Assessment of the safety of chemicals administered intravenously in the neonatal rat.
A 3-day-old neonatal rat model for the safety assessment of various drugs, chemicals, and nutrients administered intravenously is described. This model was used to assess the safety of di(2-ethylhexyl) phthalate (DEHP), cyclohexanone, and a 3:1 mixture of medium and long-chain triglyceride emulsions following subchronic administration using the intravenous route. The administration of DEHP at dosage of 164.8 mg/kg for 18 consecutive days resulted in a small but statistically significant increase in liver weight and SGOT activity. However, no conclusive histopathological alternations could be discerned between livers from DEHP and normal saline (control) animals. No effects were observed among neonates treated with cyclohexanone at dosages up to 25 mg/kg for 18 consecutive days. Because of technical difficulties emanating from high dosage volumes, the administration of lipid emulsion mixture lasted 9 consecutive days only. Except for transient ataxia and sedation, no adverse effects were observed among neonates that received 3:1 medium- and long-chain triglyceride emulsion for 9 consecutive days beginning on day 3 postpartum. No adverse effects were observed among neonates receiving the lipid emulsions for 7 consecutive days beginning on day 12 postpartum.
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D003512:Cyclohexanones / Q000008:administration & dosage / Q000633:toxicity; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000633:toxicity; D004341:Drug Evaluation / Q000379:methods*; D004655:Emulsions; D007275:Injections, Intravenous; D051381:Rats; D014280:Triglycerides / Q000008:administration & dosage / Q000633:toxicity
D003512:Cyclohexanones; D004655:Emulsions; D014280:Triglycerides; C036468:cyclohexanone; D004051:Diethylhexyl Phthalate