Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 July 2016 to 17 October 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 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid: viscous
Specific details on test material used for the study:
- Purity: >99%
- Physical state/Appearance: Brown paste

Test animals

Species:
rat
Strain:
other: Wistar (RccHan™:WIST)
Sex:
female
Details on test animals and environmental conditions:
Female Wistar (RccHan™:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail. A color coded card was prepared with details of the test item, study number, dose level, sex, number of animals, route of administration and initials of the Study Director. At the start of the study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the mean body weight at the start of treatment. Housing, diet, water and environmental conditions were as per those described in the standardised guidelines.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing.
Doses:
Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.
No. of animals per sex per dose:
Five animals per dose
Control animals:
no
Details on study design:
- Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days
- Morbidity and mortality checks were made twice daily, early and late during normal working days and once daily on weekends and public holidays
- Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14
Statistics:
Statistical analysis was not performed.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no unscheduled deaths.
Clinical signs:
Signs of systemic toxicity noted in all animals were hunched posture, pilo-erection and tiptoe gait. Ataxia was also noted in the additional four treated animals. Isolated incidents of lethargy and labored respiration were noted in one animal. Animals appeared normal 5, 6 or 11 days after dosing.
6.3 Body Weight
Body weight:
Two animals showed body weight loss during the first week but weight gains during the second week resulted in body weights within the expected historical range for this strain. Based on historical data from the supplier for this strain, the remaining animals showed expected gains in body weight over the observation period.
Gross pathology:
Epithelial sloughing of the gastric mucosa was noted at necropsy of one animal. No abnormalities were noted at necropsy of the remaining animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study, the acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System: Unclassified).
Executive summary:

An acute oral toxicity study was carried out in the female Wistar rat. The study was performed to the standardized guidelines OECD 420, EU Method B.1 and EPA OPPTS 870.1100, under GLP conditions.

 

Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test item, as a solution in dimethyl sulphoxide, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

 

There were no unscheduled deaths. Signs of systemic toxicity commonly noted were hunched posture, pilo-erection, tiptoe gait and ataxia. Isolated incidents of lethargy and labored respiration were noted in one animal. Animals appeared normal 5, 6 or 11 days after dosing. Two animals showed body weight loss during the first week but weight gains during the second week resulted in body weights within the expected historical range for this strain. Based on historical data from the supplier for this strain, the remaining animals showed expected gains in body weight over the observation period. Epithelial sloughing of the gastric mucosa was noted at necropsy of one animal. No abnormalities were noted at necropsy of the remaining animals.

 

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System: Unclassified).