Monosodium 4-amino-5-hydroxy-2,7-naphthalenedisulfonate

4-アミノ-5-ヒドロキシ-2,7-ナフタレンジスルホン酸モノナトリウム

CAS No. 5460-09-3

Monosodium 4-amino-5-hydroxy-2,7,-naphthalenedisulfonate was studied for oral toxicity in rats in a single dose toxicity test at a dose of 2000 mg/kg and in a 28-day repeat dose toxicity test at doses of 0, 30, 100, 300 and 1000 mg/kg/day. Monosodium 4-amino-5-hydroxy-2,7,-naphthalenedisulfonate was also tested for mutagenicity with assays for reverse mutation in bacteria and chromosomal aberrations in cultured Chinese hamster (CHL) cells.

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

In the repeat dose study, the high dose group showed caecum enlargement, without any associated pathological changes. NOEL for repeat dose toxicity was achieved at 1000 mg/kg/day.

Monosodium 4-amino-5-hydroxy-2,7-naphthalenedisulfonate was not mutagenic for S. typhimurium TA100, TA1535, TA98, TA1537 and E. coli WP2 uvrA with or without exogenous metabolic activation up to 5000 μg/plate. This chemical induced neither chromosomal aberrations nor polyploidy with or without exogenous metabolic activation up to the cytotoxic concentration.

Monosodium 4-amino-5-hydroxy-2,7-naphthalenedisulfonate[5460-9-3]

1. Single Dose Oral Toxicity 1)

Purity:87.4 %
Test species/strain:Rat/Crj:CD (SD)
Test method:OECD Test Guideline 401
　Dose:2000 mg/kg
　Number of animals:Male; 5, Female; 5
GLP:Yes
Test results:LD50: Male, > 2000 mg/kg; Female, > 2000 mg/kg

2. Repeat Dose Toxicity 1)

Purity:87.4 %
Test species/strain:Rat/Crj:CD (SD)
Test method:Guidelines for 28-Day Repeat Dose Toxicity Test of Chemicals (Japan)
　Route:Oral (gavage)
　Doses:0 (vehicle), 30, 100, 300, 1000 mg/kg/day
　Number of animals:Male, 6; Female, 6/group
　Vehicle:1 w/v% methylcellulose solution
　Administration period:Male and Female, 28 days
　Terminal kill:Male and Female, days 29 or 43
GLP:Yes

　Test results:
The test substance at 30, 100, and 300 mg/kg/day did not induce any toxic effects in terms of clinical signs, body weight, food consumption, hematology, blood chemical analysis, and pathological including microscopic findings. The 1000mg/kg/day males and females showed a slight enlargement of the caecum, which was not accompanied with any histopathological changes, clinical signs, or any effect on growth. Thus these findings are considered not of biological or toxicological significance. Some rats killed after the recovery period showed a decrease in serum albumin in males accompanied with a lowering of the A/G ratio and a decrease in inorganic phosphorus in females. Since these were not observed in rats killed just after the administration period, they were accordingly considered not due to the test substance treatment. Although some females killed after the recovery period revealed decreases in relative brain weights and in absolute adrenal weights, these were secondary changes caused by lower body weights than those of the control groups.

NOEL: 1000 mg/kg/day

3. Genetic Toxicity

3-1 Bacterial test 2)

Purity:87.4%
Test species/strains:S. typhimurium TA100, TA1535, TA98, TA1537
E. coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
　Procedure:Plate method
　Solvent:DMSO
　Positive controls:-S9, AF-2 (TA100, WP2 uvrA, TA98), sodium azide(TA1535) and 9-aminoacridine (TA1537)
+S9, 2-Aminoanthracene (all strains)
　Doses:0, 312.5, 625, 1250, 2500, 5000 μg/plate
　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:3
　Number of replicates:2

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

Genotoxic effects:
S. typhimurium TA100, TA1535, TA98, TA1537
+?-
with metabolic activation:[ ][ ][*]
without metabolic activation:[ ][ ][*]

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

3-2 Non-bacterial in vitro test (Chromosomal aberration) 2)

Purity:87.4%
Type of cell used:Chinese hamster CHL cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
　　Solvent:0.5% CMC Na solution
　　Positive controls:-S9, Mitomycin C
+S9, Cyclophosphamide
　　Doses:-S9: 0, 0.55, 1.1, 2.2 mg/ml
+S9: 0, 0.85, 1.7, 3.4 mg/ml
　　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　　Plates/test:2
GLP:Yes

　Test results:
Monosodium 4-amino-5-hydroxy-2,7-naphthalenedisulfonate induced neither chromosomal aberrations nor polyploidy up to the cytotoxic concentration (without exogenous metabolic activation) or the limit concentration (10 mM; with exogenous metabolic activation).

Lowest concentration producing cytogenetic effects in vitro:
with metabolic activation: > 3.4 mg/ml
without metabolic activation: > 2.2 mg/ml

Genotoxic effects:
+?-
with metabolic activation:[ ][ ][*]
without metabolic activation:[ ][ ][*]

1)The tests were performed by the Research Institute for Animal Science in Biochemistry and Toxicology, 3-7-11 Hashimotodai, Sagamihara-shi, Kanagawa, 229, Japan. Tel 81-427-62-2775 Fax 81-427-62-7979
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