A single oral toxicity test revealed an LD50 value of more than 2000 mg/kg for divinylbenzene in both sexes.
Divinylbenzene 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 and one female became moribund in the 1000 mg/kg group(12 animals of each sex).
In the males, the relative liver weights were increased at 100 mg/kg or more groups. Suppression of body weight gain, increased absolute and relative kidney weights were seen at 300 mg/kg and 1000 mg/kg groups. Decreased food consumption, increased GPT, γ-GPT and total bilirubin, and decreased blood glucose were seen at 1000 mg/kg group. In the females, suppression of body weight gain during the pregnancy period, decrease in food consumption during the lactation period and increased relative kidney weights were seen at 300 mg/kg and 1000 mg/kg groups. Suppression of body weight gain and decrease in food consumption during the pre-mating, pregnancy and lactation periods, atrophy of the thymus, atrophy of marginal zone in the spleen, and degeneration/necrosis of the renal tuble of cortico-medullary junction in the kidney were seen at 1000 mg/kg group. The NOELs for repeat dose toxicity are considered to be 30 mg/kg/day for males, and 100 mg/kg/day for females.
With regard to reproductive/developmental toxicity, seven out of the nine females lost their pups at 1000 mg/kg group. Numbers of corpora lutea and implantation scars were decreased at 1000 mg/kg group. The NOELs for reproductive performance are considered to be 1000 mg/kg/day for males, and 300 mg/kg for females.
With regard to pups, decreased body weights of both sexes at birth were seen at 100 mg/kg or more groups. Decreased numbers of live pups born, live birth index and viability index and decreased body weights of both sexes on day 4 after birth were seen at 1000 mg/kg group. The NOEL for pup development is considered to be 30 mg/kg/day.
Divinylbenzene was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98 and TA1537 or Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.
Genotoxicity of divinylbenzene was studied by the chromosomal aberration test in cultured Chinese hamster lung(CHL/IU)cells.
Divinylbenzene did not induce structural chromosomal aberrations in the concentration range of 0.0075 - 0.060 mg/mL on continuous treatment, and on short-term treatment with and without an exogenous metabolic activation system. Polyploidy was significant at 0.030 mg/mL(mid concentration) on continuous treatment. However, we concluded that divinylbenzene did not induce polyploidy since the frequency was low level and no significance was observed with a trend test.
| Purity | : | 96.2 % |
| 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/goup | : | Males, 5; females, 5 |
| Vehicle | : | Corn oil |
| GLP | : | Yes |
Test results:
Based on the above results, the LD50 value of divinylbenzene was concluded to be more than 2000 mg/kg for both sexes.
| Purity | : | 96.2 % |
| 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 relative liver weights were increased in the 100 mg/kg or more groups. Suppression of body weight gain and increased absolute and relative kidney weights were found in the 300 mg/kg or more groups. Decreased food consumption, increased GPT, γ-GPT and total bilirubin, and decreased blood glucose were seen in the 1000 mg/kg group.
For the females, suppression of body weight gain during the pregnancy period, decrease in food consumption during the lactation period and increased relative kidney weights were seen in the 300 mg/kg or more groups. Suppression of body weight gain and decrease in food consumption during the pre-mating, pregnancy and lactation periods, atrophy of the thymus, atrophy of the marginal zone in the spleen, and degeneration/necrosis of the renal tuble of cortico-medullary junction in the kidney were seen in the 1000 mg/kg group. One female died and one female became moribund in the 1000 mg/kg group.
The NOELs for repeat dose toxicity are considered to be 30 mg/kg/day for males, and 100 mg/kg/day for females.
<Reproductive/Developmental Toxicity>
With regard to reproductive/developmental toxicity, seven of the nine 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/day for males, and 300 mg/kg/day for females.
With regard to pups, decreased body weights of both sexes at birth were seen in the 100 mg/kg or more groups. Decreased numbers of live pups born, live birth index and viability index, and decreased body weights of both sexes on day 4 after birth were seen in the 1000 mg/kg group. The NOEL for pup development is considered to be 30 mg/kg/day.
| Purity | : | 96.2 wt% |
| Test species/strains | : | Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA |
| Test method | : | Guidelines for Screening Toxicity Testings of Chemicals (Japan) and OECD Guidelines No. 471 and 472 |
| Procedures | : | Pre-incubation method |
| Solvent | : | DMSO |
| 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, 0.781, 1.56, 3.13, 6.25, 12.5, 25.0, 50.0 μg/plate (TA1535(Test 1)); 0, 1.56 - 50.0 μg/plate(TA1535(Test 2)); 0, 3.13 - 100 μg/plate(TA100, TA98, TA1537); 0, 6.25 - 200 μg/plate(WP2 uvrA) +S9 mix; 0, 6.25 - 200 μg/plate(TA100, TA1535, TA98, TA1537); 0, 15.6 - 500 μg/plate(WP2 uvrA) |
| 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 | : | 96.2 wt% |
| 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, 0.015, 0.030, 0.060 mg/mL -S9 mix(short-term treatment): 0, 0.0075, 0.015, 0.030 mg/mL +S9 mix(short-term treatment): 0, 0.015, 0.030, 0.060 mg/mL |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 2 |
| GLP | : | Yes |
Test results:
Polyploidy was significant at 0.030 mg/mL(mid concentration) on continuous treatment. However, we concluded that divinylbenzene did not induce polyploidy since the frequency was low(1.88 %)and no significance was observed with a trend test.
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 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 |