Differences in ethoxyquin nephrotoxicity between male and female F344 rats.
Dose-response studies have shown a sharp threshold for the renal papillary toxic effect in male rats between 0.25% and 0.5% ethoxyquin (Eto) in the diet over 6 months. Although similar elevated urinary protein (albumin) levels resulted from dietary Eto (0.5%) in both males and females, papillary necrosis was male specific. Following [14C]Eto administration, radiolabel was associated with urinary albumin but not alpha 2 globulin (alpha(2mu)-g). Autoradiographic studies indicated that the sex differences in nephrotoxicity do not involve differences in distribution or retention of Eto. Faecal and urinary metabolic profiles were also similar in the two sexes. The sharp threshold of toxicity in the male rat could indicate a fine balance between toxifying/detoxifying metabolism of Eto.
Neal
G E
GE
MRC Toxicology Unit, Hodgkin Building, University of Leicester, Leicester LE1 9HN, UK.
Judah
D J
DJ
Hard
G G
GG
Ito
N
N
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005015:Ethoxyquin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D007679:Kidney Medulla / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009336:Necrosis; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics
D000975:Antioxidants; D005015:Ethoxyquin