Dilactide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2010-05-28 to 2010-09-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted in 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

adopted in 2008

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

224-832-0

EC Name:

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

Cas Number:

4511-42-6

Molecular formula:

C6H8O4

IUPAC Name:

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

Specific details on test material used for the study:

- Name of test material (as cited in study report): L-Lactide
- batch: 0911001952
- purity: 99%
- Expiration date of the lot/batch: 2010-11-23
- Stability under test conditions: stable
- Storage condition of test material: in refrigerator (2-8 °C) in the dark under nitrogen

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: approximately 10 weeks old.
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean (males: 297 g, females: 201 g).
- Fasting period before study: not applicable.
- Housing: Individually housed in labeled Macrolon cages (MIII type; height 18 cm) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF@Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Macrolon cages (MIV type).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0°C (actual range: 19.9 - 21.5°C).
- Humidity (%): relative humidity of 40-70% (actual range: 39-72%).
- Air changes (per hr): approximately 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 17 June 2010 To: 01 July 2010

Administration / exposure

Type of coverage:

occlusive

Vehicle:

polyethylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 10% of the total body surface, i.e. approximately 25 cm² for males and 18 cm² for females.
- % coverage: Approximately 10% of the total body surface.
- Type of wrap if used:The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D, Laboratoires Stella s.a., Liege, Belgium), successively covered with aluminium foil and Coban elastic bandage (3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore)).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was cleaned of residual test substance using tap water.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (10 mL/kg) body weight.

VEHICLE
Polyethylene glycol 400 (Merck, Darmstadt, Germany) (specific gravity 1.125). The vehicle was dehydrated before the formulation was prepared. The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle. In order to obtain homogeneity, the test substance formulation was heated in a water bath with a temperature of 49 °C for 31 minutes. The test substance formulation was allowed to cool down below 40 °C prior to dosing.

Duration of exposure:

24 hours

Doses:

2000 mg/kg (10 mL/kg) body weight

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/viability: Twice daily
Body weights: Day 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed:
clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The time of onset, degree and duration were recorded and the symptom graded according to fixed scales.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred

Clinical signs:

other: Chromodacryorrhoea (snout) was noted for one male on Day 1. No further clinical signs were observed

Body weight:

other body weight observations

Remarks:

No adverse effects observed

Gross pathology:

Reddish discolouration of the uterine adipose tissue in the abdominal cavity was observed for one female.

Applicant's summary and conclusion

Interpretation of results:

other: CLP criteria not met

Conclusions:

The dermal LD50 value of L-lactide in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study conducted according to OECD guideline 402, a group of young adult Wistar rats (5 males and 5 females) was dermally exposed to L-lactide (purity 99%) in polyethylene glycol 400 for 24 hours to approximately 10% of body surface area at 2000 mg/kg bw. Animals were observed for 14 days. No mortality occurred. There were no treatment related clinical signs, necropsy findings or changes in body weight. The dermal LD50 value of L-lactide in Wistar rats was established to exceed 2000 mg/kg body weight.