Glycerol triacetate was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 40, 200 and 1000 mg/kg/day.
With regard to repeat dose toxicity, the compound had no general toxicological effects in both sexes. The NOEL for repeat dose toxicity is considered to be 1000 mg/kg/day for both sexes. In terms of reproductive/developmental toxicity, the compound had no effects on any relevant parameters. The NOEL for reproductive/developmental toxicity is considered to be 1000 mg/kg/day for parental animals and offspring.
Glycerol triacetate 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 glycerol triacetate was studied by the chromosomal aberration test with cultured Chinese hamster lung(CHL/IU)cells. Glycerol triacetate induced structural chromosomal aberrations at 2.2 mg/mL(10 mM, high conentration) on short-term treatment with an exogenous metabolic activation system. However, glycerol triacetate showed decreased pH(pH 4.9) value of the medium at 2.2 mg/mL on short-term treatment with an exogenous metabolic activation system. Therefore, it was suggested that the chromosome aberrations induced with glyceryl triacetate were caused by lowering of the pH of the medium rather than by DNA damage per se. Polyploidy was not induced under any conditions.
| Purity | : | 98.2 % |
| Test species/strain | : | Rats/Crj:CD(SD)IGS |
| Test method | : | OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test |
| Route | : | Oral(gavage) |
| Dosage | : | 0(Vehicle), 40, 200, 1000 mg/kg/day |
| Number of animals/group | : | Males, 12; females, 12 |
| Vehicle | : | 3 % gum arabic solution |
| Administration period | : | Males, 44 days Females, from 14 days before mating to day 3 of lactation |
| Terminal kill | : | Males, day 45 Females, day 4 of lactation |
| GLP | : | Yes |
Test results:
The compound had no effects on clinical signs, body weight, food consumption, organ weights or necropsy findings. No histopathological changes ascribable to the compound were observed in either sex. There were no effects on hematological or blood chemical parameters in males.
The NOEL for repeat dose toxicity is considered to be 1000 mg/kg/day for both sexes.
<Reproductive and developmental toxicity>
The compound had no effects on reproductive parameters such as the mating index, the fertility index, number of corpora lutea or implantations, the implantation index, the delivery index, the gestation index, gestation length, parturition or maternal behavior. On examination of neonates, there were no significant differences in numbers of offspring or live offspring, the sex ratio, the live birth index, the viability index or body weights. No abnormal findings ascribable to the compound were found for external features, clinical signs or necropsy of the offspring.
The NOEL for reproductive and developmental toxicity is considered to be 1000 mg/kg/day for parental animals and offspring.
| Purity | : | 98.2 % |
| Test species/strains | : | Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA |
| Test method | : | Guidelines for Screening Toxicity 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, 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 - 5000 μg/plate(five strains) |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 3 |
| Number of replicates | : | 2 and 3(WP2 uvrA without S9 mix) |
| 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 | : | 98.2 % |
| Type of cell used | : | Chinese hamster lung(CHL/IU)cells |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guideline No. 473 |
| Solvent | : | DMSO |
| Positive controls | : | -S9 mix, Mitomycin C +S9 mix, Cyclophosphamide |
| Doses | : | -S9 mix(continuous treatment): 0, 0.55, 1.1, 2.2 mg/mL -S9 mix(short-term treatment): 0, 0.55, 1.1, 2.2 mg/mL +S9 mix(short-term treatment): 0, 0.55, 1.1, 2.2 mg/mL |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 2 |
| GLP | : | Yes |
Test results:
Structural chromosomal aberrations(including gaps) were induced on short-term treatment with an exogenous metabolic activation system(2.2 mg/mL(10 mM):high concentration, 43.5%). However, glycerol triacetate decreased pH of the medium at 2.2 mg/mL on short-term treatment with an exogenous metabolic activation system. Therefore, it was suggested that the chromosome aberrations induced with glycerol triacetate were caused by lowering of the pH of the medium rather than by DNA damage per se. Polyploidy was not induced under any conditions.
Lowest concentration producing cytogenetic effects in vitro:
With metabolic activation(short-term treatment): 2.2 mg/mL(clastogenicity)
Genotoxic effects:
| clastogenicity | polyploidy | |||||
| + | ? | - | + | ? | - | |
| 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, 257-0025, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627 |