N,N'-[6,13-diacetamido-2,9-diethoxy-3,10-triphenodioxazinediyl]bis(benzamide)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

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:

N,N'-[6,13-diacetamido-2,9-diethoxy-3,10-triphenodioxazinediyl]bis(benzamide)

EC Number:

241-734-3

EC Name:

N,N'-[6,13-diacetamido-2,9-diethoxy-3,10-triphenodioxazinediyl]bis(benzamide)

Cas Number:

17741-63-8

Molecular formula:

C40H34N6O8

IUPAC Name:

N,N'-(6,13-diacetamido-2,9-diethoxy[1,4]benzoxazino[2,3-b]phenoxazine-3,10-diyl)dibenzamide

Test material form:

solid: nanoform

Specific details on test material used for the study:

- Purity: 98.3%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 243 - 203g
- Housing: singly
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5d
- Fasting: 16h before administration

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

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

corn oil

Remarks:

suspension

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal and dorso-lateral parts of the trunk
- % coverage: 10
- Type of wrap if used: semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 6.67 g/kg bw (paste)
- For solids, paste formed: yes

Duration of exposure:

24h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: days 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred.

Clinical signs:

other: No signs of systemic toxicity were observed in the animals.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Other findings:

Violet discoloration of the skin at the application site (evaluation of erythema formation was not possible)

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of the test substance 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), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test substance (as suspension/paste 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.

No signs of systemic toxicity were observed in the animals.

The following test item-related local effects were recorded during the course of the study, local effects occurred within the first 3 days after administration:

- Violet discoloration of the skin at the application site (evaluation of erythema formation was not possible)

- No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

The mean body weight of the male animals increased within the normal range throughout the study period. In the female group 4 animals showed a stagnation or marginal loss of body weight during the first week, but body weights were in a normal range during the second week.

This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth. Due to the fact that stagnation of body weight is commonly known for females dermally applied, this stagnation is considered to be unspecific. Accordingly, the acute dermal median lethal dose (LD50) was determined to be greater than 2000 mg/kg bw.