Propanoic acid, 2-hydroxy-, propyl ester, (2S)-

Endpoint summary

Description of key information

The potential of propyl (S)-lactate to induce skin corrosion/irritation and eye irritation was tested in vivo and in vitro. Based on the results, propyl (S)-lactate must be considered as not irritating to the skin but damaging to eyes. Based on the available data and according to CLP Regulation 1272/2008, propyl (S)-lactate is classified as Eye Dam. 1, H318.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-06-13 to 2000-02-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 17th July 1992

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): n-propyl lactate
- Analytical purity: 99.5%
- Lot/batch No.:3
- Appearance: clear, colourless liquid
- Storage condition of test material: ambient

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- undiluted

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: young adult
- Weight at study initiation: 2260-2470 g
- Housing: individually in stainless steel cages, fitted with perforated floor
- Diet: standard laboratory rabbit diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 12 or 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 46-77.5 (upper limit higher than the intended 70%, because of meteorological circumstances or because of wet cleaning of the animal room; the 77.5% peak occurred for ca one hour at most)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

VEHICLE
no vehicle used

Duration of treatment / exposure:

4 h

Observation period:

14 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 100%
- Type of wrap if used: self-adhesive-gauze (Fixomull, BDF, Germany)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, application site was cleaned with a paper tissue and water
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 1, 24, 48 and 72 hours and at 7 and 14 days after end of treatment.

SCORING SYSTEM: according to Draize et al., 1944 (see Table 1 in box "Any other information on materials and methods incl. tables")

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test substance showed slightly skin irritating properties, which had resolved within 48 hours to 7 days. Individual results are shown in Table 2 (please refer to box "Any other information on results incl. tables).

Table 2: Results after a 4 hours dermal exposure propyl (S)-lactate

Rabbit No	1 h A B	24 h A B	48 h A B	72 h A B	7 d A B	14 d A B
31	1-0^1	1-0^2	0-0^1	0-0^1	0-0^1	0-0
32	1-0^1	2-1^1	1-0^3	1-0^1	0-0^1	0-0
33	1-0^1	1-0^1	0-0^1	0-0^1	0-0^1	0-0

A: erythrema

B: oedema

¹= slight scaliness

²= moderate scaliness

³= very slight scaliness

 

Interpretation of results:

other: CLP criteria not met

Conclusions:

In an acute dermal irritation/corrosion study conducted according to OECD 404, the test item was found to be non-irritating.

Executive summary:

In a primary dermal irritation study conducted according to OECD TG 404, three male New Zealand white rabbits were dermally exposed to 0.5 mL of the test item (99.5% purity) for 4 hours to a body surface area of 2.5 x 2.5 cm under semi-occlusive conditions. Animals then were observed for 1, 24, 48 and 72 hours and 7 and 14 days after removal of the dressings and test substance. Irritation was scored by the method of Draize.

The test item did not cause any skin effects, except a very slight erythema and edema in the treated skin-area, which had completely resolved within 24 hours to 7 days. Based on the results and in accordance with the criteria identified in the CLP Regulation 1272/2008, the test item is non-irritating.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

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

Adequacy of study:

supporting study

Justification for type of information:

For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Irritation / corrosion parameter:

other: Epidermal cell proliferation in skin organ cultures

Run / experiment:

rabbit skin

Value:

5.2

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

other: not statistically different from control

Irritation / corrosion parameter:

other: Epidermal cell proliferation in skin organ cultures

Run / experiment:

Human skin

Value:

49.9

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

other: similar to control

Irritation / corrosion parameter:

other: MTT conversion expressed as OD560 per gram dry weight

Run / experiment:

Rabbit skin

Value:

10.69

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

other: Statistically significantly lower than the non-exposed control group (p< 0.05)

Irritation / corrosion parameter:

other: MTT conversion expressed as OD560 per gram dry weight

Run / experiment:

Human skin

Value:

22.42

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

other: similar to control

Other effects / acceptance of results:

MTT conversion was reduced in a statistically significant way by n-propyl lactate exposure in rabbit skin cultures, but not in human skin cultures. Epidermal cell proliferation was not inhibited by n-propyl lactate.

Interpretation of results:

other: Propyl lactate is toxic in vitro to rabbit skin, but not to human skin

Conclusions:

In a non-guideline in vitro skin toxicity study, the test substance n-propyl lactate (purity 99.5%) appeared to be toxic to rabbit skin, but not to human skin organ cultures. In conclusion, this in vitro skin toxicity study revealed that rabbit skin was more sensitive to n-propyl lactate than human skin. The in vitro toxicity data obtained for the six lactate esters did not correlate well with the degree of skin irritation observed in previously performed in vivo tests with lactate esters in rabbits.

