Incorporating children's toxicokinetics into a risk framework

Environmental Health Perspectives

Volumn 112, Issue 2, 2004, Pages 272-283

  Ginsberg, Gary ^a   Slikker Jr , William ^b   Bruckner, James ^c   Sonawane, Babasaheb ^d  

^a CDC   (United States)

^b CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^c UNIVERSITY OF GEORGIA   (United States)

^d U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

Author keywords

Children; Dosimetry; Risk assessment; Toxicokinetics

Indexed keywords

CYTOCHROME P450; ENVIRONMENTAL CHEMICAL; XENOBIOTIC AGENT;

ANALYTIC METHOD; CHILD; CHILD DEVELOPMENT; CHILD HEALTH; DATA ANALYSIS; DECISION MAKING; DEVELOPMENTAL STAGE; DOSIMETRY; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG METABOLISM; ENVIRONMENTAL EXPOSURE; ENZYME ANALYSIS; ENZYME METABOLISM; HUMAN; IN VITRO STUDY; PRENATAL DEVELOPMENT; PRIORITY JOURNAL; QUALITATIVE ANALYSIS; QUANTITATIVE ANALYSIS; REVIEW; RISK ASSESSMENT; TOXICOKINETICS; TOXICOLOGY;

ANIMALIA;

EID: 1042304192     PISSN: 00916765     EISSN: None     Source Type: Journal    
DOI: 10.1289/ehp.6013     Document Type: Review

References (156)

