Search

Newborn rat studies were conducted with oral administration of 3-ethylphenol (3EP) and 4-ethylphenol (4EP) on postnatal days (PND) 4-21 to allow comparison of no observed adverse effect level (NOAEL) and unequivocally toxic level (UETL) with those from 28-day studies of young rats starting at 5-6 weeks of age. In the newborn rat studies, slightly lowered body weight was observed after 3EP treatment, and deaths, hypoactivity, Straub tail, deep respiration and delayed righting reflex were clearly observed after 4EP treatment. In the young rat studies, salivation, staggering gait, changes in the liver including high values of liver weight and alanine aminotransferase or total cholesterol and the lesions in the forestomach were clearly observed after 3EP and 4EP treatments. NOAELs of 3EP and 4EP in the newborn rat studies appeared to be almost 3 times lower than those in the young rat studies. As a clear toxicity of 3EP was not observed in newborn rats, UETLs were not established for 3EP. Regarding 4EP, UETL of young rats was 4-5 times higher than that of newborn rats. In conclusion, newborn rats were 3-5 times more susceptible to 3EP and 4EP than young rats.

To elucidate the comparative susceptibility of newborn rats to chemicals, newborn and young animals were administered six industrial chemicals by gavage from postnatal days (PND) 4 to 21, and for 28 days starting at 5-6 weeks of age respectively, under the same experimental conditions as far as possible. As two new toxicity endpoints specific to this comparative analysis, presumed no-observed-adverse-effect-levels (pNOAELs) were estimated based on results of both main and dose-finding studies, and presumed unequivocally toxic levels (pUETLs) were also decided. pNOAELs for newborn and young rats were 40 and 200 for 2-chlorophenol, 100 and 100 for 4-chlorophenol, 30 and 100 for p-(alpha,alpha-dimethylbenzyl) phenol, 100 and 40 for (hydroxyphenyl)methyl phenol, 60 and 12 for trityl chloride, and 100 and 300 mg/kg/day for 1,3,5-trihydroxybenezene, respectively. To determine pUETLs, dose ranges were adopted in several cases because of the limited results of experimental doses. Values for newborn and young rats were thus estimated as 200-250 and 1000 for 2-chlorophenol, 300 and 500 for 4-chlorophenol, 300 and 700-800 for p-(alpha,alpha-dimethylbenzyl) phenol, 140-160 and 1000 for (hydroxyphenyl)methyl phenol, 400-500 and 300 for trityl chloride, and 500 and 1000 mg/kg/day for 1,3,5-trihydroxybenzene, respectively. In most cases, newborn rats were 2-5 times more susceptible than young rats in terms of both the pNOAEL and the pUETL. An exception was that young rats were clearly more susceptible than their newborn counterparts for trityl chloride.

In order to determine the susceptibility of newborn rats to 2-tert-butylphenol (2TBP) and 2,4-di-tert-butylphenol (DTBP) toxicity, studies were conducted with oral administration from postnatal days (PND) 4 to 21 and the findings were compared with results for young rats exposed from 5 or 6 weeks of age for 28 days. In the newborn rats, specific effects on physical and sexual development and reflex ontogeny were not observed. While there were no clear differences in toxicological profiles between newborn and young rats, the no-observed-adverse-effect levels (NOAELs) differed markedly. For 2TBP, clinical signs such as ataxic gait, decrease in locomotor activity and effects on liver, such as increase in organ weight, were observed and the NOAELs were concluded to be 20 and 100 mg/kg/day in newborn and young rats, respectively. Based on hepatic and renal toxicity (histopathological changes and increase in organ weight with blood biochemical changes), the respective NOAELs for DTBP were concluded to be 5 and 20 mg/kg/day. Therefore, the susceptibility of newborn rats to 2TBP and DTBP was found to be 4-5 times higher than that of young rats.

The toxicity of oral 2,4,6-trinitrophenol (TNP) was determined in newborn rats, and compared with that in young rats. In newborn rats, males and females were given TNP at 0, 16.3, 81.4 or 407 mg/kg per day on postnatal days (PND) 4-17 for the dose-finding study, and at 0, 4.1, 16.3 or 65.1 mg/kg per day on PND 4-21 for the main study. Deaths, lower body weight (BW) and behavioral changes were found at 81.4 and 407 mg/kg per day in the dose-finding study, and lower BW was observed in males at 65.1 mg/kg per day during the dosing period of the main study. In young rats, 5-week-old males and females were given TNP at 0, 20, 100 or 500 mg/kg per day for 14 days as the dose-finding study and at 0, 4, 20 or 100 mg/kg per day for 28 days as the main study. Deaths were observed at 500 mg/kg per day in the dose-finding study. Deaths or changes in BW were not found at 100 mg/kg per day or less. At 100 mg/kg per day, hemolytic anemia and testicular toxicity were found. In conclusion, toxicity profiles induced by TNP were markedly different between newborn and young rats.