Registration Dossier

Administrative data

Description of key information

Oral: The LD50 value of the test substance was found to be 1000 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:
2015-11-24 to 2015-12-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
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 information:
Composition 1
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
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.
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.
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.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 000 mg/kg bw
Quality of whole database:
reliable study report, sufficient for assessment

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Only basic information given.
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
In an acute dermal toxicity study, the shaved skin of 6 male mice were exposed to the test item with 0.25 % esterine over a period of 2 hours. The detection of the esterine resorption was used as a indirect proof of the inclusion of the solvent.
GLP compliance:
no
Test material information:
Composition 1
Species:
mouse
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
no data
Type of coverage:
occlusive
Details on dermal exposure:
TEST SITE
- Area of exposure: The contact area was limited by small cylindrical glass containers (diameter 17, height 10 mm) which were closed at the top with waterproof adhesive tape and fixed with commercially available glue on the abdominal skin. Thus, the area of exposure was 2.2 cm².
Duration of exposure:
2 hours
Doses:
Test substance was tested as solution agent together with 0.25 % eserine.
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
No data
Statistics:
No data
Mortality:
No mortality occurred.
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data

Results of the resorption test of the test item with 0.25 % eserine

Solution agent for eserine (0.25 % solution)

Minutes to increase the lifting height (mean)

More minutes until reaching the maximum lift height (mean)

Number of analyzed trials

Test item

- (10)

-

6

- An application of the test item alone also did not lead to an intoxication.

Interpretation of results:
study cannot be used for classification
Conclusions:
In the present study, the test item showed no dermal absorption after an exposure period of 2 hours in mice. Thus, a toxic effect at this dose can be excluded under the experimental conditions chosen.
Executive summary:

In this study the percutane resorption of the test item with 0.25 % eserine was observed. The shaved skin of 6 male mice were exposed to the test item with 0.25 % eserine over a period of 2 hours. The detection of the eserine resorption was used as an indirect proof of the inclusion of the solvent. Eserine was not absorbed under the said experimental conditions. It can be concluded that the test item was also not absorbed. Thus, a toxic effect of the test item at this dose can be excluded under the experimental conditions chosen. An exposure to the test item alone also did not lead to an intoxication.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute oral toxicity:
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 = 1,000 mg/kg bw.

Shelanski, 1971 (RIFM Report 2030)
In a supporting study, 5 Wistar rats per sex were orally (gavage) dosed with 5000 mg/kg of the test item. After a single application of the test substance all animals had died.Thus, the LD50 is < 5000 mg/kg.

Acute inhalation toxicity:

In accordance with column 2 of REACH Annex VIII, the study does not need to be conducted as two other routes for acute toxicity are provided.

Acute dermal toxicity:

Shelanski, 1971 (RIFM Report 2031)

In an acute dermal toxicity study, 6 albino rabbits were exposed to 5000 mg/kg of the test item. Three animals with intact skin and three animals with abraded skin were tested. All animals had died, after the exposure to the test substance. Thus, the acute oral LD50 is < 5000 mg/kg in rabbits.

Meyer & Kerk ,1960 (Archiv für Toxikologie 18: 131-139)
In another study the percutane resorption of the test item with 0.25 % eserine was observed. The shaved skin of 6 male mice were exposed to the test item with 0.25 % eserine over a period of 2 hours. The detection of the eserine resorption was used as an indirect proof of the inclusion of the solvent. Eserine was not absorbed under the said experimental conditions. It can be concluded that the test item was also not absorbed. Thus, a toxic effect of the test item can be excluded under the experimental conditions chosen. An exposure to the test item alone also did not lead to an intoxication.

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 1272/2008 (CLP). As a result the substance is considered to be classified for acute oral toxicity under Regulation (EC) No 1272/2008, as amended for the ninth time in Regulation (EC) No 2016/11792 as cat. 4, H302, harmful if swallowed.