1,4-Dioxane-2,5-dione, 3,6-dimethyl-, (3R,6R)-

Endpoint summary

Description of key information

L-lactide (purity 99 %) was tested negative for skin sensitisation properties in a study conducted according to OECD 429. L-lactide is the enantiomer of D-lactide and therefore a suitable read-across partner.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

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

Adequacy of study:

key 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

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 5, 10 and 25% were 1.7, 2.7 and 8.8 respectively. An EC3 value of 10.7% was calculated using linear interpolation. The calculated EC3 value was found to be in the acceptable range of 2 and 20%.

Parameter:

SI

Value:

2.1

Test group / Remarks:

low dose (10% test substance)

Parameter:

SI

Value:

1.5

Test group / Remarks:

mid-dose (25% test substance)

Parameter:

SI

Value:

0.9

Test group / Remarks:

high-dose (50% test substance)

Cellular proliferation data / Observations:

DETAILS ON STIMULATION INDEX CALCULATION:
The SI values calculated for the substance concentrations 10, 25 and 50% were 2.1, 1.5 and 0.9, respectively. Since there was no indication that the test substance elicit an SI ≥ 3 when tested up to 50%, L-lactide was considered not to be a skin sensitizer. It was established that the EC3 value (the estimated test substance concentration that will give a SI=3) (if any) exceeds 50%. See Table 2 below.

CLINICAL OBSERVATIONS:
No irritation of the ears was observed in any of the animals examined. White remnants of the test substance were present on the ears at the 50% concentration, but this did not hamper the scoring of erythema. All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. Red discolouration of the left auricular lymph node was noted for one male (no. 12) at 25%. 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.

SIGNS OF TOXICITY (including dermal irritation at the site of administration, if any, e.g. increased ear thickness):
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 substance^1(% w/w)	animal	DPM/animal
1	0% (vehicle)	1	481
		2	378
		3	391
		4	273
		5	379
2	10%	6	681
		7	1173
		8	381
		9	786
		10	914
3	25%	11	524
		12	366
		13	842
		14	707
		15	405
4	50%	16	324
		17	207
		18	426
		19	501
		20	211

¹Vehicle: Dimethyl formamide.

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

group	test substance^1 (% w/w)	median DPM ± SEM	SI ± SEM
2	10%	787 ± 131	2.1 ± 0.4
3	25%	569 ± 90	1.5 ± 0.3
4	50%	334 ± 58	0.9 ± 0.2
1	0% (vehicle)	380 ± 33	1.0 ± 0.1

¹Vehicle: Dimethyl formamide.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results derived from in a mouse local lymph node assay, L-lactide is considered not to be a skin sensitizer.

Executive summary:

In a dermal senisitization study with L-lactide (purity 99%) in dimethyl formamide, young adult CBA/J mice (5 females/group) were tested (0, 10, 25 and 50% substance concentration) according to OECD 429 (LLNA). As positive control material alpha-hexylcinnamicaldehyde was used. No irritation of the ears was observed in any of the animals examined. Red discouloration of the left auricular lymph node was noted for one male in the 25% treatment group. 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 10, 25 and 50% were 2.1, 1.5 and 0.9 respectively. Since there was no indication that the test substance elicits an SI≥ 3 when tested up to 50%, L-lactide was considered not to be a skin sensitizer.

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 sensitising)

Additional information:

Only data from L-lactide is available. L-lactide is the enantiomer of D-lactide and therefore suitable as read-across partner.

In a dermal sensitization study conducted according to OECD 429 (LLNA), mice were tested negative for L-lactide (purity 99%) at 0, 10, 25 and 50% substance concentration. Based on the results from the read across partner L-lactide, D-lactide can be considered to be non-sensitizing.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data from a suitable read-across partner, D-lactide is considered to be non-sensitising and classification of D-lactide for skin sensitisation is not warranted according to CLP Regulation 1272/2008.