Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
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 secondary source

Data source

Referenceopen allclose all

Reference Type:
other: authoritative database
Title:
Acute Dermal Toxicity in Rats
Author:
U.S. National Library of Medicine
Year:
2017
Bibliographic source:
HSDB (Hazardous Substances Data Bank); US national Library of Medicine,2017
Reference Type:
secondary source
Title:
Acute Dermal toxicity in rabbits
Author:
National Technical Reports Library
Year:
1982
Bibliographic source:
National Technical Reports Library, Fiche No. OTS 206237,1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Acute dermal 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 rabbits.
GLP compliance:
not specified
Test type:
other: no data
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):Lumisol blue VG
- Molecular formula :C32H20Cu2N6Na4O16S4
- Molecular weight :1087.82 g/mol
- Substance type:organic
- Physical state:Dark Grey Powder
- Purity :100%

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Details on test animal
TEST ANIMALS
- Age at study initiation: approximately 8 to 11 weeks
- Housing: The rabbits were individually housed in elevated wire mesh cages in temperature controlled rooms reserved exclusively for rabbits on acute tests
- Diet (e.g. ad libitum): Purina Rabbit Chow was provided ad libitum
- Water (e.g. ad libitum): water was provided ad libitum
- Acclimation period:7 days

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure: The test substance was applied to the the intact and abraded skin.
-Type of wrap if used: The test site was covered with gauze and the trunk was wrapped with impervious material for 24 hours.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test site was washed with warm tap water

Details on exposure
VEHICLE
- Amount of vehicle (if gavage): 50% w/v

DOSAGE PREPARATION (if unusual):test substance was soluble in distilled water
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Total: 4 animals
2000 mg/kg bw:2 male and 2 female
Control animals:
not specified
Details on study design:
Details on study design
- Duration of observation period following administration: 14 days
- Frequency of observations : Skin sites were read again at 7 and 14 days. The rabbits were observed daily for 14 days for signs of toxicity and mortality.
-frequency of weighing: Body weights were recorded pretest and at 7 and 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights
Statistics:
no data

Results and discussion

Preliminary study:
no data
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
No mortality was observed at dose 2000 mg/kg bw
Clinical signs:
Animal 1 - Diarrhea, days 10 and 11; bloated abdomen, day 11:Few feces in pan, days 11 and 12.
Animal 2 - Lethargy, day 12.
Body weight:
Changes in body weight were observed
Gross pathology:
Necropsy findings concluded that all animals appeared normal.
Other findings:
no data

Any other information on results incl. tables

TABLE 1:AcuteDermalToxicity in Rabbits

Individual Body Weights and Skin Grades

Rabbit Number

Sex

Weights - kg

Redness

Edema

0

7

14

25H

7

14

25H

7

14

1

M

2.8

2.8

2.8

0

0

0

0

0

0

2ab

M

2.5

2.7

2.7

0

0

0

0

0

0

3

F

2.2

2.4

2.7

0

0

0

0

0

0

4ab

F

2.3

2.5

2.7

0

0

0

0

0

0

ab = abraded

Evaluation of Skin Reactions

value

Erythema & Eschar Formation:

     No erythema

     Very slight erythema (barely perceptible)

     Well defined erythema

     Moderate to severe erythema

     Severe erythema (beet redness) to slight eschar formation (injuries in depth)

 

0

1

2

3

4

Ederra Formation:

    No edema

    Very slight edema (barely perceptible)

    Slight edema (edges of area well defined by definite raising)

    Moderate edema (raised approximately 1 millimeter)

    Severe edema (raised more than 1 millimeter and extending beyond the area of exposure)

 

0

1

2

 

3

 

 

4

 

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Conclusions:
The LD50 value was considered to be >2000 mg/kg bw,when male and female New Zealand white rabbits were occlusively 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) by dermal application following 14 days of observation period.
Executive summary:

In acute dermal toxicity study, male and femaleNew Zealand white rabbitswere occlusively 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) in the concentration of 2000 mg/kg bw by dermal application.Distilled water was used as vehicle.Twenty-four hours prior to dosing the backs of the rabbits were clipped free of fur with an Oster ANG-RA clipper head designed specifically for clipping rabbits. The rabbits were returned to their cages overnight. Just prior to dosing, the backs of even-numbered rabbits were abraded with a 21 gauge bent tip needle. The abrasions, made every 2 to 3 cm longitudinally, scratched the stratum corneum but did not disturb the derma or produce bleeding.The test site was covered with gauze and the trunk was wrapped with impervious material for 24 hours.Following removal of the binder at 24 hours. The test site was washed with warm tap water. One hour after washing, the test sites were graded for skin irritation according to the attached scale. Skin sites were read again at 7 and 14 day.No mortality was observed in treated rabbits at dose 2000 mg/kg bw.Clinical signs such asDiarrhea, bloated abdomen, Few feces in pan and Lethargy was observed in treated rabbits. Changes in body weight were observed. Necropsyfindings concluded that all animals appeared normal.Hence,The LD50 value was considered to be >2000 mg/kg bw,when 2male and 2 female New Zealand white rabbitswere occlusively 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)by dermal application following 14 days of observation period.