(3S-cis)-3,6-dimethyl-1,4-dioxane-2,5-dione

Endpoint summary

Description of key information

L-lactide (>99.5 %) was tested negative for acute dermal irritating properties in a study conducted according to OECD 404. The substance caused reversible eye irritating effects in an acute eye irritation/corrosion study in rabbits conducted according to OECD 405.

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:

1998-06-22 to 1998-07-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: Lot/batch No.: DA 778 FN
- Purity, including information on contaminants, isomers, etc.: >99.5%
- bulk density: 0.8 kg/L

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at ca -20 °C.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Upon arrival, the rabbits were checked for overt signs of ill health and anomalies. Test animals were females, young adult and were quarantined 54 or 55 days upon arrival. At the start of the study, body weight was 3060-3405 g. Animals were housed individually in stainless steel cages with perforated floor under a 12h light/12h dark cycle at 20 ± 3 °C and 50-76 % humidity (upper limit higher than 70 %, because of wet cleaning of the animal room and/or meteorological circumstances; the 76 % peak occurred for one hour at most); ventilation was ca 10 air changes/hour. Animals were fed standard laboratory rabbit diet ad libitum. Each batch of this diet is analyzed by the supplier (SDS Special Diets services, Whitham, England) for the nutrients and contaminants and the results are available upon request). Tap water (N.V. Waterleidingbedrijf Midden-Nederland) was available ad libitum. Results of routine physical, chemical and microbiological examination of drinking water as conducted by the supplier are available upon request.
Three or four days prior to the start of the study, the hair was removed from the back and flanks of the animals using electric clippers in a way as to avoid abrasions. The clipping was repeated if considered necessary.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test substance, moistened with 0.5 mL water

Duration of treatment / exposure:

4 hour exposure

Observation period:

Observation at 1, 24, 48, 72 hours after exposure

Number of animals:

3 female rabbits

Details on study design:

TEST SITE
- Area of exposure: diameter: ± 2.5 cm
- % coverage: full
- Type of wrap if used: covered with a cup.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): moistened tissue
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize et al. (1944)

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:

At 1-72 hours after treatment, no signs of skin irritation were observed in any of the three rabbits

Other effects:

None

Interpretation of results:

other: CLP criteria not met

Conclusions:

In conclusion, in the acute dermal irritation/corrosion study according to OECD 404, the test item L-lactide is considered to be non-irritating.

Executive summary:

In a primary dermal irritation study (according to OECD Guideline 404),femaleyoung adultSPF bred New Zealand White albino rabbits(n=3)were dermally exposed to0.5 gofL-lactide(purity: >99.5%.)under semi-occlusivefor4hours.Animals then were observed1, 24, 48 and 72 hours after exposure.Irritation was scored by the method ofDraize et al. (1944).

 

In this study,L-lactide did not cause any skin effects. Thus, under the conditions of this study, L-lactide can be considered non-irritating.

Reference 2

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

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:

key study

Study period:

1998-06-09 to 1998-07-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

dosing-volume of 0.01 mL powdered onto the cornea, instead of 0.1 ml instilled in the conjunctival cul-de-sac.

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): L-dilactide or L-lactide
- General appearance: white crystalline powder
- Lot/batch No.: DA 778 FN
- Storage condition of test material: at ca. -20°C
- bulk density: 0.8 kg/L
- Analytical purity: >99.5%

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Upon arrival, the rabbits were checked for overt signs of ill health and anomalies. Test animals were females, young adult and were quarantined 54 days upon arrival. At the start of the study, body weight was 2917-3085 g. Animals were housed individually in stainless steel cages with perforated floor under a 12h light / 12h dark cycle at 20 ± 3 °C and 50-76% humidity (upper limit higher than 70%, because of wet cleaning of the animal room and/or meteorological circumstances; the 76% peak occurred for one hour at most); ventilation was ca 10 air changes/hour. Animals were fed standard laboratory rabbit diet ad libitum. Each batch of this diet is analyzed by the supplier (SDS Special Diets services, Whitham, England) for the nutrients and contaminants and the results are available upon request). Tap water (N.V. Waterleidingbedrijf Midden-Nederland) was available ad libitum. Results of routine physical, chemical and microbiological examination of drinking water as conducted by the supplier are available upon request.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.01 mL of the test substance (i.e. 0.008 g, density to be: 0.8 kg/L)

