Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Aug- Oct 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report Date:
2019

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001-12-17
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Landesanstalt für Umwelt Baden-Württemberg
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:
Test material is the main constituent of the registered substance.

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: [yes/no] : yes
- Age at study initiation: Approx. 10 weeks
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight) 173-182 g
- Fasting period before study: At least 16 h before administration
- Housing: Single housing in fully air-conditioned rooms
- Acclimatization: At least 5 d
- Feeding: R/M maintenance, low phytoestrogen; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany), ad libitum
- Water (e.g. ad libitum): Tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 – 70%
- Air changes (per h): Approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h



Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
for 300 mg/kg bw treatment
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 15 g/100 mL
- Justification: Solution in corn oil Ph.Eur.

MAXIMUM DOSE VOLUME APPLIED: 2 mL/kg bw for doses of 300 mg/kg bw; 2.26 mL/kg bw for doses of 2000 mg/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: By request of the sponsor
Doses:
300 mg/kg bw; 2000 mg/kg bw
No. of animals per sex per dose:
3 female rats/ dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations of clinical signs: Several times on the day of administration and at least once a week
- Frequency of weighing: Day 0, 7d, 14d
- Necropsy of survivors performed: yes
Statistics:
Calculations were performed using Microsoft Excel 2010 and checked with a calculator

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:
Remarks:
no mortality occured
Mortality:
no mortality occured
Clinical signs:
Clinical signs in the second 2000 mg/kg test group: impaired general state and piloerection from hour 1 until hour 4 after administration, while dyspnea and cowering position were noted in these animals at hour 2. No clinical signs were observed after exposure to 300 mg/kg bw and in the first test group dosed with 2000 mg/kg bw.
Body weight:
All animals gained weight in a normal range throughout the study period
Gross pathology:
There were no macroscopic pathological findings

Any other information on results incl. tables

Tab. 2: Mortality

Mortality

 

Dose (mg/kg bw):

2000

2000

300

Sex:

female

female

female

Administration:

1

2

1

No. of animals:

3

3

3

Mortality (animals):

No mortality

No mortality

No mortality

Tab. 3: Maximum incidence of clinical signs

Maximum incidence of systemic clinical signs

Dose (mg/kg bw):

2000

Sex:

female

Administration:

1

No. of animals:

3

Animal No.:

R300

R301

R302

Abnormalities:

-

-

-

 

 

 

 

Dose (mg/kg bw):

2000

Sex:

female

Administration:

2

No. of animals:

3

Animal No.:

R312

R313

R314

Abnormalities:

 

 

 

Impaired general state:

h1-h4

h1-h4

h1-h4

Piloerection:

h1-h4

h1-h4

h1-h4

Dyspnea:

h2

h2

h2

Cowering position:

h2

h2

h2

 

 

 

 

Dose (mg/kg bw):

300

Sex:

female

Administration:

1

No. of animals:

3

Animal No.:

R281

R282

R283

Abnormalities:

-

-

-

* h - hour

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 2000 mg/kg bw in female rats.
Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, doses of 2000 and 300 mg/kg bw of the test item (undiluted or preparations in corn oil Ph.Eur.) were administered by gavage to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 6 females and 300 mg/kg bw in 3 females).

All animals gained weight in a normal range throughout the study period.

There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (9 females).

Clinical signs (impaired general state and piloerection, dyspnea and cowering position) were observed in the second 2000 mg/kg test group.

The acute oral LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw.