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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute 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 1 Wistar 1 CrlGlxBrlHan:WI from Charles River Deutschland GmbH, Sandhofer Weg 7, 97633 Sulzfeld
- Age at study initiation: young adult animals (male animals approx. 8- 12 weeks, female animals approx. 14-18 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight, the study); actual weights: 208.8±1.9 mg for female and 241.6±5.1mg for the male animals.
- Housing: The animals 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).
- 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: ml 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 5 days


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

Type of coverage:

semiocclusive

Vehicle:

other: olive oil PH.EUR./DAB

Details on dermal exposure:

TEST SITE
- Area of exposure: about 40 cm2
- % coverage: corresponds to at least 10% of the body surface area)
- Type of wrap if used: Single application to the clipped epidermis (dorsal and dorsolateral parts of the trunk); covering of the application site with a semi-occlusive dressing (the bandage consists of four layers absorbent gauze (adhesive fleece)) for 24 hours.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): removal of the dressing, and rinsing of the application site with warm water.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Dose (2,000 mg/kg), Administration volume (4.0 ml/kg)
- Concentration (if solution): 50 g/1 00 ml


VEHICLE
- Amount(s) applied (volume or weight with unit): 4.0 ml/kg

Duration of exposure:

once (in the morning)

Doses:

single dose: 2000 mg/kg bw

No. of animals per sex per dose:

5

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; these records are maintained with the raw data; a check for any dead or moribund animal was made twice each workday and once an Saturdays, Sundays and an public holidays.
- Necropsy of survivors performed: yes; necropsy with gross-pathology examination on the last day of the observation period after killing with CO2.
- 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.

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 occurred.

Clinical signs:

Systemic effects: no systemic clinical observations were observed during clinical examination.
Local effects: no local effects were observed.

Body weight:

The mean body weights of the animals increased throughout the study period.
------------------------------------------------------------------------------------------
Animals Weight at day 0 Weight at day 7 Weight at day 14
Male 241.6±5.1 266.2±8.5 287.6±9.0
Female 208.8±1.9 217.6±8.1 231.8±8.8
-----------------------------------------------------------------------------------------

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at termination of the study.

Any other information on results incl. tables

CONCLUSION: Under the conditions of this study the acute dermal median lethal dose of the test substance after dermal application was found to be greater than 2,000 mg/kg body weight in male and female rats.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met