Evaluation of Child/Adult Pharmacokinetic Differences from a Database Derived from the Therapeutic Drug Literature

Ginsberg, Gary; Hattis, Dale; Sonawane, Babasaheb; Russ, Abel; Banati, Prerna; Kozlak, Mary; Smolenski, Susan; Goble, Robert

doi:10.1093/toxsci/66.2.185

Cited by 288 publications

(206 citation statements)

References 50 publications

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“…The physiological and biochemical characteristics of children that influence metabolism and disposition of chemicals at different stages of development need to be considered in risk assessment. Physiological parameters, such as tissue growth rates, and biochemical parameters, such as enzyme induction, may differentially affect the responses of infants and children to environmental chemicals at different developmental stages (Cresteil 1998;Ginsberg et al 2002). Physiologically based pharmacokinetic models can be used to estimate the dose of toxic metabolites reaching target tissues at different developmental stages (O'Flaherty 1997;Welsch 1995).…”

Section: Critical Issues For Improved Assessment Of Environmental Heamentioning

confidence: 99%

Children's health and the environment: public health issues and challenges for risk assessment.

Landrigan

Kimmel

Correa

et al. 2004

Environ Health Perspect

357

206

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Infants and children are not little adults. They are uniquely vulnerable to environmental toxicants. To protect infants and children against toxicants, the National Research Council in 1993 called for development of an approach to risk assessment that considers children's unique patterns of exposure and their special vulnerabilities to pesticides. Many aspects of that call were codified into federal law in the Food Quality Protection Act (FQPA) of 1996. This report highlights the central elements needed for development of a child-protective approach to risk assessment: a) improved quantitative assessment of children's exposures at different life stages, from fetal life through adolescence, including acute and chronic exposures, exposures via multiple routes, and exposures to multiple agents; b) development of new approaches to toxicity testing of chemicals that can detect unanticipated and subtle outcomes and that evaluate experimental subjects over the entire life span from early exposure to natural death to replicate the human experience; c) development of new toxicodynamic and toxicokinetic models that account for the unique physiologic characteristics of infants and children; d) development of new approaches to assessment of outcomes, functional, organ, cellular and molecular, over the entire life span; these measures need to be incorporated into toxicity testing and into long-term prospective epidemiologic studies of children; and e) application of uncertainty and safety factors in risk assessment that specifically consider children's risks. Under FQPA, children are presumed more vulnerable to pesticides than adults unless evidence exists to the contrary. Uncertainty and safety factors that are protective of children must therefore be incorporated into risk assessment when data on developmental toxicity are lacking or when there is evidence of developmental toxicity. The adequate protection of children against toxic agents in the environment will require fundamental and far-reaching revisions of current approaches to toxicity testing and risk assessment.

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Section: Critical Issues For Improved Assessment Of Environmental Heamentioning

confidence: 99%

Children's health and the environment: public health issues and challenges for risk assessment.

Landrigan

Kimmel

Correa

et al. 2004

Environ Health Perspect

357

206

View full text Add to dashboard Cite

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“…Ginsberg et al (2002) compiled these toxicokinetic parameters for children and adults for 45 drugs. Analysing these data, Hattis et al (2003) reported that the half-lives of orally administered drugs in children of 2 months to 18 years were within a factor of 3.2 of the adult half-lives.…”

Section: Dose To Targetmentioning

confidence: 99%

“…Quantitatively, adjustments to adult physiologically based toxicokinetic models can be used to develop an appropriate dose metric for a specific life stage in children. In an evaluation of child/adult pharmacokinetic differences based on the therapeutic drug literature, Ginsberg et al (2002) reported that half-lives of drugs are three to nine times longer in neonates than in adults, the difference disappearing by two to six months of age. This range of longer half-lives exceeds the 3.16 uncertainty factor that is applied to account for interindividual pharmacokinetic variability.…”

