Registration Dossier

Administrative data

Description of key information

2-Ethylhexyl-S-lactate is irritating to the eye, to the skin, and to the respiratory tract.

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:
weight of evidence
Study period:
October 1995–February 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline available
Principles of method if other than guideline:
The study was conducted according to a protocol entitled "Protocol for an in vitro skin irritation study with a series of lactic acid esters using rabbit and human skin organ cultures". The irritative potential of seven lactic acid esters and one positive control (sodium dodecyl sulfate) was determined in both human and rabbit skin organ cultures. The test substances were applied topically for a period of 4 h, corresponding with the in vivo exposure time in rabbits (OECD guideline no. 404). The following endpoints were determined 48 h after removal of the compounds: cytotoxicity (MTT assay), histomorphology, epidermal cell proliferation and release of pro-inflammatory hydroxy fatty acids. The experimental groups consisted of three to five skins discs.
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- PURAC Biochem B.V., batch no. EHL 950326
- Expiration date of the lot/batch: No data
- Purity test date: 23/06/1995

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, dark
- Stability under test conditions: No indications of instability
- Solubility and stability of the test substance in the solvent/vehicle: No solvent/vehicle used
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No reacitivity known

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None
- Preliminary purification step (if any): None
- Final dilution of a dissolved solid, stock liquid or gel: None
- Final preparation of a solid: Not applicable
Test system:
isolated skin discs
Source species:
human
Cell type:
other: epidermiis
Cell source:
skin obtained from plastic surgery from a single donor
Source strain:
not specified
Justification for test system used:
At the time of study performance (1995/1996), the latest update of OECD guideline no. 404 (acute dermal irritation/corrosion, adopted on 17 July 1992) states that it may not be necessary to test in vivo materials for which corrosive properties are predicted on the basis of results from in vitro tests. Moreover, in vitro skin irritation testing offers the possibility to include human skin, thereby contributing to a more detailed hazard identification.
Vehicle:
unchanged (no vehicle)
Remarks:
test substance plus prefilter
Details on test system:
SKIN DISC PREPARATION
- Procedure used: Circular discs (2 cm²} were punched out from the isolated skin after careful removal of subcutaneous fat, and washed three times for ca. 15 min in medium supplemented with bactericides and fungicides to prevent microbiological contamination
of the cultures
- Quality control for skin discs: Determination of epidermal cell proliferation; after a 24-h incubation period with 5-bromo-2'-deoxyuridine (BrdU, 1 0 μl from a stock solution of 2 mg BrdU/ml phosphate-buffered saline, 0. 1 M), the skin discs were fixed in 70% (v/v) aqueous ethanol at 4-8°C for at least 72 h. The tissues required for microscopic examination were embedded in paraffin wax and sectioned at 4 μm.
For examination of proliferating epithelial cells, tissue sections were stained immunohistochemically and counter-stained with haematoxylin. Cell proliferation was assessed by counting epidermal cells containing a BrdU-positive nucleus. Hair follicles and the epiboly, standardized as 1 mm from both edges of the skin disc, were excluded from the counting procedure. Cell proliferation was scored by one person in a "blind" fashion.
For histopathological examination, tissue sections were stained with haematoxylin and eosin. Individual cross sections were analysed and the epidermal damage was scored as slight, moderate or pronounced. Parameters of histomorphological damage were intra-epidermal separation, dermalepidermal separation, epidermal eosinophilic staining, pycnosis in epidermis, and vacuolization of epidermal cells.

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment/exposure: No data
- Temperature of post-treatment incubation (if applicable): No data

REMOVAL OF TEST MATERIAL AND CONTROLS
- Number of washing steps: 3
- Observable damage in the tissue due to washing: No data
- Modifications to validated SOP: Fresh skin was fixed in 70 % ethanol instead of 4 % formaldehyde. After exposure to the test substances and prior to washing the skin discs, a clean prefilter was applied to the skin discs to remove traces of the test substances. The data of the MTT assay are presented as 0D5wfg tissue instead of 0D560 in order to compensate for the size of the skin tissue. For this reason, the skin tissue was dried overnight at 37°C and weighed on an analytical balance.