1. Adams J, Barone S Jr, LaMantia A, Philen R, Rice DC, Spear L et al. 2000. Workshop to identify critical windows of exposure for children's health: neurobehavioral work group summary. Environ Health Perspect 108(suppl 3):S535-S544.
2. Adinolfi M. 1985. The development of the human blood-CSF-brain barrier. Dev Med Child Neurol 27:532-537.
3. Andersen ME, Clewell HJ III, Gargas ML, Smith FA, Reitz RH. 1987. Physiologically based pharmacokinetics and the risk assessment process for methylene chloride. Toxicol Appl Pharmacol 87:185-205.
4. Anderson ME, Clewell H III, Krishnan K. 1995. Tissue dosimetry, pharmacokinetic modeling, and interspecies scaling factors. Risk Anal 75:533-537.
5. Anderson BJ, McKee AD, Holford NH. 1997. Size, myths, and the clinical pharmacokinetics of analgesia in pediatric patients. Clin Pharmacokinet 33:313-327.
6. Arcuri F, Sestini S, Cintorino M. 1999. Expression of 11β-hydroxysteroid dehydrogenase in early pregnancy: implications in human trophoblast-endometrial interactions. Semin Reprod Endocrinol 17:53-61.
7. Atterberry TT, Burnett WT, Chambers JE. 1997. Age-related differences in parathion and chlorpyrifos toxicity in male rats: target and nontarget esterase sensitivity and cytochrome P450-mediated metabolism. Toxicol Appl Pharmacol 147:471-418.
8. Augustinsson KB, Barr M, 1963. Age variation in plasma arylesterase activity in children. Clin Chim Acta 8:568-573.
9. Barr M, Brent RL. 1978. Uterine vascular interruption and combined radiation and surgical procedures. In: Handbook of Teratology (Wilson JG, Fraser C, eds). New York:Plenum, 275-304.
10. Behrman RE, Lees MH, Peterson EN, De Lannoy CW, Seeds AE. 1970. Distribution of the circulation in the normal and asphyxiated fetal primate. Am J Obstet Gynecol 108:956-969.
11. Benke GM, Murphy SD. 1975. The influence of age on the toxicity and metabolism of methyl parathion and parathion in male and female rats. Toxicol Appl Pharmacol 31:254-269.
12. Bertz RJ, Granneman GR. 1997. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic inter-actions. Clin Pharmacokinet 32:210-258.
13. Besunder JB, Reed MD, Blumer JL, 1988. Principles of drug biodisposition in the neonate. A critical evaluation of the pharmacokinetic-pharmacodynamic interface (part I). Clin Pharmacokinet 14:189-216.
14. Bogaert MC, Thiery M. 1983. Pharmacokinetics and pregnancy. Eur J Obstet Gynecol Reprod Biol 16:229-235.
15. Bois FY, Zeise L, Tozer TN. 1990. Precision and sensitivity of pharmacokinetic models for cancer risk assessment: tetrachloroethylene in mice, rats, and humans. Toxicol Appl Pharmacol 102:300-315.
16. Brock-Utne JG, Downing JW, Mankowitz E. 1980. Drugs and the fetomaternal unit. S Afr Med J 58:366-369.
17. Bruckner JV. 2000. Differences in sensitivity of children and adults to chemical toxicity: the NAS panel report, Regul Toxicol Pharmacol 31:280-285.
18. Carpenter SP, Savage DD, Schultz ED, Raucy JL. 1997. Ethanolmediated transplacental induction of CYP2E1 in fetal rat liver. J Pharmacol Exp Ther 282:1028-1036.
19. Cazeneuve C, Pons G, Rey E, Treluyer JM, Cresteil T, Thiroux G, et al. 1994. Biotransformation of caffeine in human microsomes rom foetuses, neonates, infants and adults. Br J Clin Pharmacol 37:405-412.
20. Chen H, Brzezinski MR, Fantel AG, Juchau MR. 1999. Catalysis of drug oxidation during embryogenesis in human hepatic tissues using imipramine as a model substrate. Drug Metab Dispos 27:1306-1308.
21. Conrad S, Ha J, Lohr C, Sackett G. 1995. Ultrasound measurement of fetal growth in Macaca nemestrina. Am J Primatol 36:15-35.
22. Cummings AJ. 1983. A survey of pharmacokinetic data from pregnant women. Clin Pharmacokinet 8:344-354.
