Methyl (S)-(-)-lactate

Endpoint summary

Description of key information

By way of read-across from the structurally equivalent substances Etyhl (S)-lactate and Propyl (S)-lactate, it is concluded that the target substance Methyl (S)-lactate is not irritating to the skin.

By way of read-across from the structurally equivalent substances Etyhl (S)-lactate, Butyl (S)-lactate and Propyl (S)-lactate, it is concluded that the target substance Methyl (S)-lactate is corrosive to the eye and classification as Eye Dam. 1, H318 is warranted in accordance with CLP Regulation 1272/2008. In accordance with the harmonised classification (Annex VI of CLP Regulation 1272/2008) and based on available data , classification as STOT SE 3, H335 is additionally warranted.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

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 parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

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

Other effects:

At 7 days after treatment, slight scaliness was observed in the two rabbits that showed skin irritation during the first days on the edges of the application area (<1 mm) only. At 14 days after treatment, the scaliness had cleared.

Table 1 - Skin irritation scores of ethyl lactate, after a single 4-hour dermal exposure

Animal no.	Hours or days after removal of the test material:
	1 hr	24 hr	48 hr	72 hr	7 d
	A-B	A-B	A-B	A-B	A-B
12	0-0 (1-1)	0-0 (2-2)	0-0 (2-2)	0-0 (2-1)	0-0
8	0-0 (1-1)	0-0 (2-2)	0-0 (2-2)	0-0 (2-1)	0-0
14	0-0 (1-1)	0-0 (1-1)	0-0	0-0
Erythema (A):	0.0	0.0	0.0	0.0	0.0
Oedema (B):	0.0	0.0	0.0	0.0	0.0

 

() Skin effects were located on a very small skin area on the edge of the application area (width less than 1 mm), most probably caused by pressure of the bandage on the test patch underneath. Therefore, the toxicological significance of these skin effects is considered dubious.

Interpretation of results:

other: CLP criteria not met

Conclusions:

Under the given conditions, the test item is not irritating to the skin of rabbits.

Executive summary:

In a primary dermal irritation study (according to OECD Guideline 404), young adult male SPF bred New Zealand White albino rabbits (n= 3; weight 2130 - 2220 g) were dermally exposed to 0.5 mL of ethyl (S)-lactate (purity: 98%) to an area of 2.5 x 2.5 cm under occlusive conditions for 4 hours. Animals were then observed for 14 days and irritation was scored by the method of Draize et al. Only mild skin effects were observed on a very small skin area on the edge of the application area, most probably by pressure of the bandage on the test patch underneath. Since normally these kind of exposure conditions will not occur in humans, the toxicological significance of these skin effects was considered dubious. Furthermore, the mean erythema and oedema scores were 0. Based on these results, Ethyl (S)-lactate can be considered as non-irritant to the skin of rabbits. Therefore, classification for skin irritation according to CLP Regulation 1272/2008 is not warranted.

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 vivo

Type of information:

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

Adequacy of study:

weight of evidence

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 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

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 of the study

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 in accordance with CLP Regulation 1272/2008.

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.

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 vitro / ex vivo

Type of information:

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

Adequacy of study:

weight of evidence

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 parameter:

corneal swelling 

Run / experiment:

at 30 min

Value:

10

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Irritation parameter:

cornea opacity score

Run / experiment:

at 30 min

Value:

1

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Irritation parameter:

fluorescein retention score

Run / experiment:

at 30 min

Value:

3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Remarks on result:

other:

Remarks:

fluorescein retention was only determined at t = 30 min

Irritation parameter:

corneal swelling 

Run / experiment:

at 75 min

Value:

15

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Irritation parameter:

cornea opacity score

Run / experiment:

at 75 min

Value:

2

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Irritation parameter:

corneal swelling 

Run / experiment:

at 120 min

Value:

24

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Irritation parameter:

cornea opacity score

Run / experiment:

at 120 min

Value:

2

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Irritation parameter:

corneal swelling 

Run / experiment:

at 180 min

Value:

27

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Irritation parameter:

cornea opacity score

Run / experiment:

at 180 min

Value:

2

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Irritation parameter:

corneal swelling 

Run / experiment:

at 240 min

Value:

31

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Irritation parameter:

cornea opacity score

Run / experiment:

at 240 min

Value:

2.3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Other effects / acceptance of results:

After treatment, the thickness of the cornea of the test eyes gradually increased considerably; a maximum mean corneal swelling of 31% was obtained at 240 min after treatment. Moderate or severe corneal opacity and severe fluorescein retention by damaged epithelial cells were observed in the test eyes. In addition, the three test eyes showed wrinkling of the corneal epithelium. The irritancy categories assigned to these findings for corneal swelling, corneal opacity, and fluorescein retention were: III, III and IV.

