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

Endpoint summary

Description of key information

- oral: LD50 > 2000 mg/kg bw (OECD 401)

- dermal: LD50> 2000 mg/kg bw (OECD 402)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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.

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)

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).

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.
------------------------------------------------------------------------------------------
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
-----------------------------------------------------------------------------------------

Gross pathology:

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

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.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

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

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.

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)

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.

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.

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.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

One acute oral study according to OECD guideline 401 and one acute dermal study according to OECD guideline 402 is available.

Mortality, clinical abnormalities, systemic clinical effects, local dermal effects and macroscopic pathological abnormalities were not observed in either study.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. No mortality occurred at the limit dose of 2000 mg/kg bw. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008,as amended for the seventh time in Regulation (EC) No 2015/1221.