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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
data is from peer-reviewed journal

Data source

Referenceopen allclose all

Reference Type:
other: authoritative database
Title:
Acute oral toxicity study of Copper,[tetrahydrogen-3,3'-[(3,3'-dihydroxy-4,4'-biphenylylene)bis(azo)]bis[5-amino-4-hydroxy-2,7-naphthalenedisulfonato](4-)]di-,tetrasodium salt (7CI) (28407-37-6) in rat
Author:
U.S. National Library of Medicine
Year:
2017
Bibliographic source:
Chemidplus Database,U.S. National Library of Medicine,2017
Reference Type:
review article or handbook
Title:
Acute oral toxicity study of Copper,[tetrahydrogen-3,3'-[(3,3'-dihydroxy-4,4'-biphenylylene)bis(azo)]bis[5-amino-4-hydroxy-2,7-naphthalenedisulfonato](4-)]di-,tetrasodium salt (7CI) (28407-37-6) in rat
Author:
S. Gangolli
Year:
1999
Bibliographic source:
The Dictionary of Substance and their effects,2nd edition,vol.2 (part 6)
Reference Type:
secondary source
Title:
Acute Oral Toxicity Study
Author:
National Technical Reports Library
Year:
1972
Bibliographic source:
National Technical Reports Library, Fiche No. OTS 215154,1972
Reference Type:
secondary source
Title:
Acute oral toxicity study of Copper,[tetrahydrogen-3,3'-[(3,3'-dihydroxy-4,4'-biphenylylene)bis(azo)]bis[5-amino-4-hydroxy-2,7-naphthalenedisulfonato](4-)]di-,tetrasodium salt (7CI) (28407-37-6) in rat
Author:
RTECS
Year:
2018
Bibliographic source:
RTECS (registry of toxic effect of chemical substance database ), 2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Acute Oral toxicity test was carried out to study the effects of Copper,[tetrahydrogen-3,3'-[(3,3'-dihydroxy-4,4'-biphenylylene)bis(azo)]bis[5-amino-4-hydroxy-2,7-naphthalenedisulfonato](4-)]di-,tetrasodium salt (7CI) (28407-37-6) on rats.
GLP compliance:
not specified
Test type:
other: no data available
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (IUPAC name): Copper,[tetrahydrogen-3,3'-[(3,3'-dihydroxy-4,4'-biphenylylene)bis(azo)]bis[5-amino-4-hydroxy-2,7-naphthalenedisulfonato](4-)]di-,tetrasodium salt (7CI)
- Common name: Direct Blue 218
- Molecular formula: C32H20Cu2N6Na4O16S4
- Molecular weight: 1087.82 g/mol
- Smiles notation: c12c3c(c(S(=O)(=O)[O-])cc1cc(S(=O)(=O)[O-])cc2N)N=Nc1ccc(cc1O[Cu]O3)c1cc2c(N=Nc3c(cc4c(c3O[Cu]O2)c(cc(c4)S(=O)(=O)[O-])N)S(=O)(=O)[O-])cc1.[Na+].[Na+].[Na+].[Na+]
- InChl: 1S/C32H24N6O16S4.2Cu.4Na/c33-19-11-17(55(43,44)45)5-15-9-25(57(49,50)51)29(31(41)27(15)19)37-35-21-3-1-13(7-23(21)39)14-2-4-22(24(40)8-14)36-38-30-26(58(52,53)54)10-16-6-18(56(46,47)48)12-20(34)28(16)32(30)42;;;;;;/h1-12,39-42H,33-34H2,(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54);;;;;;/q;2*+2;4*+1/p-8/b37-35-,38-36-;;;;;;
- Substance type: Organic
Specific details on test material used for the study:
- Name of test material (as cited in study report):Solantine Blue 10GL
- Molecular formula :C32H20Cu2N6Na4O16S4
- Molecular weight :1087.82 g/mol
- Substance type:organic

Test animals

Species:
rat
Strain:
other: Albino SASCO
Sex:
male/female
Details on test animals and environmental conditions:
Details on test animal
TEST ANIMALS
- Weight at study initiation: 190 to 304 grams
- Fasting period before study: the animals were fasted overnight
- Housing: The animals were individually housed in metal, wire-bottomed cages elevated above the droppings.
- Diet (e.g. ad libitum): Purina Laboratory Chow was provided ad libitum
- Water (e.g. ad libitum): water was provided ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: deionized water
Details on oral exposure:
Details on exposure
VEHICLE
- Amount of vehicle (if gavage): 50% w/w
MAXIMUM DOSE VOLUME APPLIED: 6330 mg/kg bw

DOSAGE PREPARATION (if unusual):test substance was soluble in deionized water
Doses:
2520, 3170, 3990, 5020 and 6330 mg/kg bw
No. of animals per sex per dose:
Total: 25 animals
Control animals:
not specified
Details on study design:
Details on study design
- Duration of observation period following administration: 14 days
- Frequency of observations :
Gross pathology: The animals were observed for gross effect at regular intervals on the day of dosing and daily thereafter for 14 days.
- Frequency of weighing: Following the observation period, all surviving animals were weighed.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
The acute oral LD50 calculated by the method of Weil, C.S.

