1-Chloro-2-(chloromethyl)benzene was studied for oral toxicity in rats of both sexes in a single dose toxicity test at doses of 0, 350, 500, 700, 1000, 1400 mg/kg. This revealed LD50 values of 951 mg/kg for males and 783 mg/kg for females.
1-Chloro-2-(chloromethyl)benzene was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 2, 10 and 50 mg/kg/day.
With regard to repeat dose toxicity, suppression of body weight gain and decrease in food consumption were observed in both sexes of the 50 mg/kg group. An increase in liver weight was observed in females of the 50 mg/kg group. Thickening of the forestomach wall, squamous hyperplasia, erosion and ulcer in the forestomach were observed in males of the 10 mg/kg or more groups and in females of the 50 mg/kg group. Hyaline droplets in the proximal tubular epithelium of the kidneys were increased in males of the 50 mg/kg group.
The NOELs for repeat dose toxicity are considered to be 2 mg/kg/day for males and 10 mg/kg/day for females. In terms of reproductive and developmental toxicity: The compound had no effects on any relevant parameters. The NOEL for reproductive and developmental toxicity is considered to be 50 mg/kg/day for parent animals and offspring.
1-Chloro-2-(chloromethyl)benzene was possibly mutagenic in Salmonella typhimurium TA100 without an exogenous metabolic activation system.
Genotoxicity of 1-chloro-2-(chloromethyl)benzene was studied by chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.
1-Chloro-2-(chloromethyl)benzene induced structural chromosomal aberrations and polyploidy at the high dose of 0.10 mg/mL with short-term treatment and a metabolic activation system. Polyploidy was induced at 0.010 mg/mL with continuous treatment for 24 hr.
| Purity | : | 99.65 % |
| Test species/strain | : | Rats/Crj:CD(SD)IGS |
| Test method | : | OECD Test Guideline 401 |
| Route | : | Oral (gavage) |
| Dosage | : | 0 (vehicle), 350, 500, 700, 1000, 1400 mg/kg |
| Number of animals/group | : | Males, 5; females, 5 |
| Vehicle | : | 0.1 % Tween 80 solution |
| GLP | : | Yes |
Test results:
The assessed LD50 values were 951 mg/kg for males and 783 mg/kg for females.
| Purity | : | 99.65 % |
| Test species/strain | : | Rats/Crj:CD(SD)IGS |
| Test method | : | OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test |
| Route | : | Oral (gavage) |
| Dosage | : | 0 (vehicle), 2, 10, 50 mg/kg/day |
| Number of animals/group | : | Males, 12; females, 12 |
| Vehicle | : | 0.1 % Tween 80 solution |
| Administration period | : | Males, 45 days Females, from 14 days before mating to day 3 of lactation |
| Terminal kill | : | Males, day 46 Females, day 4 of lactation |
| GLP | : | Yes |
Test results:
In the 50 mg/kg group, suppression of body weight gain and decrease in food consumption were observed in both sexes in the early-period of administration. At necropsy, thickening of the forestomach wall was observed in males of the 10 mg/kg or more groups and in females of the 50 mg/kg group. An increase in liver weight was observed in females. Histopathological examination revealed squamous hyperplasia, erosion and ulceration in the forestomach in males of the 10 mg/kg or more groups and in females of the 50 mg/kg group. In addition, hyaline droplets in the proximal tubular epithelium of the kidneys were increased in males of the 50 mg/kg group. There were no effects on hematological or blood chemical parameters or organ weights in males.
The NOELs for repeat dose toxicity are considered to be 2 mg/kg/day for males and 10 mg/kg/day for females.
<Reproductive and developmental toxicity>
The compound had no effects on reproductive parameters such as the mating index, the fertility index, number of corpora lutea or implantations, the implantation index, the delivery index, the gestation index, gestation length, parturition or maternal behavior. On examination of neonates, there were no significant differences in number of offspring or live offspring, the sex ratio, the live birth index, the viability index or body weights. No abnormal findings ascribable to the compound were found for external features, clinical signs or necropsy of the offspring.
The NOEL for reproductive and developmental toxicity is considered to be 50 mg/kg/day for parental animals and offspring.
| Purity | : | 99.65 % |
| 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 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, 15.6, 31.3, 62.5, 125, 250, 500 μg/plate (five strains) 0, 90.0, 120, 150, 180, 210, 240 μg/plate (two additional and one confirmation tests in TA100) +S9 mix; 0, 15.6, 31.3, 62.5, 125, 250, 500 μg/plate (five strains) |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavon |
| Plates/test | : | 3 |
| Number of replicates | : | 2 |
| GLP | : | Yes |
Test results:
Genetic effects:
Salmonella typhimurium TA100
| + | ? | - | |
| Without metabolic activation: | [ ] | [*] | [ ] |
| With metabolic activation: | [ ] | [ ] | [*] |
Salmonella typhimurium TA1535, TA98, TA1537
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
Escherichia coli WP2 uvrA
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
| Purity | : | 99.65 % |
| Type of cell used | : | Chinese hamster lung (CHL/IU) cells |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Test Guideline 473 |
| Solvent | : | Dimethyl sulfoxide |
| Positive controls | : | -S9 mix, Mitomycin C +S9 mix, Cyclophosphamide |
| Doses | : | -S9 mix (24 and 48 hr continuous treatment); 0, 0.0025, 0.0050, 0.010 mg/mL -S9 mix (short-term treatment); 0, 0.0025, 0.0050, 0.010 mg/mL +S9 mix (short-term treatment); 0, 0.025, 0.050, 0.10 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 ) | : | 0.010 mg/mL (polyploidy) |
| With metabolic activation (short-term treatment) | : | 0.10 mg/mL(clastogenicity and polyploidy) |
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, 314-0255, 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 |