A repeated dose oral toxicity study of diethylbiphenyl was conducted in rats according to OECD Test Guideline 407, at doses of 0, 15, 60 and 240 mg/kg. On hematological and biochemical examinations at the end of the dosing period, prolonged partial prothrombin and activated partial thromboplastin times were observed in males and the total cholesterol level was increased in females of the 240 mg/kg group. Liver weights in females and relative liver weights in both sexes were significantly increased in the 240 mg/kg group. Histological examination revealed centrilobular hypertrophy of hepatocytes in males of the 240 mg/kg group.

From these results, the NOAEL is considered to be 60 mg/kg/day for both sexes.

Genotoxicity of diethylbiphenyl was studied by a reverse mutation test in bacteria. This substance was not mutagenic in Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

Genotoxicity of diethylbiphenyl was studied by a chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells with Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Test Guideline 473. Diethylbiphenyl did not induce structural chromosomal aberrations or polyploidy under the present test conditions, with or without metabolic activation.

1. Repeated Dose Oral Toxicity1)

Purity	:	97.74 %
Test species/strain	:	Rat/Crj:CD(SD)IGS
Test method	:	OECD Test Guideline 407
Route	:	Oral(gavage)
Dosage	:	0(vehicle), 15, 60, 240 mg/kg/day
Number of animals/group	:	Males, 10; females, 10(0, 240 mg/kg) Males, 5; females, 5(15, 60 mg/kg)
Vehicle	:	Corn oil
Administration period	:	Males and females, 28 days
Terminal killing	:	Males and females, days 29 or 43
GLP	:	Yes

　Test results:

In the 240 mg/kg group, transient salivation immediately after administration was observed frequently in both sexes after the 9th day of observation. On hematological and biochemical examinations at the end of the dosing period, prolonged partial prothrombin and activated partial thromboplastin times in males and increased total cholesterol levels in females were observed in the 240 mg/kg group. Liver weights in females and relative liver weights in both sexes were increased at 240 mg/kg, and histological examination revealed centrilobular hypertrophy of hepatocytes in the males.

At the end of the recovery period, the above changes observed at the end of the dosing period had disappeared.

From these results, the NOAEL is considered to be 60 mg/kg/day for both sexes.

2. Genetic Toxicity

2-1. Bacterial test 1)

Purity	:	97.74 %
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, WP2 uvrA), sodium azide (TA1535) and 9-aminoacridine (TA1537) +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 (TA100, TA1537, WP2 uvrA), 0, 78.1, 156, 313, 625, 1250, 2500, 5000 μg/plate (TA1535), 0, 39.1, 78.1, 156, 313, 625, 1250, 2500, 5000 μg/plate (TA98)
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	3(1 for cytotoxicity test)
Number of replicates	:	2(plus 1 cytotoxicity test)
GLP	:	Yes

　Test results:

This chemical did not induce gene mutations in S. typhimurium TA100, TA98, TA1535, TA1537 or E. coli WP2 uvrA strains with or without S9 mix. Growth inhibition was not observed up to 5000 μg/plate in any strain, with or without S9 mix.

Genetic effects:

Salmonella typhimurium TA100, TA98, TA1535, TA1537

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

Escherichia coli WP2 uvrA

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

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

Purity	:	97.74 %
Type of cell used	:	Chinese hamster lung (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; Mitomycin C +S9; Cyclophosphamide
Dosages	:	-S9 (short-term treatment); 0, 0.013, 0.020, 0.030 mg/mL +S9 (short-term treatment); 0, 0.056, 0.11, 0.23 mg/mL -S9 (continuous treatment); 0, 0.013, 0.020, 0.030 mg/mL
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

The incidence of cells with structural chromosomal aberrations and polyploidy was not statistically or biologically significant at any dose in either test system.

Genotoxic effects:

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