Dicyclohexylcarbodiimide was studied for oral toxicity in rats in a single dose toxicity test at doses of 500, 700, 1000, 1400 and 2000 mg/kg and in a 28-day repeat dose toxicity study at doses of 0, 15, 100 and 500 mg/kg/day.
Dicyclohexylcarbodiimide was also tested for mutagenicity with assays for reverse mutation in bacteria and chromosomal aberrations in cultured Chinese hamster (CHL) cells.
The acute oral toxicity test revealed LD50s of 1110mg/kg for both sexes.
In the repeat dose toxicity test, animals of both sexes in the 500 mg/kg group showed reduced locomotor activity, salivation, inhibition of body weight gain, decreased food consumption, increased water intake, decreased blood hemoglobin concentration and alkaline phosphatase, and increased blood potassium and platelet counts. Pathological examination revealed increased relative liver weight, enlargement of the duodenum due to mucosal thickening, and hepatocellular swelling in both sexes of the high dose group. These changes disappeared or tended to recover after the recovery period. The NOEL for repeat dose toxicity was 100 mg/kg/day.
Dicyclohexylcarbodiimide was not mutagenic for S. typhimurium TA100, TA1535, TA98, TA1537, and E. coli WP2 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 a cytotoxic concentration.
| Purity | : | 99.7% |
| Test species/strain | : | Rat/Crj:CD (SD) |
| Test method | : | OECD Test Guideline 401 |
| Doses | : | 700, 1000, 1400, 2000 mg/kg |
| Number of animals | : | Male, 5; Female, 5/group |
| GLP | : | Yes |
| Test results | : | LD50: Male, 1110 mg/kg; Female, 1110 mg/kg |
| Purity | : | 99.9 % |
| Test species/strain | : | Rat/Crj:CD (SD) |
| Test method | : | Guidelines 28-Day Repeat Dose Toxicity Test of Chemicals (Japan) |
| Route | : | Oral (gavage) |
| Doses | : | 0 (vehicle), 15, 100, 500mg/kg/day |
| Number of animals | : | Male, 6; Female, 6/group |
| Vehicle | : | Olive oil |
| Administration period | : | Male and Female, 28 days |
| Terminal kill | : | Male and Female, days 29 or 43 |
| GLP | : | Yes |
Test results:
Body weight gain was reduced among the high-dose males and females. Food consumption decreased in the high dose group males and females in the first week of administration, while water intake increased in this group.
On hematological and blood biochemical analyses, mean corpuscular hemoglobin was decreased and protholombin time was shortened in the high-dose males, while platelet counts were increased and activated partial thromboplastin time was reduced in the high-dose females. A decrease in alkaline phosphatase was observed in the high-dose males and an increase in potassium in the high-dose males and females. Urine volume tended to increase in both sexes, while urinary pH was increased in the high-dose females.
There was an increase in relative liver weight in both the high-dose males and females. On gross examination at necropsy, enlargement of the duodenum was observed in both high-dose sexes. Histopathologically, the high-dose males and females showed enlarged hepatocytes around the Glissons capsules, eosinophilic hepatocyte cytoplasm, and thickening of the duodenal mucosa.
After the recovery period, histological changes of the liver and duodenum had disappeared, and other charged parameters tended to show values almost within the normal range.
| Purity | : | 99.7% |
| 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, 39.1, 78.1, 156.3, 312.5, 625, 1250, 2500, 5000 μg/plate |
| S-9 | : | 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
| + | ? | - | |
| with metabolic activation: | [ ] | [ ] | [*] |
| without metabolic activation: | [ ] | [ ] | [*] |
E. coli WP2 uvrA
| + | ? | - | |
| with metabolic activation: | [ ] | [ ] | [*] |
| without metabolic activation: | [ ] | [ ] | [*] |
| Purity | : | > 99 % |
| Type of cell used | : | Chinese hamster CHL cells |
| Test method | : | Guideline for Screening Mutagenicity Testing of Chemicals (Japan) |
| Solvent | : | Acetone |
| Positive controls | : | -S9, Mitomycin C +S9, Cyclophosphamide |
| Doses | : | -S9: 0.00048, 0.00095, 0.0019 mg/ml +S9: 0.0078, 0.0153, 0.031 mg/ml |
| S-9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 2 |
| GLP | : | Yes |
Test results:
Lowest concentration producing cytogenetic effects in vitro:
| + | ? | - | |
| with metabolic activation: | [ ] | [ ] | [*] |
| without metabolic activation: | [ ] | [ ] | [*] |
| 1) | The tests were performed by the Mitsubishi-Kasei Institute of Toxicological and Environmental Sciences, 14 Sunayama, Hazaki-machi, Kashima-gun, Ibaraki, 314-02, 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, Japan. Tel 81-463-82-4751 Fax 81-463-82-9627 |