Disperse Yellow 42

ディスパーズイエロー 42

[CAS No. 5124-25-4]

4-Anilino-3-nitro-N-phenylbenzenesulfonamide

4-アニリノ-3-ニトロ-N-フェニルベンゼンスルホンアミド

Molecular formula: C₁₈H₁₅N₃O₄S　Molecular weight: 369.40

ABSTRACT

Disperse Yellow 42 was studied for oral toxicity in rats in a 28-day repeated dose toxicity test at doses of 0, 100, 300 and 1000 mg/kg/day. No deaths were observed in either sex. Repeated administration of test substance caused increase of liver and spleen weights in females of the 1000 mg/kg group, and centrilobular hypertrophy of hepatocytes in males of the 1000 mg/kg group. Thus, the NOEL for the 28-day repeat dose oral toxicity test of Disperse Yellow 42 is considered to be 300 mg/kg/day for males and females.

Disperse Yellow 42 was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

Disperse Yellow 42 induced structural chromosomal aberrations in CHL/IU cells after short term treatment, with and without an exogenous metabolic activation system. Polyploidy was not induced in any treatment group.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity ¹⁾

Purity	:	68 %
Test species/strain	:	Rats/Crj:CD(SD)IGS
Test method	:	OECD Test Guideline 401
Route	:	Oral (gavage)
Dosage	:	0 (vehicle), 2000 mg/kg
Number of animals/group	:	Males, 5; females, 5
Vehicle	:	0.5 % CMC Na solution
GLP	:	Yes

　Test results:

No deaths were observed in either sex.

All animals excreted yellowish feces and urine during the early period of observation.

No abnormalities were noted in body weight change or necropsy findings.

LD₅₀ values were estimated to be more than 2000 mg/kg in both sexes.

2. Repeated Dose Oral Toxicity ¹⁾

Purity	:	68 %
Test species/strain	:	Rats/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)
Dosage	:	0 (vehicle), 100, 300, 1000 mg/kg/day
Number of animals/group		Males, 10; females, 10 (0, 1000 mg/kg) Males, 5; females, 5 (100, 300 mg/kg)
Vehicle	:	0.5 % CMC Na solution
Administration period	:	Males and females, 28 days
Terminal killing	:	Males and females, on days 29 or 43
GLP	:	Yes

　Test results:

No deaths were observed in either sex during the administration or recovery periods, and no abnormalities were detected in terms of general condition, body weight change, food consumption, urinalysis, hematology or blood chemistry. Relative liver weights, and absolute and relative spleen weights were increased in females of the 1000 mg/kg group. Livers of males in the 1000 mg/kg group demonstrated centrilobular hypertrophy of hepatocytes.

Thus the NOEL for the 28-day repeated dose toxicity is considered to be 300 mg/kg/day for males and females.

3. Genetic Toxicity

3-1. Bacterial test ²⁾

Purity	:	68 %
Test species/strain	:	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	:	Dimethyl sulfoxide
Positive controls	:	-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98), Sodium azide (TA1535), 9-Aminoacridine hydrochloride (TA1537) and N-Ethyl-N'-nitro-N-nitrosoguanidine (WP2 uvrA) +S9 mix; 2-Aminoanthracene (five strains)
Dosage	:	-S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate (five strains) +S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate (five strains)
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 Salmonella typhimurium or Escherichia coli strains. Toxicity was not observed up to 5000 μg/plate in the five strains tested with or without metabolic activation.

Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98, 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	:	68 %
Type of cell used	:	Chinese hamster CHL/IU cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 473
Solvent	:	Dimethyl sulfoxide
Positive controls	:	-S9 mix; Mitomycin C +S9 mix; Benzo[a]pyrene
Dosage	:	-S9 mix (6 hr short-term treatment); 0, 10, 20, 40, 60, 80, 100 μg/mL (main test) -S9 mix (6 hr short-term treatment); 0, 60, 70, 80 μg/mL (confirmation test) +S9 mix(6 hr short-term treatment); 0, 10, 20, 40, 60, 80, 100 μg/mL (main test) +S9 mix(6 hr short-term treatment); 0, 70, 80, 90, 100 μg/mL (confirmation test)
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

Structural chromosomal aberrations were induced after 6 hr short-term treatment with S9 mix (23.0 and 14.0 % at 80 and 100 μg/mL [main test], 11.0 % at 90 μg/mL [confirmation test]) and without S9 mix (32.8 % at 80 μg/mL [main test], 39.0 % at 80 μg/mL [confirmation test]). Polyploidy was not induced in any treatment group.

Genotoxic effects:

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

1)	The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257-8523, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627
2)	The tests were performed by the Kashima Laboratory, Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Hasaki-machi, Kashima-gun, Ibaraki, 314-0255, Japan. Tel +81-479-46-2871 Fax +81-479-46-2874