Cyclohexane-1,2-dicarboxylic anhydride

Endpoint summary

Description of key information

Acute toxicity:
Oral - LD50 - 4040 mg/kg
Inhalation: LD50 - > 1100 mg/m3
Dermal: LD50 - > 2000 mg/kg

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline available

Principles of method if other than guideline:

Four groups, each of 5 male and 5 female rats, administered a single oral dose, by gavage. Animals assessed for 7 days after which survivors were killed and subjected to necropsy examination.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Zucht Winkelmann, Paderborn, Germany
- Weight at study initiation: 120 - 145 g
- Fasting period before study: Yes - 16 hours
- Diet (e.g. ad libitum): Rodent diet, ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 deg C
- Humidity (%): 45 - 55%
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20%
- Amount of vehicle (if gavage): 12.5 - 24.8 mL/kg body weight
- Justification for choice of vehicle: Substance unstable in aqueous media

MAXIMUM DOSE VOLUME APPLIED: 24.8 mL/kg body weight

Doses:

2520, 3180, 3980 and 5000 mg/kg

No. of animals per sex per dose:

5 males / 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Examination 2, 24 and 48 hours post-dose and again after 7 days. Weighing on day of dosing and again after 7 days
- Necropsy of survivors performed: Yes

Statistics:

Litchfield and Wilcoxon

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 040 mg/kg bw

Based on:

test mat.

95% CL:

3 580 - 4 570

Mortality:

Dose level [mg/kg] - 2520; Males 0% Females 0%
- 3180: Males 20% Females 20%
- 3980: Males 40% Females 40%
- 5000: Males 100% Females 100%

Clinical signs:

other: Reduced activity, piloerection and ataxia observed following dosing and for at least 24 hours.

Gross pathology:

No notable findings in surviving animals

Interpretation of results:

GHS criteria not met

Conclusions:

Acute oral toxicity (LD50) of hexahydrophthalic anhydride is 4040 mg/kg body weight

Executive summary:

Acute oral toxicity following administration of a single dose has been investigated in the rat according to FHSA test methods. The median lethal dose (LD50) of hexahydrophthalic anhydride was determined to be 4040 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

4 040 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP compliant study. Some details on methods / results not available

Qualifier:

no guideline followed

Principles of method if other than guideline:

4 hours exposure to maximum aerosol concentration achievable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

not specified

Details on inhalation exposure:

VEHICLE
- Composition of vehicle (if applicable): Ethanol
- Concentration of test material in vehicle (if applicable): 80%
- Justification of choice of vehicle: Substance stable in selected vehicle

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 75% of the particles were less than 10 μm indicating a respirable aerosol.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 5.8 μm (GSD = 2.2).

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

1100 mg/m3

No. of animals per sex per dose:

5 male / 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations - Daily; Body weights - Days 3, 4, 5, 8 and 15
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LC0

Effect level:

1 100 mg/m³ air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 100 mg/m³ air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

None

Clinical signs:

other: Decreased activity noted during exposure.

Body weight:

Depressed during the first week, followed by recovery during second week.

Gross pathology:

Not remarkable

Conclusions:

Acute inhalation toxicity following 4 hours exposure to the highest achievable aerosol concentration has been investigated in the rat. The LC50 was in excess of 1100 mg/m³.

Executive summary:

Acute inhalation toxicity following 4 hours exposure to the highest achievable aerosol concentration has been investigated in the rat. The LC50 was in excess of 1100 mg/m³.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

1 100 mg/m³ air

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP compliant study conducted to internationally recognised test methods. Some details on methods / results not available

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- % coverage: 10%
- Type of wrap if used: porous gauze dressing

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Constant volume or concentration used: yes
- For solids, paste formed: no

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 male / 5 female

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed daily. Bodyweights recorded on Day 1, 8 and 15
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: minimal irritation on Day 2 following 24 hours exposure

Gross pathology:

Not remarkable

Interpretation of results:

GHS criteria not met

Conclusions:

Acute dermal toxicity has been investigated in the rabbit according to OECD test methods. No mortality occurred at a dose level of 2000 mg/kg body weight.

Executive summary:

Acute dermal toxicity has been investigated in the rabbit according to OECD test methods. No mortality occurred at a dose level of 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity following administration of a single dose has been investigated in the rat according to FHSA test methods. The median lethal dose (LD50) of hexahydrophthalic anhydride was determined to be 4040 mg/kg body weight.

Acute dermal toxicity has been investigated in the rabbit according to OECD test methods. No mortality occurred at a dose level of 2000 mg/kg body weight.

Acute inhalation toxicity following 4 hours exposure to the highest achievable aerosol concentration has been investigated in the rat. The LC50 was in excess of 1100 mg/m3

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 (EC) No 1272/2008. Based on available data on acute toxicity, the test item is not classified for the oral, dermal and inhalation route according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.