1,4-Diethylbenzene

1,4-ジエチルベンゼン

CAS No. 105-05-5

p-Diethylbenzene

p-ジエチルベンゼン

Molecular formula: C10H14 Molecular weight: 134.22

ABSTRACT

1,4-Diethylbenzene was studied for oral toxicity in rats in a single dose toxicity test at a dose of 2000 mg/kg and in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 30, 150 and 750 mg/kg/day. Genotoxicity of 1,4-diethylbenzene was also studied by the reverse mutation assay in bacteria and the chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

The single dose oral toxicity test revealed an LD50 of more than 2000 mg/kg for both sexes.

With regard to repeat dose toxicity, the final body weights of both males and females given 750 mg/kg were lower than those of the controls. Food consumption decreased in males given 750 mg/kg until day 8 and increased from day 29. Blood chemical examination revealed increases in levels of BUN and GPT in males given 150 and 750 mg/kg, as well as increases in levels of total protein, albumin, creatinine and total bilirubin, and a decrease in the glucose level in the 750 mg/kg males. Kidney weights were elevated significantly in the 150 and 750 mg/kg males. Males and females of the 750 mg/kg group also demonstrated a significant increase in liver weights. Necropsy revealed brown colored and enlarged livers in males given 750 mg/kg. Histopathological examination in this group showed swelling of the liver cells. NOELs for repeat dose toxicity are considered to be 30 mg/kg/day for males and 150 mg/kg/day for females. In terms of reproductive/developmental toxicity, the compound showed no effects on any relevant parameters. NOELs for reproductive performance of males and females, and for pups development are considered to be both 750 mg/kg/day.

1,4-Diethylbenzene was not mutagenic in Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA. Neither structural nor numerical chromosomal aberrations were induced in CHL/IU cells up to the concentration going 50% cell growth inhibition or the concentration of 10 mM, in the absence or presence of an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity	:	97.2%
Test species/strain	:	Rats/Crj:CD (SD)
Test method	:	OECD Test Guideline 401
Route	:	Oral (gavage)
Doses	:	2000 mg/kg
Number of animals	:	Male, 5 ; female, 5/group
Vehicle	:	Corn oil
GLP	:	Yes

　Test results:: During the course of the study, a decrease of spontaneous motor activity was observed in both males and females, and lacrimation was additionally observed in one female as a clinical sign. However, no deaths occurred in either male or female groups. The test substance did not cause any changes in body weight. No macroscopic abnormalities that could be attributed to treatment with the test substance were seen on pathological examination. LD50: Male, > 2000 mg/kg; female, > 2000 mg/kg

2. Repeat Dose and Reproductive/Developmental Toxicity 1)

Purity	:	97.2%
Test species/strains	:	Rats/Slc:SD
Test method	:	OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test
Route	:	Oral (gavage)
Dosage	:	0(Vehicle), 30, 150,750mg/kg/day
Number of animals	:	Male, 12; female, 12/group
Vehicle	:	Corn oil
Administration period	:	Male, 44 days Female, from 14 days before mating to day 3 of lactation
Terminal kill	:	Male, day 45 Female, day 4 of lactation
GLP	:	Yes

　Test results:

There were no deaths or abnormal clinical signs attributable to the treatment in males or females of any group throughout the dosing period. Body weights decreased in both males and females given 750 mg/kg. Food consumption decreased in males given 750 mg/kg until Day 8 and increased from Day 29.

There were no observed effects due to the test substance in the hematological findings for the treated males. Blood chemical examination revealed increases in levels of BUN and GPT in males given 150 and 750 mg/kg, and increases in levels of total protein, albumin, creatinine and total bilirubin and a decrease in the glucose level in the 750 mg/kg dose males. Absolute and relative kidney weights were elevated in the 150- and 750 mg/kg dose males. Moreover, absolute and relative weights of the liver were elevated in the 750 mg/kg-dose males and females. Necropsy revealed brown colored and enlarged livers in males given 750 mg/kg. Histopathological examination showed swelling of the liver cells in these animals.

NOELs for repeat dose toxicity are considered to be 30 mg/kg/day for males and 150 mg/kg/day for females.

The compound showed no effects on any reproductive/developmental parameters.

NOELs for reproductive performance of males and females, and for pups development are considered to be both 750 mg/kg/day.

3. Genetic Toxicity

3-1 Bacterial test 2)

Purity	:	97.0%
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	:	Acetone
Positive controls	:	-S9, AF-2 (TA100, WP2, TA98), sodium azide (TA1535) and 9-aminoacridine (TA1537) +S9, 2-aminoanthracene (all strains)
Dosage	:	0, 2.441, 4.882, 9.765, 19.53, 39.06, 78.12 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 the test substance at which toxicity was observed:

Toxicity was observed at a concentration of 39.06 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	[ ]	[ ]	[*]

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

Purity	:	97%
Type of cell used	:	Chinese hamster CHL/IU cells
Test method	:	Guideline for Screening Mutagenicity Testing of Chemicals (Japan)
Solvent	:	Acetone
Positive controls	:	-S9, Mitomycin C +S9, Cyclophosphamide
Doses	:	-S9 (continuous treatment): 0, 0.03, 0.06, 0.11 mg/ml -S9 (short-term treatment): 0, 0.33, 0.65, 1.30 mg/ml +S9 (short-term treatment): 0, 0.33, 0.65, 1.30 mg/ml
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

Lowest concentration producing cytogenetic effects in vitro:

without metabolic activation (continuous treatment ): > 0.11 mg/ml

without metabolic activation (short-term treatment): > 1.30 mg/ml

with metabolic activation (short-term treatment): > 1.30 mg/ml

Genotoxic effects:

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

1) The tests were performed by the Biosafety Research Center, Foods, Drugs, and Pesticides (An-pyo Center), 582-2 Shioshinden Arahama, Fukude-cho, Iwata-gun, Shizuoka 437-12, Japan.
Tel +81-538-58-1266 Fax +81-538-58-1393

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

1)	The tests were performed by the Biosafety Research Center, Foods, Drugs, and Pesticides (An-pyo Center), 582-2 Shioshinden Arahama, Fukude-cho, Iwata-gun, Shizuoka 437-12, Japan. Tel +81-538-58-1266 Fax +81-538-58-1393
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