Heptanoic anhydride

Endpoint summary

Description of key information

LD50 oral (rat): > 2000 mg/kg bw
LD50 dermal (rat): > 2000 mg/kg bw

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:

July to Aug 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Tierzucht Schönwalde GmbH, Schönwalde, Germany
- Weight at study initiation: 95-110 g (males), 95-108 g (females)
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: ≥ 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23°C
- Humidity (%): 42-62 %
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidest water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg

Doses:

2000 mg/kg

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 weighing: day 1, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

none

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died in the course of the study.

Clinical signs:

other: After single oral application of 2000 mg/kg no compound-related findings occurred.

Gross pathology:

Macroscopic examinations revealed a diminished size of testes, epidydimis, prostate and seminal vesicle in all male animals and of uterus and ovaries in all female animals.

Executive summary:

A single oral administration of the test substance by gavage to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, clinical signs and effects on body weight gain. Macroscopic examinations revealed a diminished size of testes, epididymis, prostate and seminal vesicle in all male animals and of uterus and ovaries in all female animals. According to OECD TG 423 the oral LD50 of the test substance is therefore > 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The study is GLP compliant and is of high quality (Klimisch score=1)

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:

Aug 2002 to Feb 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

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: Tierzucht Schönwalde GmbH, Schönwalde, Germany
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 276-313 g (males), 188-193 g (females)
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: >= 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23°C
- Humidity (%): 54-62 %
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

- Administration volume: 0.59 -0.67 mL / male animal or 0.40 -0.42 mL / female animal

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of clinical observation: 4 times on day 1 and thereafter once daily until day 14
- Frequency of weighing: day 1, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

none

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died in the course of the study.

Clinical signs:

other: No compound-related clinical findings were observed in any of the animals.

Gross pathology:

Autopsy revealed no compound-related findings.

Executive summary:

A single dermal administration of the test substance to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, compound-related clinical findings and gross pathological findings. A transient slight decrease in body weight in three male animals and in one female animal on day 7 of the test was observed. This effect was reversible at the end of the observation period. According to OECD TG 402 the dermal LD50 of ZK 56406 is therefore > 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The study is GLP compliant and is of high quality (Klimisch score=1)

Additional information

The acute oral toxicity of the test substance was low with a LD50 value exceeding 2000 mg/kg bw in rats according to OECD TG 423 (Kurth, 2005). At the limit-dose 2000 mg/kg no animal died and no clinical signs or effects on body weight gain were observed during the 14-day post observation period. Macroscopic examinations revealed a diminished size of testes, epididymis, prostate and seminal vesicle in all male animals and of uterus and ovaries in all female animals.

The acute dermal toxicity of the test substance was low with a LD50 value exceeding 2000 mg/kg bw in male rats according to OECD TG 402 (Kurth, 2006). At the limit-dose 2000 mg/kg no animal died and no clinical signs or gross pathological findings were observed during the 14-day post observation period. A transient slight decrease in body weight in three male animals and in one female animal on day 7 of the test was observed. This effect was reversible at the end of the observation period.

Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for selection of acute toxicity – dermal endpoint
Only one study available

Justification for classification or non-classification

Based on the study results a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.