2-Propenoic acid, 4-[[(4-benzoylphenoxy)carbonyl]oxy]butyl ester

Endpoint summary

Description of key information

dermal:
Under the conditions of the study the median lethal dose (LD50) of the test substance after dermal application was found to be greater than 2000 mg/kg bw  in male and female rats.
oral:
Under the conditions of the study the range of mortality following a single oral administration was found to be greater than 2200 mg/kg bw  for the male and female animals.

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

Study period:

1992-03-04 to 1992-03-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Qualifier:

according to guideline

Guideline:

other: EEC Directive 84/449, 1984

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab.

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Age at study initiation: young adult animals
- Weight at study initiation: 150 g- 300 g
- Housing: singel housing in stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, Germany)
- Diet: Kliba Labordiaet 343, Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland
- Water: tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

Acclimatization period: at least 1 week
Fasting period: at least 16 hours before administration; water was available ad libitum
Form of administration: emulsion
Amounts administered: 2200 mg/kg - concentration: 44.000 g/100 mL - administration volume: 5.00 mL/kg

Doses:

2200 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
A check was made twice each working day and once on Saturdays, Sundays and public holidays for general observations and for any dead or moribund animal.
Body weight determination: shortly before application and then weekly and at the end of the study (before fasting period).
Signs and symptoms were recorded several times on the day of administration, at least once each working day for the individual animals.
Necropsy was done at the last day of the observation period (withdrawal of food at least 16 h before killing with CO2; then necrospy with gross-pathological examination.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 200 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: none

Gross pathology:

nothing abnormal detected

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 200 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

Study period:

2011-12-06 to 2012-01-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147

Deviations:

yes

Remarks:

as in line with OECD 402

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: Young adult animals (male animals approx. 8 weeks, female animals approx. 11 weeks)
- Weight at study initiation: Animals of comparable weight (mean ± SD: males 240 ± 3.8 g, females 213 ± 9.4 g)
- Housing: single housing in Makrolon cages, type III
- Diet: VRF1(P) (SDS Special Diets Services, Altrip, Germany)
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12 (6.00 p.m. - 6.00 a.m. / 6.00 a.m. - 6.00 p.m.)

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: about 40 cm²
- % coverage: at least 10% of the body surface
- Type of wrap if used: an air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 1.77 mL/kg bw
- Concentration: undiluted

Duration of exposure:

24 hours

Doses:

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: A check for any dead or moribund animals was made at least once each workday. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. Individual body weights were determined shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: Scoring of skin findings (assessment according to Draize; individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly and on the last day of observation).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality and no systemic clinical signs

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Other findings:

Local effects: No local effects were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

comparable to guideline requirements and scientifically valid

Additional information

Acute Toxicity (dermal):

A study was performed according to OECD guideline 402 and in compliance with GLP.

In this acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi- occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.

The following test item-related effects were recorded during the course of the study:

No mortality occurred. No signs of systemic toxicity or skin effects such as erythema or edema were observed. The mean body weight of the male animals increased throughout the study period within the normal range. The mean body weights of the female animals stagnated during the first post-exposure observation week probably due to the bandage procedure, but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. As a conclusion, the LD50 value for acute dermal toxicity was found to be greater than 2000 mg/kg bw.

Acute Toxicity (oral):

The study was performed to assess the range of mortality following oral administration of the test material, applied as an emulsion in olive oil DAB 9 to Wistar rats. The study procedure was based on the EEC guideline and modified according to BGA-model (1991). A group of 6 fasted animals (3 males and 3 females) was given a single oral dose of test material preparation in olive oil DAB 9 at a dose level of 2200 mg/kg bw. Signs of toxicity have not been noted. The expected body weight gain has been observed in the course of the study. No mortality occured. No abnormalities where noted at a necropsy of animals sacrificed at the end of the study. Under the conditions of the study the LD50 following a single oral administration was found to be greater than 2200 mg/kg bw for the male and female animals.

Justification for selection of acute toxicity – oral endpoint
guideline study conducted in accordance to GLP

Justification for selection of acute toxicity – dermal endpoint
guideline study conducted in accordance to GLP

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)
The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EG.

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation No 605/2014.