Disperse Red 206

ディスパーズレッド206


[CAS No. 26630-87-5]

5'-[Bis(2-hydroxyethyl)amino]-2'-[(6-chlorobenzothiazol-2-yl)azo]benzanilide diacetate

5'-[ビス(2-ヒドロキシエチル)アミノ]-2'-[(6-クロロベンゾチアゾール-2-イル)アゾ]ベンツアニリドジアセタート

Molecular formula: C28H26ClN5O5S　Molecular weight: 580.06

ABSTRACT

Disperse red 206 was studied for oral toxicity in rats in a single dose toxicity test at doses of 0 and 2000 mg/kg, and a repeated dose toxicity test at doses of 0, 250, 500 and 1000 mg/kg/day, and in a repeated dose toxicity additional test at does of 0, 80 and 250 mg/kg/day for males only.

With regard to the single dose toxicity, no deaths occurred in the 2000 mg/kg group in both sexes. Males and females given 2000 mg/kg showed no signs or symptoms of toxicity. Abnormalities were not observed in body weight change or autopsy findings. The LD50 value was estimated to be 2000 mg/kg or more for both sexes.

With regard to the repeated dose toxicity, hematocrit and MCH were decreased in males given 500 mg/kg, and in males and females given 1000 mg/kg. At the end of the recovery period, the MCV and MCHC were decreased in males and females given 1000 mg/kg, and Hb was decreased in females given 1000 mg/kg. γ-Globulin was decreased in males given 250 mg/kg. At the end of the recovery period, inorganic phosphorus was increased in females given 1000 mg/kg.

Liver weights were increased in males given 250 mg/kg or more, and in females receiving 1000 mg/kg. Thymus weights were decreased in males and females given 500 mg/kg and ovary weights in females given 1000 mg/kg. At the end of the recovery period, liver weights were increased in males given 1000 mg/kg, while spleen weights in males given 1000 mg/kg and pituitary weights in females given 1000 mg/kg were decreased.

With regard to the additional repeated dose toxicity test, increase of liver weights and decrease of g-globulin were not observed in males given 80 or 250 mg/kg.

The NOELs are considered to be 80 mg/kg/day for males and 250 mg/kg/day for females.

Genotoxicity of Disperse Red 206 was studied by a reverse mutation test in bacteria. This substance was mutagenic in Salmonella typhimurium TA98 with and without an exogenous metabolic activation system.

Genotoxicity of Disperse Red 206 was studied by a chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

Disperse Red 206 induced structural chromosomal aberrations with short-term treatment at 5.0 mg/mL with metabolic activation. Moreover, it weakly induced polyploidy with all treatments.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:97.65 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Dosage:0 (vehicle), 2000 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:0.5 % Methylcellulose
GLP:Yes

　Test results:

No deaths occurred in the 2000 mg/kg group in ether sex. Males and females given 2000 mg/kg showed no signs or symptoms of toxicity. Abnormalities were not observed in body weight change or autopsy findings.

The LD50 value was estimated to be 2000 mg/kg or more for both sexes.

2. Repeated Dose Oral Toxicity 1)

Purity:97.65 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:Guideline for the 28-Day Repeated Dose Toxicity Test in Mammalian Species (Chemical Substances Control Law of Japan)
　Route:Oral (gavage)
　Dosage:0 (vehicle), 250, 500, 1000 mg/kg
　Number of animals/groupMales, 7; females, 7
　Vehicle:0.5 % Methylcellulose
　Administration period:Males and females, 28 days
　Terminal killing:Males and females, days 29 or 43
GLP:Yes

　Test results:

Hematocrit and MCH were decreased in males given 500 mg/kg, and in males and females given 1000 mg/kg. At the end of the recovery period, MCV and MCHC were decreased in males and females given 1000 mg/kg, and Hb was decreased in females given 1000 mg/kg.

γ-Globulin was decreased in males given 250 mg/kg. At the end of the recovery period, inorganic phosphorus was increased in females given 1000 mg/kg.

Liver weights were increased in males given 250 mg/kg or more, and females given 1000 mg/kg. Thymus weights were decreased in males and females given 500 mg/kg and ovary weights in females given 1000 mg/kg. At the end of the recovery period, liver weights were increased in males given 1000 mg/kg, while spleen weight in males given 1000 mg/kg and pituitary weights in females given 1000 mg/kg were decreased.

