Registration Dossier

Administrative data

Description of key information

Acute oral toxicity

The study was performed in accordance with OECD Guidelines for Testing of Chemicals No 420 (fixed dose method) and EU-Method B1. No treatment-related effects were noted. The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley rat was estimated to be greater than 2000 mg/kg bodyweight. The registered chemical is unstable in water. A supporting acute oral toxicity test of the hydrolysis product Pyromellitic acid PMA with identical study design resulted in a LD50 of > 2000 mg/kg.

Acute dermal toxicity

An acute dermal toxicity study was performed in Wistar rats, in compliance with OECD Guideline No. 402. A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as a single dermal 24-hour exposure followed by a 14-day observation period.. The test item did not cause mortality at the dose level of 2000 mg/kg bw. There were no systemic clinical signs noted in any animal throughout the study. No local dermal signs were observed after treatment with the test item during the 14 days observation period. Body weight gains of treated animals during the study showed no indication of a test item-related effect. There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw. In conclusion, the acute dermal median lethal dose (LD50 value) of the test item was found to be above 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:
May-June 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
- Description: pale yellow crystalline solid
- Batch number: 7X18A
- Storage conditions: approximately 4 °C in the dark over silica gel
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 204-281 g
- Fasting period before study: overnight before dosing
- Housing: in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): certified Rat and Mouse Diet
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): 15 changes/hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: solubility & stability (test item is unstable in water)
Doses:
Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose. One female was treated first. In the absence of toxicity at a dose level of 2000 mglkg, an additional group of 4 animals was treated with the same dose of 2000 mg/kg. A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study. All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
No. of animals per sex per dose:
5 animals at a dose of 2000 mg/kg
Control animals:
no
Details on study design:
- Frequency of weighing: Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14
- Frequency/duration of observation period following administration: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and subsequently once daily for fourteen days
- Necropsy: At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
none
Preliminary study:
Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose. One female was treated first. In the absence of toxicity at a dose level of 2000 mglkg, an additional group of 4 animals was treated with the same dose of 2000 mg/kg
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deatha observed.
Clinical signs:
No signs of systemic toxicity were noted.
Body weight:
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley rat was estimated to be greater than 2000 mg/kg bw.
Executive summary:

The study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley rat. The method was designed to meet the requirements of the OECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method" (adopted 17 December 2001) and Method Bl bis Acute Toxicity (Oral) of Commission Directive 2004/73/EC Method. Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test material, as a suspension in arachis oil, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths. There were no signs of systemic toxicity. All animals showed expected gains in bodyweight. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley rat was estimated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Guideline study; Klimisch 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:
June-August 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Batch number: NJC1506009
- Appearance: White crystals
- Manufacturing date: 11 June 2015
- Expiry date: 10 December 2016
- Storage conditions: Controlled room temperature (15-25°C, below 70 RH%), under inert gas, protected from humidity
- Safety precautions: Routine safety precautions (lab coat, gloves, safety glasses, face mask) for unknown materials were applied to assure personnel health and safety.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: young healthy adult rats
- Weight at study initiation: between 201 g and 249 g
- Fasting period before study: no data
- Housing: individual caging
- Diet (e.g. ad libitum): ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" from ssniff Spezialdiäten GmbH, D-59494 Soest, Germany
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 – 25.0 °C
- Humidity (%): 34 – 70%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
The back of each animal was shaved (approximately 10% area of the total body surface) approximately 24 hours prior to treatment. The test item was applied as a single dose to the shaved skin and remained in contact with the skin for the 24-hour exposure period. The test material was dampened with sufficient water before application to ensure good contact with the skin. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours. At the end of the exposure period, the area of skin treated with the test item was washed with water of body temperature.
Duration of exposure:
24 hours
Doses:
The test item was not expected to be lethal at 2000 mg/kg bw. A limit test wastherefore performed.
No. of animals per sex per dose:
5 males and 5 females at 2000 mg/kg
Control animals:
no
Details on study design:
Clinical Observations:
Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Skin Irritation:
Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.

Body Weight Measurement:
The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14 just before necropsy.

Necropsy:
Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia (Euthanimal 40%). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.
Statistics:
none
Preliminary study:
No pre-test performed. The test item was not expected to be lethal at 2000 mg/kg bw. A limit test was therefore performed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test item did not cause mortality at the dose level of 2000 mg/kg bw.
Clinical signs:
Clinical Observations:
There were no systemic clinical signs noted in any animal throughout the study.

Local Dermal Signs:
No local dermal signs were observed after treatment with the test item during the 14 days observation period.
Body weight:
Body weight gains of test item treated animals during the study showed no indication of a test item-related effect.
Gross pathology:
There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute dermal median lethal dose (LD50 value) of the test item was found to be above 2000 mg/kg bw.
Executive summary:

An acute dermal toxicity study was performed in Wistar rats, in compliance with OECD Guideline No. 402. A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as a single dermal 24-hour exposure followed by a 14-day observation period.. The test item did not cause mortality at the dose level of 2000 mg/kg bw. There were no systemic clinical signs noted in any animal throughout the study. No local dermal signs were observed after treatment with the test item during the 14 days observation period. Body weight gains of treated animals during the study showed no indication of a test item-related effect. There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw. In conclusion, the acute dermal median lethal dose (LD50 value) of the test item was found to be above 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Guideline study; Klimisch 1

Additional information

Justification for classification or non-classification

Based on the data available the substance is not classified or labeled according to Regulation 1272/2008/EC (CLP).