Registration Dossier

Administrative data

Description of key information

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

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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:
other: GLP study according to OECD guideline 404
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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:
overall irritation score
Basis:
mean
Time point:
other: 1
Score:
0
Max. score:
0
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24
Score:
0
Max. score:
0
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48
Score:
0
Max. score:
0
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72
Score:
0
Max. score:
0
Irritant / corrosive response data:
No irritation
Other effects:
None
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, in the acute dermal irritation/corrosion study accordign to OECD 404, the test item L-dilactide is considered to be non-irritating.
Executive summary:

A sample of L-dilactide (> 99.5%) was tested in female rabbits for acute dermal irritating properties according to OECD guideline 404. The dermal exposure period was 4 hours under semi-occlusive conditions. L-dilactide did not cause any skin effects. Thus, under the conditions of this study, L-dilactide can be considered non-irritating.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-06-04 to 1998-07-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study
Qualifier:
according to
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:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
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:
other: 24, 48, 72 h
Score:
0.43
Max. score:
1.3
Reversibility:
fully reversible within: 7d
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.1
Max. score:
0.3
Reversibility:
fully reversible within: 7d
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7d
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1.13
Max. score:
1.7
Reversibility:
fully reversible within: 7d

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-dilactide
 
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:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, in this acute eye irritation/corrosion study according to OECD 405, L-dilactide is inducing reversible irritation in the eyes of rabbits.
Executive summary:

L-dilactide (> 99.5%) was tested for acute eye irritating properties in an experiment with three albino rabbits according to OECD guideline 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-dilactide is irritating for the eyes of rabbits and needs be to classified as eye irritant (CLP category 2).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

L-dilactide (>99.5 %) was tested negative for acute dermal irritating properties according to OECD 404. After a dermal exposure period of 4 hours no skin effects were observed in rabbits. In contrast, L-dilactide 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-dilactide is considered to be not irritating to skin, but irritating to the eye.


Justification for selection of skin irritation / corrosion endpoint:
GLP study according to OECD guideline 404

Justification for selection of eye irritation endpoint:
GLP study according to OECD guideline 405.

Effects on eye irritation: irritating

Justification for classification or non-classification

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

L-dilactide 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-dilactide meets the classification criteria according to CLP. The substance is classified for reversible eye irritation (Eye Irrit. 2).