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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015-11-24 to 2015-12-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2016

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 (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7 weeks and 8-9 weeks
- Weight at study initiation: 166.2-175.8 g and 177.2-208.1 g
- Housing: One animal/cage
- Diet: ad libitum pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C
- Water: tap water ad libitum
- Acclimation period: 14 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9-23.1
- Humidity (%): 46.1-54-4
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/ 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 400 and 60 mg/mL
- Lot/batch no.: MKBS6944V and MKBV2080V

DOSE VOLUME APPLIED: 5 mL/kg

Doses:
2000 and 300 mg/kg bw
No. of animals per sex per dose:
3 females at the highest dose (2000 mg/kg bw), 6 females at the lower dose (300 mg/kg bw)
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for mortality, general condition and clinical signs (type, severity, time of onset and recovery) at 30 minutes after dosing and at 1, 2, 4 and 6 hours after dosing on Day 0 and once daily thereafter for 14 days. The body weight was recorded prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy, Day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
Statistical analysis was not performed. Mean scores and values are determined.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 000 mg/kg bw
Based on:
test mat.
Mortality:
Two animals of the 2000 mg/kg bw dose group died. There were no deaths of animals at 300 mg/kg bw.
Clinical signs:
In one surviving animal, irregular respiration and mucous stool were observed at 2000 mg/kg bw on the day of dosing. Mucous stool and tremor were observed on Day 1, and then they disappeared on Day 2. In two dead animals, irregular respiration was observed at 2000 mg/kg bw on the day of dosing. No test substance-related effects were observed in any animal at 300 mg/kg bw.
Body weight:
No effects were observed in the animals of the 300 mg/kg bw dose group. A tendency for suppression of body weight gain was observed in one surviving animal of the 2000 mg/kg bw dose group on Day 1 after dosing and a decrease in body weight was observed in one dead animal at 2000 mg/kg bw on Day 1. Then, normal body weight gain was observed in one surviving animal from Day 3.
Gross pathology:
No gross visible evidence of morphologic abnormalities was observed in any animal dosed at 300 mg/kg bw. Test substance-related macroscopic findings were not observed in any dead animal or surviving animal of the 2000 mg/kg bw dose group.
Other findings:
Histopathology: At necropsy, black foci were observed in the glandular stomach in one dead animal dosed at 2000 mg/kg bw. A multifocal ulcer was observed at slight severity following histopathological examination in concordance with gross changes in the stomach. This finding was considered to be a test substance-related change to be discriminated from postmortem/spontaneous changes.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral toxicity study in Sprague Dawley rats revealed a LD50 value of 1000 mg/kg bw.
Executive summary:

An acute oral toxicity study was carried out to assess the potential toxicity of the test substance after a single oral administration. The acute toxic class method was followed. Three dose groups of three females each were utilized as follows: Group 1 (Step 1): 2000 mg/kg bw of the test substance Groups 2 and 3 (Steps 2 and 3): 300 mg/kg bw of the test substance Step 1: A dose of 2000 mg/kg bw was administered and then, there were two dead animals at 2000 mg/kg bw (Step 1). Steps 2-3: There were two dead animals (Step 1), thus a second dose of 300 mg/kg bw was administered. Then, there was no mortality (Step 2). A third dose of 300 mg/kg bw was administered (Step 3). All animals were monitored for clinical signs and body weight changes during the 14-day observation period after administration. They were subjected to a gross necropsy at the end of the observation period. There were no deaths of animals at 300 mg/kg bw. No test substance-related effects were observed in clinical signs, body weight data or necropsy findings in any animal at 300 mg/kg bw. Based on the result of the acute oral toxicity study in Sprague-Dawley rats, the test substance, was classified as Category 4 according to the GHS classification and the median lethal dose derived was: LD50 = 1000 mg/kg bw.