3-Methyl-4-nitrophenol

3-メチル-４-ニトロフェノール

CAS No. 2581-34-2

4-Nitro-m-cresol

4-ニトロ-m-クレゾール

Molecular formula: C7H7NO3 Molecular weight: 153.15

ABSTRACT

Death of one male occurred in the 300 mg/kg group which showed a decrease in spontaneous activity, adaption of a prone position and bradypnea. Two females in the same dose group showed the same clinical signs. The NOEL for repeat dose toxicity for both sexes is considered to be 100 mg/kg/day. No effects were observed on reproductive performance in either sex or on development of the next generation. NOELs for reproductive and developmental performances are considered to be 300 mg/kg/day.

3-Methyl-4-nitrophenol was not mutagenic in Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA. This chemical substance induced structural chromosomal aberrations in CHL/IU cells, in the presence of an exogenous metabolic activation system. Numerical aberrations were not induced under the experimental conditions used.

SUMMARIZED DATA FROM THE STUDIES

1. Reproductive/Developmental Toxicity 1)

Purity	:	98.5%
Test species/strain	:	Rat/Crj:CD (SD)
Test method	:	OECD Preliminary Reproductive/Developmental Toxicity Screening Test
Route	:	Oral (gavage)
Doses	:	0 (vehicle), 30, 100, 300 mg/kg/day
Number of animals	:	Male, 12; female, 12/group
Vehicle	:	10% gum arabic solution
Administration period	:	Male, 46 days Female, from 14 days before mating to day 3 of lactation
Terminal kill	:	Male, day 47 Female, day 4 of lactation
GLP	:	Yes

　Test results:

<Reproductive and developmental toxicity>

No effects were observed on the following items: reproductive ability, organ weights and histopathological appearance of the reproductive organs, delivery and maternal behavior of dams, viability, clinical signs, body weight change and autopsy findings for offspring.

NOELs for reproductive and developmental performances are considered to be 300 mg/kg/day.

<Repeat dose toxicity>

One male of the 300 mg/kg group died on day 1 of administration. The animal showed decreased spontaneous activity, adaption of prone position and bradypnea. Histopathological examination revealed thrombis in the kidney, heart and lung. Two females of the 300 mg/kg group showed the same clinical signs on days 20 or 21 of gestation. Yellow-discolored urine caused by the color of the test substance was observed in all treated surviving animals during the administration period. No effects were observed on body weight change or food consumption in either sex.

The NOEL for repeat dose toxicity for both sexes is considered to be 100 mg/kg/day.

2. Genetic Toxicity

2-1 Bacterial test 2)

Purity	:	99.9%
Test species/strains	:	S.typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Procedures	:	Plate incorporation method
Solvent	:	DMSO
Positive controls	:	-S9, AF-2 (TA100, WP2, TA98), sodium azide (TA1535) and 9-aminoacridine (TA1537) +S9, 2-aminoanthracene (all strains)
Dosage	:	0, 78.12, 156.2, 312.5, 625, 1250, 2500 μg/plate
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	3
Number of replicates	:	2
GLP	:	Yes

　Test results:

Minimum concentration of test substance at which toxicity was observed:

Toxicity was observed at a concentration of 1250 μg/plate with or without metabolic activation.

Genetic effects:

S. typhimurium TA100, TA1535, TA 98, TA1537

	+	?	-
with metabolic activation	[ ]	[ ]	[*]
without metabolic activation	[ ]	[ ]	[*]

E. coli WP2 uvrA

with metabolic activation	[ ]	[ ]	[*]
without metabolic activation	[ ]	[ ]	[*]

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

Purity	:	99.9%
Type of cell used	:	Chinese hamster CHL/IU cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Solvent	:	DMSO
Positive controls	:	-S9, Mitomycin C +S9, Cyclophosphamide
Doses	:	-S9 (continuous treatment): 0, 0.006, 0.012, 0.023 mg/ml -S9 (short-term treatment): 0, 0.04, 0.08, 0.15 mg/ml +S9 (short-term treatment): 0, 0.04, 0.08, 0.15 mg/ml
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

In the high concentration group (0.15 mg/ml) short-term treatments without S9 mix resulted in structural aberrations (including gap) in 9% of the cells. In all concentration groups, short-term treatment with S9 mix caused structural aberrations (including gap) in more than 10% of the cells.

Lowest concentration producing cytogenetic effects in vitro:

without metabolic activation (continuous treatment ): > 0.023 mg/ml

without metabolic activation (short-term treatment): 0.15 mg/ml (clastogenicity)

with metabolic activation (short-term treatment): 0.04 mg/ml (clastogenicity)

Genotoxic effects:

	clastogenicity			polyploidy
	+	?	-	+	?	-
without metabolic activation:	[ ]	[*]	[ ]	[ ]	[ ]	[*]
with metabolic activation:	[*]	[ ]	[ ]	[ ]	[ ]	[*]

1)	The test was performed by the Safety Research Institute for Chemical Compound Co., Ltd., 363-24, Shin-ei, Toyohira-ku, Sapporo, Hokkaido 004, Japan. Tel +81-11-885-5031 Fax +81-11-885-5313
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