2-Pyridinecarboxamide, 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March to April 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide

EC Number:

608-209-4

Cas Number:

284461-73-0

Molecular formula:

C21 H16 Cl F3 N4 O3

IUPAC Name:

4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide

Constituent 2

Reference substance name:

2-Pyridinecarboxamide, 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-

IUPAC Name:

2-Pyridinecarboxamide, 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-

Constituent 3

Reference substance name:

4-{ 4-[( {[ 4-chloro-3-(trifluoromethyl)phenyl]amino }carbonyl)amino ]phenoxy }-Nmethyl-2-pyridinecarboxamide

IUPAC Name:

4-{ 4-[( {[ 4-chloro-3-(trifluoromethyl)phenyl]amino }carbonyl)amino ]phenoxy }-Nmethyl-2-pyridinecarboxamide

Details on test material:

- Purity not specified

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan GmbH (Horst, Netherlands)
- Age at study initiation: 8-14 weeks
- Weight at study initiation: 276-308 g for males and 235-259 g for females
- Fasting period before study: none
- Housing: individually in polycarbonate cages on low dust wood granulate bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 30 cm2
- % coverage: approx. 10
- Type of wrap if used: gauze patch fixed with an elastic adhesive tape pervious to air

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with tepid water using soap
- Time after start of exposure: approx. 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 18.4-20.5 mg/cm2 (males) and 15.7-17.3 mg/cm2 (females)

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: several times on the day of application as well as at least once daily during observation period (clinical signs, mortality); surviving animals were weighed individually at application, after one week and at the end of the 14-day observation period.
- Necropsy of survivors performed: yes

Statistics:

no (limit test)

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:

All male and female animals survived the treatment.

Clinical signs:

other: At 2000 mg/kg bw reddish encrustations of the nose were observed in all animals. In addition, one female displayed piloerection and sunken flanks on day 15.

Gross pathology:

The necropsies performed at the end of the study revealed no particular findings.

Other findings:

no

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Single semiocclusive administration of 2000 mg/kg bw for 24 hours was tolerated without mortalities, effects on body weight gain or gross pathological findings. Clinical signs (reddish encrustations of the nose) were observed in all male and female animals. In addition, one female displayed piloerection and sunken flanks on day 15.

Executive summary:

In an acute dermal toxicity study according to OECD Guideline 402, groups of Wistar rats (5/sex) were dermally exposed to Bay 43-9006 at a dose of 2000 mg/kg bw for 24 h under semiocclusive conditions and observed for 14 days. The administration was tolerated without mortalities, effects on body weight gain or gross pathological findings. Clinical signs (reddish encrustations of the nose) were observed in all male and female animals. In addition, one female displayed piloerection and sunken flanks on day 15. The dermal LD50 was >2000 mg/kg bw.