Executive summary:

Propyl lactate, and five other lactate esters, were examined for in vitro skin toxicity in rabbit skin organ cultures and humans skin organ cultures. The toxicity was studied after an exposure time of 30 minutes. Toxicity was determined by measuring epidermal cell proloferation and the conversion of the tetrazolium salt MTT.

In rabbit skin, MTT conversion and epidermal cell proliferation were statistically significantly reduced after exposure to n-propyl lactate. In human skin, n-propyl lactate caused no statistically significant effects. The in vitro toxicity data obtained in this study for n-propyl lactate and five other lactate esters with rabbit skin did not correlate well with the degree of skin irritation observed in previously performed in vivo tests with lactate esters in rabbits.

Possible species-specific irritant effects of n-propyl lactate were tested in vitro by comparing rabbit skin to human skin. Based on the MTT assay and inhibition of epidermal cell proliferation, rabbit skin was clearly more sensitive to n-propyl lactate than human skin. A possible explanation for this difference is a lower skin absorption of the test substances in human skin, since rabbit skin is generally more permeable for topically applied chemicals than humans skin (ECETOC, 1993).

The anionic surfactant sodium dodecyl sulfate (SDS) was used as a reference substance to enable comparison of the in vitro results of this study to previous data obtained with the skin organ culture method. Exposure of rabbit skin for 30 minutes to 5% SDS induced an decrease of MTT conversion of approximately 15%. Human skin was less sensitive to SDS than rabbit skin, which is in agreement with results obtained in previously performed studies (van de Sandt and Rutten (1995b) and unpublished data). It has been reported that 5% SDS is a moderate irritant in rabbits (Gad et al., 1986) and human volunteers (Willes et al., 1988).

In conclusion, this in vitro skin toxicity study revealed that rabbit skin was more sensitive to n-propyl lactate than human skin.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reference 3

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

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

Adequacy of study:

supporting study

Justification for type of information:

For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Remarks on result:

other: see "any other information on results" section below

Other effects / acceptance of results:

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 n-propyl lactate induced a moderate to pronounced increase of eosinophilic staining of both rabbit and human skin cultures. In addition, separation between dermis and epidermis was observed in the exposed rabbit skin cultures, and to a lesser extent in human skin cultures. Slight 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 propyl lactate.

Epidermal cell proliferation:
Propyl lactate clearly reduced epidermal cell proliferation. This reduction was more pronounced in rabbit skin cultures than in human skin cultures.

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

Interpretation of results:

study cannot be used for classification

Conclusions:

Propyl lactate was very toxic to skin in vitro, but no clear relation for in vitro toxicity of lactate esters with in vivo irriation potential was found. Human skin cultures were less sensitive compared to rabbit skin cultures.

Executive summary:

Propyl lactate 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 propyl lactate, 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.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

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:

weight of evidence

Study period:

1994-06-14 to 2020-02-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 31st July 1992

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): n-propyl lactate
- Analytical purity: 99.5%
- Lot/batch No.: 3
- Appearance: clear, colourless liquid
- Storage conditions: ambient

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: 2940 g
- Housing: individually in a stainless steel cage, fitted with a perforated floor
- Diet: standard laboratory rabbit diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 27 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 42-82.5
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

VEHICLE
- Amount(s) applied (volume or weight with unit): no vehicle used

Duration of treatment / exposure:

An amount of 0.1 mL of the test substance was instilled in the conjunctival cul-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.

Observation period (in vivo):

42 days post-treatment (scoring: 1, 24, 48 and 72 hours and 7, 14, 21, 25, 28, 35 and 42 days after treatment)

Number of animals or in vitro replicates:

one animal (due to severe effects observed)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: non-relevant

SCORING SYSTEM: in accordance with the OECD guideline 405
The reactions were scored 1 h, 24, 48 and 72 h, as well as at 7, 14, 21, 25, 28, 35, and 42 days after treatment

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 42 d

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 25 d

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 25 d

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

See Table 1 in box 'Any other information on results incl. tables'.

Table 1: Individual irritation scores given to the ocular lesions exerted by the test material.

