ABSTRACT

7-Amino-4-hydroxy-2-naphthalenesulfonic acid was mutagenic to Salmonella typhimurium, TA100, TA98, TA1535 and TA1537 with an exogeneous metabolic activation system.

7-Amino-4-hydroxy-2-naphthalenesulfonic acid induced neither structural chromosomal aberrations nor polyploidy in CHL/IU cells, in the absence or presence of an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Repeat Dose Toxicity １）

Purity	:	91.8%
Test species/strain	:	Rat/Crj:CD (SD)
Test method	:	Guidelines for 28-day Repeat Dose Toxicity Testing of Chemicals (Japan)
Route	:	Oral (gavage)
Doses	:	0 (vehicle), 250, 500, 1000 mg/kg/day
Number of animals/group	:	Males, 6 and 12 (0, 1000 mg/kg) Females, 6 and 12 (0, 1000 mg/kg)
Vehicle	:	5% gum arabic solution
Administration period	:	Males and females, 28 days
Terminal kill	:	Days 29 or 43
GLP	:	Yes

　 Test results:

The test substance did not cause any changes in clinical signs, body weights, food consumption, urinalysis, hematology, blood chemistry or organ weights. There were also no macroscopic or microscopic abnormalities that could be attributed to treatment with the test substance. The NOEL is considered to be 1000 mg/kg/day for males and females.

2. Genetic Toxicity

2-1. Bacterial test ２）

Purity	:	91.8%
Test species/strains	:	S. typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Procedures	:	Pre-incubation method
Solvent	:	DMSO
Positive controls	:	-S9 mix;AF-2 (TA100, TA98 and WP2 uvrA), Sodium azide (TA1535), 9-Aminoacridine (TA1537) +S9 mix;2-Aminoanthracene (all strains)
Doses	:	156, 313, 625, 1250, 2500, 5000 μg/plate
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	3
Number of replicates	:	2
GLP	:	Yes

　Test results:

Positive mutagenic responses were clearly obtained in S. typhimurium strains with metabolic activation.

Genetic effects:
S. typhimurium TA100, TA1535, TA98 and TA1537

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

E. coli WP2 uvrA

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

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

Purity	:	91.8%
Type of cell used	:	Chinese hamster lung (CHL) cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Solvent	:	DMSO
Positive controls	:	long-term treatment; Mitomycin C (24 h and 48 h) short-term treatment; Cyclophosphamide (+S9 and -S9 mix)
Doses	:	long-term treatment; 0, 375, 750, 1500 μg/ml (24 h and 48 h) short-term treatment; 0, 375, 750, 1500 μg/ml (+S9 and -S9 mix)
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

This chemical did not induce structural chromosomal aberrations or polyploidy in the absence or presence of an exogeneous metabolic activation system.

Genetic effects:

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

1)	The tests were performed by Safety Assessment Laboratory, Panapharm Laboratories Co., Ltd. 1285 Kurisaki-machi, Uto-shi, Kumamoto, 869-04, Japan. Tel +81-964-23-5111 Fax +81-964-23-2282
2)	The tests were performed by the Biosafety Research Center, Foods, Drugs and Pesticides (An-pyo Center), Japan, 582-2 Shioshinden Arahama, Fukude-cho, Iwata-gun, Shizuoka, 437-12, Japan. Tel +81-538-58-1266 Fax +81-538-58-1393