Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
yes
Remarks:
At the time of issue/approval the study plan did not contain test item identification, it is however included in the final study report. This deviation was considered to have not affected the integrity or validity of the study.
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Identification: OK (640-2) (Furoxy Hydroxy)
Batch: G316533
Purity: 94.032% w/w
Physical state/Appearance: cream colored solid
Expiry Date: 25 March 2018
Storage Conditions: Store cold at 4° C in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Animal Information
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 and a number written on a cage card. 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 of any previously dosed animals.
3.2.2 Animal Care and Husbandry
The animals were housed in groups of up to four in suspended solid-floor polypropylene
cages furnished with woodflakes. With the exception of an overnight fast immediately before
dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water
and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon,
UK) was allowed throughout the study. The diet, drinking water and bedding were routinely
analyzed and were considered not to contain any contaminants that would reasonably be
expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to
70% respectively. The rate of air exchange was at least fifteen changes per hour and the
lighting was controlled by a time switch to give 12 hours continuous light and 12 hours
darkness.
The animals were provided with environmental enrichment items which were considered not
to contain any contaminant of a level that might have affected the purpose or integrity of the
study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
For the purpose of the study the test item was freshly prepared, as required, as a solution in
dimethyl sulfoxide. Dimethyl sulfoxide was used as it produced the most suitable
formulation at the required concentration. 30mg substance/Ml or 200 mg substance /ml DMSO
The test item was formulated within 2 hours of being applied to the test system. It is assumed
that the formulation was stable for this duration.
No analysis was conducted to determine the homogeneity, concentration or stability of the
test item formulation. This is an exception with regard to GLP and has been reflected in the
GLP compliance statement.
Doses:
300 mg/kg bw
2000 mg/kg bw
No. of animals per sex per dose:
1 female @ 300 mg/kg bw
5 females @ 2000 mg/kg bw
Control animals:
no
Details on study design:
In the absence of information on the toxicity of the test item, 300 mg/kg was chosen as the
starting dose; a single animal was treated.
In the absence of evident toxicity at a dose level of 300 mg/kg, an additional animal was
treated.
In the absence of toxicity at a dose level of 2000 mg/kg, an additional group of 4 animals was
treated.
A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.
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. Treatment of animals was sequential. Sufficient time was
allowed between each dose group to confirm the survival of the previously dosed animals.
Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for
up to 14 days. Morbidity and mortality checks were made twice daily, early and late 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. This consisted of an external examination and
opening of the abdominal and thoracic cavities. The appearance of any macroscopic
abnormalities was recorded. No tissues were retained.
Statistics:
N/A

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
All animals showed expected gains in body weight over the observation period, except for
one female treated at a dose level of 2000 mg/kg which showed an expected gain in body
weight during the first week of the study but body weight loss during the second week.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
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).