DYE BINDING METHOD
- Dye used in the dye-binding assay: MTT
- Spectrophotometer: Cary 1 E UV-visible spectrophotometer, Varian Analytical Instruments, Houten, the Netherlands
- Wavelength: 560 nm
- Filter: No data
- Filter bandwidth: No data

NUMBER OF INDEPENDENT TESTING RUNS/EXPERIMENTS TO DERIVE FINAL PREDICTION: 3–5

PREDICTION MODEL/DECISION CRITERIA:
- Holistic assessment of the results of the MTT assay, epidermal cell proliferation, and release of hydroxy fatty acids
- Justification for the selection of the cut-off point(s) if different than recommended in TG 430: Study performed a long time before adoption of TG 430
Control samples:
yes, concurrent no treatment
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied: 100 µL
- Concentration (if solution): 100 %

VEHICLE
- No vehicle used

NEGATIVE CONTROL
- Untreated

POSITIVE CONTROL
- Amount(s) applied: 100 µL
- Concentration (if solution): 5 %
Duration of treatment / exposure:
4 h
Duration of post-treatment incubation (if applicable):
48 h
Number of replicates:
3–5
Irritation / corrosion parameter:
dye content (µg/disc)
Remarks:
measured as OD560/g tissue
Run / experiment:
mean
Value:
ca. 20.6
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Irritation / corrosion parameter:
other: epidermal cell prol iferation
Run / experiment:
mean
Value:
ca. 0.6
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Irritation / corrosion parameter:
other: release of hydroxy fatty acids
Remarks:
ng per mL culture medium
Run / experiment:
mean
Value:
ca. 721
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Irritation / corrosion parameter:
other: Histomorphology: Intra-epidermal separation
Run / experiment:
1–3
Value:
>= 0 - <= 2
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Irritation / corrosion parameter:
other: Histomorphology: Dermal/epidermal separation
Run / experiment:
1–3
Value:
>= 0 - <= 2
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Irritation / corrosion parameter:
other: Histomorphology: Epidermal eonsiniphilic staining
Run / experiment:
1–3
Value:
>= 0 - <= 3
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Irritation / corrosion parameter:
other: Histomorphology: Pycnosis in epidermis
Run / experiment:
1–3
Value:
>= 0 - <= 0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Irritation / corrosion parameter:
other: Histomorphology: Vacuolisation of epidermal cells
Run / experiment:
1–3
Value:
>= 0 - <= 0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Interpretation of results:
other: 2-ethylhexyllactate was very toxic to skin in vitro.
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
2-Ethylhexyllactate was very toxic to skin in vitro, but no clear relation for in vitro toxicity of lactate esters with in vivo irritation potential was found.
Human skin cultures were less sensitive compared to rabbit skin cultures.
Executive summary:

2-Ethylhexyllactate and five other lactate esters were examined for in vitro skin irritation potential in rabbit and human skin organ cultures. The results of this study were compared to in vivo skin irritation data obtained with rabbits. The anionic surfactant sodium dodecyl sulfate (SDS) was used as a positive control to enable comparison of the in vitro results of this study to previous dat obtained with the skin organ culture model.

Histomorphology, MTT conversion and epidermal cell proliferation were strongly affect by all lactate esters, and these effects were more pronounced than expected from the in vivo irritating capacity of these substances. All six lactate esters increased the release of total hydroxy fatty acids. The compounds that were shown to be the most irritating in rabbits, also induced the highest release of hydroxy fatty acids.

Species-specific effects of the lactate esters were observed only with repect to epidermal cell proliferation. These substances induced a less pronounced decrease of epidermal cell proliferation in human skin cultures compared to rabbit skin cultures. Human skin was also less sensitive to 5 % SDS, as observed by histomorphology, MTT conversion, cell proliferation and release of hydroxy fatty acids.

