4-[(1-butyl-5-cyano-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridyl)azo]-N-(2-ethylhexyl)benzenesulphonamide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 12, 2014 - June 04, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402.

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay - Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515-519, 69120 Heidelberg

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-[(1-butyl-5-cyano-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridyl)azo]-N-(2-ethylhexyl)benzenesulphonamide

EC Number:

259-571-1

EC Name:

4-[(1-butyl-5-cyano-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridyl)azo]-N-(2-ethylhexyl)benzenesulphonamide

Cas Number:

55290-62-5

Molecular formula:

C25H35N5O4S

IUPAC Name:

4-[(1-butyl-5-cyano-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]-N-(2-ethylhexyl)benzenesulfonamide

Details on test material:

- Physical state: Solid / yellow
- Storage condition of test material: Room temperature; protect against humidity

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: mean body weights m: 229.6g, f: 205.6g
- Housing: Single housing in Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: May 19, 2014 - June 03, 2014

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk, about 40 cm²
- % coverage: at least 10% of the body surface
- Type of wrap if used:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing of the application site with warm water
- Time after start of exposure: 24h

VEHICLE
- Amount(s) applied (volume or weight with unit): 6.67 ml/kg bw
- Concentration (if solution): 30g/100ml

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Details on study design:

- Duration of observation period following administration: 14 days
- Mortality: A check for any dead or moribund animals was made at least once each workday.
- Frequency of observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
- Frequency of weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times (see results) until the last day of observation.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred

Clinical signs:

other: No systemic clinical signs were observed during clinical examination. In all five male animals strong yellowish discoloration of the application area was noted on study day 1, which prevented evaluation of erythema. The strong discoloration decreased to s

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of the test article after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Executive summary:

In an acute dermal toxicity study (Limit Test) according to OECD guideline 402 performed under GLP, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test item (as suspension in corn oil Ph.Eur.) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred and no clinical signs were observed. Due to the strong yellowish discoloration of the application site on study day 1 no erythema could be determined. Thereafter the application area was slight yellowish discolored from study day 2 until study day 9 or 14, respectively. No erythema was noted. The mean body weight of the male animals increased within the normal range throughout the study period. The body weight of the female animals only slightly increased or stagnated during the first observation week, probably due to the bandage procedure, but increased within the normal range during the second week. Due to the fact that stagnation of body weight is commonly known for females dermally applied, this stagnation is considered to be unspecific. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw.