Benzoic acid, 4-[[[4-[(1-oxo-2-propenyl)oxy]butoxy]carbonyl]oxy]-, 2-methyl-1,4-phenylene ester

Acute Toxicity: oral

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:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Reference 3

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Physical state: powder / grey-white
- Analytical purity: 95.8% (per weight; HPLC)
- Lot/batch No.: ZD 1151/ 31 (production: 03-Dec-1997)
- Stability under test conditions: the stability of the test substance in olive oil DAB 10 for a time period of 4 hours was confirmed
by analysis. The homogeneity of the test substance preparations was provided by stirring. Additionally the homogeneity was confirmed by analysis.
- Storage condition of test material: refrigerator, protected from light.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Rat / Wistar / chbb: thorn (SPF) from Boehringer Ingelheim Pharma KG
- Age at study initiation: young adult animals (male animals approx. 8- 12 weeks, female animais approx. 14-18 weeks)
- Weight at study initiation: animals of comparable weight (150g - 300g ±20% of the mean weight); actual weights: 185.3±6.5 mg for female and 176.7±7.2 mg for the male animals.
- Fasting period before study: the animals were given no feed at least 16 hours before administration, but water was available ad libitum.
- Housing: The animais were single-housed in fully air-conditioned rooms in Stainless steel wire mesh cages Stainless steel wire mesh cages, type DK-lll (Becker & Co., Castrop-Rauxel, FRG). The animals were identified individually using cage cards and group identification by tail marking. No bedding in the cages; wood shavings in the waste trays.
- Diet, ad libitum: Kliba-Labordiaet, Klingentalmuehle AG Kaiseraugst, Switzerland, (about 130 g per animal per day). The feed used in the study was assayed for chemical and microbiological contaminants. In view of the aim and duration of the study the contaminants occurring were seen as not likely to influence the results.
- Water, ad libitum: tap water. The drinking water is regularly assayed for chemical contaminants by the municipal authorities of Frankenthal and the technical services of BASF Aktiengesellschaft as well as for the presence of germs by a contract laboratory. In view of the aim and duration of the study the contaminants occurring were seen as not likely to influence the results.
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Central air-conditioning guaranteed a range of 20 - 24 degrees
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12 hours (6.00 am - 600 pm/ 6.00 pm - 6.00 am)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40.0 g/100 ml
- Amount of vehicle (if gavage): 5.0 ml/kg
- Justification for choice of vehicle: the test substance could be weIl homogenized in olive oil DAB 10.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on the physical and chemical characteristics of the test substance and the composition no pronounced acute oral toxicity was expected. Therefore a dose of 2000 mg/kg body weight has been chosen in a first step with 3 male animals. Because no mortality occurred, 2000 mg/kg bw were tested in a second step with animals of the other sex (3 female rats).

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: recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals. A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Necropsy of survivors performed: yes; necropsy at the last day of the observation period. Withdrawal of food at least 16 hours before killing with CO2; then necropsy with gross pathology examination. Necropsy of all animals that died before as early as possible.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: individual body weights shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality was observed

Clinical signs:

no abnormalities were observed

Body weight:

The mean body weights of the animals increased throughout the study period.
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Animals Weight at day 0 Weight at day 7 Weight at day 14
Male 176.7±7.2 248.7±9.6 281.0±11.8
Female 185.3±6.5 217.3±6.7 281.0±11.8
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Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at termination of the study (organs without particular findings).

Any other information on results incl. tables

Under the conditions of this study the median lethal dose of the test substance after oral application was found to be greater than 2000 mg/kg body weight for the male and female animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met