The lactate esters tested in this study, including 2-ethylhexyllactate, were shown to be very toxic to the skin in vitro. For these substances, no clear relation with the in vivo irritating properties was found. Species-specific effects of the lactate esters were observed with respect of epidermal cell proliferation, human skin cultures being less sensitive compared to rabbit skin cultures.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
June 1994–September 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
The test substance was also examined in an alternative ex vivo bioassay, namely the Enucleated Eye Test with chicken eyes (CEET).
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Broekman Instituut B.V., Someren, the Netherlands
- Age at study initiation: young adult
- Weight at study initiation: 2250-2940 g
- Housing: individually in a stainless steel cage, fitted with a perforated floor
- Diet (e.g. ad libitum): standard laboratory rabbit diet, ad libitum
- Water (e.g. ad libitum):tap water, ad libitum
- Acclimation period: 27 or 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 42-82.5 % (upper limit higher than the intended 70 %, because of meteorological circumstances or because of wet cleaning of the animal room; the 82.5 % peak occurred for ca one hour at most)
- Air changes (per hr): ca 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light

IN-LIFE DATES: May 18, 1994 or June 1, 1994 to July 8, 1994
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml 2-ethylhexyl lactate
Duration of treatment / exposure:
Single application
Observation period (in vivo):
25 days
Number of animals or in vitro replicates:
3
Details on study design:
In vivo test:
An amount of 0.1 ml of the test substance was instilled in the conjunctival dul-de-sac of the right eye. After administration, the upper and lower eye lid were carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The left eye remaining untreated, served as a control.
The reactions of the test eyes were judged at circa one hour, 24, 48, and 72 hours, and at 7, 14, 21 and 25 days after treatment using the scoring scale which is given in the appendix in the section "Attached background material".

Ex vivo pre-screening, CEET:
Experimental design:
Approximately 7 weeks old, male or female chickens (ROSS, spring chickens), body weight range approximately 2.5-3.0 kg, were used as eye-donors. Heads of these animals were obtained from the poultry slaughterhouse v.d. Bor, Amersfoortseweg 118, Nijkerkerveen, the Netherlands. Heads of the animals were cut off immediately after sedation of the animals by electric shock and incission of the neck for bleeding, and before they reached the next station on the process in line. The heads were placed in small plastic boxes (3 heads per box) on a bedding of paper tissues moistened with isotonic saline. Next, they were transported to the testing facility. During transportation, the heads were kept at ambient temperature. Within 2 hours after kill, eyes were carefully dissected and placed in a superfusion apparatus using the following procedure: First the eye-lids were carefully removed without damaging the cornea and a small drop of Fluorescein sodium BP 2 % w/v (Minims, Smith & Nephew Ltd., Romford, England) was applied to the corneal surface for a few seconds and subsequently rinsed off with isotonic saline of ambient temperature. Next, the head with the fluorescien-treated cornea was examined with a slit-lamp microscope (Slit-lamp 900 CN, Haag-Streit AG, Liebefeld-Bern, Switzerland), to ensure that the cornea was not damaged. If undamaged, the eye was further dissected from the head without damaging the eye or cornea. Care was taken to remove the eye-ball from the orbit without cutting off the optical nerve too short. The enucleated eye was placed in a stainless steel clamp with the cornea postitioned vertically and transferred to a chamber of the superfusion apparatus. (TNO, Zeist, the Netherlands). The clamp holding the eye was positioned in such a way that the entire cornea was supplied with isotonic saline from a bent, stainless steel tube, at a rate of ca 0.10-0.15 ml/min (peristaltic pump, Desaga STA 131900, Heidelberg, Germany). The chambers of the superfusion apparatus as well as the saline were temperature controlled at 32 ± 1.5 °C (waterpump, Thermomix 1441, B. Braun Melsungen AG, Melsungen, Germany). Four eyes were selected and after placing in the superfusion apparatus, the eyes were examined again with the slit-lamp microscope to ensure that they were not damaged. Corneal thickness was measured using the Depth Measuring Attachement no. II for the Haag-Streit Slit-lamp microscope. Thickness of the cornea was expressed in instrument units. An accurate measurement was taken at the corneal apex of each eye. Eyes with a corneal thickness deviating more than 10 % of the average corneal thickness of the eyes, or eyes that were unacceptably stained with fluorescein (score higher than 0.5), indicating the cornea to be permeable, or eyes that showed any other signs of damage, were rejected as test eyes and were replaced. After an equilibration period of 45-60 minutes, the corneal thickness of the eyes were measured again to determine the zero reference value for corneal swelling calculations. The test substance was tested undiluted on three test eyes. At time t = 0, i.e. immediately after the zero reference measurement, the appropriate sample was applied to the cornea. For this purpose, the clamp holding the eye was placed on a paper tissue outside the chamber with the cornea facing upwards. The liquid material was applied in amounts of 0.03 ml from a micropipette (Nichirryo Co., Ltd., model 8100, Tokyo, Japan), in such a way that the entire surface of the cornea was batched with the test substance. After a total exposure period of 10 seconds, the corneal surface was rinsed thoroughly with 20 ml of isotonic saline of ambient temperature. Next, the eye in the holder was returned to its chamber. This procedure was repeated each test eye. The control was treated with saline only. The eyes were examined at 30, 75, 120, 180, and 240 minutes after treatment, using the criteria and scoring system, given in the appendix 2 in the section "Attached background material". All examinations were carried out with the slit-lamp microscope.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
> 0 - <= 1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
24/48/72 h
Score:
>= 2 - <= 3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
>= 3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
>= 1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
At 1 hour after treatment, the eye effects observed in the three rabbits consisted of slight corneal opacity, slight iritis, slight redness and moderate swelling of the conjunctivae, and severe ocular discharge.
At 24 hours after treatment, the eye effects observed consisted of slight or moderate corneal opacity, slight iritis, moderate or severe redness and slight swelling of the conjunctivae, and slight or severe ocular discharge.
At 48 hours after treatment, the eye effects observed consisted of slight or moderate corneal opacity, slight iritis (two rabbits), moderate or severe redness and slight or moderate swelling of the conjunctivae, and slight or severe ocular discharge.
At 72 hours after treatment, the eye effects observed consisted of slight or moderate corneal opacity, slight iritis (one rabbit), slight, moderate or severe redness and slight or moderate swelling of the conjunctivae, and moderate ocular discharge (one rabbit).
At 7 days after treatment, the eye effects observed consisted of slight corneal opacity and vascularization of the cornea in one rabbit, and slight redness and slight swelling of the conjunctuvae in two rabbtis.
At 14 days after treatment, eye effects were still observed in one rabbit and consisted of slight corneal opacity, vascularization of the cornea, and slight redness and slight swelling of the conjunctivae.
At 21 days, these eye effects except minor vascularization of the cornea had cleared completely.
At 25 days, this eye effect had also cleared completely.
Other effects:
Vascularization of the cornea occurred in one rabbit at day 14. The degree diminished gradually,and had disappeared completely at day 25.
Results for the ex vivo study according to CEET:
Mean values for corneal swelling, corneal opacity, and fluorescein retention are presented in Table 2.
After treatment, the thickness of the cornea of the test eyes gradually increased; a maximum mean corneal swelling of 18 % was obtained at 240 min after treatment. Moderate corneal opacity and moderate fluorescein retention by damaged epithelial cells were observed in the three test eyes.
The irritancy categories assigned to these findings are also presented in Table 2, together with the final irritancy classification. The categories defined for corneal swelling, corneal opacity, and fluorescein retention were: II, III, and III.

