Sex and Age Differences in the Distribution of 14C-Sterigmatocystin in Immature and Mature Rats: A Multiple Dose Study

Abstract

Sterigmaltocystin, a secondary fungal metabolite, produces a toxic reaction upon administration to experimental animals. Examination of rats that have received multiple doses of ''C-sterigmatocystin may indicate the response elicited by repeated exposure to foodstuffs containing the mycotoxin. Daily doses of sterigmatocystin, 8 mg/kg equally divided over 13 days, 'were administered in the feed. Immature rats (50-150 g) and mature rats (200-300 g) of both sexes were studied. On the 14th day, an 8 mg/kg dose of 14C-sterigmatocystin dissolved in wheat germ oil was orally intubated into the rats. Five rats of each sex and age group were sacrificed at 3,6,12,24,48, and 96 hours. Biological specimens were collected and analyzed for total radioactivity. Tukey's paired comparison procedure was used to analyze for statistically significant differences in tissue exposure to 14sterigmatocystin due to age and sex. Statistically significant differences in tissue levels were found in 60% or more of the tissues when comparing mature males vs. immature females and mature males vs. mature females. Age and sex differences were also observed in 45% or less of the tissues in other age or sex comparisons. The sterigmatocystin plasma levels vs. time curves contain multiple peaks that may indicate enterohepatic recirculation. The gradual decline in the log-linear phase resulted in long half-lives, ranging from 61.5 to 130 hours. This stuldy examines distribution characteristics of 14C-~terigmatocy~tin in immature and mature

Scientific information on mycotoxins and natural plant toxicants

“…Approximately 3% of the total STC administered was eliminated in the first 24 h. This value is considerably lower than the data obtained by Walkow et al (1985), when 14 C-labeled STC was used (8 mg/kg/13 days, administered in the feed); they found as much as 7.5 % of the total radioactivity in the first 24-h urine sample. Wang et al, (1991) described the excretion of radioactively labelled STC in rats after administration of 0.5 microCurie/g bw.…”

“…A study indicated that the volume of distribution of STC shows age and sex differences (Walkow et al, 1985). Oral administration to immature (50-150 g) and mature (200-300 g) rats of both sexes of 14 C-STC (8 mg/kg/13 days in feed and on the 14th day was orally intubated into the rats) resulted in plasma levels in male rats which were consistently higher than those found in the females.…”

Scientific Opinion on the risk for public and animal health related to the presence of sterigmatocystin in food and feed

“…The highest level of tissue radioactivity was found in mature males and the lowest in immature females. Significant age differences were demonstrated, with tissue levels in different organs varying between mature and immature males and to a lesser extent between mature and immature females (Walkow et al, 1985).…”

“…The study of Walkow et al (1985) showed that most of the orally given STC in Sprague-Dawley rats was eliminated in the faeces (64-92 %), and about 10 % via urine. The calculated elimination half-life in these Sprague-Dawley rats varied between 61.5 h in immature females and 130 h in mature male rats and the cumulative total elimination rate (urine and faeces) after 96 h exceeded 99 % in immature and mature males, and varied between 71.5 and 77.4 % in immature and mature females, respectively.…”

“…In Sprague-Dawley rats, peak plasma levels were reached after 30 minutes following an oral bolus administration of 8 mg/kg b.w. of 14 C-STC (Walkow et al, 1985; details of the study are described below in Section 7.1.2). In this study the rate of absorption was not calculated, but plasma concentration-time curves showed significant differences between female and male rats in both age groups tested.…”