2,4,6-Tribromophenol was studied for oral toxicity in rats of both sexes in a single dose toxicity test at doses of 1000, 1300, 1690, 2197 and 2856 mg/kg. This revealed a LD50 value of 1486 mg/kg for both sexes.
2,4,6-Tribromophenol was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 100, 300 and 1000 mg/kg/day.
In the repeat toxicity, no mortalities were observed in any treatment group. Salivation in the 300 mg/kg or more groups was observed in both sexes. Body weight gain and food consumption were decreased in the 1000mg/kg animals of both sexes. There were no adverse effects of the test substance on hematology and coagulation parameters in male rats. On blood chemistry examination, increase in creatinine was observed in the 300 mg/kg or more groups and total protein, albumin, A/G and ALP were significantly increased in the 1000 mg/kg group. Further, BUN tended to increase and total bilirubin and potassium decreased significantly in the same group. Increases in liver and kidney weights in both sexes and decreases in thymus weights in male were observed in the 1000 mg/kg group. As gross necropsy findings, enlargement of liver was observed and histologically the incidence of hepatocyte hypertrophy was increased whereas that of fatty change was decreased in the 1000 mg/kg group males. In addition, renal papillary necrosis, dilatation of tubules, lymphocytes infiltration, basophilic tubular epithelium and hyaline casts were observed in the kidney of the same group of males.
On the basis of these findings, the NOEL for repeat dose toxicity in parent animals of both sexes is considered to be 100 mg/kg/day.
In terms of reproductive/developmental toxicity, no adverse effects were observed in estrus cycle, copulation, fertility results and duration of gestation period as well as findings for delivery, number of corpora lutea, implants, total pups and live pups born and implantation and delivery indices in any treatment groups. With regard to the effects on neonates, viability on day 4 of lactation and body weights on days 0 and 4 of lactation in the 1000 mg/kg group were lowered in both sexes.
In conclusion, NOELs for reproductive/developmental toxicity are considered to be 1000 mg/kg/day for parents, and 300 mg/kg/day for the F1 generation, respectively.
2,4,6-Tribromophenol 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 2,4,6-tribromophenol was studied by chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells. On the short-term treatment, 2,4,6-tribromophenol induced structural chromosomal aberrations at high doses of 0.10 mg/mL and 0.050 mg/mL, with and without metabolic activation systems, respectively. No polyploidy was induced.
| Purity | : | 99.8 wt% |
| Test species/strain | : | Rat/Crj:CD(SD) |
| Test method | : | OECD Test Guideline 401 |
| Route | : | Oral (gavage) |
| Doses | : | 1000, 1300, 1690, 2197, 2856 mg/kg |
| Number of animals/group | : | Males, 5; females, 5 |
| Vehicle | : | Corn oil |
| GLP | : | Yes |
Test results:
The LD50 value was 1486 mg/kg for both sexes.
| Purity | : | 99.8 wt% |
| Test species/strains | : | Rat/Crj:CD(SD) |
| Test method | : | OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test |
| Route | : | Oral (gavage) |
| Doses | : | 0 (vehicle), 60, 200, 600mg/kg/day |
| Number of animals/group | : | Males, 12; females, 12 |
| Vehicle | : | Corn oil |
| Administration period | : | Males, 48 days Females, from 14 days before mating to day 3 of lactation |
| Terminal kill | : | Males, day 48 Females, day 4 of lactation |
| GLP | : | Yes |
Test results:
In the repeat dose study, no mortalities were observed in any treatment group. Salivation observed in both sexes in groups receiving 300 mg/kg or more. Body weight gain and food consumption were decreased in the 1000 mg/kg group. There were no adverse effects of the test substance on hematology and coagulation parameters in male rats. On blood chemistry examination, increased creatinine was observed in the 300 mg/kg or more groups and total protein, albumin, A/G and ALP increased significantly in the 1000 mg/kg group. Further, BUN tended to increase and total bilirubin and potassium decreased significantly in the same group.