Table 1. Individual scores awarded to the ocular lesions elicited by 2-ethylhexyl-lactate.

rabbit

corneal

iris

conjunctivae

ocular

number

opacity

effects

redness

chemosis

discharge

 

after one hour

37

1 (4)

1

1

2

3

29

1 (4)

1

1

2

3

30

1 (4)

1

1

2

3

 

after 24 hours

37

2 (4)

1

3

1

3

29

1 (4)

1

3

1

3

30

2 (4)

1

2

1

1

 

after 48 hours

37

2 (2)

1

3

1

1

29

2 (2)

1

3

2

3

30

1 (2)

0

2

1

1

 

after 72 hours

37

2 (2)

0

2

1

0

29

2 (4)

1

3

2

2

30

1 (1)

0

1

1

0

 

after 7 days

37

0

0

1

1

0

29

1 (4)1

0

1

1

0

30

0

0

0

0

0

 

after 14 days

37/30

0

0

0

0

0

29

1 (3)1

0

1

1

0

 

after 21 days

29

01

0

0

0

0

 

after 25 days

29

0

0

0

0

0

 

 

 

 

 

 

The scores are explained in the appendix in the attached background material section

() = area of opacity; 1 = one quarter (or less) but no zero, 2 = half area, 3 = three quarters, 4 = whole area.

