ρ-Nitrophenol sodium salt

ρ-ニトロフェノールナトリウム


[CAS No. 824-78-2]

Sodium 4-nitrophenoxide

ナトリウム 4-ニトロフェノキシド

Molecular formula: C6H4NNaO3 Molecular weight: 161.09

ABSTRACT

A single dose oral toxicity test of p-nitrophenol sodium salt revealed an LD50 value of 550 mg/kg for males and 467 mg/kg for females.

ρ-Nitrophenol sodium salt was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 60, 160, 400 and 1000 mg/kg.

All males and females given 1000 mg/kg died from some affects of the test article on the central nerve system without obvious organic change. In the survivors, decrease in spontaneous movement, oligopnea and adoption of a prone/lateral position were observed in both sexes in the 1000 mg/kg group in the early stage of the administration period. A decrease in urine pH was observed in males in the 400 mg/kg group. Histopathological examination in the kidneys revealed an increased incidence of eosinophilic bodies in tubular epithelium in males in the 400 and 1000 mg/kg groups. All the changes had disappeared after a 14-day recovery period. The NOELs are considered to be 160 mg/kg/day for males and 400 mg/kg /day for females.

Genotoxicity of p-nitrophenol sodium salt was studied by reverse mutation test in bacteria and chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells. ρ-Nitrophenol sodium salt was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

ρ-Nitrophenol sodium salt induced structural chromosomal aberrations in CHL/IU cells after short-term treatment, with and without an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:79.4 %
Test species/strains:Rat/Crj:CD(SD)
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Doses:0(vehicle), 125, 250, 500, 1000 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:0.5 w/v% Carmellose sodium solution
GLP:Yes

　Test results:

Deaths occurred in males and females given 500 mg/kg or more. Decrease in spontaneous movement and prone/lateral position were observed in the 250 mg/kg and higher groups and tonic convulsions were observed in the 500 mg/kg and higher groups. All clinical signs observed in the survivors had disappeared 2 hours after administration. No effects were detected in terms of body weight or autopsy findings.
Estimated LD50 values Males, 550 mg/kg; Females, 467 mg/kg

2. Repeat Dose Toxicity 1)

Purity:79.4 %
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), 60, 160, 400, 1000 mg/kg/day
　Number of animals/group:Males, 6; females, 6
　Vehicle:0.5 w/v% Carmellose sodium solution
　Administration period:Males and females, 28 days
　Terminal kill:Males and females, on days 29 and 43
GLP:Yes

　Test results:

All males and females given 1000 mg/kg died from some affect of the test article on the central nerve system without obvious organic change. In the survivors, decrease in spontaneous movement, oligopnea and, adoption of a prone/lateral position were observed in both sexes given 1000 mg/kg, in the early stage of the administration period. A decrease in urinany pH was observed in males given 400 mg/kg. Histopathological examination of the kidneys revealed increased incidences of eosinophilic bodies in tubular epithelium in males given 400 and 1000 mg/kg groups. All the changes had disappeared after a 14-day recovery period.
The NOELs are considered to be 160 mg/kg/day for males and 400 mg/kg/day for females.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:79.4 %
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, WP2 uvrA), Sodium azide (TA1535) and 9-Aminoacridine (TA1537)
+S9 mix; 2-Aminoanthracene (all strains)
　Doses:-S9 mix; 0, 156, 313, 625, 1250, 2500, 5000 μg/plate
+S9 mix; 0, 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:

This chemical did not induce gene mutations in the S. typhimurium and E. coli strains. Toxicity was observed at or more than 2500 μg/plate (TA1535, TA98, TA1537) and at 5000 μg/plate (TA100, WP2 uvrA) without S9 mix, and at 5000 μg/plate (all stains) with S9 mix.

Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98 and 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:79.4 %
Type of cell used:Chinese hamster CHL/IU cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemical
(Chemical Substances Control Law of Japan) and
OECD Test Guideline 473
　Solvent:DMSO
　Positive controls:-S9 mix; 1-Methyl-3-nitro-1-nitrosoguanidine
+S9 mix; 3,4-Benzo[a]pyrene
　Doses:-S9 mix(6 hr short-term treatment); 0, 100, 200, 400, 800, 1200, 1600 μg/mL
+S9 mix(6 hr short-term treatment); 0, 600, 800, 1000, 1200, 1400, 1600 μg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

With 6 hr short-term treatment, structural chromosomal aberrations were induced at 800 and 1200 μg/mL (7.5 and 28.0 %) without S9 mix, and at 600, 800, 1000 and 1200 μg/mL(11.5, 19.0, 33.5 and 48.0 %) with S9 mix, respectively. Polyploidy was not induced in any treatment group.

Cytotoxicity was observed at 1600 μg/mL without S9 mix, and at 1400 and 1600 μg/mL with S9 mix on 6 hr short-term treatment.

Lowest concentration producing cytogenetic effects in vitro:
　With metabolic activation (6 hr short-term treatment):600 μg/mL(clastogenicity)

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

1)The tests were performed by Bozo Research Center Inc, 1284, Kamado, Gotemba-shi, Shizuoka, 412-0039, Japan. Tel +81-550-82-2000 Fax +81-550-82-2379
2)The tests were performed by the Research Institute for Animal Science in Biochemistry and Toxicology, 3-7-11 Hashimotodai, Sagamihara-shi, Kanagawa 229-1132, Japan. Tel +81-42-762-2775 Fax +81-42-762-7979