2-Amino-1-naphthalenesulfonic acid

2-アミノ-1-ナフタレンスルホン酸


CAS No. 81-16-3

2-Naphthylamine-1-sulfonic acid

2-ナフチルアミン-1-スルホン酸

Molecular formula: C10H9NO3S Molecular weight: 223.26

ABSTRACT

2-Amino-1-naphthalenesulfonic acid was studied for oral toxicity in rats with a single dose toxicity test at doses of 0, 500, 1000 and 2000 mg/kg and with an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 8, 40, 200 and 1000 mg/kg/day. Genotoxicity of 2-amino-1-naphthalenesulfonic acid was studied by the reverse mutation assay in bacteria and the chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

The single dose oral toxicity test revealed LD50s of above 2000 mg/kg in both sexes.

In the repeat dose study, the test substance at 1000 mg/kg was found to cause salivation in both sexes and a decrease of liver weight in the males. Accordingly, the NOELs is considered to be 200 mg/kg in terms of general toxicological effects. The test substance showed no reproductive/developmental toxicity. NOELs for reproductive performance of both sexes and offspring development are considered to be in each case 1000 mg/kg/day.

2-Amino-1-naphthalenesulfonic acid was mutagenic in Salmonella typhimurium TA1537 with an S9 mix.

Structural chromosomal aberrations were induced at the mid concentration (1.1 mg/ml) in the short-term treatment group with an S9 mix. However, the induction could have been due to the lowered pH of medium. Polyploidy was not induced.

SUMMARIZED DATA OF THE STUDIES

1. Single Dose Oral Toxicity1)

Purity:98.7%
Test species/strain:Rat/Crj:CD (SD)
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Dosage:0 (Vehicle), 500, 1000, 2000 mg/kg
　Number of animals:Males, 5; Females, 5/group
　Vehicle:0.5% CMC
GLP:Yes

　Test results:

No deaths occurred. In the 2000 mg/kg group at 1 day after administration, a loose stool and soiling of the perineal region were found. The treated and control groups showed virtually the same body weight changes. No remarkable changes were found in any of the groups necropsied.
LD50: Male >2000 mg/kg, Female >2000 mg/kg

2. Repeat Dose and Reproductive/Developmental Toxicity1)

Purity:98.7%
Test species/strain:Rat/Crj:CD (SD)
Test method:OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test
　Route:Oral (gavage)
　Dosage:0 (Vehicle), 8, 40, 200, 1000 mg/kg/day
　Number of animals:Males, 12; Females, 12/group
　Vehicle:0.5% CMC
　Administration period:Males, 49 days
Females, from 14 days before mating to Day 3 of lactation
　Terminal kill:Males, Day 50 of administration
Females, Day 4 of lactation
GLP:Yes

　Test results:

<Repeat dose toxicity>
In both sexes of the 1000 mg/kg group, salivation was found after administration, but this symptom disappeared after about 5 minutes. In the 1000 mg/kg group males, significantly lower values for absolute and relative weights of liver were obtained. There were no significant differences between any of the treated groups and the control group in body weight changes and food consumption of either sex. No remarkable changes were found in either male or female animals on necropsy and histopathological examination.
NOELs for reproductive performance of both sexes and offepring development are considered to be 1000 mg/kg/day in each cases.
<Reproductive and developmental toxicity>
There were no effects of the test substance on the frequency of estrus, copulation index, days of copulation, number of pregnant females, gestation length, fertility index, number of corpora lutea, number of implantation scars, implantation index and gestation index of any of the treated groups. The number of pups born, delivery index, number of live pups on Day 0 of lactation, number of dead pups, live birth index, sex ratio, number of live pups on Day 4 of lactation, viability index and body weights of live pups of both sexes of each treated group were virtually the same as those of the control group.
NOELs for reproductive performance of both sexes and offepring development are considered to be 1000 mg/kg/day in each cases.

3. Genetic Toxicity

3-1. Bacterial test2)

Purity:98.7%
Test species/strain:S.typhimurium TA100, TA1535, TA98, TA1537 E. coli WP2 uvrA
Test method:Guideline for Screening Mutageuicity Testing of Chemicals (Japan)
Procedures:Plate incorporation method
　Solvent:Acetone
　Positive controls:-S9 Mix, AF-2 (TA100, WP2, TA98), sodium azide (TA1535) and 9-aminoacridine (TA1537)
+S9 Mix, 2-aminoanthracene (all strains)
　Doses:0, 312.5, 625, 1250, 2500, 5000 μg/plate
　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavon
　Plates/test:3
　Number of replicates:2
GLP:Yes

　Test results:
Minimum concentration of test substance at which toxicity was observed:
No toxicity was observed up to a concentration of 5000 μg/plate with or without metabolic activation.

　Genotoxic effects:
S. typhimurium TA1535
+?-
without metabolic activation:[ ][ ][*]
with metabolic activation:[*][ ][ ]

S. typhimurium TA100, TA98 and TA1537
+?-
without metabolic activation:[ ][ ][*]
with metabolic activation:[ ][ ][*]

E. coli WP2 uvrA
+?-
without metabolic activation:[ ][ ][*]
with metabolic activation:[ ][ ][*]

1)The tests were performed by Nihon Bioresearch Inc. Hashima Laboratory, 6-104 Majima, Fukuju-cho, Hashima, Gifu 501-62, Japan. Tel +81-58-392-6222 Fax +81-58-391-3171
2)The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257 Japan, Tel +81-463-82-4751 Fax +81-463-82-9627