2,5-Furandione, dihydro-, mono-C15-20-alkenyl derivs.

Endpoint summary

Description of key information

- Oral (rat): > 2000 mg/kg bw (f) (OECD 423)
- Dermal (rat): >2000 mg/kg bw (m+f) (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:

other: GLP- and guideline compliant

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: 10 weeks
- Weight at study initiation: 176.7-179.3 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum
- Housing:Makrolon cage, type III; Single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24°C
- Humidity (%): 20 – 80%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.08 mL

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: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of
observation.Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. A check for any dead or moribund animal was made at least once each workday.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were observed during clinical examination.

Gross pathology:

There were no macroscopic pathological findings in the animals sacrificed at the end of
the observation period.

Other findings:

none

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of ASA after oral administration was found to be greater than 2000 mg/kg bw in rats.

Executive summary:

In an acute oral toxicity study performed according to the OECD 423 under GLP, 2000 mg/kg bw of the undiluted test-item was administered to two test groups of three fasted Wistar rats each by gavage. Because no mortality occurred in the six females administered 2000 mg/kg bw within the 14 day observation perid, the LD50 was estimated to be >2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

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:

other: GLP- and guideline compliant

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

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, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: male: 253.8 g (mean); female: 201,8 (mean)
- Housing: Makrolon cage, type III; Single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 – 26°C
- Humidity (%): 20 – 80%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: 10



REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinsing of the application site with warm water
- Time after start of exposure: 24h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.08 ml/kg
- Concentration (if solution): 2000 mg/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males, 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of
observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination. Skin effects at the application site comprised erythema (grade 1 or 2), edema (grade 1), scaling and incrustations and were observed on study day 1 until study day 9 after application.

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:

none

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of ASA after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity:

In an acute oral toxicity study performed according to the OECD 423 under GLP, 2000 mg/kg bw of the undiluted test-item was administered to two test groups of three fasted Wistar rats each by gavage. Because no mortality occurred in the six females administered 2000 mg/kg bw within the 14 day observation period, the LD50 was estimated to be >2000 mg/kg bw.

 

Acute dermal toxicity:

The LD50 was found >2000 mg/kg bw in a study on acute dermal toxicity performed in accordance with GLP and ORCD 402 with five male and five female Wistar rats. No  systemic clinical signs were noted and no mortality occurred during the 14 day observation period.

Justification for selection of acute toxicity – oral endpoint
Guideline study according to GLP

Justification for selection of acute toxicity – dermal endpoint
Guideline study according to GLP

Justification for classification or non-classification

There available data are conclusive but not sufficient data for classification with regard to acute toxicity via oral or dermal route in accordance the CLP Regulation (EC) No 1272/2008.