Registration Dossier

Administrative data

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 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:
Reduced activity, piloerection and ataxia observed following dosing and for at least 24 hours.
Body weight:
Changes in body weight were unremarkable
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
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:
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
1 100 mg/m³

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:
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:
minimal irritation on Day 2 following 24 hours exposure
Body weight:
Not remarkable
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
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.