4,4’-Isopropylidenebis(2,6-dibromophenol)

4,4'-イソプロピリデンビス(2,6-ジブロモフェノール)


[CAS No. 79-94-7]

2,2',6,6'-Tetrabromobisphenol A

2,2',6,6'-テトラブロモビスフェノールA

Molecular formula: C15H12Br4O2　Molecular weight: 543.87

ABSTRACT

The single oral dose LD50 of 4,4'-isopropylidenebis(2,6-dibromophenol) was found to be more than 2000 mg/kg.

Oral toxicity of 4,4'-isopropylidenebis(2,6-dibromophenol) was studied in a 28-day repeat dose toxicity test in rats. Dose levels were 0, 8, 40, 200, and 1000 mg/kg.

No animals died or became moribund.

There were no changes in clinical observation, body weight, food consumption, hematological examination, blood chemical examination, urinalysis or pathological examination.

The NOEL is considered to be 1000 mg/kg/day for males and females from this study.

A reverse mutation test of 4,4'-isopropylidenebis(2,6-dibromophenol) on bacteria was carried out. This substance was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

Genotoxicity of 4,4'-isopropylidenebis(2,6-dibromophenol) was studied by chromosomal aberration test using cultured Chinese hamster lung (CHL/IU) cells.

4,4'-Isopropylidenebis(2,6-dibromophenol) did not induce structural chromosomal aberrations or polyploidy at any dose, with or without a metabolic activation system.

SUMMARIZED DATA OF 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)
　Dosage:0(vehicle), 2000 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:0.5 % CMC-Na aqueous solution mixed with 0.1 % Tween 80
GLP:Yes

　Test results:

No deaths occurred in males and females given 2000 mg/kg. No abnormalities were observed for clinical observation, body weight and necropsy.

The LD50 value was considered to be more than 2000 mg/kg for males and females.

2. Repeat Dose 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), 8, 40, 200, 1000 mg/kg/day
　Number of animals/group:Males, 12; females, 12(0, 200, 1000 mg/kg)
Males, 6; females, 6(8, 40 mg/kg)
　Vehicle:0.5 % CMC-Na aqueous solution mixed with 0.1 % Tween 80
　Administration period:Males and females, 28 days
　Terminal kill:Days 29 and 43
GLP:Yes

　Test results:

No animals died or became moribund. No changes were observed in body weights, food consumption, hematological examination, blood chemical examination, urinalysis or pathological examination.

The NOEL was considered to be 1000 mg/kg/day for males and females in this study.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:99.5 %
Test species/strains:Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testings of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 471
　Procedures:Pre-incubation method
　Solvent: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)
　Doses:-S9 mix; 0, 78.1, 156, 313, 625, 1250, 2500 μg/plate(TA100)
-S9 mix; 0, 19.5, 39.1, 78.1, 156, 313, 625 μg/plate(TA1535)
-S9 mix; 0, 156, 313, 625, 1250, 2500, 5000 μg/plate(WP2 uvrA, TA98)
-S9 mix; 0, 4.88, 9.77, 19.5, 39.1, 78.1, 156 μg/plate(TA1537)
+S9 mix; 0, 156, 313, 625, 1250, 2500, 5000 μg/plate(TA100, TA98, TA1535, WP2 uvrA)
+S9 mix; 0, 9.77, 19.5, 39.1, 78.1, 156, 313 μg/plate(TA1537)
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavon
　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, TA1535, TA98, TA1537 and E. coli WP2 uvrA strains with or without S9 mix. Toxicity was observed at 156 μg/plate (TA1537), at and above 313 μg/plate (TA1535) and at 2500 μg/plate (TA100) without S9 mix and at and above 156 μg/plate (TA1537) with S9 mix. No toxicity was observed in other strains up to 5000 μg/plate (WP2 uvrA, TA98) without S9 mix and up to 5000 μg/plate (TA100, TA1535, TA98, WP2 uvrA) mix with 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 %
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:Dimethyl sulfoxide
　Positive controls:-S9 mix; Mitomycin C
+S9 mix; Cyclophosphamide
　Doses:-S9 mix(short-term treatment); 0, 0.0016, 0.0033, 0.0065 mg/mL
+S9 mix(short-term treatment); 0, 0.0075, 0.015, 0.030 mg/mL
-S9 mix(continuous treatment for 24 hr); 0, 0.015, 0.030, 0.060 mg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

Neither structural chromosome aberrations nor polyploidy were manifested in any treatment system.

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

1)The tests were performed by the 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
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