2-ethylhexyl lactate

Endpoint summary

Description of key information

By read-across from 2-ethylhexyl-S-lactate, 2-ethylhexyl lactate is assessed as irritating to the eye and to the skin.

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:

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

Adequacy of study:

supporting study

Study period:

October, 1995-February 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study; test substance was 2-ethylhexyl-S-lactate, hence read-across to the non-stereospecific 2-ethylhexyl lactate (unspecified stereochemistry) is feasible without restrictions.

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. QA statement)

Species:

other: in vitro rabbit skin and human skin organ culture

Strain:

other: rabbit: New Zealand White

Details on test animals or test system and environmental conditions:

Rabbit skin was obtained from one New Zealand White albino rabbit (male, young adult) (ENKI, Someren, the Netherlands). The animal was clipped free of hair one day before the start of the study. Human skin was obtained directly after surgery from one female caucasian donor of 37 years old (code TNA/9503) at the Department of Plastic and Reconstructive Surgery (Academic Hospital Utrecht, the Netherlands). The skin was transported on ice to the laboratory within 1 h of dissection. Directly after arrival, skin discs were isolated for culture.
Skin was cultured in a two-compartment skin organ culture model as described by Rutten et al. (1990) and Sandt et al. (1993, 1995a,b). Briefly, circular discs (2 cm²) were punched out from the isolated skin after careful removal of subcutaneous fat. Skin discs were washed three times for c. 15 min in medium supplemented with bactericides and fungicides to prevent microbiological contamination of the cultures. Skin explants were cultured in 6-well plates on a microporous membrane (Millicel-HA insert unit, Millipore, Bedfort, MA), which allows transport of culture medium via the dermis into the epidermis, while the epidermal side of the skin remains free of contact with the culture medium. The skin discs were cultured in a humidified incubator gassed with 5 % CO2 and 40 % O2 at 37 °C. To obtain optimal culture conditions and a homogenous distribution of the receptor fluid the 6-well plates were rocked on a platform c. 9 times per min.

Type of coverage:

other: test substance plus prefilter

Preparation of test site:

other: The epidermal side of the skin discs were carefully dried using sterile prefilters (Millipore filter, type AP10, 1.3 cm²).

Vehicle:

unchanged (no vehicle)

Controls:

other: non-exposed skin discs

Amount / concentration applied:

100 µl of pure test substance

Duration of treatment / exposure:

4 hours

Observation period:

24 and 48 hours

Number of animals:

Not applicable, three to five skin discs per skin type and test substance.

Details on study design:

Topical application of the test substance in vitro:
One day after the isolation of the skin, the culture medium was removed and fresh medium was added to the cultures. The epidermal side of the skin discs were carefully dried using sterile prefilters (Millipore filter, type AP10, 1.3 cm²). Subsequently, fresh sterile prefilters were applied to the epidermal side together with 100 µl of the test solution. After a 4-h treatment period, the filters and the culture medium were removed. Traces of the test substances were removed with a fresh sterile prefilter. Furthermore, each skin disc was washed three times with 4 ml sterile 0.1 M phosphate-buffered saline (pH=7.2) (Flow Laboratories, Irvine, Scotland) while remaining in the insert units. Subsequently, fresh culture medium was added to the skin discs.

Sampling and measurements:
Collection of skin tissue:
Before starting the culture of the skin discs, a sample of non-cultured skin was fixed in 70 % (v/v) aqueous ethanol (4-8 °C) (encoded T0). Culture medium was collected 24 and 48 h after removal of the test substances. The culture medium was stored at c. -80 °C till further analysis. At 48 h after removal of the test substances, each skin sample was cut in two with a scalpel knife. One half was fixed in 70 % (v/v) aqueous ethanol (4-8 °C) for (immuno)histochemical analysis, the other half was placed back into the original well for cytotoxicity measurement (MTT assay).

Determination of epidermal cell proliferation and histomorphology:
Determination of epidermal cell proliferation was carried out according to the method described by Van de Sandt et al. (1995b). In brief, after a 24-h incubation period with 5-bromo-2'-deoxyuridine (BrdU, 10 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 l 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 haemotoxylin 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, dermal-epidermal separation, epidermal eosinophilic staining, pycnosis in epidermis, and vacuolization of epidermal cells.

