a swelling above normal. Animal #3 showed some conjunctival vessels definitely injected.
48 hours after application of the test article all four animals were free of any signs of eye irritation.
72 hours after application of the test article all four animals were free of any signs of eye irritation, too.

Interpretation of results:

other: Not an eye irritant.

Remarks:

According to EU CLP Regulation (EC) No. 1272/2008 and its amendments

Conclusions:

In an eye irritation study with 4 rabbits, performed according to OECD 405 guideline and GLP principles, all rabbits had slight reddening of the conjuctivae observed at 24 hours only. Three rabbits showed also showed slight chemosis at 24 hours only. All signs of irritation were reversible within 48 hours, the substance is not an eye irritant.

Executive summary:

The substance was tested in an eye irritation test in 4 rabbits according to OECD TG 405 test guideline and GLP principles. All rabbits had slight reddening of the conjuctivae observed at 24 hours only. Three rabbits also showed slight chemosis at 24 hours only. All signs of irritation were reversible within 48 hours, the substance is not an eye irritant.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: read-across information

Justification for type of information:

The read across justification is presented in the Endpoint summary on irritation. The accompanying files are also attached there.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

other: animal #1, #2, #3 and #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

other: animal #1, #2, #3 and #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

other: animal #1, #2, #3 and #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

other: animal #1, #2 and #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One hour after application of the test article animal #1 showed a diffuse, crimson red conjunctiva with individual vessels not easily discernible, a swelling above normal and a discharge different from normal. In animal #2 were observed some conjunctival vessels definitely injected, a swelling above normal and a discharge with moistening of the lids and hairs just adjacent to lids. The animal #3 showed some conjunctival vessels definitely injected, a swelling above normal and a discharge different from normal. In animal #4 were observed a diffuse, crimson red conjunctiva with individual vessels not easily discernible, a swelling above normal and a discharge with moistening of the lids and hairs just adjacent to lids.
24 hours after application of the test article in animals #1, #2 and #4 were observed some conjunctival vessels definitely injected and a swelling above normal. Animal #3 showed some conjunctival vessels definitely injected.
48 hours after application of the test article all four animals were free of any signs of eye irritation. 72 hours after application of the test article all four animals were free of any signs of eye irritation, too.

Interpretation of results:

other: Not an eye irritant.

Remarks:

According to EU CLP Regulation (EC) No. 1272/2008 and its amendments

Conclusions:

Ethylphenylglycidate is not irritating to eyes.

Reference 3

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

The executive summaries of the source studies are presented first followed by the read-across rationale.

Skin and eye irritation of Ethylphenylglycidate (CAS 121-39-1) using read across from Ethyl 3-methylphenylglycidate (CAS 77-83-8).

1.  Introduction and hypothesis for the read across

Ethylphenylglycidate has an oxirane ring (epoxide) with a phenyl at C1 and a carboxylic acid ethyl ester at C2. For this substance no relevant data on skin and eye irritation is available.

In accordance with Article 13 of REACH, lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing skin and eye irritation of Ethylphenylglycidate the analogue approach is selected because skin and eye irritation information on a closely related analogue is available which can be used for read across.

Hypothesis:Ethylphenylglycidate has no skin and eye irritation properties similar to Ethyl 3-methylphenylglycidate.

Available information: The source substance Ethyl 3-methylphenylglycidate has been tested in well conducted skin and eye irritation studies, performed according to OECD TG 439 and 405 and GLP (Klimisch 1), respectively. In the skin irritation test viability was similar to control) and therefore the substance is not considered an irritant. In the eye irritation test only minimal irritation of conjunctivae and chemosis was observed which disappeared within 48 hours not resulting in irritation to the rabbit eye.

2.  Target chemical and source chemical:

Chemical structures of Ethylphenylglycidate (target) and Ethyl 3-methylphenylglycidate (source) are shown in Table 1, Data matrix, including physico-chemical properties and toxicological information, thought relevant for skin- and eye irritation.

