diethyl pyridine-2,4-dicarboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3.9.2002 - 30.1.2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study has been performed under GLP and according to OECD guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EC Directive No. 92/69/EEC, B.1 bis, 31st July 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Mexoryl SBU

Cas Number:

41438-38-4

Molecular formula:

C11H13N04

IUPAC Name:

Mexoryl SBU

Constituent 2

Reference substance name:

diethyl pyridine-2,4-dicarboxylate

EC Number:

680-341-5

Cas Number:

41438-38-4

Molecular formula:

C11H13N04

IUPAC Name:

diethyl pyridine-2,4-dicarboxylate

Details on test material:

- Name of test material: MEXORYL SBU

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals:- Species, strain: rat, Sprague-Dawley Rj: SD (IOPS Han).- Breeder: Janvier, Le Genest-Saint-Isle, France.- Number and sex: two females for the sighting test and one group of ten animals (five males and five females) for the main experiment.- Age/weight: on the day of treatment, the animals were approximately 6 weeks old. In the main experiment, they had a mean body weight ± standard deviation of 186 ± 5 g for the males and 164 ± 10 g for the females. Females were nulliparous and non pregnant.- Fasting period before study: fasted for an overnight period of approximately 18 hours before dosing, but had free access to water- Diet (e.g. ad libitum): free access to A04 C pelleted diet- Water (e.g. ad libitum): ad libitum- Housing: polycarbonate cage, max 7 animals per 48 x 27 x 20 cm- Acclimation: at least 5 days before the beginning of the study.- Identification: individually by earnotches.Environmental conditions:- temperature: 22 ± 2°C- relative humidity: 30 to 70%- light/dark cycle: 12 h/12 h- ventilation: approximately 12 cycles/hour of filtered, non-recycled air.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% suspension of methylcellulose

Details on oral exposure:

VEHICLE- Concentration in vehicle: 200 mg/mL- Amount of vehicle (if gavage): 10 mL- Justification for choice of vehicle: not reportedMAXIMUM DOSE VOLUME APPLIED: 10 mL/kgDOSAGE PREPARATION (if unusual): On the day of treatment, the test item was ground using a mortar and pestle, then was prepared at the chosen concentration in the vehicle.

Doses:

Sighting test: 500, 2000 mg/kg Main test: 2000 mg/kg

No. of animals per sex per dose:

Sighting test: 1 female per doseMain test: one group of ten animals (five males and five females).

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (main test), 7 days (sighting test)- Frequency of observations and weighing: day 1, day 8, day 15- Necropsy of survivors performed: yes- Examinations performed: Mortality, clinical signs, body weight, macroscopic necropsy examination

Results and discussion

Preliminary study:

No clinical signs and no mortality were observed at the 500 mg/kg dose-level. Dyspnea and piloerection were observed on day 1 in the animal given 2000 mg/kg.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no death

Clinical signs:

At the 2000 mg/kg dose-level, except for piloerection noted on day 1 in all animals, no clinical signs were recorded during the study.

Body weight:

The body weight gain of the animals was not affected by treatment with the test item.

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions, no deaths were observed at 2000 mg/kg. The test item can be considered as devoid of significant acute oral toxicity.

Executive summary:

The acute oral toxicity of the test item MEXORYL SBU was evaluated in rats according to OECD 420. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

A preliminary test was conducted at 500 mg/kg and 2000 mg/kg with one female rat each. In the main test, the test item was administered by oral route (gavage) to one group of ten fasted Sprague-Dawley rats (five males and five females). The test item was prepared in 0.5% methylcellulose and administered to the animals at the dose of 2000 mg/kg. Clinical signs and mortality were checked for a period of 14 days following the single administration of the test item. The animals were checked for body weight gain and were subjected to necropsy.

In the sighting test, no clinical signs and no mortality were observed at the 500 mg/kg dose-level. Dyspnea and piloerection were observed on day 1 in the animal given 2000 mg/kg. In the main test, at the 2000 mg/kg dose-level, except for piloerection noted on day 1 in all animals, no clinical signs and no death were recorded during the study. The body weight gain of the animals was not affected by treatment with the test item. At necropsy, no apparent abnormalities were observed.

Under the experimental conditions, no deaths were observed at 2000 mg/kg and the test item was considered as devoid of significant acute oral toxicity. According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), concerning the potential toxicity by oral route, the test item should not be classified.