Red or dark green staining of the contents in the digestive tract (jejunum, ileum and cecum), and organs and tissues (jejunum, ileum, abdominal adipose tissues, and subcutaneous tissues throughout the body) was observed in males and females given 250 mg/kg or more. This staining was expected from the color of the test substance. At the end of the recovery period, similar staining in the subcutaneous tissues throughout the body, and adipose tissues in abdomen was observed.

The NOEL is considered to be below 250 mg/kg/day for both males and females.

3. Repeated Dose Oral Toxicity (Additional Test)1)

Purity:96.97 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:Guideline for the 28-Day Repeated Dose Toxicity Test in Mammalian Species (Chemical Substances Control Law of Japan)
　Route:Oral (gavage)
　Dosage:0 (vehicle), 80, 250 mg/kg
　Number of animals/groupMales, 7
　Vehicle:0.5 % Methylcellulose
　Administration period:Males 28 days
　Terminal killing:Males, day 29
GLP:Yes

　Test results:

Red or dark green staining of the contents of the digestive tract (ileum and cecum), and organs and tissues (ileum and abdominal adipose tissues) was observed in males given 250 mg/kg. Liver weight increase and g-globulin decrease were not observed in this additional test.

The NOEL, from the 28-day repeated dose toxicity test results is considered to be 80 mg/kg/day for males.

4. Genetic Toxicity

4-1. Bacterial test 2)

Purity:96.77 %
Test species/strain:Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 471
　Procedures:Pre-incubation method
　Solvent:Dimethyl sulfoxide
　Positive controls:-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98, WP2 uvrA), Sodium azide (TA1535) and 9-Aminoacridine (TA1537)
+S9 mix; 2-Aminoanthracene (five strains)
　Dosage:-S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate (five strains)
+S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate (five strains)
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:3 (1 for cytotoxicity test)
　Number of replicates:2 (3 for -S9 mix TA1537 and +S9 mix TA100 and plus 1 cytotoxicity test for all the strains)
GLP:Yes

　Test results:

This chemical induced gene mutations in S. typhimurium TA98 with and without S9 mix. Growth inhibition was not observed up to 5000 μg/plate in any strain, with or without S9 mix.

Genetic effects:
Salmonella typhimurium TA100, TA1535, TA1537
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

Salmonella typhimurium TA98
+?-
Without metabolic activation:[*][ ][ ]
With metabolic activation:[*][ ][ ]

Escherichia coli WP2 uvrA
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

4-2. Non-bacterial in vitro test (chromosomal aberration test)2)

Purity:96.77 %
Type of cell used:Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 473
　Vehicle:0.5 % Sodium carboxymethylcellulose
　Positive controls:-S9 mix; Mitomycin C
+S9 mix; Cyclophosphamide
　Dosage:-S9 mix (continuous treatment); 0, 0.44, 0.88, 1.8 mg/mL
-S9 mix (short-term treatment); 0, 0.63, 1.3, 2.5 mg/mL
+S9 mix (short-term treatment); 0, 1.3, 2.5, 5.0 mg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

Cells with structural chromosomal aberrations were significantly increased at a dose of 5.0 mg/mL with short-term treatment (frequencies:29.0 %). Moreover, polyploidy was significantly increased, but not dose-dependently, in all the test systems (frequencies:1.3-1.9 %).

Lowest concentration producing cytogenetic effects in vitro:
Without metabolic activation (continuous treatment):0.44 mg/mL (polyploidy)
Without metabolic activation (short-term treatment):2.5 mg/mL (polyploidy)
With metabolic activation (short-term treatment):2.5 mg/mL (polyploidy)
5.0 mg/mL (clastogenicity)

Genotoxic effects:
clastogenicitypolyploidy
+?-+?-
Without metabolic activation:[ ][ ][*][*][ ][ ]
With metabolic activation:[*][ ][ ][*][ ][ ]

1)The tests were performed by the Safety Research Institute for Chemical Compounds Co., Ltd., 363-24 Shin-ei, Kiyota-ku, Sapporo-shi, Hokkaido, 004-0839, Japan. Tel +81-11-885-5031 Fax +81-11-885-5313
2)The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257-8523, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627