Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 - 28 Apr 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
08 Feb 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom, UK
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan:WIST
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 162 - 211 g
- Fasting period before study: animals were fasted overnight before dosing
- Housing: in groups of up to 4 in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: 2014C Teklad Global Rodent diet, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 33.3 and 221.8 mL/kg bw
- Justification for choice of vehicle: DMSO was used because the test item did not dissolve/suspend in distilled water or arachis oil BP

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: The recommended starting dose of 300 mg/kg bw according to the current OECD TG was used
Doses:
300 and 2000 mg/kg bw (Due to the purity of the test material, the animals were dosed with 333 and 2218 mg/kg bw of the test material, respectively.)
No. of animals per sex per dose:
3 (2000 mg/kg bw/day) and 6 (300 mg/kg bw/day)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed 30 min, 1, 2 and 4 h after dosing and subsequently once daily for up to 14 days. Body weights were determined prior to dosing and on Day 7 and 14 after treatment or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
500 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
300 mg/kg bw: 0/6 animals died
2000 mg/kg bw: 1/3 animals killed for humane reasons on Day 1, 2/3 animals died on Day 1
Clinical signs:
300 mg/kg bw: no clinical signs of toxicity were observed up to the end of the 14-day observation period in 6/6 animals
2000 mg/kg bw: hunched posture in 3/3 animals, piloerection, lethargy, diarrhea, hypothermia, tonic convulsions, chromodacryorrhea and splayed gait in 1/3 animals, which was killed for humane reasons
Body weight:
300 mg/kg bw: except for one animal, all animals gained weight as expected over the observation period.
2000 mg/kg bw: not applicable due to mortality
Gross pathology:
300 mg/kg bw: necropsy revealed no substance-related findings in 6/6 animals
2000 mg/kg bw: dark kidneys, gaseous stomach, pale brown colored liquid present in the stomach, hemorrhage and epithelial sloughing of the gastric mucosa and non-glandular epithelium of the stomach in 3/3 animals. Dark liver in 2/3 animals and patchy pallor of the liver in 1/3 animals

Any other information on results incl. tables

Table 1: Acute oral toxicity

Dose Mortality Clinical signs
[mg/kg bw]
  N* N*
Females
300 0/3 0/3
300 0/3 0/3
2000 3/3 3/3

*N = Number of animal / number of animals used

Applicant's summary and conclusion

Interpretation of results:
other: Cat. 4, H302 according to Regulation (EC) No 1272/2008
Conclusions:
CLP: Acute Oral 4, H302