Increases in liver and kidney weights in both sexes and decreased thymus weights were observed in 1000 mg/kg males. As gross necropsy findings, enlargement of liver was observed and histopathologically the incidence of hepatocyte hypertrophy was increased whereas that of fatty change was decreased in males of the 1000 mg/kg group. In addition, renal papillary necrosis, dilatation of tubules, cellular infiltration of lymphocyte, basophilic tubules and hyaline casts were observed in the kidney of the same group of males.
On the basis of these findings, the NOEL for repeat dose toxicity in parent animals of both sexes is considered to be 100 mg/kg/day.
<Reproductive and developmental toxicity>
In terms of reproductive/developmental toxicity, no adverse effects were observed on the estrus cycle, copulation, fertility results and duration of gestation period as well as findings for delivery, number of corpora lutea, implants, total pups and live pups born and implantation and delivery indices in any treatment groups. With regard to the effects on neonates, viability on day 4 of lactation and body weights on days 0 and 4 of lactation in 1000 mg/kg group were lowered in both sexes.
In conclusion, NOELs for reproductive/developmental toxicity are considered to be 1000 mg/kg/day for parents, and 300 mg/kg/day for the F1 generation, respectively.
| Purity | : | 99.8 % |
| Test species/strains | : | Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA |
| Test method | : | Guidelines for Screening Toxicity Testings of Chemicals (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, 15.6, 31.3, 62.5, 125, 250, 500 μg/plate (TA100, TA1535, TA98) 0, 31.3, 62.5, 125, 250, 500, 1000 μg/plate (TA1537) 0, 156, 313, 625, 1250, 2500, 5000 μg/plate (WP2 uvrA) +S9 mix; 0, 15.6, 31.3, 62.5, 125, 250, 500 μg/plate (TA100, TA1535, TA1537) 0, 31.3, 62.5, 125, 250, 500, 1000 μg/plate (TA98) 0, 156, 313, 625, 1250, 2500, 5000 μg/plate (WP2 uvrA) |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 3 |
| Number of replicates | : | 2 |
| GLP | : | Yes |
Test results:
Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98, TA1537
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
Escherichia coli WP2 uvrA
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
| Purity | : | 99.8 % |
| Type of cell used | : | Chinese hamster lung (CHL/IU) cells |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guideline 473 |
| Solvent | : | Dimethyl sulfoxide |
| Positive controls | : | -S9 mix, Mitomycin C +S9 mix, Cyclophosphamide |
| Doses | : | -S9 mix (24 hr continuous treatment); 0, 0.025, 0.050, 0.10 mg/mL -S9 mix (48 hr continuous treatment); 0, 0.013, 0.025, 0.050 mg/mL -S9 mix (short-term treatment); 0, 0.013, 0.025, 0.050 mg/mL +S9 mix (short-term treatment); 0, 0.025, 0.050, 0.10 mg/mL |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 2 |
| GLP | : | Yes |
Test results:
| Lowest concentration producing cytogenetic effects in vitro: | ||
| Without metabolic activation (short-term treatment) | : | 0.050 mg/mL |
| With metabolic activation (short-term treatment) | : | 0.10 mg/mL |
Genotoxic effects:
| clastogenicity | polyploidy | |||||
| + | ? | - | + | ? | - | |
| Without metabolic activation: | [*] | [ ] | [ ] | [ ] | [ ] | [*] |
| With metabolic activation: | [*] | [ ] | [ ] | [ ] | [ ] | [*] |
| 1) | The tests were performed by the Biosafety Research Center, Foods, Drugs and Pesticides (An-pyo Center), 582-2 Shioshinden Arahama, Fukude-cho, Iwata-gun, Shizuoka, 437-1213, Japan. Tel +81-538-58-1266 Fax +81-538-58-1393 |
| 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 |