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 ethyl-(S)-lactate (purity: 98 %) 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 4 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 31 % was obtained at 240 min after treatment. Moderate or severe corneal opacity and severe fluorescein retention by damaged epithelial cells were observed in the test eyes. In addition, the three test eyes showed wrinkling of the corneal epithelium. Based on this results the test item was considered severely irritating to the eyes. Therefore, classification of ethyl-(S)-lactate as Eye Dam. 1 (H318) according to the CLP Regulation 1272/2008 is warranted.

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 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

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

Adequacy of study:

weight of evidence

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 parameter:

percent corneal swelling

Remarks:

after 240 min

Run / experiment:

1

Value:

39

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:

after 240 min

Run / experiment:

2

Value:

44

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:

after 240 min

Run / experiment:

3

Value:

41

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:

after 240 min

Run / experiment:

1

Value:

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:

after 240 min

Run / experiment:

2

Value:

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:

after 240 min

Run / experiment:

3

Value:

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:

after 30 min

Run / experiment:

1

Value:

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:

after 30 min

Run / experiment:

2

Value:

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:

after 30 min

Run / experiment:

3

Value:

3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

positive indication of irritation

Interpretation of results:

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

Conclusions:

n-Butyl-S-lactate is highly irritating and possibly corrosive to the eye of chicken when tested with a single application under the conditions of the present test. On the basis of these results, it is recommended not to perform the standard rabbit eye irritation test with n-butyl-S-lactate in rabbits, but to classify the test substance as an eye irritant Category 1.

Executive summary:

n-Butyl-S-lactate was examined for eye irritating/corrosive potential in an ex vivo bioassay, the enucleated eye test with chicken eyes (CEET). The chicken eyes were obtained from slaughter animals for human consumption. Four chicken eyes were used (one as a control, washed with physiological saline). Although the study was performed before the adoption of the OECD guideline 438 for this test, the design was very similar to the design proposed in the aforementioned guideline. The sample 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 obtained with this investigation and according to the scheme for (EC) classification applied, it is concluded that n-butyl-S-lactate is severely irritating and possibly corrosive to eyes. On the basis of these results, it is recommended not to perform the standard rabbit eye irritation test with n-butyl-S-lactate in rabbits, but to classify the test substance as an eye irritant Category 1.

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:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

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 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.

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:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

There are no studies available for the assessment of the skin and eye irritation properties with the target substance Methyl (S)-lactate. Therefore, data from suitable read-across partners were used to assess the skin and eye irritation potential of the target substance. For details and justification of read-across please refer to the report attached in IUCLID section 13.

Based on the results from two primary dermal irritation studies conducted in accordance with OECD TG 404 with the source substances Ethyl (S)-lactate and Propyl (S)-lactate, it can be concluded that classification for skin irritation according to CLP Regulation 1272/2008 is not warranted for the target substance Methyl (S)-lactate.

Two in vitro enucleated eye tests with chicken eyes were conducted equivalent to OECD TG 438 with the source substances Ethyl (S)-lactate and Butyl (S)-lactate. Both test items induced severe corneal effects. In addition, Propyl (S)-lactate was tested for acute eye irritating in a study conducted according to OECD TG 405. The test was started with one rabbit and 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 Propyl (S)-lactate is severely irritating to the eyes of rabbits and classification as Eye Dam. 1, H318 is warranted according to CLP Regulation 1272/2008.

Based on these results, it can be concluded that classification as Eye Dam. 1, H318 according to CLP Regulation 1272/2008 is warranted for the target substance Methyl (S)-lactate.

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 Methyl (S)-lactate is also hydrolyzed to lactic acid, it is expected to have an irritating effect to the respiratory tract as well and the target substance will be classified as STOT SE3, H335 in accordance with CLP Regulation 1272/2008.

 

Justification for classification or non-classification

Based on the results from suitable read-across substances, Methyl (S)-lactate can be considered to be not irritating to the skin, but corrosive to the eye and classifcation as Eye Dam. 1, H318 is warranted. Moreover, based on the irritating effects to the respiratory tract seen in sub-acute inhalation studies classification as STOT SE 3, H335 is warranted as well.