1= vascularization of the cornea; the degree diminished gradually

Table 2. Mean values for corneal swelling, corneal opacity and fluorescein retention values of the test eyes treated with 2-ethylhexyl-lactate, and the irritancy categories based on the maximum mean scores, and the final EC-classification

Time intervals

Corneal swelling %

Corneal opacity

Fluorescein retention

30

  7 (1)

1.0 (0)

2.0 (0.0)

75

 9 (2)

1.5 (0)

 

120

14 (3)

2.0 (0)

 

180

16 (4)

2.0 (0)

 

240

18 (5)

2.0 (0)

 

 

Parameter

Maximum score

Category

Corneal swelling

18

II

Corneal opacity

2

III

Fluorescein retention

2

III

EC-classification: Irritating to eyes (R36)

between brackets = mean standard error of the mean

Interpretation of results:
irritating
Conclusions:
2-Ethylhexyl-lactate is distinctly irritating for the eyes of rabbits, and needs labelling as "Category 2: irritating to eyes" according to the EC standards (former label R36, irritating to eyes).
The results of the alternative test method with enucleated chicken eyes were in agreement with the results of the in vivo rabbit eye test.
Executive summary:

2-Ethylhexyl-lactate caused moderate reaction in CEET. Therefore it was decided to preceed with the in vivo rabbit eye test. In a primary eye irritation study, 0.1 ml of undiluted 2-ethylhexyl-lactate was instilled into the conjunctival sac of the right eye of three young adult New Zealand White rabbits of unknown sex. The eyes were not washed. Animals were observed for 25 days. Irritation was scored by the method of Draize.

The test substance caused moderate corneal opacity, slight iritis, moderate or severe redness and moderate swelling of the conjunctivae and severe ocular discharge in the three rabbits. In addition, one rabbit showed vascularization of the cornea. At 21 days all effects except the vascularization in the one rabbit had cleared; at day 25 this effect had also cleared completely.

In this study, 2-ethylhexyl-lactate is an eye irritant based on EC standards and needs labeling as "Category 2, irritating to eyes" (formerly R36).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

In a primary dermal irritation study with albino rabbits exposure to 2-ethylhexyl-S-lactate gave a mean erythema or oedema score over the 24–72 hour observation period of 2, but the effects appeared fully reversible within 14 days. 2-Ethylhexyl-S-lactate is a dermal irritant.

In an in vivo study with rabbit and human skin, 2-ethylhexyl-S-lactate appeared very toxic to skin in vitro, but no clear relation for in vitro toxicity of lactate esters with in vivo irritation potential was found. Human skin cultures were less sensitive compared to rabbit skin cultures.

2-Ethylhexyl-S-lactate caused moderate reaction in CEET. Therefore, it was decided to proceed with the in vivo rabbit eye test. In a primary eye irritation study with rabbits, 2-ethylhexyl-S-lactate caused moderate corneal opacity, slight iritis, moderate or severe redness and moderate swelling of the conjunctivae and severe ocular discharge in the three rabbits. In addition, one rabbit showed vascularization of the cornea. At 21 days all effects except the vascularization in the one rabbit had cleared; at day 25 this effect had also cleared completely. In this study, 2-ethylhexyl-S-lactate is an eye irritant.

Effects on skin irritation/corrosion: irritating
Effects on eye irritation: irritating
Effects on respiratory irritation: irritating

Justification for classification or non-classification

In a primary dermal irritation study with albino rabbits exposure to 2-ethylhexyl-S-lactate gave a mean erythma or oedema score over the 24–72 hour observation period of 2, but the effects appeared fully reversible within 14 days. 2-Ethylhexyl-S-lactate is a dermal irritant based on EU standards and should be labelled as "Skin irritant: Category 2".

2-Ethylhexyl-S-lactate caused moderate reaction in CEET. Therefore, it was decided to proceed with the in vivo rabbit eye test. In a primary eye irritation study with rabbits, 2-ethylhexyl-S-lactate caused moderate corneal opacity, slight iritis, moderate or severe redness and moderate swelling of the conjunctivae and severe ocular discharge in the three rabbits. In addition, one rabbit showed vascularization of the cornea. At 21 days all effects except the vascularization in the one rabbit had cleared; at day 25 this effect had also cleared completely.

In this study, 2-ethylhexyl-S-lactate is an eye irritant based on EU standards and needs labeling as "Eye irritant: Category 2".