4-Chlorophenol

4-クロロフェノール


[CAS No. 106-48-9]

p-Chlorophenol

p-クロロフェノール

Molecular formula: C6H5ClO Molecular weight: 128.56

ABSTRACT

4-Chlorophenol was studied for oral toxicity in rats in a single dose toxicity test at doses of 0, 690, 980, 1400 and 2000 mg/kg for both sexes. The single dose oral toxicity test revealed approximate lethal doses of 2000 mg/kg for males and of 1400 mg/kg for females.

4-Chlorophenol was studied for oral toxicity in Crj:CD(SD)IGS rats in a 28-day repeat dose toxicity test at doses of 0, 20, 100 and 500 mg/kg. No deaths occurred in either males or females. Tremor, tachypnea and salivation were observed in males and females of the 500 mg/kg group. Urinalysis showed increase or an increasing trend for urine volume in the males of the 100 mg/kg group and in males and females of the 500 mg/kg group, decreases in osmotic pressure and specific gravity in males of the 100 mg/kg group, and a decreasing trend for osmotic pressure in males of the 500 mg/kg group. Further, marked occult blood in the urine and appearance of erythrocytes in the urinary sediment were detected in one male of the 500 mg/kg group. Hematological examination showed increase in leukocytes in males of the 500 mg/kg group. No effects related to the test substance were observed with regard to body weight, food consumption, blood chemical examination, necropsy, organ weight or histopathological examination. In the recovery test, the changes observed during the administration period demonstrated recovery. The NOELs are considered to be 20 mg/kg/day for males and 100 mg/kg/day for females.

Genotoxicity of 4-chlorophenol was studied by reverse mutation test in bacteria and by chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

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

4-Chlorophenol induced structural and numerical chromosomal aberrations in CHL/IU cells after short-term treatment with and without an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:99.29 %
Test species/strains:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Doses:0(vehicle), 690, 980, 1400, 2000 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:Corn oil
GLP:Yes

　Test results:

Deaths occurred of males of the 2000 mg/kg group and of females of the 1400 mg/kg or more groups. Treatment-related clinical signs were noted as follows: tachypnea, hypoactivity, tremor, a prone position, bradypnea, salivation, a lateral position, clonic convulsions and cyanosis. Depression of body weight gain was observed in males of the 1400 mg/kg or more groups. In the dead animals, dark red maculae in the lung were noted macroscopically, and edema in the lung was evident histopathologically. In addition, dark red spots in the thymus were observed macroscopically, and hemorrhage was apparent histopathologically. In the surviving animals, there were no changes at necropsy and histopathological examination.
Approximate lethal dose: Males, 2000 mg/kg; females, 1400 mg/kg

2. Repeat Dose Toxicity 1)

Purity:99.29 %
Test species/strain:Rat/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)
　Doses:0(vehicle), 20, 100, 500 mg/kg/day
　Number of animals/group:Males, 6 or 12(0, 500 mg/kg)
Females, 6 or 12(0, 500 mg/kg)
　Vehicle:Corn oil
　Administration period:Males and females, 28 days
　Terminal kill:Males and females, on days 29 and 43(0, 500 mg/kg)
GLP:Yes

　Test results:

No deaths occurred in either males or females. Tremor, tachypnea and salivation were observed in males and females of the 500 mg/kg group. Urinalysis showed increase or an increasing trend for urine volume in males of 100 mg/kg group and in males and females of the 500 mg/kg group, decreases in osmotic pressure and specific gravity in males of the 100 mg/kg group, and a decreasing trend for osmotic pressure in males of the 500 mg/kg group. Further, marked occult blood in the urine and appearance of erythrocytes in the urinary sediment were detected in one male of the 500 mg/kg group. Hematological examination showed increase in leukocytes in males of the 500 mg/kg group. No effects related to the test substance were observed with regard to body weight, food consumption, blood chemical examination, necropsy, finding organ weights or histopathological examination. In the recovery test, the changes observed during the administration period demonstrated recovery.

The NOELs are considered to be 20 mg/kg/day for males and 100 mg/kg/day for females.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:99.29 %
Test species/strains: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:DMSO
　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 (all strains)
　Doses:-S9 mix; 0, 62.5, 125, 250, 500, 1000, 2000 μg/plate
+S9 mix; 0, 62.5, 125, 250, 500, 1000, 2000 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. Toxicity was observed at more than 1000 μg/plate (TA100, TA1535, TA98, TA1537) and at 2000 μg/plate (WP2 uvrA) without S9 mix, and at more than 1000 μg/plate (TA100, TA1535) and at 2000 μg/plate (WP2 uvrA, TA98, TA1537) with S9 mix.

Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98 and 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:99.29 %
Type of cell used:Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemical
(Chemical Substances Control Law of Japan) and
OECD Test Guideline 473
　Solvent:DMSO
　Positive controls:-S9 mix; 1-Methyl-3-nitro-1-nitrosoguanidine
+S9 mix; 3,4-Benzo[a]pyrene
　Doses:-S9 mix(6 hr short-term treatment); 0, 50, 100, 200, 300, 400 μg/mL
+S9 mix(6 hr short-term treatment); 0, 50, 100, 200, 300, 400 μg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

With 6 hr short-term treatment, structural chromosomal aberrations were induced at 300 μg/mL (12.0 %) without S9 mix, and at 50, 100 and 200 μg/mL (11.5, 9.5, and 7.0 %) with S9 mix, respectively. Polyploidy was induced at 100 and 200 μg/mL (6.5 and 8.0 %) without S9 mix, and at 100 and 200 μg/mL (4.5 and 6.0 %) with S9 mix, respectively.

Cytotoxicity was observed at 400 μg/mL without S9 mix, and at 300 and 400 μg/mL with S9 mix in after 6 hr short-term treatment.

Lowest concentration producing cytogenetic effects in vitro:
　With metabolic activation (6 hr short-term treatment):50 μg/mL(clastogenicity)

Genotoxic effects:
clastogenicitypolyploidy
+?-+?-
　Without metabolic activation:[*][ ][ ][*][ ][ ]
　With metabolic activation:[*][ ][ ][*][ ][ ]

1)The tests were performed by Safety Assessment Laboratory, Panapharm Laboratories Co., Ltd., 1285 Kurisaki-machi, Uto-shi, Kumamoto, 869-0425, Japan Tel +81-964-23-5111 Fax +81-964-23-2282
2)The tests were performed by the Research Institute for Animal Science in Biochemistry and Toxicology, 3-7-11 Hashimotodai, Sagamihara-shi, Kanagawa 229-1132, Japan. Tel +81-42-762-2775 Fax +81-42-762-7979