Registration Dossier

Administrative data

Description of key information

Acute toxicity:

Oral - LD50: <2000 mg/kg

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:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source of test material: Sample from production lot
- Lot/batch No.of test material: Lab sample of October 9th 2015
- Expiration date of the lot/batch: 2016-10-08
- Purity: 99.91%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient conditions
- Stability under test conditions: Stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS srl, San Pietro al Natisone, Italy
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 7 - 9 weeks
- Weight at study initiation: 168 - 233 g
- Fasting period before study: Overnight prior to dosing and for approximately 4 hours following dosing
- Housing:Group caged in solid bottomed cages
- Diet (e.g. ad libitum): Commerical rodent diet, ad libitum
- Water (e.g. ad libitum): Municipal supply drinking water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 deg C
- Humidity (%): 40 - 70%
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 2016-09-21 To: 2016-11-04
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30, 200 and 500 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): Test substance dissolved/suspended in vehicle on a w/v basis

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As specified by test guidelines
Doses:
5000 mg/kg
2000 mg/kg
300 mg/kg
No. of animals per sex per dose:
1 at 5000 mg/kg
3 at 2000 mg/kg
6 at 300 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations - at least daily; Weighing - weekly
- Necropsy of survivors performed: Yes
Sex:
female
Dose descriptor:
LD0
Effect level:
300 mg/kg bw
Based on:
test mat.
Mortality:
5000 mg/kg - 100% (1/1)
2000 mg/kg - 67% (2/3)
300 mg/kg - 0% (0/6)
Clinical signs:
5000 mg/kg - Piloerection and hunched posture
2000 mg/kg - Piloerection, hunched posture, reduced activity and part-closed eyes
300 mg/kg - No clinical signs of treatment
Body weight:
No abnormalities in surviving animals
Gross pathology:
No abnormalities noted
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute toxicity of tetrahydrophthalic anhydride (tTHPA) has been investigated following a single oral administration to the rat.
Mortality was observed in animals following dosing at 5000 and 2000mg/kg. No mortality occurred and no signs of toxicity were observed following dosing at 300mg/kg.
Executive summary:

The acute toxicity of tetrahydrophthalic anhydride (tTHPA) has been investigated following a single oral administration to the rat.

Mortality was observed in animals following dosing at 5000 and 2000mg/kg. No mortality occurred and no signs of toxicity were observed following dosing at 300mg/kg.

Based on these findings the substance should be classified in Category 4 according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
300 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute oral toxicity has been investigated using methods as described or similar to those of OECD/EU test guidelines. The LD50 following administration of a single oral dose to rats was approximately 3200 mg/kg body weight. A value of 5410 mg/kg body weight is reported, in a peer reviewed handbook. A more recent study suggests greater toxicity to the substance, the indicated LD50 being below 2000 mg/kg body weight.

Acute dermal toxicity has been investigated in accordance with OECD/EU test methods. A single dose of 2000 mg/kg was administered to a group of 5 male and 5 female animals for 24 hours. No toxicity occurred and the lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.

Justification for classification or non-classification

Findings from oral administration studies are not consistent. Two studies suggest no classification to be necessary while one study indicates classification in Category 4 - Harmful if swallowed (H302) to be relevant.

The lack of observed toxicity in acute single exposure studies by the dermal route does not indicate classification as being necessary.