A single oral dose toxicity test revealed an LD50 value of more than 2000 mg/kg for both sexes.
2-Ethylhexyl methacrylate 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. One female died in the 1000 mg/kg group(12 animals of each sex).
In the males, the absolute kidney weights and the relative pituitary, liver and kidney weights were increased in the 300 and 1000 mg/kg groups. Suppression of body weight gain, decreased food consumption, RBC, hemoglobin, hematocrit, WBC and total protein, and increased GOT, GPT, A/G ratio, BUN and Cl, as well as focal necrosis in the liver and decreased extramedullary hematopoiesis in the spleen were seen in the 1000 mg/kg group. In the females, the relative kidney weights were increased in the 100 mg/kg or more groups. Suppression of body weight gain during the pre-mating, pregnancy and lactation periods and decrease in food consumption during the pre-mating period, atrophy of the thymus, increased absolute kidney, relative thyroid and liver weights, and decreased extramedullary hematopoiesis in the spleen and focal malacia in the medulla oblongata were seen in the 1000 mg/kg group. The NOELs for repeat dose toxicity are considered to be 100 mg/kg for males, and 30 mg/kg for females.
With regard to reproductive/developmental toxicity, three of the seven females lost their pups in the 1000 mg/kg group. Numbers of corpora lutea and implantation scars were decreased in the 1000 mg/kg group. The NOELs for reproductive performance are considered to be 1000 mg/kg for males, and 300 mg/kg for females.
With regard to pups, decreased numbers of live pups born were seen in the 300 and 1000 mg/kg groups. Decreased birth, live birth and viability indices, and decreased body weights of both sexes on day 0 and day 4 after birth were seen in the 1000 mg/kg group. The NOEL for pup development is considered to be 100 mg/kg.
2-Ethylhexyl methacrylate was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2uvrA.
2-Ethylhexyl methacrylate did not induce structural chromosomal aberrations or polyploidy in CHL/IU cells, with or without an exogenous metabolic activation system.
| Purity | : | 99.4 % |
| Test species/strain | : | Rat/Crj:CD(SD)IGS |
| Test method | : | OECD Test Guideline 401 |
| Route | : | Oral(gavage) |
| Doses | : | 0(vehicle), 500, 1000, 2000 mg/kg/day |
| Number of animals/group | : | Males, 5; females, 5 |
| Vehicle | : | Corn oil |
| GLP | : | Yes |
Test results:
Based on the above results, the LD50 value of 2-ethylhexyl methacrylate was concluded to be more than 2000 mg/kg for both sexes.
| Purity | : | 99.4 % |
| Test species/strain | : | Rat/Crj:CD(SD)IGS |
| 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, 12; females, 12 |
| Vehicle | : | Corn oil |
| Administration period | : | Males, 49 days Females, from 14 days before mating to day 3 of lactation |
| Terminal kill | : | Males, day 50 Females, day 4 of lactation |
| GLP | : | Yes |
Test results:
For the males, the absolute kidney weights and the relative pituitary, liver and kidney weights were increased in the 300 and 1000 mg/kg groups. Suppression of body weight gain and decreased food consumption, RBC, hemoglobin, hematocrit, WBC and total protein, and increased GOT, GPT, A/G ratio, BUN and Cl, as well as focal necrosis in the liver and decrease of extramedullary hematopoiesis in the spleen were seen in the 1000 mg/kg group.
For the females, the relative kidney weights were increased in the 100 mg/kg or more groups. Suppression of body weight gain during the pre-mating, pregnancy and lactation periods, decrease in food consumption during the pre-mating period, atrophy of the thymus, the increased absolute kidney, relative thyroid and liver weights, and decrease of extramedullary hematopoiesis in the spleen and focal malacia in the medulla oblongata were seen in the 1000 mg/kg group, one animal of which died.
The NOELs for repeat dose toxicity are considered to be 100 mg/kg for males, and 30 mg/kg for females.
<Reproductive/Developmental Toxicity>
With regard to reproductive/developmental toxicity, three of the seven females lost their pups in the 1000 mg/kg group. Nos. of corpora lutea and implantation scars were decreased in the 1000 mg/kg group. The NOELs for reproductive performance are considered to be 1000 mg/kg for males, and 300 mg/kg for females.
With regard to pups, decreased numbers of live pups born were seen in the 300 and 1000 mg/kg groups. Decreased birth, live birth and viability indices, and decreased body weights of both sexes on day 0 and day 4 after birth were seen in the 1000 mg/kg group. The NOEL for pup development is considered to be 100 mg/kg.
| Purity | : | 99.4 % |
| 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 Guidelines No. 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; 39.1, 19.5, 9.77, 4.88, 2.44, 1.22, 0.610 μg/plate(TA100, TA1535, TA1537); 313, 625, 1250, 2500, 5000 μg/plate(WP2 uvrA,TA98) +S9 mix; 625, 313, 156, 78.1, 39.1, 19.5, 9.77 μg/plate (TA100, TA1535, TA1537); 39.1, 78.1, 156, 313, 625, 1250, 2500 μg/plate(WP2 uvrA, TA98) |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 3 |
| Number of replicates | : | 2 |
| GLP | : | Yes |
Test results:
Genotoxic effects:
S. typhimurium TA100, TA1535, TA98, TA1537
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
E. coli WP2 uvrA
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
| Purity | : | 99.4 % |
| 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 | : | Acetone |
| Positive controls | : | -S9 mix, Mitomycin C +S9 mix, Benzo[a]pyrene |
| Doses | : | -S9 mix(24 hr continuous treatment): 0, 10, 20, 40, 80 μg/mL -S9 mix(48 hr continuous treatment): 0, 10, 20, 40, 80 μg/mL -S9 mix(6 hr short-term treatment): 0, 10, 20, 40, 80 μg/mL +S9 mix(6 hr short-term treatment): 0, 625, 1250, 2500, 5000 μg/mL |
| 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: | [ ] | [ ] | [*] | [ ] | [ ] | [*] |
| 1) | The test was performed by Nihon Bioresearch Inc. Hashima Laboratory, 6-104 Majima, Fukuju-cho, Hashima, Gifu, 501-6251, Japan Tel +81-58-392-6222 Fax +81-58-391-3171 |
| 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 |