Nonylphenol

ノニルフェノール

[CAS No. 25154-52-3]

Mixed isomers of nonylphenol

ノニルフェノール異性体混合物

Molecular formula: C15H24O Molecular weight: 220.36

ABSTRACT

Nonylphenol was not mutagenic to Salmonella typhimurium, TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogeneous metabolic activation system.

Nonylphenol induced neither structural chromosomal aberrations nor polyploidy in CHL/IU cells, in the absence or presence of an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Repeat Dose Toxicity １）

Purity	:	99.0 %
Test species/strain	:	Rat/Crj:CD (SD)
Test method	:	Guidelines for 28-Day Repeat Dose Toxicity Testing of Chemicals (Japan)
Route	:	Oral (gavage)
Doses	:	0 (vehicle), 4, 15, 60, 250 mg/kg/day
Number of animals/group	:	Males, 6; females, 6
Vehicle	:	Olive oil
Administration period	:	Males and females, 28 days
Terminal kill	:	Days 29 or 43
GLP	:	Yes

　Test results:

In the repeat dose test, retarded body weight gain was noted in males given 250 mg/kg. Urinalysis revealed an increase in urine volume and a decrease in the specific gravity in both sexes. Increase in the squamous epithelial cells and occurrence of small round epithelial cells in the urinary sediments were obseared in females given 250 mg/kg. Hematology revealed decreases in hemoglobin and hematocrit values in females given 250 mg/kg. Blood biochemistry revealed increases in blood urea nitrogen and inorganic phosphorus and a decrease in chloride in males, and increases in total protein and triglycerides in females given 250 mg/kg. The liver weight increased in males given 60 mg/kg and both sexes given 250 mg/kg, and histopathologically, hypertrophy of the centrilobular hepatocytes was noted in both sexes given 250 mg/kg. Kidney weights were increased in males given 250 mg/kg and disseminated white spots, enlargement and pelvic dilatation were noted in females given 250 mg/kg on gross examination. Histopathologically, the following lesions were noted in the 250 mg/kg group: basophilic change of the proximal tubules in both sexes, single cell necrosis of the proximal tubules, inflammatory cell infiltration in the interstitium and casts in females, basophilic change and dilatation of the collecting tubules in both sexes, simple hyperplasia in the pelvic mucosa and pelvic dilatation in females. In the urinary bladder, simple hyperplasia of the transitional cells was noted in both sexes given 250 mg/kg. In the cecum, dilatation was noted on gross examination in both sexes given 250 mg/kg; however, no histopathological changes were noted. Almost all changes except those in the kidney had disappeared after a 14-day recovery period. The NOELs for males and females are considered to be 15 mg/kg/day and 60 mg/kg/day, respectively, under the conditions of the present study.

2. Genetic Toxicity

2-1. Bacterial test ２）

Purity	:	> 99.0%
Test species/strain	:	S. typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Procedures	:	Pre-incubation method
Solvent	:	DMSO
Positive controls	:	-S9 mix AF-2 (TA100, TA98 and WP2 uvrA) Sodium azide (TA1535) 9-Aminoacridine (TA1537) +S9 mix 2-Aminoanthracene (all strains)
Doses	:	-S9 mix (TA100, TA98, TA1535 and TA1537) 0.195, 0.391, 0.781, 1.56, 3.13, 6.25, 12.5 μg/plate -S9 mix (WP2 uvrA) 1.56, 3.13, 6.25, 12.5, 25.0, 50.0 μg/plate +S9 mix (TA100, TA1535 and TA1537) 1.56, 3.13, 6.25, 12.5, 25.0, 50.0 μg/plate +S9 mix (TA98 and WP2 uvrA) 6.25, 12.5, 25.0, 50.0, 100, 200 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.

Genetic effects:

S. typhimurium TA100, TA1535, TA98 and TA1537

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

E. coli WP2 uvrA

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

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

Purity	:	> 99.0%
Type of cell used	:	Chinese hamster lung (CHL) cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Solvent	:	DMSO
Positive controls	:	long-term treatment; Mitomycin C (24 h and 48 h) short-term treatment; Cyclophosphamide (+S9 mix and -S9 mix)
Doses	:	long-term treatment; 6.25, 12.5, 25.0, 50.0 μg/ml (24 h) long-term treatment; 3.13, 6.25, 12.5, 25.0 μg/ml (48 h) short-term treatment; 7.50, 15.0, 30.0, 60.0 μ g/ml (+S9 mix and -S9 mix)
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

Neither structural nor numerical chromosomal aberrations were induced under the experimental conditions used.

Genotoxic effects:

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

1)	The tests were performed by Bozo Research Center Inc, 1284, Kamado, Gotemba-shi, Shizuoka, 412, Japan. Tel +81-550-82-2000 Fax +81-550-82-2379
2)	The tests were performed by the Biosafety Research Center, Foods, Drugs and Pesticides (An-pyo Center), Japan, 582-2 Shioshinden Arahama, Fukude-cho, Iwata-gun, Shizuoka, 437-12, Japan. Tel +81-538-58-1266 Fax +81-538-58-1393