Duration of treatment / exposure:

The rabbit selected was treated as follows: An amount of ca 0.01 mL of the test substance (i.e. ca 0.008 g; density to be ca 0.8 kg/L) was powdered onto the cornea 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):

The reactions of the test eyes were judged at circa 1, 24, 48, and 72 hours, and at 7 days after treatment

Number of animals or in vitro replicates:

3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.43

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

2

Reversibility:

fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7d

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.13

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritant / corrosive response data:

At 1 hour after treatment, slight comeal opacity (two rabbits), slight iritis (one rabbit), slight redness and slight or severe swelling of the conjunctivae (three rabbits), and severe ocular discharge (two rabbits) were observed.
At 24 hours after treatment, slight corneal opacity (one rabbit), slight iritis (one rabbit), slight or severe redness and moderate swelling of the conjunctivae (two rabbits), and moderate ocular discharge (two rabbits) were observed. In addition, one rabbit showed haemorrhages on the nictitating membrane.
At 48 hours after treatment, the eye effects had cleared in one rabbit, whereas the other two rabbits showed moderate comeal opacity (one rabbit), severe redness and moderate swelling of the conjunctivae, and moderate ocular discharge. The haemorrhages on the nictitating membrane was still observed in one rabbit.
At 72 hours after treatment, slight comeal opacity (one rabbit), moderate or severe redness and slight swelling of the conjunctivae (two rabbits), slight ocular discharge (one rabbit) and haemorrhages on the nictitating membrane (one rabbit) were observed.
At 7 days after treatment, all eye effects had cleared completely.

 Table 1: Mean values for corneal opacity, iritis, redness and swelling of the conjunctivae of each rabbit scored at 24, 48, 72 hours after treatment with L-lactide

Animal	Opacity	Iritis	Redness	Swelling
A19	0.0	0.0	0.3	0.0
A21	1.3	0.3	2.7	1.7
A23	0.0	0.0	3.0	1.7

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In conclusion, in this acute eye irritation/corrosion study conducted according to OECD 405, L-lactide is inducing reversible irritation in the eyes of rabbits.

Executive summary:

L-lactide (> 99.5%) was tested for acute eye irritating properties in an experiment with three albino rabbits conducted according to OECD 405. Undiluted substance (0.01 mL) was powdered onto the cornea and caused slight to moderate corneal opacity, slight iritis, slight to severe redness (score >2) and slight to severe swelling on the conjunctivae and severe ocular discharge in the rabbits. At 7 days after treatment, all eye effects had cleared completely.

Based on the results it was concluded, that L-lactide is irritating for the eyes of rabbits and needs be to classified as eye irritant (CLP category 2).

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

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

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

L-lactide (>99.5 %) was tested negative for acute dermal irritating properties in a study conducted according to OECD 404. After a dermal exposure period of 4 hours no skin effects were observed in rabbits. In contrast, L-lactide was irritating in the eyes of rabbits in an acute eye irritation study (OECD 405). The effects were reversible within seven days after treatment. Based on these results, L-lactide is considered to be not irritating to skin, but irritating to the eye.

Justification for classification or non-classification

L-lactide did not cause any skin effects in an acute dermal irritating study conducted in accordance to OECD 404. Therefore, L-lactide does not warrant classification for skin irritation.

L-lactide was irritating to the eyes of rabbits in an OECD 405 study. The irritation was reversible with mean scores (24, 48, 72h) of > 2.7 in two of three animals. Therefore, L-lactide meets the classification criteria according to CLP Regulation 1272/2008. The substance is classified for reversible eye irritation (H319, Eye Irrit. 2).