1-[2-fluoro-6-(trifluoromethyl)benzyl]-5-iodo-6-methylpyrimidine-2,4(1H,3H)-dione

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4th June 2018 to 29th October 2018

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

Guideline:

other: Acute Dermal Toxicity (TG402) published by the Ministry of Environmental Protection of Peoples Republic of China in the year 2013

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-5-iodo-6-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione

EC Number:

687-893-6

Cas Number:

1150560-54-5

Molecular formula:

C13H9F4IN2O2

IUPAC Name:

1-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-5-iodo-6-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Physical check up and acclimation were made to all animals on arrival. Healthy young animals were acclimatised to the laboratory conditions and housed two per cage in the facility of Room D101 for 7 days prior to the test. All animals were weighed and marked on the hair. Clinical observations were performed daily until grouping. Animals were raised in suspended stainless steel cages. Animals were housed individually during the test.
Temperature: 20-25oC
Humidity: 40-70%
Light sequence: 12 hour light / 12 hour dark
Food: Sterilised diet with complete nutrition (Beijing keaoxieli Feed Co. Ltd.)
Water: ad libitum

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

According to body weights, the theoretical amounts of the test item were calculated.

Theoretical Weighed Test Item (mg/animal) = Body Weight (kg) x Dose (mg/kg)

The test item was weighed on a piece of gauze (6cm x 6cm) stuck on a small piece of medical tape (non-irritating) moistened with 0.5ml vehicle. Approximately 24 hours before the test, fur was removed from the dorsal area of the trunk of the test animal by clipping. Only animals with healthy and intact skin were used. The gauze was placed over the treatment area and wrapped with a piece of self-adhesive bandage. Shortly after dosing, the dressings were examined to ensure that the animals cannot ingest test item.

Duration of exposure:

14 days

Doses:

One dose

No. of animals per sex per dose:

5 males
5 females

Details on study design:

Clinical observations were performed once during the first 30 mins and at 1, 2 and 4 hours, then once each day for 14 days.

Careful observations and records of fur changes, eye & mucosa, respiratory, circulatory, nervous system, limb activity and behavioural changes.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: There were no abnormal findings during the test

Gross pathology:

There were no findings during gross necropsy in any of the animals at the end of study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results, the acute dermal toxicity of Methyl iodourcil was estimated to be above 2000 mg/kg and therefore classified as a Hazard Category of 5 according to Globally Harmonized System (GHS). However, since category 5 for acute dermal tox has not been adopted by the EU, the classification will be GHS criteria not met.

Executive summary:

Objective
The study was performed to assess the acute dermal toxicity of methyl iodouracil in  the Sprague Dawley rat.  The method was designed to meet the guidelines for the Testing of Chemicals - Acute Dermal Toxicity (TG402) published by the Ministry of Environmental Protection of Peoples Republic of China in the year 2013. 

General Procedure
A limit test at one dose level of 2000 mg/kg bw was carried out via a dermal route in a group of 10 animals (5 male, 5 female).  Clinical observations were performed once during the first 30 mins and at 1, 2 and 4 hours, then once each day for 14 days. Individual weights were determined within 24 hours after arrival, at grouping, on Day 0, Day 7 and Day 14. At the end of the test, a gross necroscopy was performed on all animals under test.

Results

Mortality: No deaths or moribund states were observed during the study. 

Clinical observations: There were no abnormal findings during the study. 

Skin Reactions: No signs of dermal irritation were observed during the study.

Body Weights:All animals gained weight over the course of the study.

Gross necropsy: There were no findings during gross necropsy. 

Conclusions: Based on the results, the acute dermal toxicity of Methyl iodourcil was estimated to be above 2000 mg/kg and therefore classified as a Hazard Category of 5 according to Globally Harmonized System (GHS).