Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2017-04-07 to 2017-05-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Batch: 16136R88B
Purity: not specified

Test animals

Species:
rat
Strain:
other: not specified
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
Source: Charles River Deutschland, Sulzfeld, Germany.
Age at study initiation: Young adult animals (approximately 8 weeks old) were selected.
Weight at study initiation: 150 to 167 g.
Housing: On arrival and following assignment to the study, animals were group housed (up to 5 animals of the same sex and same dosing group together) in polycarbonate cages containing sterili zed sawdust as bedding material equipped with water bottles.
Diet: Pelleted rodent diet was provided ad libitum throughout the study.
Water: Municipal tap-water was freely available to each animal via water bottles.
Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS Temperature (°C): 18°C to 24°C (Target), 21°C (Actual)
Humidity (%): 40% to 70% (Target), 44 to 49% (Actual)
Air changes (per hr): Ten or greater
Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% Aqueous carboxymethyl cellulose
Details on oral exposure:
VEHICLE
Amount of vehicle: 10 mL/kg body weight was used for each dose.
Justification for choice of vehicle: Trial preparations were performed at the Test Facility to select the suitable vehicle and to establish a suitable formulation procedure.

CLASS METHOD
Rationale for the selection of the starting dose:The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.
Doses:
300 and 2000 mg/kg body weight
No. of animals per sex per dose:
Three female Wistar rats each group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily. Body weights: A fasted weight was recorded on the day of dosing. Terminal body weights were collected from animals found dead or euthanized moribund after Day 1 (predose), 8 and 15. Clinical signs: at periodic intervals on the day of dosing (at least three times) and once daily thereafter.
- Necropsy of survivors performed: yes, at the end of observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
At 2000 mg/kg, two animals were found dead on Day 1 and one animal was found dead on Day 2. At 300 mg/kg, one animal was found dead on Day 2. No further mortality occurred.
Clinical signs:
At 2000 mg/kg, lethargy, clonic spasms, lateral recumbency, hunched posture, uncoordinated movements, slow breathing, shallow respiration, piloerection, salivation, watery discharge from both eyes, pale appearance and/or ptosis were noted for all animals on Day 1. At 300 mg/kg, lethargy, flat posture, hunched posture, laboured respiration, gasping, piloerection, chromodacryorrhoea (mouth and nose) and/or ptosis were noted on Days 1 and/or 2.
Body weight:
The mean body weight gain shown by the surviving animals over the study period was considered to be normal.
Gross pathology:
Abnormalities of the lungs (swollen and several dark red foci) were found in the animal dosed at 300 mg/kg that died during the study, at macroscopic post mortem examination. Macroscopic post mortem examination of the other animals that died during the study and of the surviving animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 value of test item in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.
Executive summary:

The study was carried out in compliance with the guidelines OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method".

Initially, the test item was administered by oral gavage to three female Wistar rats at 2000 mg/kg body weight. In a stepwise procedure two additional groups of three females were dosed at 300 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

The oral LD50 value of test item in Wistar rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.