Time post-treatment	Corneal opacity	Iris effect	Conjunctivae		Ocular discharge
			Redness	Chemosis
1 h	2(4)	1	2	3	3
24 h	2(4)	1	3^1	3	3
48 h	2(4)	1	3^1	3	3^2
72 h	2(4)	1	3^1	3	3^2
7 d	2(4)^3	1	2	2	1
14 d	2(2)^3	0	2	2	0
21 d	1(2)^3	0	1	1	0
25 d	1(4)^3°	0	0	0	0
28 d	1(4)^3°	0	0	0	0
35 and 42 d	1(3)^3°	0	0	0	0

( ) = area of opacity; 2 = half area, 3 = three quart area, 4 = entire cornea

1= severe ischemic necrosis; 2= haemorrhagic discharge; 3=vascularization of the cornea; ° = slight ulcus corneae

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In an acute eye irritation/corrosion study conducted according to the OECD TG 405, n-propyl lactate was found as severely irritating to the eyes of rabbits.

Executive summary:

In an eye irritation/ corrosion study conducted according to the OECD TG 405, 0.1 mL of n-propyl lactate (purity 99.5%) was instilled into the conjunctival sac of the right eye of 1 young adult New Zealand White albino rabbit. The left eye remaining untreated, served as a control. The eyes were not washed after treatment. The animal then was observed for 42 days. Irritation was scored by the method of Draize.

The test substance caused moderate corneal opacity, slight iritis, severe redness, severe ischemic necrosis, and severe swelling of the conjunctivae, and severe ocular discharge in this rabbit. In addition, vascularization of the cornea and ulcus corneae were observed. At 21 days after treatment, residual corneal effects were still present. Therefore, the observation period was extended with another 3 weeks. After this period, vascularization of the cornea, ulcus corneae, and corneal opacity were still observed. Based on the results of this study, the test item Propyl (S)-lactate is severely irritating to the eye and in accordance with CLP Regulation 1972/2008 classification as Eye Dam. 1 (H318) is warranted.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Remarks:

Chicken Enucleated Eye Test (validated alternative test)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1995-01-20 to 2000-02-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): n-propyl lactate
- Analytical purity: 99.5%
- Lot/batch No.: 3
- Appearance: clear, colourless liquid
- Storage conditions: ambient

TREATMENT OF TEST MATERIAL PRIOR TO TESTING:
- undiluted

Species:

chicken

Strain:

other: not relevant

Details on test animals or tissues and environmental conditions:

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 poultry slaughterhouse v.d. Bor, Amersfoortseweg 118, Nijkerkerveen, the Netherlands.
Within 2 hours after kill, eyes were carefully dissected and placed in a supervision apparatus. The enucleated eyes were placed in a stainless steel clamp with the cornea positioned vertically and transferred to a chamber of the superfusion apparatus (TNO, Zeist, the Netherlands). The corneal integrity was assessed in all eyes. 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 replaced, if necessary. Seven eyes were selected for testing.

Vehicle:

unchanged (no vehicle)

Controls:

other: One control eye for each test treated with isotonic saline

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.03 mL

Duration of treatment / exposure:

10 sec

Duration of post- treatment incubation (in vitro):

The control eye and test eyes were examined at 0, 30, 75, 120, 180 and 240 minutes after treatment.

Number of animals or in vitro replicates:

Seven eyes were selected for testing.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 10 sec the corneal surface of the eyes was rinsed with 20 mL of isotonic saline

SCORING SYSTEM
Corneal swelling: [(CT at t - CT at t=0)/ CT at t=0] X 100% , where CT: corneal thickness

Corneal opacity: Opacity degree of density (area most dense taken for scoring)
0= no opacity; 0.5 = very faint opacity; 1= scattered or diffuse areas, details of iris clearly visible; 2= easily discernible translucent area, details of iris slightly obscured; 3= severe corneal opacity, no specific details of iris visible, size of pupil barely discernible; 4= complete corneal opacity, iris invisible

Fluorescein retention:
0= no fluorescein retention; 0.5 = very minor single cell staining; 1= single cell staining scattered throughout the treated area of the cornea; 2= focal or confluent dense single cell staining; 3= confluent large areas of the cornea retaining fluorescein.

All examinations were performed with the slit-lamp microscope.

On the basis of the severity of the findings, the effects are divided into the following categories: I = none; II = slight; III = moderate; IV = severe
* Details for the scoring system can be found in the Guideline OECD 438 (adopted in Sept. 2009).

