Effects of bis(4-chlorophenyl) sulfone on rats following 28-day dietary exposure.
The short-term oral toxicity of a recently identified environmental pollutant, bis(4-chlorophenyl) sulfone (BCPS), was studied. Groups of male Sprague-Dawley rats (n = 6) were administered BCPS via the diet at 0 (control), 10, 100, or 1000 ppm for 4 wk. Additional control and 1000 ppm groups were also treated for 1, 2, and 3 wk. At termination, high-dose animals showed depressed growth rate and food consumption, and 1 high dose animal in each of the wk-1, -3, and -4 groups had marked hematuria. Increased liver to body weight ratio was present at 100 ppm and increased kidney to body weight ratio at 1000 ppm. Marked increases in hepatic benzoylresorufin O-dealkylase (BROD) and pentoxyresorufin O-dealkylase (PROD) activities were detected starting at 10 ppm. There was a significant decrease in methoxyresorufin O-dealkylase (MROD) activity at 1000 ppm. Hepatic UDP-glucuronosyltransferase (UDPGT) and glutathione S-transferase (GST) activities also increased starting at 100 ppm. A marked increase in urinary excretion of ascorbic acid was apparent starting at 10 ppm, while there were no changes in urinary N-acetylglucosaminidase (NAG) activity and protein levels. A threefold increase in serum cholesterol and a 30% increase in platelet counts were observed in the 1000 ppm group. Levels of thiobarbituric acid-reactive substances (TBARS) were increased by threefold in the liver of the high-dose animals but were not significantly altered in the serum. Tissue BCPS concentrations were dose dependent and followed the order: adipose tissue >>> liver > kidneys > brain, spleen, lungs. In the time-course study involving the control and high-dose groups, most of the treatment effects were clearly present in wk 1, and the severity of the effects remained at more or less the same levels thereafter. The exceptions were hepatic BROD and PROD activities, which showed a trend toward further increases with time of treatment. Liver and adipose tissue concentrations of BCPS remained unchanged from wk 1 to wk 4, while kidney concentrations increased with time. The results indicated that BCPS produced hepatic effects at the lowest dose level tested (10 ppm in the diet or 0.8 mg/kg/d).
Poon
R
R
Environmental Health Directorate, Health Canada, Ottawa. raymond_poon@hc-sc.gc.ca
Lecavalier
P
P
Chu
I
I
Yagminas
A
A
Nadeau
B
B
Bergman
A
A
Larsson
C
C
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000008:administration & dosage / Q000633:toxicity*; D014018:Tissue Distribution
D013450:Sulfones; C034224:4,4'-dichlorodiphenyl sulfone