23. Dancis J, Money WL, Condon GP, Motimer L. 1958. The relative transfer of estrogens and their glucuronides across the placenta in the guinea pig. J Clin Invest 37:1373-1378.
24. Daston G, Faustman E, Ginsberg G, Fenner-Crisp P, Olin S, Sonawane B, et al. 2004. A framework for assessing risks to children from exposure to environmental agents. Environ Health Perspect 112:238-256.
25. Davis JM, Otto DA, Weil DE, Grant LD. 1990. The comparative developmental neurotoxicity of lead in humans and animals. Neurotoxicol Teratol 12:215-229.
26. Dawes GS. 1968, Umbilical blood flow and vascular resistance: changes with age. In: Foetal and Neonatal Physiology (Dawes GS, ed). Chicago:Year Book Medical Publications.
27. Dempsey D, Jacob P III, Benowitz NL. 2000. Nicotine metabolism and elimination kinetics in newborns. Clin Pharmacol Ther 67:458-465.
28. Diggory HJ, Landrigan PJ, Latimer KP, Ellington AC, Kimbrough RD, Liddle JA et al. 1977. Fatal parathion poisoning caused by contamination of flour for international commerce. Am J Epidemiol 106:145-153.
29. Dollery C. 2000. Therapeutic Drugs. 2nd ed. Edinburgh:Churchill Livingstone.
30. Done AK. 1964. Developmental pharmacology. Clin Pharmacol Ther 5:432-479.
31. Dorne JL, Walton K, Renwick AG. 2001. Uncertainty factors for chemical risk assessment: human variability in the pharmacokinetics of CYP1A2 probe substrates. Food Chem Toxicol 39:681-696.
32. Dutton GJ. 1978. Developmental aspects of drug conjugation, with special reference to glucuronidation. Annu Rev Pharmacol Toxicol 18:17-35.
33. Dutton GJ, Leakey JE. 1981. The perinatal development of drug-metabolizing enzymes: what factors trigger their onset? Prog Drug Res 25:189-273.
34. Dvorchik BH. 1981. Nonhuman primates as animal models for the study of fetal hepatic drug metabolism. In: Drug Metabolism in the Immature Human (Soyka LF, Redmond GP, eds). New York:Raven Press, 146-162.
35. Dziegielewska KM, Knott GW, Saunders NR. 2000. The nature and composition of the internal environment of the developing brain. Cell Mol Neurobiol 20:41-56.
36. Ecobichon DJ, Stephens DS. 1972. Perinatal development of human blood esterases. Clin Pharmacol Ther 14:41-47.
37. Eichelbaum M, Ekbom K, Bertilsson L, Ringberger VA, Rane A. 1975. Plasma kinetics of carbamazopine and its epoxide metabolite in man after single and multiple doses. Eur J Clin Pharmacol 8:337-341.
38. Eichelbaum M, Tomson T, Tybring G, Bertilsson L. 1985. Carbamazepine metabolism in man induction and pharmacogenetic aspects. Clin Pharmacokinet 10:80-90.
39. Eltom SE, Babish JG, Schwark WS. 1993. The postnatal development of drug-metabolizing enzymes in hepatic, pulmonary and renal tissues of the goat. J Vet Pharmacol Ther 16:152-163.
40. Farin FM, Omiecinski CJ. 1993. Regiospecific expression of cytochrome P-450s and microsomal epoxide hydrolase in human brain tissue. J Toxicol Environ Health 40:317-335.
41. Fichtl B, Nieciecki AV, Walter K. 1991. Tissue binding versus plasma binding of drugs: general principles and pharmacokinetic consequences. In: Advances in Drug Research, Vol 20 (Testa B, ed). London:Academic Press, 117-166.
42. Garbis-Berkvens JM, Peters PW. 1987. Comparative morphology and physiology of embryonic and fetal membranes, In: Pharmacokinetics in Teratogenesis, Vol 1 (Nau H, Scott WJ, eds). Elkins Park, PA:Franklin Book Company, 14-44.
43. Gentry R, Teeguarden J, Sarangapani R, Covington T, Lawrence G, McDonald T, et al. 2002. Evaluation of the potential impact of age- and gender-specific pharmacokinetic differences on tissue dosimetry [Abstract]. Toxicol Sci 66:1-S.
