3-Methylbenzoic acid was studied for oral toxicity in rats in a single dose oral toxicity test at doses of 0, 1000 and 2000 mg/kg. An LD50 value of more than 2000 mg/kg was found for both sexes.
3-Methylbenzoic acid was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 30, 100, 300 and 1000 mg/kg/day.
With regard to repeat dose toxicity in males, decreased locomotor activity was detected in the 1000 mg/kg group. Hematological and blood chemical examinations revealed increases in prothrombin time and GOT, and a decrease in platelet counts in the 1000 mg/kg group. An increase in relative weight of the pituitary was observed in the 1000 mg/kg group. In females, histopathological examinations revealed hepatocellular vacuolar degeneration in the 300 and 1000 mg/kg groups. Absolute and relative liver weights were increased in the 1000 mg/kg group. The NOELs for repeat dose toxicity are considered to be 300 mg/kg/day for males and 100 mg/kg/day for females. In terms of reproductive and developmental toxicity, the test substance showed no effects on any reproductive parameters of the parental animals or developmental parameters of the offspring. The NOELs for reproductive/developmental toxicity are considered to be 1000 mg/kg/day for reproductive performance of parental animals and offspring development.
3-Methylbenzoic acid was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.
3-Methylbenzoic acid induced structural chromosomal aberrations in CHL/IU cells with 6 hr short-term treatment without an S9 mix and on continuous treatment for 48 hr. Polyploid cells were not induced in any treatment group.
| Purity | : | 98.79 % |
| Test species/strain | : | Rat/Crj:CD(SD) |
| Test method | : | OECD Test Guideline 401 |
| Route | : | Oral (gavage) |
| Dosage | : | 0 (vehicle), 1000, 2000 mg/kg |
| Number of animals/group | : | Males, 5; females, 5 |
| Vehicle | : | 1 % methylcellulose solution |
| GLP | : | Yes |
Test results:
The LD50 value was estimated to be more than 2000 mg/kg for males and females.
| Purity | : | 98.79 % |
| Test species/strain | : | Rat/Crj:CD(SD) |
| Test method | : | OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test |
| Route | : | Oral (gavage) |
| Dosage | : | 0 (vehicle), 30, 100, 300, 1000 mg/kg/day |
| Number of animals/group | : | Males, 10; females, 10 |
| Vehicle | : | 1 % methylcellulose 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:
In males, decreased locomotor activity was detected in the 1000 mg/kg group. Hematological and blood chemical examinations revealed increases in prothrombin time and GOT, and a decrease in platelet counts in the 1000 mg/kg group. An increase in pituitary relative weights was observed in the 1000 mg/kg group. In females, histopathological examination revealed hepatocellular vacuolar degeneration in the 300 and 1000 mg/kg groups. Absolute and relative liver weights were increased in the 1000 mg/kg group.
The NOELs for repeat dose toxicity are considered to be 300 mg/kg/day for males and 100 mg/kg/day for females.
<Reproductive and developmental toxicity>
The parental animals exhibited no alteration in reproductive parameters. There were no significant differences in offspring parameters.
The NOELs for reproductive/developmental toxicity are considered to be 1000 mg/kg/day for reproductive performance of parental animals and offspring development.
| Purity | : | 98.79 % |
| Test species/strain | : | Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Test Guidelines 471 and 472 |
| Procedures | : | Pre-incubation method |
| Solvent | : | DMSO |
| Positive controls | : | -S9 mix; AF-2 (TA100, TA98), Sodium azide (TA1535), ENNG (WP2 uvrA) and 9-Aminoacridine (TA1537) +S9 mix; 2-Aminoanthracene (all strains) |
| Doses | : | -S9 mix; 156, 313, 625, 1250, 2500 and 5000 μg/plate +S9 mix; 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:
Salmonella typhimurium TA100, TA1535, TA98, TA1537
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
Escherichia coli WP2 uvrA
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
| Purity | : | 98.79 % |
| Type of cell used | : | Chinese hamster CHL/IU cells |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Test Guideline 473 |
| Solvent | : | DMSO |
| Positive controls | : | -S9 mix, Mitomycin C +S9 mix, Benzo[a]pyrene |
| Doses | : | -S9 mix (24 hr continuous treatment); 0, 250, 500, 1000, 2000 μg/mL -S9 mix (48 hr continuous treatment); 0, 62.5, 125, 250, 500, 1000 μg/mL -S9 mix (6 hr short-term treatment); 0, 250, 500, 1000, 2000 μg/mL (main test) 0, 1000, 1500, 2000 μg/mL (confirmation test) +S9 mix (6 hr short-term treatment); 0, 250, 500, 1000, 2000 μg/mL (main test) 0, 500, 750, 1000 μg/mL (confirmation test) |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 2 |
| GLP | : | Yes |
Test results:
Genotoxic effects:
| clastogenicity | polyploidy | |||||
| + | ? | - | + | ? | - | |
| Without metabolic activation: | [*†] | [ ] | [ ] | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] | [ ] | [ ] | [*] |
| † | : | 6 hr short term treatment and 48 hr continuous treatment |
| 1) | The tests were performanced by the Research Institute for Animal Science in Biochemistry and Toxicology, 3-7-11 Hashimotodai, Sagamihara-shi, Kanagawa, 229-1132, Japan. Tel +81-42-762-2775 Fax +81-42-762-7979 |
| 2) | 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 |