3,4-Dimethylaniline

3,4-ジメチルアニリン

CAS No. 95-64-7

3,4-Xylidine

3,4-キシリジン

Molecular formula: C8H11N　　Molecular weight: 121.20

ABSTRACT

3,4-Dimethylaniline was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 10, 50 and 250 mg/kg/day. Genotoxicity of 3,4-dimethylaniline acid was also studied by the reverse mutation assay in bacteria and the chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

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.

SUMMARIZED DATA FROM THE STUDIES

1. Repeat Dose Toxicity1)

Purity	:	99.8%
Test species/strain	:	Rats/Crj:CD (SD)
Test method	:	Guidelines for 28-day Repeated Dose Toxicity Testing of Chemicals (Japan)
Route	:	Oral
Dosage	:	0 (vehicle), 10, 50, 250 mg/kg/day
Vehicle	:	Corn oil
Number of animals	:	Males, 5; females, 5/group
Administration period	:	Males and females, 28 days
Terminal kill	:	Males and females, days 29 to 43
GLP	:	Yes

　Test results:

Increased salivation, suppression of body weight gain and decrease in food consumption were noted in males of the 250 mg/kg group. Hematological examination revealed decrease of HCT and HGB levels and RBC counts and increase of PLT and reticulocyte counts in both sexes receiving 250 mg/kg, and increase of WBC in males of the 250 mg/kg group. Blood chemical examination revealed increase in levels of total cholesterol, GOT and total bilirubin in both sexes given 250 mg/kg. Total cholesterol levels also increased in females of the 50 mg/kg group. Absolute and relative liver and spleen weights increased in both sexes receiving 250 mg/kg. Macroscopically, enlargement and/or flecking of the spleen and liver were observed in both sexes given 250 mg/kg. Histopathologically, increase in hematopoiesis in the bone marrow, congestion, increase in hematopoiesis and deposits of pigment 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 treated with 250 mg/kg group.

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.

2. Genetic Toxicity

Non-bacterial in vitro test (chromosomal aberration test)2)

Purity	:	99.8%
Type of cell used	:	Chinese hamster lung (CHL/IU) cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Solvent	:	Dimethyl sulfoxide
Positive controls	:	-S9, Mitomycin C +S9, Cyclophosphamide
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
Plates/test	:	2
GLP	:	Yes