Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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 402 (Acute Dermal Toxicity)
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:
yes

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: approximately 4 °C in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Animal Information
Five male and five 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 weighed at least 200 g, and were 8 to 12 weeks of age. The weight
variation did not exceed ±20% of the mean weight for each sex.

Animal Care and Husbandry
The animals were housed in suspended solid floor polypropylene cages furnished with
woodflakes. The animals were housed individually during the 24-Hour exposure period and
in groups of five, by sex, for the remainder of the study. 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 could 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

Type of coverage:
semiocclusive
Vehicle:
DMSO
Details on dermal exposure:
The appropriate amount of test item, moistened with dimethyl sulfoxide, was applied as
evenly as possible to an area of shorn skin (approximately 10% of the total body surface
area). A piece of surgical gauze was placed over the treatment area and semi-occluded with a
piece of self-adhesive bandage. The animals were caged individually for the 24-Hour
exposure period. Shortly after dosing the dressings were examined to ensure that they were
securely in place.
After the 24-Hour contact period the bandage was carefully removed and the treated skin and
surrounding hair wiped with cotton wool moistened with dimethyl sulfoxide to remove any
residual test item. The animals were returned to group housing for the remainder of the study
period.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 (five)
Control animals:
no
Details on study design:
The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours
after dosing and subsequently once daily for 14 days.
After removal of the dressings and subsequently once daily for 14 days, the test sites were
examined for evidence of primary irritation.
Any other skin reactions, if present were also recorded.
Individual body weights were recorded prior to application of the test item on Day 0 and on
Days 7 and 14..
At the end of the study 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.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
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 two
females 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.
Other findings:
Dermal Reactions

Signs of dermal irritation noted were dried blood, glossy skin, scab lifting to reveal glossy
skin, small superficial scattered scabs, hardened dark brown/black colored scab and scab
cracking.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found
to be greater than 2000 mg/kg body weight.
The test item did not meet the criteria for classification according to the Globally Harmonized
Classification System.