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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2020
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3,4,6,7,9,9b-heptaazaphenalene-2,5,8-triamine
EC Number:
216-122-4
EC Name:
1,3,4,6,7,9,9b-heptaazaphenalene-2,5,8-triamine
Cas Number:
1502-47-2
Molecular formula:
C6H6N10
IUPAC Name:
1,3,4,6,7,9,9b-heptaazaphenalene-2,5,8-triamine
Test material form:
solid
Details on test material:
Test Item Name: Exolit 775
Sample Number: Ba-Ha-19-025-1; Deflam 20 20151106 JOB D02441
CAS No.: 1502-47-2

Chemical name (IUPAC): 1,3,4,6,7,9,9b-Heptaazaphenalene-2,5,8-triamine/Melem
CAS No.: 1502-47-2
Sample No.: Ba-Ha-19-025-1; Deflam 20 20151106 JOB D02441
Manufactured Date: 2019-09-06
Expiry Date: 2034-09-06
Purity as per Certificate of Analysis: 95.75%
Physical Appearance: Solid White
Storage Conditions: Cool and Dry (+2 to +8 °C)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Environmental conditions: Rats were housed under standard laboratory conditions, air conditioned with adequate fresh air supply (13.4 air changes/hour). Environment: with temperature 21 to 25°C, relative humidity 65 to 68%, with 12 hours light and 12 hours dark cycle. The maximum and minimum temperature and relative humidity in the experimental room were recorded once daily. The relative humidity in the experimental room was calculated from dry and wet bulb temperature recordings.

Housing: Rats were housed in the groups in standard polysulfone cages (Size: approximately: L 425 x W 266 x H 185 mm), with stainless steel top grill having facilities for pelleted food and drinking water. Additionally, polycarbonate rat huts were placed inside the cage as an enrichment object and were changed along with the cage at least once a week. Bedding material: Steam sterilized corn cob was used and changed along with the cage at once a week.

Diet: ad libitum: Hypro Rat & Mice pellet feed, manufactured by Krishna Valley Agrotech LLP, MIDC Kupwad block, Sangli, Maharashtra, India was provided to animals.
Water: ad libitum: Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd, Mumbai 400 001, India, was provided to animals in polycarbonate bottles with stainless steel sipper tubes.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
The prepared test item dose formulations were administered at the dose volume of 10 mL/kg bodyweight to attain the dose of 300 mg/kg body weight (G1–FTS and G1-STS) and 2000 mg/kg body weight (G2–FTS and G2-STS) as a single oral gavage to overnight fasted rats (16 to 18 hours). Each animal was administered orally by gavage using disposable plastic syringe attached with metal feeding cannula. Food was offered about 3 to 4 hours after dosing. Water was not withheld
Doses:

Dose selection

300 mg/kg:
- As there were no information available on the LD50 of test item, hence the test was started as per Annex 2c of the OECD 423 test guideline. The starting dose of 300 mg/kg body weight.
- As there was no test item-related mortality observed at the starting dose of 300 mg/kg body weight (G1- FTS), the test was continued with same dose with three additional female rats, second treatment step (G1-STS) and all rats survived.

2000 mg/kg
As per scheme three additional animals dosed with higher dose of 2000 mg/kg body weight (FTS) and all rats survived, the test was confirmed with three additional animals with the same dose of 2000 mg/kg body weight (STS) all the rats survived. As per scheme, no further test is needed. Hence testing was stopped and the LD50 cut-off value was arrived at.
No. of animals per sex per dose:
6 animals (females) / treatment step
Control animals:
no
Details on study design:
Group Dose
(mg/kg) No. of
Rats Sex Rat numbers
From To
G1 (FTS) 300 3 Female Rw5550 Rw5552
G1 (STS) 300 3 Female Rw5553 Rw5555
G2 (FTS) 2000 3 Female Rw5556 Rw5558
G2 (STS) 2000 3 Female Rw5559 Rw5561
FTS: First treatment step STS: Second treatment step

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Nil
Clinical signs:
Nil
Body weight:
G1 - [300 mg/kg body weight - FTS and STS]: The body weights of all the rats increased throughout the observation period.
G2- [2000 mg/kg body weight - FTS and STS]: The body weights of all the rats increased throughout the observation period
Gross pathology:
There were no gross pathological changes at necropsy

Any other information on results incl. tables

TABLE 1.  Body weight, body weight change and pre-terminal deaths

Group and

Dose

(mg/kg

body weight)

Rat

No.

Sex

Body weight (g)

No. dead/

 No. tested

Pre-terminal deaths

(%)

Initial

(Day 1)

8thday

Weight change

(day 8 – Initial)

15thday

Weight change          

(day 15 – Initial)

At Death

G1

(FTS)

300

 

Rw5550

F

199.9

218.3

18.4

231.5

31.6

NA

0/3

 

 

 

0

Rw5551

F

215.7

228.1

12.4

237.9

22.2

NA

Rw5552

F

210.0

223.3

13.3

243.1

33.1

NA

G1

(STS)

300

 

Rw5553

F

199.6

216.2

16.6

228.3

28.7

NA

0/3

 

0

Rw5554

F

197.8

221.7

23.9

229.9

32.1

NA

Rw5555

F

201.0

219.8

18.8

235.6

34.6

NA

F: Female   FTS: First Treatment Step       STS: Second Treatment Step       NA: Not Applicable

           

 

  TABLE 1 contd. Body weight, body weight change and pre-terminal deaths

 

Group and

Dose

(mg/kg

body weight)

Rat

No.

Sex

Body weight (g)

No. dead/

 No. tested

Pre-terminal deaths

(%)

Initial

(Day 1)

8thday

Weight change

(day 8 – Initial)

15thday

Weight change          

(day 15 – Initial)

At Death

G2

(FTS)

2000

 

Rw5556

F

199.8

218.1

18.3

231.8

32.0

NA

 

0/3

 

 

 

0

Rw5557

F

198.6

220.4

21.8

237.5

38.9

NA

Rw5558

F

210.3

223.6

13.3

241.2

30.9

NA

G2

(STS)

2000

 

Rw5559

F

195.0

203.8

8.8

228.7

33.7

NA

 

0/3

 

0

Rw5560

F

197.9

208.7

10.8

231.7

33.8

NA

Rw5561

F

197.6

205.0

7.4

224.5

26.9

NA

F:  Female FTS: First Treatment Step       STS: Second Treatment Step      NA: Not Applicable

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The registration substance was investigated for its acute oral toxicity according to the OECD Guideline 423. Six females rats each were treated at 300 mg/kg and at 2000 mg/kg. No effect was found. LD50 > 2000 mg/kg was obtained.
Executive summary:

The registration substance was investigated for its acute oral toxicity according to the OECD Guideline 423. Six females rats each were treated at 300 mg/kg and at 2000 mg/kg. No effect was found. LD50 > 2000 mg/kg was obtained.

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