Aniline: early indicators of toxicity in male rats and their relevance to spleen carcinogenicity.
Early indicators of aniline hydrochloride (AH) toxicity were investigated in male Fisher 344 rats for 1 or 4 weeks at dietary dose levels of 10, 30 or 100 mg/kg body weight (bw)/day (actual intake at least 6, 17 and 57 mg/kg). The doses were based on earlier studies that had shown spleen toxicity and carcinogenicity in male rats at 100 mg/kg/day but not at 10 mg/kg/day. In the present study a dose-related formation of haemoglobin adducts and Heinz bodies was found from 10 and 30 mg/kg bw/ day, respectively, onwards. Signs of anaemia (decreased red blood cell counts and increased reticulocytes) were recorded from 30 mg/kg onwards. At 100 mg/kg, an overt haemolytic anaemia was associated with increases in serum transferrin concentration and total iron binding capacity in the blood reflecting major perturbations in iron metabolism. At this dose there was an increase in peripheral neutrophil leucocytosis in the blood, indicating an inflammatory process in the spleen. Histopathologic evaluation showed a focal perisplenitis and haemosiderin deposition in sinusoidal Kupffer cells of the liver at 100 mg/kg. These results corroborate the contention that carcinogenic doses of aniline cause early effects on haematological parameters, inflammatory reaction in the spleen and perturbations in iron metabolism as a result of haemolytic anaemia. Accordingly, the carcinogenicity of aniline may be linked to definable threshold-related processes.
Mellert
W
W
BASF Aktiengesellschaft, Product Safety, Z 470, D-67056 Ludwigshafen, Germany.
Deckardt
K
K
Gembardt
C
C
Zwirner-Baier
I
I
Jäckh
R
R
van Ravenzwaay
B
B
D000284:Administration, Oral; D000743:Anemia, Hemolytic / Q000139:chemically induced; D000814:Aniline Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006366:Heinz Bodies; D006454:Hemoglobins / Q000378:metabolism; D007249:Inflammation; D007501:Iron / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013160:Splenic Neoplasms / Q000175:diagnosis* / Q000503:physiopathology*
D000814:Aniline Compounds; D002273:Carcinogens; D006454:Hemoglobins; D007501:Iron; C023650:aniline