The single doses were 0, 500, 700, 1000, 1400 mg/kg, and revealed LD50 values of 693 mg/kg for males and 856 mg/kg for females.
In the 28-day repeat dose toxicity test, males and females given 720 mg/kg showed tremors and salivation. Their body weights were reduced on Day 2, and suppressed thereafter in males. Regarding food consumption, males given 240 mg/kg had low values on Day 2, and males and females given 720 mg/kg low values in some cases. On urinalysis, males and females given 80 mg/kg or more showed brownish black urine and increase in volume with water consumption. Females given 720 mg/kg showed decrease of specific gravity. An anemic condition was evident in males at the end of the recovery period, and in females at the end of the administration period. Males and females given 720 mg/kg showed increase in GPT and total bilirubin, and males also showed increase in total cholesterol and trigriceride. At autopsy, males and females given 720 mg/kg showed discoloration of the liver and spleen, and females of the kidney. Males and females given 720 mg/kg showed increase in absolute and relative weights of spleen, and relative liver and kidney weights. On histopathological examination, females given 240 mg/kg and males and females given 720 mg/kg showed brown pigment in renal proximal tubular epithelium, and deposition of hemosidelin in spleen. Males and females given 720 mg/kg also demonstrated deposition of brown pigment in Kupffer cells, and hypertrophy of thyroid follicular cells. All these changes appeared to be reversible.
The NOELs are considered to be less than 80 mg/kg/day for males and females.
A reverse mutation test of 3-aminophenol 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 3-aminophenol was studied by chromosomal aberration test using cultured Chinese hamster lung (CHL/IU) cells. 3-Aminophenol induced structural chromosomal aberrations at three doses (0.034-0.14 mg/mL) on continuous treatment for 24 hr without metabolic activation.
| Purity | : | 99.70 % |
| Test species/strain | : | Rat/Crj:CD(SD)IGS |
| Test method | : | OECD Test Guideline 401 |
| Route | : | Oral(gavage) |
| Doses | : | 0(vehicle), 500, 700, 1000, 1400 mg/kg |
| Number of animals/group | : | Males, 5; Females, 5 |
| Vehicle | : | 1 % carboxymethylcellulose sodium |
| GLP | : | Yes |
Test results:
The LD50 values were estimated to be 693 mg/kg for males and 856 mg/kg for females.
| Purity | : | 99.70 % |
| 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), 80, 240, 720 mg/kg/day |
| Number of animals/group | : | Males and females, 14, 7, 7 and 14/group for the 0, 80, 240 and 720 mg/kg, respectively |
| Vehicle | : | 1 % Carboxymethylcellulose sodium |
| Administration period | : | Males and females, 28 days |
| Terminal kill | : | Days 29 and 43 |
| GLP | : | Yes |
Test results:
The NOELs are considered to be less than 80 mg/kg/day for males and females.
| Purity | : | 99.70 % |
| 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 | : | 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, 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-benzoflavon |
| Plates/test | : | 3(1 for cytotoxicity test) |
| Number of replicates | : | 2(plus 1 cytotoxicity test) |
| 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 | : | 99.70 % |
| 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 | : | Distilled water |
| Positive controls | : | -S9 mix; Mitomycin C +S9 mix; Cyclophosphamide |
| Doses | : | -S9 mix(short-term treatment); 0, 0.28, 0.55, 1.1 mg/mL +S9 mix(short-term treatment); 0, 0.015, 0.030, 0.060 mg/mL -S9 mix(continuous treatment for 24 hr); 0, 0.034, 0.069, 0.14 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 (continuous treatment) | : | 0.034 mg/mL(clastogenicity) |
Genotoxic effects:
| clastogenicity | polyploidy | |||||
| + | ? | - | + | ? | - | |
| Without metabolic activation: | [*] | [ ] | [ ] | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] | [ ] | [ ] | [*] |
| 1) | The tests were performed by the Safety Research Institute for Chemical Compounds Co., Ltd., 363-24, Shin-ei, Kiyota-ku, Sapporo, Hokkaido, 004-0839, Japan. Tel +81-11-885-5031 Fax +81-11-885-5313 |
| 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 |