Single dose oral toxicity of 1,2-dicyanobenzene was evaluated in rats at doses of 0, 30, 60, 120, 240 and 480 mg/kg.
The estimated LD50 value was 85 mg/kg for both sexes.
1,2-Dicyanobenzene was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 1, 6 and 30 mg/kg/day. With regard to repeat dose toxicity, the following results were obtained. An increase of total protein was observed in females of the 6 mg/kg group. Body weight gain was suppressed and decrease in food consumption was observed in males and females in the 30 mg/kg group. All females of the 30 mg/kg group developed convulsions during late pregnancy and died. An increase of total protein and total cholesterol, a decrease of serum urea nitrogen, and changes in the weight and histopathological features of the liver, kidneys, testes, and epididymis were observed in males of the 30 mg/kg group.
The NOELs for repeat dose toxicity are considered to be 1 mg/kg/day for females and 6 mg/kg/day for males.
In terms of reproductive and developmental toxicity, no abnormalities were observed in males of the 30 mg/kg group, but all of the females died during late pregnancy. No abnormalities were observed in offspring from the 6 mg/kg group.
The NOELs for reproductive and developmental toxicity are considered to be 30 mg/kg/day for males, 6 mg/kg/day for females, and 6 mg/kg/day for offspring.
A reverse mutation test of 1,2-dicyanobenzene in bacteria was carried out. This substance 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 1,2-dicyanobenzene was studied by chromosomal aberration test using cultured Chinese hamster lung (CHL/IU) cells.
1,2-Dicyanobenzene did not induce structural chromosomal aberrations, but caused polyploidy with continuous treatment (24 hr) and short-term treatment with and without a metabolic activation system.
| Purity | : | 98.7 % |
| Test species/strains | : | Rat/Crj:CD(SD)IGS |
| Test method | : | OECD Test Guideline 401 |
| Route | : | Oral (gavage) |
| Doses | : | 0(vehicle), 30, 60, 120, 240, 480 mg/kg |
| Number of animals/group | : | Males, 5; females, 5 |
| Vehicle | : | 0.5 % CMC-Na solution |
| GLP | : | Yes |
Test results:
| Purity | : | 98.7 % |
| Test species/strain | : | Rat/Crj:CD(SD)IGS |
| Test method | : | OECD Test Guideline 422 |
| Route | : | Oral(gavage) |
| Doses | : | 0(vehicle), 1, 6, 30 mg/kg/day |
| Number of animals/group | : | Males, 12; females, 12 |
| Vehicle | : | 0.5 % Sodium carboxymethylcellulose |
| Administration period | : | Males, 44 days Females, from 14 days before mating to day 4 of lactation |
| Terminal kill | : | Males, day 45 Females, day 5 of lactation |
| GLP | : | Yes |
Test results:
An increase of total protein was observed in females of the 6 mg/kg group. Body weight gain was suppressed and decrease in food consumption was observed in males and females in the 30 mg/kg group. All females of the 30 mg/kg group died, suffering convulsions on days 19-23 of gestation. The males of the 30 mg/kg group showed an increase of total cholesterol and total protein, a decrease of serum urea nitrogen, an increase in the weights of the liver, kidneys, and testes, and a decrease in the weight of the epididymis. Histopathological examination revealed centrilobular hypertrophy of hepatocytes in the liver, hyaline droplets in the proximal tubular epithelium, basophilic degeneration of the renal tubules, and atrophy of the seminiferous tubules with cell debris in the tubules.
The compound had no effects on reproductive parameters such as the estrous cycle, copulation index, fertility index, number of corpora lutea, number of implantations, or the implantation index.
| Purity | : | 98.7 % |
| Test species/strains | : | Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals(Chemical Substances Control Law of Japan) and OECD Test Guideline 471 |
| Procedures | : | Pre-incubation method |
| Solvent | : | Dimethyl sulfoxide |
| 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, 625, 1250, 2500, 5000 μg/plate(five strains) |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 3(1 for cytotoxicity test) |
| Number of replicates | : | 2(plus 1 cytotoxicity test) |
| 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 | : | 98.7 % |
| Type of cell used | : | Chinese hamster lung (CHL/IU) cells |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 473 |
| Solvent | : | Dimethyl sulfoxide |
| Positive controls | : | -S9 mix; Mitomycin C +S9 mix; Cyclophosphamide |
| Doses | : | -S9 mix(continuous treatment); 0, 0.20, 0.40, 0.80 mg/mL -S9 mix(short-term treatment); 0, 0.33, 0.65, 1.3 mg/mL +S9 mix(short-term treatment); 0, 0.33, 0.65, 1.3 mg/mL |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 2 |
| GLP | : | Yes |
Test results:
| Lowest concentration producing cytogenetic effects in vitro: | ||
| Without metabolic activation (continuous treatment) | : | 0.40 mg/mL(polyploidy) |
| Without metabolic activation (short-term treatment) | : | 0.33 mg/mL(polyploidy) |
| With metabolic activation (short-term treatment) | : | 0.33 mg/mL(polyploidy) |
Genotoxic effects:
| clastogenicity | polyploidy | |||||
| + | ? | - | + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] | [*] | [ ] | [ ] |
| With metabolic activation: | [ ] | [ ] | [*] | [*] | [ ] | [ ] |
| 1) | The tests were performed by the Mitsubishi Chemical Safety Institute Ltd., Kashima Laboratory, 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, 257-8523, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627 |