Results and discussion

Preliminary study:
Preliminary test:
the actual LD50 determination, exploratory doses were administered to six rats to estimate the order of toxicity of the test material. Based on the results of the preliminary assay, groups of five rats were dosed at levels designed to blanket the toxicity range as follows: 2520, 3170, 3990, 5020 and 6330 mg/kg bw.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 290 mg/kg bw
Based on:
test mat.
95% CL:
2 720 - 3 980
Remarks on result:
other: 50% mortality was observed
Mortality:
50% mortality was observed at dose 3290 mg/kg bw in treated animals
Clinical signs:
the following clinical signs of toxicity were observed Prostration, labored breathing, proneness, malaise, blue-black diarrhea, ptosis, morbidity, lethargy and weakness.
These appeared between 45 minutes and 6 hours after dosing .Surviving animals were normal within 6 days after dosing.
Body weight:
Final bodyweight records of survivors at termination showed weight gains within expected limits except in one animal at the 5020 mg/kg body weight level which showed no gain.
Gross pathology:
Gross necropsy of animals which succumbed showed generalized congestion of the lung,liver, kidneys and adrenal glands.
In all animals, tissues from all major organ systems and muscles were dyed blue to green by the compound. The color level was dose dependent. This dying effect was observed in muscle- and tendon.
Gross necropsy of animals sacrificed at termination showed no tissue damage from the administration of the compound except at the 5020 mg/kg body weight dosage. The two animals surviving at this level showed some gross indication of liver damage.
Other findings:
no data

Any other information on results incl. tables

Table 1: Time of Death Following Dosage

Dosage

Level

gm/kg

(Days)

%

mortality

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2.52

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0

3.17

0/5

1/5

1/5

1/5

1/5

1/5

1/5

1/5

1/5

1/5

2/5

2/5

2/5

2/5

40

3.99

0/5

2/5

4/5

4/5

4/5

4/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

100

5.02

0/5

2/5

3/5

3/5

3/5

3/5

3/5

3/5

3/5

3/5

3/5

3/5

3/5

3/5

60

6.33

0/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

100

*Specific gravity = 1.299 at 23° Centigrade

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Conclusions:
The lethal concentration (LD50) value for acute oral toxicity test was considered to be 3290 mg/kg bw,when male and female albino SASCO rats were treated with Copper,[tetrahydrogen-3,3'-[(3,3'-dihydroxy-4,4'-biphenylylene)bis(azo)]bis[5-amino-4-hydroxy-2,7-naphthalenedisulfonato](4-)]di-,tetrasodium salt (7CI) (28407-37-6) orally via gavage.
Executive summary:

Acute oral toxicity study was done in Male and female albino SASCO rats (SASCO strain) weighing 190 to 304 grams .Each animal was examined and only healthy animals were used on this study. The animals were individually housed in metal, wire-bottomed cages elevated above the droppings.Prior to dosing, the animals were fasted overnight.food and water was provided ad libitum.Prior to the actual LD50 determination, exploratory doses were administered to six rats to estimate the order of toxicity of the test material. Based on the results of the preliminary assay, groups of five rats were dosed at levels designed to blanket the toxicity range as follows: 2520, 3170, 3990, 5020 and 6330 mg/kg bw.The test material was prepared as a 50% weight/weight dilution indeionized water. The animals were observed for gross effect at regular intervals on the day of dosing and daily thereafter for 14 days. Animals which succumbed were necropsied. Following the observation period, all surviving animals were weighed, sacrificed and necropsied. The following clinical signs of toxicity were observed Prostration, labored breathing, proneness, malaise, blue-black diarrhea, ptosis, morbidity, lethargy and weakness. These appeared between 45 minutes and 6 hours after dosing .Surviving animals were normal within 6 days after dosing. Final bodyweight records of survivors at termination showed weight gains within expected limits except in one animal at the 5020 mg/kg body weight level which showed no gain. Gross necropsy of animals which succumbed showed generalized congestion of the lung,liver, kidneys and adrenal glands. In all animals, tissues from all major organ systems and muscles were dyed blue to green by the compound. The color level was dose dependent. This dying effect was observed in muscle- and tendon.Gross necropsy of animals sacrificed at termination showed no tissue damage from the administration of the compound except at the 5020 mg/kg body weight dosage. The two animals surviving at this level showed some gross indication of liver damage.Hence, Thelethal concentration (LD50) valuefor acute oral toxicity testwas considered to be3290mg/kg bw,when male and female albino SASCO rats were treated with Copper,[tetrahydrogen-3,3'-[(3,3'-dihydroxy-4,4'-biphenylylene)bis(azo)]bis[5-amino-4-hydroxy-2,7-naphthalenedisulfonato](4-)]di-,tetrasodium salt (7CI) (28407-37-6) orally via gavage.