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Diss Factsheets

Administrative data

Description of key information

No study is available elucidating the skin sensitization potential of the target substance Methyl (S)-lactate. Thus, available data from suitable read-across partners were used in a weight-of-evidence approach to assess the skin sensitizing potential of Methyl (S)-lactate. The source substance L-lactic acid was tested negative for skin sensitization in a modified Buehler test. In a dermal sensitization study conducted according to OECD 429, female CBA mice were treated with concentrations of 5, 25 or 100% (w/w) Ethyl (S)-lactate. Based on the results, the source substance Ethyl (S)-lactate can be considered as not skin sensitizing. Supporting information is derived from a dermal sensitization study conducted equivalent to OECD 406 with the source substance methanol. In this study, female guinea pigs were tested by using the method of Magnusson and Kligman. Based on the results, the source substance methanol can be considered as not skin sensitizing. Based on the available data from suitable read-across partners, the target substance Methyl (S)-lactate can be considered as not skin sensitizing.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint:
skin sensitisation: in vivo (non-LLNA)
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 report attached in section 13 of IUCLID.
Reason / purpose for cross-reference:
read-across source
Positive control results:
Erythema and edema according to Draize (1979) and for other dermal reactions at 24 and 48 hours following each induction and challenge application. Results are presented for testing on 3 groups of 10 guinea pigs. In the first 24 hrs of the challenge test, 8, 8 and 10 out of 10 animals showed positive sensitization reaction to the positive control (DNCB), and 48 hours after the beginning of the test, 8, 8 and 9 out of 10 animals still presented positive reaction to DNCB.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100% test material
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
All effects observed were deemed irritation, not sensitization
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% test material
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
All effects observed were deemed irritation, not sensitization
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% test material
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
All effects observed were deemed irritation.
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% test material
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
All effects observed were deemed irritation.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.5 mL of 0.1% DNCB
No. with + reactions:
28
Total no. in group:
30
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.5 mL of 0.1% DNCB
No. with + reactions:
25
Total no. in group:
30
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
other: CLP criteria not met
Conclusions:
Based on the result the test item is not considered to be sensitising to the skin. Therefore, classification for skin sensitisation according to the CLP Regulation 1272/2008 is not warranted.
Executive summary:

In a dermal sensitisation study with L(+)-lactic acid (100%), 10 young adult female Hartley guinea pigs/group (test article and naive control) were tested using a method according to EPA Guidelines (OPP 81 -6), 1982 (modification of the Buehler Closed Patch Technique) as described in American Biogenics Corporation (ABC) protocol A330.

The test article group received 9 times 0.5 ml induction applications (3/week) and a single 0.5 ml challenge application two weeks after the last induction application. Evaluation for erythema, edema and other lesions was performed 24 and 48 hours after test article application. DNCB (0.1%) was referred to as a positive control and induced an appropriate response.

No mortalities occurred and all animals gained body weight. The test article (100%) produced very slight erythema at 3 sites and very slight edema at 1 site after the 1st induction. Erythema grades increased in severity after the 2nd induction application. One site was graded as severe erythema. Due to the increase of severity of the reactions, the concentration of the test article was reduced to 30% and the induction site was changed to the left flank. Very slight erythema was noted after the 5th induction application. Grades ranging from very slight to severe erythema were noted from the 7th to the 9th induction applications.

After the challenge application, the test article (100%) produced grade 4 erythema in up to 6 test animals. These gradings were very similar in character as those seen during the induction applications, that is, pinpoint pitting of the skin and eschar formation, very little redness. These reactions were considered to be irritation reactions, not sensitization reactions. Other reactions noted at challenge for the test animals were very slight to moderate erythema, and very slight to moderate edema. The test article (100%) produced grade 4 erythema in up to 8 naive control animals. These reactions were considered to be irritation reactions, not sensitization reactions. Other reactions noted for the naive control animals were very slight to moderate erythema and very slight to moderate edema. The reactions seen in the naive control animals at the challenge application were similar to the reactions seen for the test group animals.

Based on the results of this study, L(+)-lactic acid was not considered to be a contact dermal sensitizer.

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

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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:
Remarks:
see box "Any other information on results incl. tables".

In the first study, no contact sensitisation was observed, in the parallel test with formaldehyde, also a negative result was seen. In the second study using 24 female animals (two tests à 12 animals), 1/12 (test 1) and 2/12 (test 2) exhibited a slight skin response (score 1) after 24 and 48 h which can be interpreted as a weak sensitising potential. The intracutaneous induction produced necroses and some open ulcerations.

In summary, the low number of 3/24 animals with score 1 gives no evidence of a notable sensitisation potential of methanol.

 

                 

Interpretation of results:
other: CLP criteria not met
Conclusions:
In the OECD SIDS report for methanol (2004), a guinea pig maximization study is reported to be the key study for the assessment of a sensitizing potential of methanol. No evidence of a notable skin sensitization potential of methanol was derived based on the results.
Executive summary:

In the OECD SIDS report for methanol (2004), guinea pig maximization studies are reported to be the key studies for the assessment of a sensitizing potential of methanol. A first guinea pig maximization test gave no evidence of contact sensitisation in 10 female animals after induction and challenge with a 50 % aqueous methanol solution (0.1 mL). In a second guinea pig sensitization test using 24 female animals (two tests with 12 animals each), 1 of 12 (test 1) and 2 of 12 (test 2) animals exhibited a slight skin response (score 1) after 24 and 48 hours. In summary, the low number (3 of 34) animals with a score of 1 show no notable sensitisation potential of methanol.

