Triphenylchloromethane

トリフェニルクロロメタン


[CAS No. 76-83-5]

Trityl chloride/Chlorotriphenylmethane

トリチルクロリド

Molecular formula: C19H15Cl　Molecular weight: 278.78

ABSTRACT

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

Triphenylchloromethane was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 12, 60 and 300 mg/kg.

Soft feces were observed in both sexes given 300 mg/kg and decrease in body weight gain was evident in females given 60 mg/kg and in both sexes given 300 mg/kg. A temporary decrease in food consumption was observed in both sexes given 300 mg/kg in the early stage of the administration and an increase in food consumption was observed in males given 60 or 300 mg/kg in the latter half of the treatment period. Hematological and blood chemical examinations revealed increases in fibrinogen, GPT activity and total cholesterol and a decrease in glucose in both sexes and increases in platelet count, blood urea nitrogen, total protein, phospholipids, total bilirubin and calcium and prolongations of PT and APTT in males given 300 mg/kg. An increase in blood urea nitrogen in males and a decrease in glucose in females were also observed in the 60 mg/kg group. A decrease in urinary pH was observed in males given 60 or 300 mg/kg along with an increase in water intake in males given 300 mg/kg. Dark discoloration and large size of the liver were observed in males given 300 mg/kg and increased liver weights and hypertrophy of centrilobular hepatocytes were observed in both sexes given 60 or 300 mg/kg. Mucosal thickening of the cecum was evident in females given 60 mg/kg and both sexes given 300 mg/kg. Increased kidney weights were observed in both sexes given 300 mg/kg. All the changes described above had disappeared or were diminished after a 14-day recovery period. The NOEL is considered to be 12 mg/kg/day for both sexes.

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

Genotoxicity of triphenylchloromethane was studied by a chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

Triphenylchloromethane did not induce either structural chromosomal aberrations or polyploidy at any dose, with or without metabolic activation.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:99.5 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Doses:0 (vehicle), 2000 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:Olive oil
GLP:Yes

　Test results:

No deaths occurred of either males or females in any of the treated groups. No effects were detected in terms of general condition, body weight changes or autopsy.

LD50: Males, >2000 mg/kg; females, >2000 mg/kg

2. Repeat Dose Oral Toxicity 1)

Purity:99.5 %
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), 12, 60, 300 mg/kg/day
　Number of animals/groupMales, 6; females, 6
　Vehicle:Olive oil
　Administration period:Males and females, 28 days
　Terminal kill:Days 29 or 43
GLP:Yes

　Test results:

Soft feces were observed in both sexes given 300 mg/kg. Decreased body weight gain was observed in females given 60 mg/kg and in both sexes given 300 mg/kg. A temporary decrease in food consumption was observed in both sexes given 300 mg/kg in the early stage of the administration and an increase in food consumption was observed in males given 60 or 300 mg/kg in the latter half of the treatment period. Hematological and blood chemical examinations revealed increases in fibrinogen, GPT and total cholesterol and a decrease in glucose in both sexes and increases in platelet count, blood urea nitrogen, total protein, phospholipids, total bilirubin and calcium and prolongations of PT and APTT in males given 300 mg/kg. An increase in blood urea nitrogen in males and a decrease in glucose in females were also observed in the 60 mg/kg group. Decrease in urinary pH was observed in males given 60 and 300 mg/kg and increase in water intake was observed in males given 300 mg/kg. Dark discoloration and large size of the liver were observed in males given 300 mg/kg and increased liver weight and hypertrophy of the centrilobular hepatocytes were evident in both sexes given 60 or 300 mg/kg. Mucosal thickening of the cecum was observed in females given 60 mg/kg and both sexes given 300 mg/kg. Increased kidney weights were observed in both sexes given 300 mg/kg. All the changes described above had disappeared or were diminished after a 14-day recovery period.

The NOEL is considered to be 12 mg/kg/day for both sexes.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:99.5 LC%
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:Anhydrous 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 (five strains)
　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 (five strains), 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:[ ][ ][*]

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

Purity:99.5 LC%
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:0.5 vol% Carboxymethyl cellulose sodium solution
　Positive controls:-S9 mix; Mitomycin C
+S9 mix; Cyclophosphamide
　Dosage:-S9 mix (6 hr short-term treatment); 0, 0.70, 1.4, 2.8 mg/mL
+S9 mix (6 hr short-term treatment); 0, 0.70, 1.4, 2.8 mg/mL
-S9 mix (24 hr continuous treatment); 0, 0.70, 1.4, 2.8 mg/mL
　S9:Rat liver, induced with phenobarbital and 5, 6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

Cytogenetic effects were not seen under the conditions of this experiment.

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

1)The tests were performed by the Bozo Research Center Inc., 1284 Kamado, Gotemba-shi, Shizuoka, 412-0039, Japan. Tel & Fax +81-550-82-9922
2)The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257-8523, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627