1,1,1-Tris(hydroxymethyl)ethane was studied for oral toxicity in rats in a single dose toxicity test at doses of 2000 mg/kg. An LD50 value of more than 2000 mg/kg was found for both sexes.
1,1,1-Tris(hydroxymethyl)ethane 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.
With regard to repeat dose toxicity, no adverse effects were noted for general condition, body weight and food consumption in any treated male and female animals except for slight suppression of body weight gain in females in the 1000 mg/kg/day group. In males, slight increase in GOT and GPT, and decrease in the plasma glucose concentration were observed in the 1000 mg/kg/day group. Histopathological examination of male and female animals revealed no adverse effects of this compound.
With regard to reproductive and developmental toxicity, no adverse effects were observed on copulation, ovulation, fertility, delivery, and lactation in any group. Administration of the compound did not affect the viability, sex ratio, body weight or morphological appearance of pups.
In conclusion, the NOEL for repeat dose toxicity of this compound is considered to be 300 mg/kg/day in male and female animals, and that for reproductive and developmental toxicity was 1000 mg/kg/day in males and females.
1,1,1-Tris(hydroxymethyl)ethane was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.
1,1,1-Tris(hydroxymethyl)ethane did not induce structural chromosomal aberrations and polyploidy in CHL cells, with or without an exogenous metabolic activation system.
| Purity | : | 99.0 % |
| Test species/strain | : | Rat/Crj:CD(SD) |
| Test method | : | OECD Test Guideline 401 |
| Doses | : | 2000 mg/kg |
| Number of animals/group | : | Males, 5; females, 5 |
| GLP | : | Yes |
Test results:
LD50: Male, > 2000 mg/kg; female, > 2000 mg/kg
| Purity | : | 99.0 % |
| Test species/strain | : | Rat/Crj:CD(Sprague-Dawley) |
| Test method | : | OECD Combined Repeat Dose and Reproductive/ Developmental Toxicity Screening Test |
| Route | : | Oral(Gavage) |
| Dosages | : | 0(vehicle), 100, 300, 1000 mg/kg/day |
| Number of animals/group | : | Males, 13; females, 13 |
| Vehicle | : | Distilled water |
| Administration period | : | Males, 42 days Females, from 14 days prior to mating to day 3 of lactation |
| Terminal kill | : | Male, day 43 Females, day 4 of lactation |
| GLP | : | Yes |
Test results:
In the male animals, no adverse effects were noted on general condition, body weight gain or food consumption when administered even at the highest dose level, 1000 mg/kg. At autopsy, there were no changes related to the administration of the compound in organ weight and the findings of histopathological and hematological examination. Although no histopathological changes were found in any organ, slight increase in the activities of GOT and GPT, and decrease in serum glucose concentration in the 1000 mg/kg group suggested that the compound may have affected hepatic function.
In the female animals, body weight gain during the pregnancy period was slightly suppressed, but there were no changes in general condition or food consumption in the 1000 mg/kg group. No adverse effects were observed on body weight during non-pregnancy, organ weight on postpartum day 4, or regarding findings of histopathological examination in any group.
< Reproductive and developmental toxicity>
No adverse effects were observed on copulation, ovulation, fertility, maintenance of pregnancy, delivery and lactation in any group. Administration of the compound did not affect the viability, sex ratio, body weight change, or morphological appearance of offspring.
The no adverse effect dose level(NOEL)for toxicity of the compound is considered to be 300 mg/kg/day in males and females, and that for reproductive and developmental toxicity is 1000 mg/kg/day in males and females.
| Purity | : | 99.0 % |
| Test species/strains | : | S. typhimurium TA100, TA1535, TA98, TA1537 E. coli WP2 uvrA |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guidelines No. 471 and 472 |
| Procedures | : | Pre-incubation method |
| Solvent | : | Distilled water |
| Positive controls | : | -S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98 and WP2 uvrA), Sodium azide(TA1535), 9-Aminoacridine hydrochloride(TA1537) +S9 mix; 2-Aminoanthracene(all strains) |
| Doses | : | -S9 mix; 156, 313, 625, 1250, 2500 and 5000 μg/plate +S9 mix; 156, 313, 625, 1250, 2500 and 5000 μg/plate |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 3 |
| Number of replicates | : | 2 |
| GLP | : | Yes |
Test results:
Genetic effects:
S. typhimurium TA100, TA1535, TA98 and TA1537
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
E. coli WP2 uvrA
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
| Purity | : | 99.0 % |
| Type of cell used | : | Chinese hamster lung(CHL)cells |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guideline No. 473 |
| Solvent | : | Saline |
| Positive controls | : | -S9 mix, Mitomycin C +S9 mix, Cyclophosphamide |
| Doses | : | -S9 mix(continuous exposure): 0, 300, 600, 1200 μg/mL -S9 mix(short-term exposure): 0, 300, 600, 1200 μg/mL +S9 mix(short-term exposure): 0, 300, 600, 1200 μg/mL |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 2 |
| GLP | : | Yes |
Test results:
Genetic effects:
| clastogenicity | polyploidy | |||||
| + | ? | - | + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] | [ ] | [ ] | [*] |
| 1) | The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257-0025, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627 |
| 2) | The tests were performed by the Biosafety Research Center, Foods, Drugs and Pesticides(An-pyo Center), Japan, 582-2 Shioshinden Arahama, Fukude-cho, Iwata-gun, Shizuoka, 437-1213, Japan. Tel +81-538-58-1266 Fax +81-538-58-1393 |