44. Gibbs JP, Murray G, Risler L, Chien JY, Dev R, Slattery JT. 1997. Age-dependent tetrahydrothiophenium ion formation in young children and adults receiving high dose busulfan. Cancer Res 57:5509-5516.
45. Ginsberg G, Hattis D, Sonawane B, Russ A, Banati P, Kozlak M, et al. 2002. Evaluation of child/adult pharmacolkinetic differences from a database derived from the therapeutic drug literature. Toxicol Sci 66:185-200.
46. 14C. Acta Endocrinol (Copenh) 70: 132-142.
47. Goebelsmann U, Wiqvist N, Diczfalusy E. 1968. Placental transfer of estriol glucosiduronates. Acta Endocrinol (Copenh) 59:426-432.
48. 50 values in newborn and adult animals. Toxicol Appl Pharmacol 18:185-207.
49. Greiss FC Jr, Gobble FL Jr. 1967. Effect of sympathetic nerve stimulation on the uterine vascular bed. Am J Obstet Gynecol 97:962-967.
50. Hakkola J, Pasanen M, Pelkonen O, Hukkanen J, Evisalmi S, Anttila S, et al. 1997. Expression of CYP1B1 in human adult and fetal tissues and differential inducibility of CYP1B1 and CYP1A1 by Ah receptor ligands in human placenta and cultured cells. Carcinogenesis 18:391-397.
51. Hakkola J, Pasanen M, Purkunen R, Saarikoski S, Pelkonen O, Maenpaa J, et al. 1994. Expression of xenobiotic-metabolizing cytochrome P450 forms in human adult and fetal liver. Biochem Pharmacol 48:59-64.
52. Hakkola J, Polkonen O, Pasanen M, Raunio H. 1998a. Xenobiotic-metabolizing cytochrome P450 enzymes in the human fetoplacental unit: role in intrauterine toxicity. Crit Rev Toxicol 28:35-72.
53. Hakkola J, Tanaka E, Pelkonen O. 1998b. Developmental expression of cytochrome P-450 enzymes in human liver. Pharmacol Toxicol 82:209-217.
54. Harroff HH Jr. 1997. Use of animal models in pediatric research. Adv Pediatr 44:453-489.
55. Hattis D, White P, Koch P. 1993. Uncertainties in pharmacokinetic modeling for perchloroethylene. II. Comparison of model predictions with data for a variety of different parameters. Risk Anal 13:599-610.
56. Hytten FE, Leitch I. 1971. The product of conception. In: The Physiology of Human Pregnancy. Oxford, UK:Blackwell Scientific Publications, 322.
57. Idanpaan-Heikkila J, Jouppila, P, Akerblom HK, Isoaho R, Kauppila E, Koivisto M. 1972. Elimination and metabolic effects of ethanol in mother, fetus, and newborn infant. Am J Obstet Gynecol 112:387-393.
58. Illsley NP, Hall S, Penfold P, Stacey TE. 1985. Diffusional permeability of the human placenta, Contrib Gynecol Obstet 13:92-97.
59. Imaoka S, Fujita S, Funae Y. 1991. Age-dependent expression of cytochrome P-450s in rat liver. Biochim Biophys Acta 1097:187-192.
60. Jahn F, Router A, Karge E, Danz M, Klinger W. 1993. Age dependent different influence of carbon tetrachloride on biotransformation of xenobiotics, glutathione content, lipid peroxidation and histopathology of rat liver. Exp Toxicol Pathol 45:101-107.
61. Juchau MR. 1980a. Extrahepatic drug biotransformation in the placenta. In: Extrahepatic Metabolism of Drugs and Other Foreign Compounds (Gram TE, ed). New York:SP Medical and Scientific Books, 211-238.
62. Juchau MR. 1980b. Drug biotransformation in the placenta. Pharmacol Ther 8:501-524.
63. Juchau MR. 1995. Placental enzymes: cytochrome P450s and their significance. In: Placental Toxicology (Rama Sastry BV, ed). Boca Raton, FL:CRC Press, 197-212.
64. Juchau MR, Faustman-Watts E. 1983. Pharmacokinetic considerations in the maternal-placental-fetal unit. Clin Obstet Gynecol 26:379-390.
65. Jusko WJ. 1972. Pharmacokinetic principles in pediatric pharmacology. Pediatr Clin North Am 19:81-100.
66. Kearns GL, Reed MD. 1989. Clinical pharmacokinetics in infants and children. A reappraisal. Clin Pharmacokinet 17(suppl 1): S29-S67.
67. Kim CS, Binienda Z, Sandberg JA. 1996. Construction of a physiologically based pharmacokinetic model for 2,4-dichlorophe-noxyacetic acid (2,4-D) dosimetry in the developing rabbit brain. Toxicol Appl Pharmacol 136:250-259.