Measurement of skin thickness:
Determination of the skin thickness was performed with the use of a microscopic raster at three levels in the cross sections of both rabbit and human skin cultures. For this purpose, a NE10 raster (Graticules Ltd., Tonbridge, Kent, UK) was calibrated with the use of a graduated microscopic ruler (J.D. Moller, Optische Werke GmbH, Wedel, Germany).

MTT assay:
The MTT assay was carried out 48 h after removal of the test substances. Culture medium without serum containing 2.0 mg MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) per ml was added to the half skin discs (4 ml/well). After a 4-h incubation period at 37 °C, 40 % O2 and 5 % CO2, the skin tissue was washed twice in prewarmed PBS (37 °C). The MTT-formazan precipitate was extracted from the tissue in polysterene tubes containing 5 ml acidified isopropanol (0.04 M HCl) for 4 days in the dark, after which the optical density was measured at 560 nm (OD560) on a Cary 1 E UV-visible spectrophotometer (Varian Analytical Instruments, Houten, the Netherlands). The skin tissue was dried overnight at 37 °C and weighed on an analytical balance. Data of the MTT assay were presented as OD560/g tissue in an absolute and relative manner.

Analysis of hydroxy fatty acids in the culture medium:
Hydroxy fatty acids were extracted from culture media by a solid phase extraction procedure, and the analysis was performed with high performance liquid chromatography (HPLC), according to the method desribed by Sandt et al. (1995a). For each skin disc, the culture medium collected 24 and 48 h after removal of the test compounds was pooled (750 µl of each time point).

Statistical analysis of the results:
The data on MTT conversion, cell proliferation and total release of hydroxy fatty acids were tested for statistical differences using a Kruskal-Wallis one way analysis of variance, followed by a Mann-Whitney U-test.

Other effects:

Skin thickness and histomorphology:
The thickness of the skin cultures was 2.66 ± 0.33 mm for rabbit skin, and 2.87 ± 0.30 mm for human skin. Histomorphological examination of the skin cultures revealed that 2-ethylhexyllactate induced a moderate to pronounced increase of eosinophilic staining of both rabbit and human skin cultures. In addition, separation between dermis and epidermis as well as intra-epidermal separation was observed in the exposed rabbit skin cultures. Slight to moderate pycnosis in epidermis was observed in the exposed human skin cultures. Moderate vacuolization of epidermal cells in all three exposed human skin cultures was observed. Since slight vacuolization of epidermal cells is also seen in non-exposed human skin cultures, this is considered not a treatment-related effect.

MTT assay:
In both human and rabbit skin cultures, MTT conversion was reduced in a statistically significant manner after exposure to 2-ethylhexyllactate.

Epidermal cell proliferation:
2-Ethylhexyllactate clearly reduced epidermal cell proliferation. This reduction was more pronounced in rabbit skin cultures than in human skin cultures.

Release of hydroxy fatty acids:
2-Ethylhexyllactate induced an increase of total release of hydroxy fatty acids (13HODE, 9 HODE, 15HETE and 12 HETE).

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:

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

Adequacy of study:

key study

Study period:

June 1994 - September 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study; test substance was 2-ethylhexyl-S-lactate, hence read-across to the non-stereospecific 2-ethylhexyl lactate (unspecified stereochemistry) is feasible without restrictions.

Qualifier:

according to guideline

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:

other: The left eye was used as control while the right eye was treated.

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:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

of three time points for three animals

Time point:

other: 24, 48 and 72 hours

Score:

> 1.7 - <= 3

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

cornea opacity score

Remarks:

(corneal opacity)

Basis:

mean

Remarks:

of three time points for three animals

Time point:

other: 24, 48 and 72 hours

Score:

> 1.3 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

mean

Remarks:

of three time points for three animals

Time point:

other: 24, 48 and 72 hours

Score:

> 0.3 - <= 1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Eye irritation scores recorded at 1 hour, 24, 48, and 72 hours, and at 7, 14, 21, and 25 days after treatment are shown in Table 1.
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	0^1	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

Remarks:

Migrated information Criteria used for interpretation of results: EU

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. By read-across from 2-ethylhexyl-S-lactate, 2-ethylhexyl lactate is assessed as 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, a finding that is extrapolated to 2-ethylhexyl lactate by read-across.

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 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.

Based on read-across from 2-ethylhexyl-S-lactate, 2-ethylhexyl lactate (non-stereospecific) is identified as an eye irritant based on EU standards and needs labelling as “Eye irritant: Category 2”.