Dibutyl adipate was studied in a 28-day repeat dose oral toxicity in rats at doses of 0, 20, 140, and 1000 mg/kg/day. Genotoxicity of Dibutyl adipate was also studied by the reverse mutation assay in bacteria and the chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.
No test substance-related changes were noted in terms of clinical observation, body weight, foods consumption, and the findings obtained from hematology tests, blood chemical examination, urinalysis, and pathological examination. The NOELs for the repeat dose toxicity are considered to be over 1000 mg/kg/day for both sexes.
Dibutyl adipate was not mutagenic in Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA.
This chemical substance dose-dependently induced structural chromosomal
aberrations at the low (0.7 mg/ml) and mid (1.3 mg/ml) concentrations
in the presence of an exogenous metabolic activation system. Polyploid
cells were not found.
| Purity | : | 99.8% | ||
| Test species/strain | : | Rat/Crj:CD (SD) | ||
| Test method | : | Guidelines for 28-Day Repeat Dose Toxicity Test of Chemicals (Japan) | ||
| Route | : | Oral (gavage) | ||
| Doses | : | 0 (vehicle), 20, 140, 1000 mg/kg/day | ||
| Number of animals | : | Males, 6 or 12/group (0, 1000 mg/kg/day) | ||
| Females, 6 or 12/group (0, 1000 mg/kg/day) | ||||
| Vehicle | : | Olive oil | ||
| Administration period | : | Males and females, 28 days | ||
| Terminal kill | : | Days 29 or 43 | ||
| GLP | : | Yes | ||
| Test results: | |
| No test substance-related changes were noted in clinical observations, body weights, food consumption, and the findings obtained from hematology testing, blood chemical examination, urinalysis, and pathological examination. The NOELs for the repeat dose toxicity are considered to be over 1000 mg/kg/day for both sexes. |
| Purity | : | 99.8% | ||
| Test species/strains | : | S.typhimurium TA100, TA1535, TA98, TA1537 | ||
| E. coli WP2 uvrA | ||||
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) | ||
| Procedures | : | Plate incorporation method | ||
| Solvent | : | DMSO | ||
| Positive controls | : | -S9, AF-2 (TA100, WP2, TA98) sodium azide (TA1535) and 9-aminoacridine (TA1537) | ||
| +S9, 2-aminoanthracene (all strains) | ||||
| Doses | : | 0, 312.5, 625, 1250, 2500, 5000 ug/plate | ||
| S-9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone | ||
| Plates/test | : | 3 | ||
| Number of replicates | : | 2 | ||
| GLP | : | Yes | ||
| Test results: | ||||||||
| Minimum concentration of test substance at which toxicity was not observed: | ||||||||
| Toxicity was observed at a concentration of 5000 ug/plate without metabolic activation in TA100. | ||||||||
| Genetic effects : | ||||||||
| S. typhimurium TA100, TA1535, TA 98, TA1537 | ||||||||
| + | ? | - | ||||||
| without metabolic activation: | [ ] | [ ] | [*] | |||||
| with metabolic activation: | [ ] | [ ] | [*] | |||||
| E. 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) | ||
| Solvent | : | Dimethyl sulfoxide | ||
| Positive controls | : | -S9, Mitomycin C | ||
| +S9, Cyclophosphamide | ||||
| Doses | : | -S9 (continuous treatment): 0, 0.7, 1.3, 2.6 mg/ml | ||
| -S9 (short-term treatment): 0, 0.012, 0.023, 0.046 mg/ml | ||||
| +S9 (short-term treatment): 0, 0.7, 1.3, 2.6 mg/ml | ||||
| S-9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone | ||
| Plates/test | : | 2 | ||
| GLP | : | Yes | ||
| Test results: | |||||||||||
|
Cytogenetic effects were seen as follows. At the low (0.7 mg/ml) and mid (1.3 mg/ml) concentrations in the short term treatment with metabolic activation, 6.5 and 12.0% cells demonstrated structural chromosomal aberrations including gaps. | |||||||||||
| Lowest concentration producing cytogenetic effects in vitro: | |||||||||||
| with metabolic activation (short-term treatment): 0.7 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, 314-02, 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, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627 |
Dibutyl adipate was studied for oral toxicity in rats in an OECD preliminary reproduction toxicity screening test at doses 0, 100, 300 and 1000 mg/kg/day.
No animals were found dead in any groups. There were no adverse effects on general condition. Slight suppression of body weight gain was observed in male rats in the 1000 mg/kg group, while body weight change and food consumption of female rats in all dibutyl adipate-treated groups were comparable to those in the control group. Macroscopic findings at necropsy and histological findings for internal genitalia showed no abnormalities associated with the administration of dibutyl adipate. Kidney weights were increased in both sexes in the 1000 mg/kg group compared to the control group values.
There were no adverse effects of this compound on copulation, ovulation, fertility, parturition or lactation.
In the 1000 mg/kg group, pup weight on postnatal days 0 and 4 was slightly decreased, along with viability on postnatal day 4 as compared with those for the control group. However, there were no malformations which were related to the administration of dibutyl adipate.
In conclusion, the no observed effect level (NOEL) for toxicity of dibutyl adipate in parent animals as administered under the condition of the present study is considered to be 300 mg/kg/day, that for reproductive toxicity to be 1000 mg/kg/day, and that in offspring to be 300 mg/kg/day.
| Purity | : | 99.0 and more wt% |
| Test species/strain | : | Rat/Crj:CD (Sprague-Dawley) |
| Test method | : | OECD Preliminary Reproduction Toxicity Screening Test |
| Route | : | Oral (Gavage) |
| Doses | : | 100, 300, 1000 mg/kg/day |
| Number of animals/group | : | Males, 13; Females, 13 |
| Vehicle | : | Corn oil |
| Administration period | : | Males, 42 days, Females, from 14 days prior to mating to day 3 of lactation |
| Terminal killing | : | Males, day 43, Females, day 4 of lactation |
| GLP | : | Yes |
Test results:
<Maternal and paternal general toxicity>
| 1) | The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627 |