68. 14C-dimethyltubocurarine. Br J Anaesth 44: 557-561.
69. 14C-dimethyltubocurarine during Caesarean section. Br J Anaesth 48:239-242.
70. Korinthenberg R, Haug C, Hannak D. 1994. The metabolism of carbamazepine to CBZ-10-11-epoxide in children from the newborn age to adolescence. Neuropediatrics 25:214-216.
71. Kostial K, Kello D, Jugo S, Rabar I, Maljkovic T, 1978. Influence of age on metal metabolism and toxicity. Environ Health Perspect 25:81-86.
72. Krauer B, Krauer F, Hytten FE. 1980. Drug disposition and pharmacokinetics in the maternal-placental-fetal-unit. Pharmacol Ther 10:301-328.
73. Krishnan K, Andersen ME. 1998. Physiological pharmacokinetic models in the risk assessment of developmental neurotoxicants. In: Handbook of Developmental Neurotoxicology (Sikker W, Chang L, eds). New York:Academic Press, 709-725.
74. Kuhnz W, Jager-Roman E, Rating D, Diechl A, Kunze J, Helge H, et al. 1983. Carbamazepine and carbamazopine-10, 11-epoxide during pregnancy and postnatal period in epileptic mothers and their nursed infants: pharmacokinetics and clinical effects. Pediatr Pharmacol (New York) 3:199-208.
75. Kurata N, Nishimura Y, Iwase M, Fischer NE, Tang BK, Inaba T, et al. 1998. Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica 28:1041-1047.
76. LaCroix D, Sonnier M, Moncion A, Cheron G, Cresteil T. 1997. Expression of CYP3A in the human liver. Evidence that the shift between CYP3A7 and CYP3A4 occurs immediately after birth. Eur J Biochem 247:625-634.
77. Leakey JEA. 1983. Ontogenesis. In: Biological Basis of Detoxication (Caldwell J, ed). New York:Academic Press, 77-103.
78. Lehmann H, Cook J, Ryan E. 1957. Pseudocholinesterase in early infancy. Proc R Soc Mad 50:147-150.
79. Levine RR. 1973. Pharmacology Drug Actions and Reactions, Boston:Little, Brown, 103.
80. Levitz M, Condon GP, Money WL, Dancis J. 1960. The relative transfer of estrogens and their sulfates across the guinea pig placenta: sulfurylation of estrogens by the placenta. J Biol Chem 235:973-977.
81. Levy G. 1981. Pharmacokinetics of fetal and neonatal exposure to drugs. Obstet Gynecol 58(suppl 5):S9-S16.
82. Levy G, Khanna NN, Soda DM, Tsuzuki O, Stern L. 1975. Pharmacokinetics of acetaminophen in the human neonate: formation of acetaminophen glucuronide and sulfate in relation to plasma bilirubin concentration and D-glucaric acid excretion. Pediatrics 55:818-825.
83. Lin JH. 1995. Species similarities and differences in pharmacokinetics. Drug Metab Dispos 23:1008-1021.
84. Luecke RH, Wosilait WD, Pearce BA, Young JF. 1994. A physiologically based pharmacokinetic computer model for human pregnancy. Teratology 49:90-103.
85. Maenpaa J, Rane A, Raunio H, Honkakoski P, Pelkonen O. 1993. Cytochrome P450 isoforms in human fetal tissues related to phenobarbital-inducible forms in the mouse. Biochem Pharmacol 45:899-907.
86. Mattsson JL, Maurissen JP, Nolan RJ, Brzak KA. 2000. Lack of differential sensitivity to cholinesterase inhibition in fetuses and neonates compared to dams pretreated perinatally with chlorpyrifos. Toxicol Sci 53:438-446.
87. Mihaly GW, Morgan DJ. 1983. Placental drug transfer: effects of gestational age and species. Pharmacol Ther 23:253-266.
88. Miller RK, Koszalka TR, Brent RL. 1976. The transport of molecules across placental membranes. In: The Cell Surface in Animal Embryogenesis and Development (Post G, Nicolson GL, eds). New York:Elsevier/North-Holland Biomedical Press, 145-223.
89. Millicovsky G, DeSesso JM. 1980. Differential embryonic cardiovascular responses to acute maternal uterine ischemia: an in vivo microscopic study of rabbit embryos with either intact or clamped umbilical cords. Teratology 22:335-343.
