Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 29 April 2013 to 26 June 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented guideline and GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
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
- Age at study initiation: 9 weeks old
- Weight at study initiation: 196 – 221 g
- Fasting period before study: the food but not water was withheld during an overnight period.
- Housing: 3 animals / cage (Type II polypropylene/polycarbonate, with Lignocel Bedding)
- Diet: ad libitum (ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany (Batch no.: 175 8935, expiry date: August 2013))
- Water: ad libitum (tap water from the municipal supply, as for human consumption)
- Acclimation period: at least 19 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21.1 – 25°C
- Humidity: 32 – 68 %
- Air changes: 15 – 20 air exchanges/hour
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From 14 May 2013 To 29 May 2013

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sunflower oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: no data
- Lot/batch no.: 19T/3-29.06.2012

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: the initial dose level was selected by the study director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Clinical Observations: at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter.
> Body Weight: on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: none
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality observed
Mortality:
K-36 did not cause mortality at a dose level of 2000 mg/kg bw.
Clinical signs:
Treatment caused red-brownish discolouration of the faeces after treatment on Day 1 (6/6) and on Day 2 (3/6). All animals were symptom free from 3 days after the treatment until the end of the observation period.
Body weight:
There was no indication of a test item-related effect on body weight gains during the study.
Gross pathology:
There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The acute oral LD50 value of K-36 was found to be above 2000 mg/kg bw in female CRL:(WI) rats.
Executive summary:

In an acute oral toxicity study according to OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.Tris, groups of fasted, young adult CRL:(WI) rats (2 groups of 3 females each) were given a single oral dose of K-36 in sunflower oil at the dose level of 2000 mg/kg bw and observed for 14 days.

 

Oral LD50 Females > 2000 mg/kg bw

No mortality, no body weight changes and no macroscopic effects were observed during the study. The only effect noted was a red-brownish discolouration of the faeces after treatment on Day 1 (6/6) and Day 2 (3/6).

 

K-36 is of low toxicity based on the LD50 in females. According to the CLP and GHS criteria, K-36 can be ranked as “Unclassified” for acute oral exposure.