Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
L-lactide
Batch no: DA 778 FN
Purity: >99.5%

Test animals

Species:
rat
Strain:
other: Crl:(WI) WU BR
Sex:
male/female
Details on test animals and environmental conditions:
Males and females, 5-6 weeks old upon arrival, were individually earmarked. A maximum of five animals per cage (stainless steel cages, fitted with wire-screen floor and front). Lighting was a 12 hours light/12 hours dark cycle. Temperature: 22±3°C. Humidity: 54-87.5% (upper limit higher than 70%, because of meteorological circumstances and/or wet cleaning of the animal room). Ventilation was ca 10 air changes/hour. Animals were fed standard laboratory rodent diet ad libitum. Each batch of this diet was 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) ad libitum. Results of routine physical, chemical and microbiological examination of drinking water as conducted by the supplier are available upon request.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The study was started with treatment of three females with a 2000 mg/kg body weight dose level. Since all females survived the first 3 days after treatment, it was decided to continue treatment with 3 males dosed with the 2000 mg/kg dose level. The animals were dosed with a 10 ml/kg b.w. dosing-volume of a 200 mg/ml dilution of the test substance in maize oil to obtain the 2000 mg/kg dose level. The exact amount of the test substance to be dosed was calculated for each animal individually and administered by means of a syringe, equipped with an oral gavage. Prior to dosing, the animals had fasted overnight. Approximately four hours after dosing, they had access to food again. The animals were observed for mortality up to 14 days after treatment.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: All visible reactions to treatment were recorded, including type, severity, onset and duration. Observations were made within l hour and within 4 hours after dosing, and subsequently at least once daily throughout the observation period. The body weighi: of each animal was recorded immediately before dosing on day O, and of the surviving animals on days 3,7 and 14 of the study.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: At the end of thes observation period, on day 14 of the study, all surviving animals were killed with carbon dioxide and examined for external changes. Next, the abdomen and the thorax of each animal was opened and examined for gross palho- logical changes.
Statistics:
N.A.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
None
Body weight:
All animals gained weight during the 14-day observation period.
Gross pathology:
Examination at autopsy of the males and females did not reveal treatment-relal:ed gross alterations.
Other findings:
N.A.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
L-Lactide is not harmful. LD50 > 2000 mg/kg bw.
Executive summary:

A sample of L-dilactide was examined for acute oral toxicity in an experiment with male and female rats (limit testing). A dose level of 2000 mg per kg body weight was examined. No mortality or distinct clinical signs were observed after treatment of 3 males and 3 females with the 2000 mg/kg dose level. Macroscopic examination of the animals at the end of the observation period did not reveal any treatment-related gross changes. Since no mortality occurred during the 14-day observation period, the oral LD50 of L-dilactide is considered to exceed 2000 mg/kg body weight, in both male and female rats. According to the EC-standards L-dilactide is considered not harmful after oral ingestion.