Chlorambucil induced congenital renal hypoplasia: effects on basal renal function in the developing rat.
Administration of chlorambucil to pregnant rats on day 11 of gestation induced dose-related alterations in renal growth and function in the postnatal offspring. These effects occurred above and beyond the reductions in body growth and were evident in animals that displayed no overt malformation of the urogenital tract. Reductions in overall growth amounted to 0, 6 and 15% in the 3,4.5 and 6 mg/kg groups, respectively, while kidney weights were reduced by 7, 15 and 23%. The weights of the kidneys relative to the body were reduced 5, 9 and 10% with increasing dose. Although basal renal function was not affected by the degree of hypoplasia seen in the low dose group, reduced glomerular and tubular function were evident following a basal clearance test in the 2 highest dose groups. The data indicate that chlorambucil induced renal hypoplasia results in reductions in renal function that persist for at least the first 3 weeks after birth in the rat and that physiological assessment of developmental toxicity can provide an extremely useful addendum to the more classical morphological criteria.
D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002699:Chlorambucil / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology* / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D002699:Chlorambucil