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

Endpoint:
skin sensitisation: in vivo (LLNA)
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 report attached in section 13 of IUCLID.
Reason / purpose for cross-reference:
read-across source
Positive control results:
The six-month reliability check with alpha-hexylcinnamicaldehyde indicates that the local lymph node assay as performed at NOTOX is an appropriate model for testing for contact hypersensitivity. The SI values calculated for alpha-hexylcinnamicaldehyde concentrations of 5, 10 and 25% were 1.3, 1.7 and 4.1 respectively. An EC3 value of 18.1% was calculated using linear interpolation. The calculated EC3 value was found to be in the acceptable range of 2 to 20%.
Parameter:
SI
Value:
0.9
Variability:
+/- 0.4
Test group / Remarks:
25 % w/w
Parameter:
SI
Value:
1
Variability:
+/- 0.4
Test group / Remarks:
50 % w/w
Key result
Parameter:
SI
Value:
0.8
Variability:
+/- 0.4
Test group / Remarks:
100 % w/w
Parameter:
EC3
Remarks on result:
not determinable
Remarks:
Since there was no indication that the test substance elicited an SI ≥ 3, no EC3 value could be calculated.
Cellular proliferation data / Observations:
Preliminary irritation study:
- No irritation was observed in any of the animals examined.

Main study:
- Skin reactions/irritation: No irritation of the ears was observed in any of the animals examined.
- Macroscopy of the auricular lymph nodes and surrounding area: All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. No macroscopic abnormalities of the surrounding area were noted in any of the animals.
- Body weights: Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. The slight body weight loss, noted in some animals, was considered not toxicologically significant.
- Radioactivity measurements: Mean DPM/animal values for the experimental groups treated with test substance concentrations 25, 50 and 100 % were 651, 706 and 589 DPM respectively.The mean DPM/animal value for the vehicle control group was 735.
- Toxicity and mortality: No mortality occurred and no symptoms of systemic toxicity were observed in the animals of the main study.

Table 1: Radioactivity measurements (individual animals)

group

Test substance1 (% w/w)

animal

DPM/animal

 

 

 

 

1

0%

(vehicle)

1

400

2

646

3

778

4

163

5

1688

 

 

 

 

2

25%

6

449

7

356

8

564

9

776

10

1110

 

 

 

 

3

50%

11

549

12

872

13

807

14

776

15

527

 

 

 

 

4

100%

16

616

17

188

18

1365

19

306

20

471

1Vehicle: Acetone/Olive oil (4:1 v/v).

Table 2: Disintegration Per Minute (DPM) and Stimulation Index (SI)

group

test substance1

(% w/w)

median

DPM

SI

2

25%

651 ± 134

0.9 ± 0.4

3

50%

706 ± 70

1.0 ± 0.4

4

100%

589 ± 207

0.8 ± 0.4

 

 

 

 

1

0% (vehicle)

735 ± 261

1.0 ± 0.5

1Vehicle: Acetone/Olive oil (4:1 v/v).

Interpretation of results:
other: CLP criteria not met
Conclusions:
Under the given conditions, the test item was considered not to be a skin sensitiser.
Executive summary:

In a dermal sensitisation study conducted according to OECD TG 429 with ethyl (S)-lactate (purity: 99.83%) in acetone/olive oil (4:1 v/v), four groups of 5 female young adult CBA/J mice/dose group were tested in the local lymph node assay. The test item was administered epidermally to the dorsal surface of both ears, once a day on three consecutive days, at concentrations of 25, 50, or 100% (w/w). The volume administered was 25 µL per ear. A positive control (hexyl cinnamic aldehyde in acetone/olive oil (4:1 v/v)) was tested concurrently under identical conditions and yielded an appropriate response.

No irritation of the ears was observed in any of the animals examined. All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. No macroscopic abnormalities of the surrounding area were noted in any of the animals. No mortality occurred and no symptoms of systemic toxicity were observed in the animals. The SI values calculated for the substance concentrations of 25, 50 and 100% were 0.9, 1.0 and 0.8 respectively. Since there was no indication that the test substance elicits an SI ≥ 3, no EC3 value could be calculated.

Based on these results, the test item was considered to be a non-skin sensitiser. Therefore, classification of ethyl (S)-lactate for skin sensitisation 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 justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Due to the rapid, enzymatically catalyzed hydrolysis of Methyl (S)-lactate into methanol and L-lactic acid, the toxicology of Methyl (S)-lactate can be understood in terms of the toxicology of methanol and L-lactic acid. No study is available elucidating the skin sensitization potential of the target substance. Thus, available data from suitable read-across partners were used in a weight-of-evidence approach to assess the skin sensitizing potential of Methyl (S)-lactate. The source substance L-lactic acid was tested negative for skin sensitization in a modified Buehler test. In a dermal sensitization study conducted according to OECD 429, female CBA mice were treated with concentrations of 5, 25 or 100% (w/w) Ethyl (S)-lactate. Based on the results, the source substance Ethyl (S)-lactate can be considered as not skin sensitizing. Supporting information is derived from a dermal sensitization study conducted equivalent to OECD 406 with the source substance methanol. In this study, female guinea pigs were tested by using the method of Magnusson and Kligman. Based on the results, the source substance methanol can be considered as not skin sensitizing. Based on the available data from suitable read-across partners, the target substance Methyl (S)-lactate can be considered as not skin sensitizing.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the negative results from suitable read-across partners, classification for Methyl (S)-lactate for skin sensitization is not warranted in accordance with CLP Regulation 1272/2008.