2-Chlorophenol

2-クロロフェノール


[CAS No. 95-57-8]

ο-Chlorophenol

o-クロロフェノール

Molecular formula: C6H5ClO Molecular weight: 128.56

ABSTRACT

The single oral dose LD50 value of 2-chlorophenol was approximate 2000 mg/kg for both sexes.

2-Chlorophenol was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at 0, 8, 40, 200 and 1000 mg/kg.

Tremors, decrease in locomotor activity, abnormal gait, and a prone or lateral position were observed in the 1000 mg/kg group, and salivation was observed in the 200 and 1000 mg/kg groups. Blood chemical examination revealed a decrease in inorganic phosphorus and an increase in triglyceride in the 1000 mg/kg group. In the liver, increases in absolute and relative weights, dark brownish color, and hypertrophys of hepatocyte were observed in the 1000 mg/kg group. The NOEL is considered to be 40 mg/kg/day for both sexes.

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

2-Chlorophenol induced structural chromosomal aberrations in CHL/IU cells after 6 hr short-term treatment without and with an exogenous metabolic activation system. Polyploidy was not induced in any treatment group.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Toxicity 1)

Purity:99.49 %
Test species/strains:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Doses:0(vehicle), 500, 1000, 2000 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:Olive oil
GLP:Yes

　Test results:

Deaths occurred in both sexes of the 2000 mg/kg groups. Decrease in locomotor activity, abnormal gait, irregular respiration, clonic convulsion, and a prone or lateral position were observed in the 500 mg/kg and above dose groups, and bradypnea was observed in the 2000 mg/kg group. Body weights were decreased in the 2000 mg/kg group at Day 4. Necropsy showed discoloration of the spleen in a dead animal of the 2000 mg/kg group.
The LD50 value was estimated to be approximate 2000 mg/kg for both sexes.

2. Repeat Dose Toxicity 1)

Purity:99.49 %
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)
　Dosage:0(vehicle), 8, 40, 200, 1000 mg/kg/day
　Number of animals/group:Males, 6; females, 6
　Vehicle:Olive oil
　Administration period:Males and females, 28 days
　Terminal kill:Males and females, on days 29 and 43
GLP:Yes

　Test results:

Tremors, decrease in locomotor activity, an abnormal gait, and a prone or lateral position were observed in both sexes of the 1000 mg/kg group, and salivation was observed in both sexes of the 200 and 1000 mg/kg groups. Blood chemical examination revealed a decrease in inorganic phosphorus in males and an increase in triglyceride in females of the 1000 mg/kg group. In the liver, increases in absolute and relative weights in females and dark brownish coloration in both sexes were observed in the 1000 mg/kg group. Histopathological examination revealed centrilobular hypertrophy of hepatocytes in both sexes of the 1000 mg/kg group. These changes disappeared or were diminished after withdrawal. No alterations attributable to the administration of 2-chlorophenol were observed in the body weight, food consumption, hematological examination, or urinalysis data.
The NOEL is considered to be 40 mg/kg/day for both sexes.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:99.49%
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), Sodium azide (TA1535), 9-Aminoacridine (TA1537) and N-Ethyl-N'-nitro-N-nitrosoguanidine (WP2 uvrA)
+S9 mix; 2-Aminoanthracene (all strains)
　Doses:-S9 mix; 39.1, 78.1, 156, 313, 625, 1250 and 2500 μg/plate(TA100, TA1535)
-S9 mix; 156, 313, 625, 1250, 2500 and 5000 μg/plate(WP2 uvrA, TA98 and TA1537)
+S9 mix; 39.1, 78.1, 156, 313, 625, 1250 and 2500 μg/plate(TA100, TA1535)
+S9 mix; 156, 313, 625, 1250, 2500 and 5000 μg/plate(WP2 uvrA, TA98 and TA1537)
　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 and Escherichia coli strains. Toxicity was observed at 1250 μg/plate or more (TA100 and TA1535) and at 2500 μg/plate or more (WP2 uvrA, TA98 and TA1537) with and without metabolic activation.

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)1)

Purity:99.49 %
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:Dimethylsulfoxide
　Positive controls:-S9 mix; Mitomycin C
+S9 mix; Benzo[a]pyrene
　Doses:-S9 mix(6 hr short-term treatment); 0, 62.5, 125, 250, 500 μg/mL(main test)
-S9 mix(6 hr short-term treatment); 0, 200, 300, 400, 500 μg/mL(confirmation test)
+S9 mix(6 hr short-term treatment); 0, 62.5, 125, 250, 500 μg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

Structural chromosomal aberrations were induced at 125, 250, and 500 μg/mL with 6 hr short-term treatment with S9 mix (6.0, 12.0, and 38.6 %, respectively) and at 500 μg/mL after 6 hr short term treatment without S9 mix (34.0 %). Polyploidy was not induced in any treatment group.

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

1)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