esterification product of 2-hydroxypropane-1,3-diyl-bis(2-methylprop-2-enoate) and 3-hydroxypropane-1,2-diyl-bis(2-methylprop-2-enoate) and diphosphorus pentoxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August to September 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted under GLP conditions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

glypho

IUPAC Name:

glypho

Details on test material:

- Name of test material (as cited in study report):Glypho
- Substance type: Yellowish liquid
- Physical state:Liquid
- Lot/batch no.:AH2/170
- Expiration date of the lot/batch:1-Feb-2002
- Stability under test conditions:Stable under storage conditions, stable for 48 hours in vehicle.
- Storage condition of test material: Refrigerator (approx. 4 degrees C)

Test animals

Species:

rat

Strain:

other: HanBrl: Wist (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd
Biotechnology and Animal Breeding Division
CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: Males: 8 weeks, Females: 10 weeks
- Weight at study initiation: 170.5-173.4 (Females); 194-203.2 (Males)
- Fasting period before study:16-20 hours with access to water
- Housing:- Diet (e.g. ad libitum): In groups of three per sex in Makrolon type-4 cages with wire mesh tops and standardized softwood bedding.
- Water (e.g. ad libitum): Community tap-water, from Itigen ad libitum.
ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 +/- 3 degrees C
- Humidity (%):30-70%
- Air changes (per hr):10-15
- Photoperiod (hrs dark / hrs light):12/12
IN-LIFE DATES: From:04 Sept 2001 To: 20 Sept 2001

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: PEG 300 (Fluka Chemie AG, CH-9471 Buchs)

Details on oral exposure:

VEHICLE
- Concentration in vehicle:2000 mg test article/10 mL vehicle
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial performed before experimental starting date.
- Lot/batch no. (if required):412565/1 51301
- Purity: Not reported
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2000 mg/kg body weight in 10 mL vehicle/kg body weight.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighing on test days 1, 8 and 15. Clinical signs daily during acclimatization and at least four times on test day 1 after the test item administration. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: None

Statistics:

None

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: The oral LD50 in the rat in both sexes was greater than 2000 mg/kg body weight.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs were noted during the course of the study.

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Based on the results of this study the test article has an oral LD50 in the rat is greater than 2000 mg/kg.

Executive summary:

The acute oral toxicity of the test article was evaluated in Wistar rats. This study was performed in accordance with Swiss GLP (2000) and OECD GLP (1997). The study design was based on OECD 423 (1996) and Directive 96/54/EEC, B.1 (1996).The test article was diluted in PEG 300 just prior to dosing. One group of 3 female rats and one group of 3 male rats received 2000 mg/kg of the test article via oral gavage at a dose volume of 10 mL/kg. The rats were observed at least 4 times during the first day postdose and then once daily for 14 days. Body weights were recorded pretest, weekly, and at termination. After the observation period, all animals were euthanized and examined for gross pathology. RESULTS: All animals survived. There were no abnormal clinical observations, body weight changes or necropsy findings in any animals. Based on the results of this study, the oral LD50 of the test article is greater than 2000 mg/kg.