[CAS No. 13936-21-5]

A repeated dose oral toxicity study of 2-pentylanthraquinone was conducted in rats according to OECD Test Guideline 407, at doses of 0, 3.75, 15 and 60 mg/kg. Salivation was observed in both sexes of the 60 mg/kg group. On hematological examination at the end of the dosing period, prothrombin time was prolonged in males of the 15 and 60 mg/kg groups. Necropsy revealed thickened forestomach mucosa in males of the 60 mg/kg group. Absolute and relative weights of the liver were increased in males of the 60 mg/kg group. Additionally, histological examination revealed centrilobular hypertrophy of hepatocytes in males of the 60 mg/kg group. In conclusion, the NOAEL is considered to be 3.75 mg/kg/day for males and 15 mg/kg/day for females.

Genotoxicity of 2-pentylanthraquinone was studied by a reverse mutation test in bacteria. This substance proved mutagenic in Salmonella typhimurium TA1537 with an exogenous metabolic activation system.

Genotoxicity of 2-pentylanthraquinone was studied by a chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells according to Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Test Guideline 473. Structural chromosomal aberrations and polyploidy was increased after the short-term (6 hr) treatment with metabolic activation.

1. Repeated Dose Oral Toxicity1)

Purity	:	98.6 %
Test species/strain	:	Rat/Crj:CD(SD)IGS
Test method	:	OECD Test Guideline 407
Route	:	Oral(gavage)
Dosage	:	0(vehicle), 3.75, 15, 60 mg/kg/day
Number of animals/group	:	Males, 10; females, 10(0, 60 mg/kg) Males, 5; females, 5(3.75, 15 mg/kg)
Vehicle	:	Corn oil
Administration period	:	Males and females, 28 days
Terminal killing	:	Males and females, days 29 or 43
GLP	:	Yes

　Test results:

Salivation was observed in both sexes of the 60 mg/kg group. On hematological examination at the end of the dosing period, prothrombin time was prolonged in males of the 15 and 60 mg/kg groups. Necropsy revealed thickened forestomach mucosa in males of the 60 mg/kg group. Absolute and relative weights of the liver were increased in males of the 60 mg/kg group. Additionally, histological examination revealed centrilobular hypertrophy of hepatocytes in males of the 60 mg/kg group.

At the end of the recovery period, the above changes observed at the end of the dosing period had disappeared.

There were no changes considered attributable to the test substance regarding body weight, food consumption, detailed clinical findings, functional testing, urinalysis, or blood biochemical examination.

In conclusion, the NOAEL is considered to be 3.75 mg/kg/day for males and 15 mg/kg/day for females under the conditions of this study.

2. Genetic Toxicity

2-1. Bacterial test 1)

Purity	:	98.6 %
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	:	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 (TA100, TA1535, TA98, WP2 uvrA), 0, 78.1, 156, 313, 625, 1250, 2500, 5000 μg/plate (TA1537)
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	3(1 for cytotoxicity test)
Number of replicates	:	2(plus 1 cytotoxicity test)
GLP	:	Yes

　Test results:

This chemical induced gene mutations in S. typhimurium TA1537 with 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, TA98, TA1535

	+	?	-
Without metabolic activation:	[ ]	[ ]	[*]
With metabolic activation:	[ ]	[ ]	[*]

Salmonella typhimurium TA1537

	+	?	-
Without metabolic activation:	[ ]	[ ]	[*]
With metabolic activation:	[*]	[ ]	[ ]

Escherichia coli WP2 uvrA

	+	?	-
Without metabolic activation:	[ ]	[ ]	[*]
With metabolic activation:	[ ]	[ ]	[*]

2-2. Non-bacterial in vitro test (chromosomal aberration test) 1)

Purity	:	98.6 %
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	:	Acetone
Positive controls	:	-S9 mix; Mitomycin C +S9 mix; Cyclophosphamide
Dosages	:	-S9 mix(short-term treatment); 0, 0.027, 0.040 0.060 mg/mL +S9 mix(short-term treatment); 0, 0.027, 0.040, 0.060 mg/mL
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	4(2: chromosome specimens, 2: measurement of growth rate)
GLP	:	Yes

　Test results:

Cells with structural chromosomal aberrations were increased dose-dependently after short-term (6 hr) treatment with metabolic activation (3.0-15.5 %). Polyploidy, including endoreduplicated cells, was increased with statistical significance and observed at the middle (0.040 mg/mL) and the high (0.060 mg/mL) doses with short-term treatment and metabolic activation (2.4 % and 1.4 %, respectively).
Lowest concentration producing cytogenetic effects in vitro:
With metabolic activation (short-term treatment): 0.060 mg/mL (clastogenicity)
　　　　　　　　　　　　　　　　　　　　　 　　　　　　　　　 0.040 mg/mL (polyploidy)

Genotoxic effects:

	clastogenicity			polyploidy
	+	?	-	+	?	-
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