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[The significance of PCDD's/PCDF's (dioxins) in pediatrics]
Insights
Dioxins exposure via breast milk can induce adverse effects in newborns. A caffeine breath-test shows 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces liver enzyme activity in rat pups, suggesting a method for human infant monitoring.
Area of Science:
- Environmental Toxicology
- Developmental Toxicology
- Biomarker Development
Background:
- Limited epidemiological data exist on dioxin adverse effects via breast milk.
- Few studies report polychlorinated dibenzodioxins/dibenzofurans (PCDDs/PCDFs) concentrations in newborns and infants.
- 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic dioxin congener, though often a minor environmental component.
Purpose of the Study:
- To investigate the enzyme-inducing effects of TCDD on hepatic monooxygenases during the perinatal period.
- To assess the utility of a caffeine breath-test for monitoring TCDD-induced biological effects.
- To determine if postnatal exposure via maternal milk is a significant route for TCDD effects.
Main Methods:
- Utilized a 14CO2-breath-test to measure the metabolic conversion of [3-methyl-14C]-caffeine.
- Studied TCDD effects on hepatic monooxygenase activity in perinatal Wistar rats and marmosets (Callithrix jacchus).
- Administered varying doses of TCDD to assess dose-dependency of enzyme induction.
Main Results:
- Apparent induction of monooxygenase activity by TCDD in rat offspring was dose-dependent.
- Postnatal exposure via mothers' milk was the primary route for TCDD-induced enzyme induction in rat pups.
- Caffeine proved to be a suitable substrate for detecting TCDD-induced P450 IA-dependent monooxygenase activities.
Conclusions:
- The caffeine breath-test is a viable method for assessing TCDD-induced biological effects in breast-fed newborns and infants.
- Findings support the need for continued efforts to reduce dioxin exposure and human milk concentrations.
- Further research can explore using a [13C]-caffeine breath-test for monitoring similar pollutants in vulnerable populations.
Abstract:
No epidemiological data are available up to now which reveal adverse effects induced by dioxins during an exposure through breast milk. Furthermore, very few data on the concentration of PCDDs/PCDFs in the newborn and during the first year of life have been published. Of all PCDDs/PCDFs, the substance with the highest toxicity is 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, in the environment this congener is often only a minor component. A sensitive biological effect triggered by TCDD is the enzyme induction of hepatic monooxygenases. Using a 14CO2-breath-test the apparent enzyme induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) of the metabolic conversion of [3-methyl14C]-caffeine was studied during the perinatal period in Wistar rats and in a non-human-primate (marmoset, Callithrix jacchus). It could be shown that the apparent induction of monooxygenase activity by TCDD in rat offspring as measured with the breath-test, is dose-dependent and mainly achieved by postnatal exposure via mothers' milk. Our data indicate that caffeine is a convenient substrate for studying monooxygenase activities (probably P450 IA-dependent) to be induced by TCDD, and very likely also by other congeners. These results, therefore, may provide the rationale for applying a [13C]-caffeine breath-test in human newborn and infants to analyse possible biological effects induced by TCDD and similar pollutants in breast-fed children. Since PCDDs/PCDFs are pollutants without any benefit, strong efforts should be continued to further reduce the output of dioxins, the human exposure, and thereby also concentrations in human milk.(ABSTRACT TRUNCATED AT 250 WORDS)