Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experimental: From October 7th, 2014 until November 20th, 2014
Reliability:
1 (reliable without restriction)

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: white solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: 160-175 g
- Fasting period before study: With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study.
- Housing: The animals were individually housed in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) , ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Doses:
55, 175, 550 and 2000 mg/kg bodyweigt
No. of animals per sex per dose:
55 mg/kg bodyweigt: 1 animal
175 mg/kg bodyweigt: 3 animals
550 mg/kg bodyweigt: 3 animals
2000 mg/kg bodyweigt: 1 animal
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: ½, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 311.9 mg/kg bw
Based on:
test mat.
Mortality:
Dose Level mg/kg Number of Animals Survived Number of Animals Died Total Number of Animals
55 1 0 1
175 2 1 3
550 1 2 3
2000 0 1 1
All doses
4
4
8
Clinical signs:
Hunched posture was noted in two animals treated at a dose level of 175 mg/kg, one animal treated at a dose level of 550 mg/kg and the animal treated at a dose level of 2000 mg/kg. Pilo-erection and noisy respiration were also noted in one animal treated at a dose level of 175 mg/kg with pilo-erection and tiptoe gait also noted in one animal treated at a dose level of 550 mg/kg.
No signs of systemic toxicity were noted during the observation period in the animal treated at a dose level of 55 mg/kg, one animal treated at a dose level of 175 mg/kg and the surviving animal treated at a dose level of 550 mg/kg.
Body weight:
Surviving animals showed expected gains in body weight over the observation period.
Gross pathology:
Abnormalities noted at necropsy of animals that died during the study were dark liver, dark kidneys, pale liquid present in the stomach or gastric mucosa, gaseous stomach or gastric mucosa, hemorrhagic gastric mucosa and non-glandular epithelium of the stomach and hemorrhagic small and large intestines. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was calculated to be 311.9 mg/kg body weight.