2-Ethylanthraquinone

2-エチルアントラキノン


[CAS No. 84-51-5]

2-Ethyl-9,10-anthracenedione

2-エチル-9,10-アントラセンジオン

Molecular formula: C16H12O2　Molecular weight: 236.27

ABSTRACT

A single dose oral toxicity test of 2-ethylanthraquinone revealed an LD50 value of more than 2000 mg/kg for both sexes.

2-Ethylanthraquinone was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 10, 50 and 250 mg/kg. No deaths were observed in either sex. The density of erythrocytes was decreased in males given 10 mg/kg or more and in females given 250 mg/kg. In parallel, decreased hematocrit values, and increases in MCHC, the proportion of reticulocytes, the level of total bilirubin, hemosiderosis in the spleen and extramedullary hematopoiesis were found mainly in the 250 mg/kg group. Moreover, the animals of both sexes given 50 mg/kg and more demonstrated centrilobular hypertrophy of hepatocytes, together with anisonucleosis in severe cases. Thus, the NOELs for the 28-day repeat dose oral toxicity test of 2-ethylanthraquinone are considered to be less than 10 mg/kg/day for males and 10 mg/kg/day for females.

Reverse mutation assays using microorganisms (Salmonella typhimurium, Escherichia coli) were conducted to assess the potential of 2-ethylanthraquinone to induce gene mutations. 2-Ethylanthraquinone did not induce gene mutations in bacteria under the conditions of this study.

In vitro chromosomal aberration tests using cultured cells (CHL/IU) were conducted to assess the potential of 2-ethylanthraquinone to induce chromosomal aberrations. 2-Ethylanthraquinone induced chromosomal aberrations in cultured cells under the conditions of this study.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:99.16 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral(gavage)
　Doses:Males, 0(vehicle), 2000 mg/kg
Females, 2000 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:0.5 w/v% CMC Na containing 0.1 w/v% polysorbate 80
GLP:Yes

　Test results:

Brown urine attributable to the treatment with test substance was observed from 5 hours to 5 days after the administration in both sexes given 2000 mg/kg. Slight depression of body weight was observed in the 2000 mg/kg group of both sexes on the day after dosing. No effects were found at autopsy.

The LD50 value was concluded to be more than 2000 mg/kg for both sexes.

2. Repeat Dose Toxicity 1)

Purity:99.16 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:Guideline for 28-Day Repeated Dose Toxicity Test in Mammalian Species (Chemical Substances Control Law of Japan)
　Route:Oral(gavage)
　Doses:0(vehicle), 10, 50, 250 mg/kg/day
　Number of animals/group:Males, 10; females, 10(0, 250 mg/kg)
Males, 5; females, 5(10, 50 mg/kg)
　Vehicle:0.5 % CMC Na containing 0.1 % polysorbate 80
　Administration period:Males and females, 28 days
　Terminal kill:Males and females, on days 29 and 43
GLP:Yes

　Test results:

In the repeat dose study, no deaths were observed in either sex. On hematological examination, the density of erythrocytes and hematocrit values were decreased in the male animals of the 50 mg/kg group and in the animals of both sexes given 250 mg/kg. A decrease in the density of erythrocytes was also found in the male animals in the 10 mg/kg group, and the males given 50 mg/kg and more demonstrated increased MCHC. In animals of both sexes in the 250 mg/kg group, the ratio of reticulocytes to whole erythrocytes was increased, and blood coagulating time was prolonged in the male animals. In blood chemistry, animals of both sexes in the 250 mg/kg group showed an increase in the concentration of albumin, female animals showed increases in total protein, total cholesterol, triglyceride and total bilirubin, and male animals showed a decrease in the level of triglyceride. In females of the 50 mg/kg group, total bilirubin concentration was also increased. Increases in liver weight in animals of both sexes, spleen weight in female animals, and kidney weight in males were observed in the 250 mg/kg group. As major findings at the autopsy carried out at the end of administration period, animals of the 250 mg/kg group showed enlarged and dark colored livers. On histopathological examination, centrilobular hypertrophy of hepatocytes was found in animals of both sexes given 50 mg/kg and more, and the degree of this change tended to be dose-dependent. Moreover, the hepatocytes showed anisonucleosis in the 250 mg/kg group. In the 250 mg/kg group, hemosiderosis and extramedullary hematopoiesis in the spleen tended to be more prevalent than in the control group.

Thus, NOELs for the 28-day repeat dose toxicity are considered to be less than 10 mg/kg/day for males and 10 mg/kg/day for females.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:99.16 %
Test species/strains: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:DMSO
　Positive controls:-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98 and WP2 uvrA), Sodium azide (TA1535) and 9-Aminoacridine hydrochloride (TA1537)
+S9 mix; 2-Aminoanthracene (all strains)
　Doses:-S9 mix; 0, 156, 313, 625, 1250, 2500, 5000 μg/plate(all strains)
+S9 mix; 0, 2.44, 4.88, 9.77, 19.5, 39.1, 78.1, 156 μg/plate(TA100)
+S9 mix; 0, 156, 313, 625, 1250, 2500, 5000 μg/plate(TA1535, TA98, TA1537)
+S9 mix; 0, 39.1, 78.1, 156, 313, 625, 1250, 2500, 5000 μg/plate(WP2 uvrA)
+S9 mix(confirmative test, 1st); 0, 2.44, 4.88, 9.77, 19.5, 39.1, 78.1, 156, 313, 625, 1250, 2500, 5000 μg/plate(TA100)
+S9 mix(confirmative test, 2nd); 0, 156, 313, 625, 1250, 2500, 5000 μg/plate(TA100)
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:3
　Number of replicates:2
GLP:Yes

　Test results:

No increase in revertant colonies was observed in the test with either the non-activation method (-S9) or activation (+S9).

Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98, TA1537
+?-
　Without metabolic activation:[ ][ ][*]
　With metabolic activation:[ ][ ][*]

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

3-2. Non-bacterial in vitro test (chromosomal aberration test)2)

Purity:99.16 %
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
　Solvent:DMSO
　Positive controls:-S9 mix; Mitomycin C
+S9 mix; Cyclophosphamide
　Doses:-S9 mix(short-term treatment); 0, 40.0, 80.0, 160, 320, 640 μg/mL
+S9 mix(short-term treatment); 0, 591, 1181, 2362 μg/mL
+S9 mix(short-term treatment, confirmative test); 0, 37.5, 75.0, 150, 300, 600 μg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

Slight increase in chromosomal aberrations was observed in the test with the short-term treatment (-S9 and +S9).

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

1)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
2)The tests were performed by the Biosafety Research Center, Foods, Drugs and Pesticides(An-pyo Center), 582-2 Shioshinden, Fukude-cho, Iwata-gun, Shizuoka, 437-1213, Japan. Tel +81-538-58-1266 Fax +81-538-58-1393