Increased salivation, suppression in body weight gain and decrease in food consumption were noted in males of the 250 mg/kg group. Hematological examination revealed anemia in the 250 mg/kg group of both sexes. Blood chemical examination revealed changes in items related to liver function in both sexes receiving 250 mg/kg and in females of the 50 mg/kg group. Absolute and relative liver and spleen weights were increased in both sexes receiving 250 mg/kg group.
Histopathologically, increased hematopoiesis in the bone marrow, congestion, increased hematopoiesis and pigment deposit in the spleen, swelling of liver cells, single cell necrosis, extramedullary hematopoiesis and deposits of pigment in Kupffer cells in the liver were observed in both sexes given 250 mg/kg.
All changes except pigment deposition in the spleen and liver were still evident at the end of the recovery period. The NOELs are considered to be 10 mg/kg for both sexes.
3,4-Dimethylaniline did not induce either structural chromosomal aberrations or polyploidy in CHL/IU cells up to the concentration giving 50% cell growth inhibition, in the absence or presence of an exogenous metabolic activation system.
|Test species/strain||:||Rats/Crj:CD (SD)|
|Test method||:||Guidelines for 28-day Repeated Dose Toxicity Testing of Chemicals (Japan)|
|Dosage||:||0 (vehicle), 10, 50, 250 mg/kg/day|
|Number of animals||:||Males, 5; females, 5/group|
|Administration period||:||Males and females, 28 days|
|Terminal kill||:||Males and females, days 29 to 43|
All changes except pigment deposit in the spleen and liver were also recorded at the and of recovery period. The NOELs are considered to be 10 mg/kg for both sexes under the conditions of the present study.
|Type of cell used||:||Chinese hamster lung (CHL/IU) cells|
|Test method||:||Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)|
|Positive controls||:||-S9, Mitomycin C|
|Doses||:||-S9 (continuous treatment): 0, 0.11, 0.23, 0.45 mg/ml|
-S9 (short-term treatment): 0, 0.24, 0.47, 0.94 mg/ml
+S9 (short-term treatment): 0, 0.24, 0.47, 0.94 mg/ml
|S-9||:||Rat liver, induced with phenobarbital and 5,6-benzoflavone|
|without metabolic activation:||[ ]||[ ]||[*]||[ ]||[ ]||[*]|
|with metabolic activation:||[ ]||[ ]||[*]||[ ]||[ ]||[*]|
|1)||The tests were performed by the Biosafety Research Center, Foods, Drugs and Pesticides (An-pyo Center), Japan, 582-2 Shioshinden Arahama, Fukude-cho, Iwata-gun, Shizuoka, 437-12, Japan. Tel 81-538-58-1266 Fax 81-538-58-1393|
|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|