2,4-Dichloro-1-methylbenzene was studied for oral toxicity in rats in a single dose toxicity test at doses of 500, 1000 and 2000 mg/kg and in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 12.5, 79, and 500 mg/kg/day. 2,4-Dichlorotoluene was also tested for mutagenicity with assays for reverse mutation in bacteria and chromosomal aberrations in cultured Chinese (CHL) hamster cells.
The single dose oral toxicity test resulted in LD50s of above 2000 mg/kg for both sexes.
For repeat dose toxicity, salivation just after administration was observed in both sexes given 12.5 mg/kg/day or more. The test chemical also exerted some effects on the liver and the kidneys when given at 79 mg/kg/day or more in the males, such as an increase in relative weight and dark brown discoloration of liver, centrilobular hypertrophy of hepatocytes, atrophy and regeneration of renal tubular epithelium, and dilatation of tubules. NOELs for repeat dose toxicity were at 12.5 mg/kg for both sexes. With regard to reproductive/developmental toxicity, the parental reproduction test revealed a lowered fertility index in the rats of both sexes treated with 500 mg/kg, and a missing vaginal plug or a sparseness of sperms in the vagina in copulated and nongestated rats. Among offspring of the 500 mg/kg group lowered body weights were exhibited on days 1 and 4 of lactation. NOELs for reproductive performance and offspring development were both 79 mg/kg/day.
2,4-Dichloro-1-methylbenzene was not mutagenic for S. typhimurium TA100, TA1535, TA98, TA1537 and E. coli WP2 uvrA with or without exogenous metabolic activation up to 5000 μg/plate. This chemical induced neither chromosomal aberrations nor polyploidy with or without exogenous metabolic activation up to the cytotoxic concentration.
| Purity | : | 98.96% |
| Test species/strains | : | Rat/Crj:CD (SD) |
| Test method | : | OECD Test Guideline 401 |
| Doses | : | 500, 1000, 2000 mg/kg |
| Number of animals | : | Male, 5; Female, 5/group |
| GLP | : | Yes |
| Test results | : | LD50: Male > 2000 mg/kg, Female > 2000 mg/kg |
| Purity | : | 98.96% |
| Test species/strains | : | Rat/Crj:CD (SD) |
| Test method | : | OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test |
| Route | : | Oral (gavage) |
| Doses | : | 0 (vehicle), 12.5, 79, 500 mg/kg/day |
| Number of animals | : | Male, 12; Female, 12/group |
| Vehicle | : | Distilled water |
| Administration period | : | Male, 46 days Female, from 14 days before mating to day 3 of lactation |
| Terminal kill | : | Male, day 47 Female, day 4 of lactation |
| GLP | : | Yes |
Test results:
On the hematological and blood chemical analyses, the 500 mg/kg males exhibited decreased numbers of platelets and increased cholinesterase values.
Increases in relative organ weights were seen for the livers of males and females, and kidneys of males at 500 mg/kg. On gross necropsy, dark brown discoloration of the liver was observed in 9/12 males receiving 500 mg/kg.
On microscopic examination, hypertrophy of hepatocytes in the centrilobular zones of the livers was observed in all 500 mg/kg males and in 2/12 79 mg/kg males. Atrophy and regeneration of kidney tubular epithelium, and dilation of tubules, were seen in 2/12 males and 1/12 females given 500 mg/kg, and in 1/12 79 mg/kg males. Occurrence of hyaline droplets and eosinophilic body deposition in tubular epithelia was increased in males receiving 79mg/kg or more.
<Reproductive and developmental toxicity>
In the parental reproduction test, the 500 mg/kg males and females were seen to have a lowered fertility index. Missing vaginal plugs or a sparseness of sperms in the vagina were rated in 6/7 copulated and nongestated rats. Male and female offspring of the 500 mg/kg group exhibited lowered body weights on days 1 and 4 of lactation. The test substance did not show any effects on delivery or maternal behavior, as well as viability, clinical signs, and gross necropsy findings for offspring.
| Purity | : | 98.96 % |
| Test species/strains | : | S. typhimurium TA100, TA1535, TA98, TA1537 E. coli WP2 uvrA |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) |
| Procedure | : | Plate method |
| Solvent | : | DMSO |
| Positive controls | : | -S9, AF-2(TA100,WP2 uvrA,TA98), sodium azide (TA1535) and 9-aminoacridine (TA1537) +S9, 2-Aminoanthracene (all strains) |
| Doses | : | 0, 15.625, 31.25, 62.5, 125, 250, 500, 1000 μg/plate |
| S-9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 3 |
| Number of replicates | : | 2 |
| GLP | : | Yes |
Genotoxic effects:
S. typhimurium TA100, TA1535, TA98, TA1537
| + | ? | - | |
| with metabolic activation: | [ ] | [ ] | [*] |
| without metabolic activation: | [ ] | [ ] | [*] |
E. coli WP2 uvrA
| + | ? | - | |
| with metabolic activation: | [ ] | [ ] | [*] |
| without metabolic activation: | [ ] | [ ] | [*] |
| Purity | : | 98.96 % |
| Type of cell used | : | Chinese hamster CHL cells |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) |
| Solvent | : | DMSO |
| Positive controls | : | -S9, Mitomycin C +S9, Cyclophosphamide |
| Doses | : | -S9: 0, 17.5, 35.0, 70.0 μg/ml +S9: 0, 22.5, 45.0, 90.0 μg/ml |
| S-9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 2 |
| GLP | : | Yes |
| + | ? | - | |
| with metabolic activation: | [ ] | [ ] | [*] |
| without metabolic activation: | [ ] | [ ] | [*] |
| 1) | The tests were performed by the Safety Research Institute for Chemical Compounds Co., Ltd., 363-24 Shinei, Toyohira-ku, Sapporo, Hokkaido, 004, Japan. Tel 81-11-885-5031 Fax 81-11-885-5313 |
| 2) | The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257, Japan. Tel 81-463-82-4751 Fax 81-463-82-9627 |