3.  Purity / Impurities:

The target has no constituents and impurities indicating differences in skin- and eye irritation potential. Impurities are all below 10%.

4.  Analogue justification

According to REACH Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation.

Analogue justification: From analogues identified in the RIFM database and in the OECD QSAR Toolbox (Tanimoto similarity 80%), Ethyl 3-methylphenylglycidate was selected because it was the only analogue with skin and eye irritation information. In view of the close analogy between Ethylphenylglycidate and Ethyl 3-methylphenylglycidate,the difference is one methyl group, further data gathering was not considered necessary.

Structural similarities and differences:Ethylphenylglycidate and Ethyl 3-methylphenylglycidatehave a similar backbone and similar functional group: a phenyl group with a conjugated oxirane ring (epoxide) and an ethyl ester. Ethyl 3-methylphenylglycidate only has an additional methyl group between the phenyl and oxirane group.

Bioavailability:Bioavailability is a parameter needed for skin and eye irritation when a substance is not corrosive. The bioavailability of Ethylphenylglycidate and Ethyl 3-methylphenylglycidate is expected to be very comparable due to a similar molecular weight, log Kow, and water solubility.

Reactivity:The reactivity of both target and source substances is considered similar in view of the similar functional groups: conjugated oxirane ring (epoxide) and an ethyl ester.

Available experimental data other than skin- and eye irritation:Both Ethylphenylglycidate and Ethyl 3-methylphenylglycidate are skin sensitisers, indicating similar skin reactivity.

Remaining uncertainty:In view of the reasoning above, there are no remaining uncertainties.

5.  Data matrix

The relevant information on physico-chemical properties and toxicological characteristics are presented in the Data matrix, Table 1.

Conclusions per endpoint for hazard assessment

When using read across the result derived should be applicable for hazard assessment and be presented with adequate and reliable documentation, which is done in the present document.

For Ethyl phenylglycidate no skin and eye irritation information is available but read across can be done from the source substance Ethyl 3-methylphenylglycidate, which shows absence of skin and eye irritation. In view of the high similarity in chemical structure, considering backbone and functional group Ethylphenylglycidate, is not a skin and eye irritant either.

Final conclusion on irritation: Ethylphenylglycidate is not a skin or eye irritant.

 

Table 1: Data matrix on information on Ethylphenylglycidate (target) and Ethyl 3-methylphenylglycidate (source) important for supporting the read across on skin and eye irritating properties of the target.

Name of substance	Ethylphenylglycidate	Ethyl 3-methylphenylglycidate
Chemical structure
Cas no.	121-39-1	77-83-8
REACH	To be registered under Annex VII	Annex VIII registered
Empirical	C11H12O3	C12H14O3
Mol weight	192.21	206.24
Phys-Chem
Appearance	Liquid	Liquid
Melting point (oC)	<-20 (IFF, 2015)	<-50 (ECHA disseminated site)
Boiling point (oC)	264.8 (IFF, 2015)	302 (ECHA disseminated site)
Vapour pressure (Pa) at 25°C	0.12 (IFF, 2015)	0.23 (20°C; ECHA disseminated site)
Water solubility at 25°C (mg/L)	748.4 (IFF, 2015)	1000 (ECHA dissemination site)
Log Kow	2.4 (IFF, 2015)	2.4 and 2.8 (ECHA disseminated site)
Human health
Skin irritation	Read across	Not irritating (OECD TG 439; ECHA disseminated site)
Eye irritation	Read across	Not irritating (OECD TG 405: ECHA disseminated site)
Skin Sensitization	Positive, EC3 4.7% (OECD TG 429, EC3 4.7%, 1B, IFF, 2011)	Positive (OECD TG 406, GPMT 1B  ECHA dissemination site)

 

Justification for classification or non-classification

Based on the results, the substance does not need to be classified for skin irritation and eye irritation according to EU CLP (EC, 1272/2008 and its amendments).