Postnatal evaluation of morphological and functional effects of prenatal exposure to Nitrofen in the long‐evans rat

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Abstract
The herbicide Nitrofen was administered to Long-Evans rats on day 11 of gestation (75 mg/kg, orally) in an effort to further evaluate its reported ability to induce hydronephrosis and to affect Harderian-gland development. This regimen did not affect the litter size at birth or postnatal growth and viability. Eye opening, recorded on postnatal day (PD) 16 figure-8 maze activity (PD 24) and vaginal opening (PD 31) were unaffected by treatment. Lung weights were lower on PD 7 and 35 but not at PD 210. Harderian-gland weights were lower at PD 35 and 210, and 12% of the Nitrofen-treated offspring had missing glands, vs. no controls. Hydronephrosis was detected in 23% of the necropsied offspring and was represented in every treated litter. Only 1 control pup (1.5%) was hydronephrotic at necropsy. Treated pups, regardless of the presence or absence of hydronephrosis, had a diminished ability to concentrate urine in fluid deprivation tests applied on PD 3 and 6. By PD 50, treated offspring were not deficient in a similar test unless hydronephrosis was present. Microscopic examination on PD 7 of morphologically normal kidneys showed no treatment-related delay in nephrogenesis. Serum chemistry values evaluated at PD 210 showed no overall treatment effect, but animals with hydronephrosis had elevated C, urea N, creatinine and K levels. A single prenatal exposure to Nitrofen altered Harderian-gland development, lung growth and renal development and function. Hydropenia tests applied to neonates detected renal dysfunction and were predictive of hydronephrosis, while a similar test in young adults did not detect dysfunction in morphologically normal animals. The neonatal hydropenia test was a useful tool in evaluating perinatally induced renal dysfunction.