90. Mirkin BL, Singh S. 1976. Placental transfer of pharmacologically active molecules. In: Perinatal Pharmacology and Therapeutics (Mirkin BL, ed). New York:Academic Press, 1-69.
91. Moghrabi N, Head JR, Andersson S. 1997. Cell type-specific expression of 17β-hydroxysteroid dehydrogenase type 2 in human placenta and fetal liver. J Clin Endocrinol Metab 82:3872-3878.
92. Morselli PL. 1989. Clinical pharmacology of the perinatal period and early infancy. Clin Pharmacokinet 17(suppl 1):13-28.
93. Moser VC, Chanda SM, Mortensen SR, Padilla S. 1998. Age- and gender-related differences in sensitivity to chlorpyrifos in the rat reflect developmental profiles of esterase activities. Toxicol Sci 46:211-222.
94. Mulhall A, de Louvois J, Hurley R. 1983. Chloramphenicol toxicity in neonates: its incidence and prevention. Br Med J (Clin Res Ed) 287:1424-1427.
95. Murray GI, Foster CO, Barnes TS, Weaver RJ, Snyder CP, Ewen SW, et al. 1992. Cytochrome P4501A expression in adult and fetal human liver. Carcinogenesis 13:165-169.
96. Nakamura H, Tanaka E, Ishikawa A, Fukao K, Tsuji K, Ohkawa H. 1998. Age-related changes in hepatic drug-oxidizing activity using trimethadione as a probe drug in humans. Hepatol Res 12:85-92.
97. NAS. 1993. Pesticides in the Diets of Infants and Children. Washington, DC:National Academy of Sciences.
98. NRC (National Research Council). 2000. Scientific Frontiers in Developmental Toxicity and Risk Assessment. Washington, DC:National Academic Press.
99. Nau H, Liddiard C. 1978. Placental transfer of drugs during early human pregnancy. In: Role of Pharmacokinetics in Prenatal and Perinatal Toxicology (Neubert D, Marker H-J, Nau H, Langman J, eds). Stuttgart, West Germany:Theime, 465-481.
100. Nau H, Neubert D. 1978. Placental transfer of drugs during early human pregnancy. In: Role of Pharmacokinetics in Prenatal and Perinatal Toxicology (Neubert D, Merker H-J, Nau H, Langman J, eds). Stuttgart, West Germany:Theime, 13-44.
101. Nedelcheva V, Gut I. 1994. P450 in the rat and man: methods of investigation, substrate specificities and relevance to cancer. Xenobiotica 24:1151-1175.
102. Neims AH, Warner W, Loughnan PM, Aranda JV. 1976. Developmental aspects of the hepatic cytochrome P-450 monooxygenase system. Annu Rev Pharmacol Toxicol 16:427-445.
103. Noschel H, Peiker G, Voigt R, Meinhold P, Muller B, Schroder S, et al. 1980, Research on pharmacokinetics during pregnancy. Arch Toxicol Suppl 4:S380-S384.
104. O'Flaherty EJ. 1991. Physiologically based models for bone-seeking elements. II. Kinetics of lead disposition in rats. Toxicol Appl Pharmacol 111:313-331.
105. O'Flaherty EJ. 1995. Physiologically based models for bone-seeking elements. V. Lead absorption and disposition in childhood. Toxicol Appl Pharmacol 131:297-308.
106. Ohmori S, Nakasa H, Asanome K, Kurose Y, Ishii I, Hosokawa M, et al. 1998. Differential catalytic properties in metabolism of endogenous and exogenous substrates among CYP3A enzymes expressed in COS-7 cells. Biochim Biophys Acta 1380:297-304.
107. Pariente-Khayat A, Pons G, Rey E, Richard MO, D'Athis P, Moran C, et al. 1991. Caffeine acetylator phenotyping during maturation in infants. Pediatr Res 29:492-495.
108. Parsons WD, Aranda JV, Neims AH. 1976. Elimination of transplacentally acquired caffeine in fullterm neonates. Pediatr Res 10:333.
109. Parsons WD, Neims AH. 1978. Effect of smoking on caffeine clearance. Clin Pharmacol Ther 24:40-45.
110. Pelekis M, Gephart LA, Lerman SE. 2001. Physiological-model-based derivation of the adult and child pharmacokinetic intraspecies uncertainty factors for volatile organic compounds. Regul Toxicol Pharmacol 33:12-20.
