Registration Dossier

Administrative data

Description of key information

Acute toxicity: via oral route

The LD50 of the test material was greater than 2000 mg/kg B.W. (OECD TG401).

Acute toxicity: via dermal route

The LD50 of Everdirect SH12 was greater than 2000 mg/kg B.W. (OECD TG402).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Range finder study only, but done to good standards and GLP
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
The substance tested was reported as the trade name Benzanil Rubine 2BL which is Direct Red 83-1. Purity was cited at 55-60% (impurities sodium chloride and water). Although dose levels do not appear to have been adjusted for purity, the absence of findings at 2000 mg/kg means that even if adjusting for purity, the disciminating dose is > 1000 mg/kg and classification is not needed. No further animal testing is justified.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Range-finding study
Dose level: 2000 mg/kg bw, one male and one female

Main study
Dose level: 2000 mg/kg bw, 5 males and 5 females
Control animals:
no
Details on study design:
Procedure
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

Range-finding study
The animals were observed for deaths or overt signs of toxicity, ½, 1, 2 and 4 hr after dosing and subsequently once daily for 5 days.

Main study
The animals were observed for deaths or overt signs of toxicity, ½, 1, 2 and 4 hr after dosing and subsequently once daily for 14 days.
Individual bodyweights were recorded prior to dosing on Day 0 and Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Preliminary study:
Range-finding study
There were no deaths or clinical signs of toxicity.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths after 14 days.
Clinical signs:
Noisy respiration was noted in one female up to two hours after treatment. Red stained faeces was noted in one female four hours after treatment and in all animal at the Day 1 observation. Red stained fur was commonly noted in the females at the 4 hours and Day 1 observations and persisted in one female up to the Day 4 observation.
No other clinical signs of toxicity were noted.
Body weight:
All animals showed expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test material, 2076 BENZANIL RUBINE 2BL, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bw.
Executive summary:

The substance tested was reported as the trade name Benzanil Rubine 2BL which is Direct Red 83-1.  Purity was cited at 55-60% (impurities sodium chloride and water).  Although dose levels do not appear to have been adjusted for purity, the absence of findings at 2000 mg/kg means that even if adjusting for purity, the disciminating dose is > 1000 mg/kg and classification is not needed. No further animal testing is justified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 11, 2016 to December 07, 2016. 24 hour exposure.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
- Source: BioLASCO Taiwan Co. Ltd.
- Age at study initiation: about 7 weeks old
- Housing: Male and female rats were fed, respectively. Two rats per cage in an autoclaved polyethylene cage.
- Acclimation period: 7 Days
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 15%
- Photoperiod: 12 hrs dark / 12 hrs light
Type of coverage:
occlusive
Vehicle:
olive oil
Duration of exposure:
24 hours
Doses:
2000 mg/kg B.W.
No. of animals per sex per dose:
For male: six
For female: six
Control animals:
yes, concurrent vehicle
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level

Table 1. Body weight of the rats in the study period

Group

Animal I.D.

Dosing volume (mL)

Body weight (g)

Weight chenges(g)

Day 1

Day 14

Control

01M

0.6

284.0

337.7

+53.7

02M

0.6

286.1

336.1

+50.0

03M

0.6

289.5

362.1

+72.6

04M

0.6

294.9

374.2

+79.3

05M

0.6

297.6

360.0

+62.4

06M

0.6

292.3

386.0

+93.7

Test

07M

0.6

284.8

340.0

+55.2

08M

0.6

286.3

345.0

+58.7

09M

0.6

291.7

340.0

+48.3

10M

0.6

295.1

350.0

+54.9

11M

0.6

295.5

340.0

+44.5

12M

0.6

295.2

360.0

+64.8

Control

13F

0.4

206.2

241.7

+35.5

14F

0.4

211.8

251.1

+39.3

15F

0.4

216.4

239.4

+23.0

16F

0.4

214.7

254.8

+40.1

17F

0.4

218.1

267.5

+49.4

18F

0.4

219.7

260.4

+40.7

Test

19F

0.4

211.0

246.3

+35.3

20F

0.4

213.1

252.6

+39.5

21F

0.4

214.6

241.1

+26.5

22F

0.4

214.6

258.7

+44.1

23F

0.4

219.2

265.1

+45.9

24F

0.4

221.3

256.2

+34.9

Table 2. Clinical observation of the rats

Animal I.D.

Clinical sign observation

30 mins

4 hours

D2

D3

D4

D5

D6

D7

D8

D9

D10

D11

D12

D13

D14

01M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

02M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

03M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

04M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

05M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

06M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

07M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

08M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

09M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

10M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

11M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

12M

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

13F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

14F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

15F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

16F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

17F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

18F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

19F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

20F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

21F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

22F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

23F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

24F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

DX: Day X in the study period

N: Normal

 

Table 3. Results of gross necropsy examination

Animal I.D.

Dose

Gross lesion

01M

No significant lesion founded

02M

No significant lesion founded

03M

No significant lesion founded

04M

No significant lesion founded

05M

No significant lesion founded

06M

No significant lesion founded

07M

2000 mg/kg B.W.

No significant lesion founded

08M

No significant lesion founded

09M

No significant lesion founded

10M

No significant lesion founded

11M

No significant lesion founded

12M

No significant lesion founded

13F

No significant lesion founded

14F

No significant lesion founded

15F

No significant lesion founded

16F

No significant lesion founded

17F

No significant lesion founded

18F

No significant lesion founded

19F

2000 mg/kg B.W.

No significant lesion founded

20F

No significant lesion founded

21F

No significant lesion founded

22F

No significant lesion founded

23F

No significant lesion founded

24F

No significant lesion founded

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 402 test method, the LD50 of Everdirect SH12 was greater than 2000 mg/kg B.W.. Therefore, Everdirect SH12 was Category 5 based on GHS criteria.
Executive summary:

This test using the procedures outlined in the SuperLab for M62-151100081001EN which is based on the SOP (SOPP-342) for the OECD 402 and OECD 402 (OECD, 1987). Six male and six female Sprague-Dawley rats for each group were used in limit test. For Test group, 12Sprague-Dawley ratsweredermally dosed with 2000 mg/kg B.W. of Everdirect SH12. All animals tolerated the test article well with increasing body weights and no mortality or gross lesions findings reported. In absence of mortality or other significant clinical signs of toxicity, LD50 of Everdirect SH12 was greater than 2,000 mg/kg B.W..

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Acute toxicity: via oral route

The study was performed to assess the acute oral toxicity of the test material, BENZANIL RUBINE 2BL, in the Sprague-Dawley CD strain rat. The test concentration was 2000 mg/kg bw, and 5 males and 5 females were tested. After 14 days, there were no deaths. No other clinical signs of toxicity were noted. All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy.

Acute toxicity: via dermal route

Six male and six female Sprague-Dawley rats for each group were used in limit test. For Test group, 12 Sprague-Dawley rats were dermally dosed with 2000 mg/kg B.W. of Everdirect SH12. All animals tolerated the test article well with increasing body weights and no mortality or gross lesions findings reported. In absence of mortality or other significant clinical signs of toxicity, LD50 of Everdirect SH12 was greater than 2,000 mg/kg B.W..

 

Justification for classification or non-classification