Irritation parameter:

percent corneal swelling

Remarks:

240 min

Run / experiment:

1

Value:

>= 46 - <= 49

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

positive indication of irritation

Irritation parameter:

percent corneal swelling

Remarks:

240 min

Run / experiment:

2

Value:

>= 40 - <= 43

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

positive indication of irritation

Irritation parameter:

percent corneal swelling

Remarks:

240 min

Run / experiment:

3

Value:

>= 47 - <= 47

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

240 min

Run / experiment:

1

Value:

>= 3 - <= 3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

240 min

Run / experiment:

2

Value:

>= 3 - <= 3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Remarks:

240 min

Run / experiment:

3

Value:

>= 3 - <= 3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

positive indication of irritation

Irritation parameter:

fluorescein retention score

Remarks:

30 min

Run / experiment:

1

Value:

>= 3 - <= 3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

positive indication of irritation

Irritation parameter:

fluorescein retention score

Remarks:

30 min

Run / experiment:

2

Value:

>= 3 - <= 3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

positive indication of irritation

Irritation parameter:

fluorescein retention score

Remarks:

30 min

Run / experiment:

3

Value:

>= 3 - <= 3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

positive indication of irritation

Other effects / acceptance of results:

As recorded above, n-propyl lactate was severely irritating to the eyes of chickens.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Under the given conditions, the test item is considered severely irritating to eyes.

Executive summary:

In an ex vivo bioassay, the Chicken Enucleated Eye Test (CEET), 0.03 mL of undiluted propyl (S)-lactate (purity 99.5%) was applied to enucleated chicken eyes for 10 seconds, after which the corneal surface was rinsed with 20 mL of isotonic saline. The eyes were then examined up to 6 hours after treatment. Irritation was scored as thickness of the cornea, corneal opacity and fluorescein retention.

After treatment, the thickness of the cornea of the test eyes gradually increased considerably; a maximum mean corneal swelling of 46 % was obtained at 240 min after treatment. Severe corneal opacity and severe fluorescein retention by damaged epithelial cells were observed in the test eyes. Based on these results the test item was considered severely irritating to the eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

In an in vivo study with rabbit and human skin, n-propyl-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.

Propyl (S)-lactate was examined undiluted for skin irritating properties in an experiment conducted according to OECD TG 404. The dermal exposure period was 4 hours under semi-occlusive conditions. The test material caused very slight or well-defined erythema, very slight oedema and slight or moderate scaliness in the three rabbits. The symptoms were fully reversible within 14 days after treatment. On the basis of the results and according to the criteria published in the CLP Regulation 1272/2008 no classification for skin irritation is warranted.

N-propyl-lactate was examined for its eye irritating/corrosive potential in an ex vivo bioassay, namely the Enucleated Eye Test with chicken eyes (CEET). The chicken eyes were obtained from slaughter animals for human consumption. The test substance caused severe corneal swelling, severe corneal opacity and severe fluorescein retention of damaged corneal epithelium in the test eyes. On the basis of the results, it is recommended to classify the test substance to be eye damaging.

In addition, n-propyl-lactate was tested for acute eye irritating in a study conducted according to OECD TG 405. Only one rabbit was tested in the present investigation, due to severe irritating effects observed in the ex vivo bioassay. The test substance caused moderate corneal opacity, slight iritis, severe redness, severe ischemic necrosis, and severe swelling of the conjunctivae, and severe ocular discharge in this rabbit. In addition, vascularization of the cornea and ulcus corneae were observed. Due to effects still observed 21 days after treatment, the observation period was extended for another three weeks. After this period, vascularization of the cornea, ulcus corneae, and corneal opacity were still observed. It can be concluded that n-propyl-lactate is severely irritating to the eyes of rabbits and classification as Eye Dam. 1, H318 is warranted according to CLP Regulation 1272/2008.

Slightly irritating effects to the respiratory tract were seen in sub-acute inhalation toxicity studies conducted with the suitable read-across partner ethyl (S)-lactate and butyl (S)-lactate (see IUCLID section 7.5.2). As propyl (S)-lactate is also hydrolyzed to lactic acid, it is expected to have an irritating effect to the respiratory tract as well and the substance will be classified as STOT SE3, H335 in accordance with CLP Regulation 1272/2008.

Justification for classification or non-classification

Based on the available data and according to CLP Regulation 1272/2008, classification as Eye Dam. 1, H318 and STOT SE 3, H335 is warranted for the target substance propyl (S)-lactate.