111. Pelkonen O. 1977. Transplacental transfer of foreign compounds and their metabolism by the foetus. Prog Drug Metab 2:119-161.
112. Pelkonen O. 1980. Biotransformation of xenobiotics in the fetus. Pharmacol Ther 10:261-281.
113. Pikkarainen PH, Raiha NC, 1967. Development of alcohol dehydrogenase activity in the human liver. Pediatr Res 1:165-168.
114. Pons G, Rey E, Carrier O, Richard MO, Moran C, Badoual J, et al. 1989. Maturation of AFMU excretion in infants. Fundam Clin Pharmacol 3:589-595.
115. Pounds JG, Marlar RJ, Allen JR. 1978. Metabolism of lead-210 in juvenile and adult rhesus monkeys (Macaca mulatta). Bull Environ Contam Toxicol 19:684-691.
116. Power GG, Longo LD. 1975. Fetal circulation times and their implications for tissue oxygenation. Gynecol Invest 6:342-355.
117. Pyonnonen S, Sillanpaa M, Frey H, Iisalo E. 1977. Carbamazepine and its 10,11-epoxide in children and adults with epilepsy. Eur J Clin Pharmacol 11:129-133.
118. Rane A, Tomson G. 1980. Prenatal and neonatal drug metabolism in man. Eur J Clin Pharmacol 18:9-15.
119. Rao HV, Ginsberg GL. 1997. A physiologically-based pharmacokinetic model assessment of methyl t-butyl ether in groundwater for a bathing and showering determination. Risk Anal 17:583-597.
120. Rasheed A, Hines RN, McCarver-May DG. 1997. Variation in induction of human placental CYP2E1: possible role in susceptibility to fetal alcohol syndrome. Toxicol Appl Pharmacol 144:396-400.
121. Ratanasavanh D, Beaune P, Morel F, Flinois JP, Guengerich FP, Guillouzo A. 1991. Intralobular distribution and quantitation of cytochrome P-450 enzymes in human liver as a function of age. Hepatology 13:1142-1151.
122. Ravindranath V, Boyd MR. 1995. Xenobiotic metabolism in brain. Drug Metab Rev 27:419-448.
123. Renwick AG. 1998. Toxicokinetics in infants and children in relation to the ADI and TDI. Food Addit Contam 15(suppl):S17-S35.
124. Renwick AG, Dorne JL, Walton K. 2000. An analysis of the need for an additional uncertainty factor for infants and children. Regul Toxicol Pharmacol 31:286-296.
125. Rudolph AM, Heymann MA. 1967. The circulation of the fetus in utero. Circ Res 21:163-184.
126. Sandberg JA, Binienda Z, Lipe G, Rose LM, Parker WB, Ali SF, et al. 1996. Placental transfer and fetal disposition of 2′,3′-dideoxycytidine (ddC) and 2′,3′-dideoxyinosine (ddl) in the rhesus monkey. Drug Metab Dispos 23:881-884.
127. Slikker W Jr. 1987. The role of metabolism in the testing of developmental toxicants. Regul Toxicol Pharmacol 7:3913-413.
128. Slikker W Jr. 1994. Placental transfer and pharmacokinetics of developmental neurotoxicants. In: Principles of Neurotoxicology (Chang LW, ed). New York:Marcel Dekker, 659-680.
129. Slikker W Jr. 1997. The Developing Nervous System, Comprehensive Toxicology (Sipes IE, McQueen CA, Gandolfi AJ, eds). New York:Pergamon, 295-307.
130. Slikker W Jr, Hill DE, Young JF. 1982. Comparison of the transpla-cental pharmacokinetics of 17β-estradiol and diethylstilbestrol in the subhuman primate. J Pharmacol Exp Ther 221:173-182.
131. Slikker W Jr, Miller RK. 1994. Placental metabolism and transfer role in developmental toxicology. In: Developmental Toxicology (Kimmel CA, Buelke-Sam J, eds). New York:Raven Press, 245-283.
132. Sonnier M, Cresteil T. 1998. Delayed ontogenesis of CYP1A2 in the human liver. Eur J Biochem 251:893-898.
133. Stevens JC, Shipley LA, Cashman JR, Vandenbranden M, Wrighton SA. 1993. Comparison of human and rhesus monkey in vitro phase I and phase II hepatic drug metabolism activities. Drug Metab Dispos 21:753-760.