Section: Tolerable Daily Intake (Tdi) and Reference Dose (Rfd)/referementioning

confidence: 99%

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

Liu

Xia

Guo

et al. 2012

J Expo Sci Environ Epidemiol

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The urinary metabolites of phthalates are well-accepted exposure biomarkers for adults and children older than 6 years but are not commonly used for infants owing to non-convenient sampling. In the light of this situation, a novel sampling method based on monitoring the urine expressed from the gel diaper was developed. The urine was expressed from the gel absorbent after mixing the absorbent with CaCl2 and then collected by a laboratory-made device; the urinary phthalate metabolites were extracted and cleaned using a solid-phase extraction (SPE) column and analyzed with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry / mass spectrometry. To evaluate the method's feasibility, the following factors were investigated: the proportion of CaCl2 to gel absorbent, the urination volume variation and the target compounds' deposition bias in the diaper, the matrix blank of the different diaper brands, the storage stabilities and the recoveries of creatinine and phthalate metabolites in the expressed urine. Mono-methyl phthalate, mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, mono-2-ethylhexyl phthalate and mono-2-ethyl-5-oxohexyl phthalate were involved. 70-80% of the urine can be expressed from the diaper, and the expressed spiking recoveries and the limit of detection of mono-phthalates ranged from 88.5-115% and 0.21-0.50 ng/ml. The method was applied to measure phthalate metabolites in 65 gel diaper samples from 15 infants, and the pilot data suggests the infants are commonly exposed to phthalates. In summary, the method for monitoring of infant exposure to phthalates is sound and validated, and the potential health effects from the vulnerable infants' exposure to phthalates should be concerned.39th Scientific Research Foundation for the Returned Overseas Chinese Scholars (SRF for ROCS); Hundred Talent Program of Chinese Academy of Sciences (CAS); CAS/SAFEA International Partnership Program for Creative Research Teams [KZCX2-YW-T08

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“…In general, there are limited data to elucidate the mode(s) of action that leads to differences in tumour incidence following exposure early in life or later. Differences in the capacity to metabolize and clear chemicals at different ages can result in larger or smaller internal doses of the active agent(s), which either increases or decreases risk (Ginsberg et al, 2002). Several studies have shown increased susceptibility of weanling animals to the formation of DNA adducts following exposure to vinyl chloride (Laib et al, 1989;Morinello et al, 2002a,b), and in-vivo transplacental micronucleus assays have indicated that fetal tissues are more sensitive than maternal tissues to the induction of micronuclei by mutagenic chemicals (Hayashi et al, 2000).…”

Section: Age-related Susceptibilitymentioning

confidence: 99%

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

Hellou¹,

Beach²,

Leonard³

et al. 2012

Polycyclic Aromatic Compounds

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initiated a programme on the evaluation of the carcinogenic risk of chemicals to humans involving the production of critically evaluated monographs on individual chemicals. The programme was subsequently expanded to include evaluations of carcinogenic risks associated with exposures to complex mixtures, life-style factors and biological and physical agents, as well as those in specific occupations. The objective of the programme is to elaborate and publish in the form of monographs critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations; to evaluate these data in terms of human risk with the help of international working groups of experts in chemical carcinogenesis Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved.The International Agency for Research on Cancer welcomes requests for permission to reproduce or translate its publications, in part or in full. Requests for permission to reproduce or translate IARC publications -whether for sale or for noncommercial distribution -should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; email: permissions@who.int).The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.The IARC Monographs Working Group alone is responsible for the views expressed in this publication. IARC Library Cataloguing in Publication Data NOTE TO THE READERThe term 'carcinogenic risk' in the IARC Monographs series is taken to mean that an agent is capable of causing cancer under some circumstances. The Monographs evaluate cancer hazards, despite the historical presence of the word 'risks' in the title.Inclusion of an agent in the Monographs does not imply that it is a carcinogen, only that the published data have been examined. Equally, the fact that an agent has not yet been evaluated in a Monograph does not mean that it is not carcinogenic.The evaluations of carcinogenic risk are made by international working groups of independent scientists and are qualitative in nature. No recommendation is given for regulation or legislation.Anyone who is aware of published data that may alter the evaluation of the carcinogenic risk of an agent to humans is encouraged to make this information available to the Section of IARC Monographs, International Agency for...

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Evaluation of Child/Adult Pharmacokinetic Differences from a Database Derived from the Therapeutic Drug Literature

Cited by 288 publications

References 50 publications

Children's health and the environment: public health issues and challenges for risk assessment.

Children's health and the environment: public health issues and challenges for risk assessment.

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

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