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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 August 2016 to ****
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

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 2000
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
CAS RN: 15337-18-5
Purity: 96.6%
Physical state/Appearance: Yellow viscous liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Wistar (RccHan™:WIST)
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: The body weight variation did not exceed ±20% of the mean body weight at the start of treatment.
- Fasting period before study: Overnight fasting immediately before dosing and for approximately 3 to 4 hours after dosing.
- Housing: Animals assigned to the study were group housed by dose level. The animals were housed in groups of up to four in suspended solid floor polypropylene cages with stainless steel mesh lids and furnished with softwood flake bedding.
- Diet and water: With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to tap drinking water and food was allowed throughout the study.
- Acclimation period: At least 5 days
- Other: The animals were provided with environmental enrichment items which were analyzed and considered not to contain any contaminant at a level that might have affected the purpose or integrity of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): At least fifteen changes
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
The test item was freshly prepared, as required, as a solution in dimethyl sulphoxide (DMSO).
DMSO was used because the test item did not dissolve or suspend in distilled water or arachis oil BP and the test item was formulated within 2 hours of being applied to the test system.
Doses:
2000 mg/kg
No. of animals per sex per dose:
1 animal per dose, followed by four animals per dose.
Control animals:
no
Details on study design:
Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose for a single female animal. In the absence of toxicity at this dose level, an additional four female animals were treated at a dose level of 2000 mg/kg.
Animals were dosed once only by gavage. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing.
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 during normal working days, and once daily at weekends and public holidays.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. The presence or absence of any macroscopic abnormalities was recorded.

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:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.

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 in one female rat at a dose level of 2000 mg/kg, an additional four fasted female rats were given a single oral dose of test item, as a suspension in DMSO, 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.

No unscheduled deaths and no signs of systemic toxicity were noted during the observation period. All animals showed expected gains in body weight. No abnormalities were noted at necropsy.

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).