134. Strange RC, Howie AF, Hume R, Matharoo B, Bell J, Hiley C, et al. 1989. The developmental expression of alpha-, mu- and pi-class glutathione S-transferases in human liver. Biochim Biophys Acta 993:186-190.
135. Szorady I, Santa A, Veress I. 1987. Drug acetylator phenotypes in newborn infants. Biol Res Pregnancy Perinatol 8:23-25.
136. Tanaka E. 1998. In vivo age-related changes in hepatic drug-oxidizing capacity in humans. J Clin Pharm Ther 23:247-255.
137. Treluyer JM, Cheron G, Sonnier M, Cresteil T. 1996. Cytochrome P450 expression in sudden infant death syndrome. Biochem Pharmacol 52:497-504.
138. Treluyer JM, Jacqz-Aigrain E, Alvarez F, Cresteil T. 1991. Expression of CYP2D6 in developing human liver. Eur J Biochem 202:583-588.
139. U.S. EPA. 1989. Risk Assessment Guidance for Superfund, Vol I. Human Health Evaluation Manual, Part A. EPA/540/1-89/002. Washington, DC:U.S. Environmental Protection Agency.
140. U.S. EPA. 1992. Draft Report: A Cross-Species Scaling Factor for Carcinogen Risk Assessment Based on Equivalence of mg/kg/day. Fed Reg 57:24152-24173.
141. U.S. EPA. 1994. Guidance Manual for the Integrated Exposure Uptake Biokinetic Model for Lead in Children. EPA 540-R-93-081. PB93-963510 Washington, DC:U.S. Environmental Protection Agency,
142. U.S. EPA. 2000. IRIS file for Vinyl Chloride and Toxicology Review of Vinyl Chloride in Support of Summary Information on IRIS. EPA/635R-00/004. Washington, DC:U.S. Environmental Protection Agency.
143. Vest MF. 1965. The development of conjugation mechanisms and drug toxicity in the newborn. Biol Neonat 8:258-266.
144. Vieira I, Sonnier M, Cresteil T. 1996. Development expression of CYP2E1 in the human liver. Hypermethylation control of gene expression during the neonatal period. Eur J Biochem 238:476-483.
145. Waddell WJ, Marlowe C. 1981. Transfer of drugs across the placenta. Pharmacol Ther 14:375-390.
146. Watanabe J, Asaka Y, Kanamura S. 1993. Postnatal development and sublobular distribution of cytochrome P-450 in rat liver: a microphotometric study. J Histochem Cytochem 41:397-400.
147. Welfare MR, Bassendine MF, Daly AK. 2000. The effect of NAT2 genotype and gender on the metabolism of caffeine in non-smoking subjects, Br J Clin Pharmacol 49:240-243.
148. Welsch F. 1982. Placental and fetal uptake of drugs. J Vet Pharmacol Ther 5:91-104.
149. Welsch F, Blumenthal GM, Conolly RE. 1995. Physiologically based pharmacokinetic models applicable to organogenesis: extrapolation between species and potential use in prenatal toxicity risk assessments. Toxicol Lett 82-83:539-547.
150. Wilson JG, Ritter EJ, Scott WJ, Fradkin R. 1977. Comparative distribution and embryotoxicity of acetylsalicylic acid in pregnant rats and rhesus monkeys. Toxicol Appl Pharmacol 41:67-78.
151. Yang HL, Namkung MJ, Juchau MR. 1995. Expression of functional cytochrome P-450A1 in human embryonic hepatic tissues during organogenesis. Biochem Pharmacol 49:717-726.
152. Yoo J-SH, Ning SM, Patten CJ, Yang CS. 1987. Metabolism and activation of N-nitrosodimethylamine by hamster and rat microsomes: comparative study with weanling and adult animals. Cancer Res 47:992-998.
153. Ziegler EE, Edwards BB, Jensen RL, Mahaffey KR, Fomon SJ. 1978. Absorption and retention of lead by infants. Pediatr Res 12:29-34.
154. Zsigmond EK, Downs JR. 1971. Plasma cholinesterase activity in newborns and infants. Can Anesth Soc J 18:278-285.
155. Zusterzeel PL, Peters WH, De Bruyn MA, Knapen MF, Merkus HM, Steegers EA. 1999. Glutathione S-transferase isoenyzmes in decidua and placenta of preeclamptic pregnancies. Obstet Gynecol 94:1033-1038.
156. Zwiener RJ, Ginsburg CM 1988. Organophosphate and carbamate poisoning in infants and children. Pediatrics 81:121-126.