Assessment of health risks resulting from early-life exposures: Are current chemical toxicity testing protocols and risk assessment methods adequate?

References

• Abjuljalil K, Jamei M, Rostami-Hodjegan A, Johnson TN. (2014). Changes in individual drug-independent system parameters during virtual paediatric pharmacokinetic trials: Introducing time-varying physiology into a paediatric PBPK model. AAAPS J, 16, 568–76.
   PubMed Web of Science ®Google Scholar
• Adeleye Y, Andersen M, Clewell R, Davies M, Dent M, Edwards S, et al. (2014). Implementing Toxicity Testing in the 21st Century (TT21C): Making safety decisions using toxicity pathways, and progress in a prototype risk assessment. Toxicology. doi:10.1016/j.tox.2014.02.007. [Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• Afsar FS. (2009). Physiological skin conditions of preterm and term neonates. Clin Exp Dermatol, 35, 346–50.
   PubMed Web of Science ®Google Scholar
• AFSSAPS. (2010). Assessment report on the safety of cosmetic products intended for children under three years of age. Agence Française de Sécurité Sanitaire des Produits de Santé [French Health Products Safety Agency], St Denis, France. April.
   Google Scholar
• Alcorn J, McNamara PJ. (2003). Pharmacokinetics in the newborn. Adv Drug Deliv Rev, 55, 667–86.
   PubMed Web of Science ®Google Scholar
• Aldridge JE, Gibbons JA, Flaherty MM, Kreider ML, Romano JA, Levin ED. (2003). Heterogeneity of toxicant response: sources of human variability. Toxicol Sci, 76, 3–20.
   PubMed Web of Science ®Google Scholar
• Andersen ME. (1981). A physiologically based toxicokinetic description of the metabolism of inhaled gases and vapors: analysis at steady state. Toxicol Appl Pharmacol, 60, 509–26.
   PubMed Web of Science ®Google Scholar
• Anderson GD. (2010). Developmental pharmacokinetics. Semin Pediatr Neurol, 17, 208–13.
   PubMed Web of Science ®Google Scholar
• ATSDR. (2000). Lead toxicity. Case Studies in Environmental Medicine. US Department of Health and Human Services. Agency for Toxic Substances and Disease Registry.
   Google Scholar
• Babich MA. (1998). Risk assessment of low-level chemical exposures from consumer products under the U.S. Consumer Product Safety Commission chronic hazard guidelines. Environ Health Perspect, 106, 387–90.
   PubMed Web of Science ®Google Scholar
• Babich MA, Chen SB, Greene MA, Kiss CT, Porter WK, Smith TP, et al. (2004). Risk assessment of oral exposure to diisononyl phthalate from children's products. Regul Toxicol Pharmacol, 40, 151–67.
   PubMed Web of Science ®Google Scholar
• Barker DJ. (1999). Fetal origins of cardiovascular disease. Ann Med, 31, 3–6.
   PubMed Web of Science ®Google Scholar
• Barnes DG and Dourson ML. (1988). Reference dose (RfD): description and use in health risk assessments. Regul Toxicol Pharmacol, 8, 471–86.
   PubMed Web of Science ®Google Scholar
• Barone S, Stanton ME, Mundy WR. (1995). Neurotoxic effects of neonatal triethyltin (TET) exposure are exacerbated with aging. Neurobiol Aging, 16, 723–35.
   PubMed Web of Science ®Google Scholar
• Bars R, Fegert I, Gross M, Lewis D, Weltje L, Weyers A, et al. (2012). Workshop Report. Risk assessment of endocrine active chemicals: Identifying chemicals of regulatory concern. Regul Toxicol Pharmacol, 64, 143–54.
   Google Scholar
• Bartelink IH, Rademaker CM, Schobben AF, van den Anker JN. (2006). Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin Pharmacokinet, 45, 1077–97.
   PubMed Web of Science ®Google Scholar
• Baum M. (2009). Postnatal developmental renal physiology: a study of historic significance. Am J Physiol, 296, F667–8.
   Google Scholar
• Beckman DA, Feuston M. (2003). Landmarks in the development of the female reproductive system. Birth Defects Res (Part B), 68, 137–43.
   PubMed Web of Science ®Google Scholar
• Bellinger DC. (2011). The protean toxicities of lead: new chapters in a familiar story. Int J Environ Res Public Health, 8, 2593–628.
   PubMed Web of Science ®Google Scholar
• Bjorkman S. (2004). Prediction of drug disposition in infants and children by means of physiologically based pharmacokinetic (PBPK) modelling: theophylline and midazolam as model drugs. Br J Clin Pharmacol, 59, 691–704.
   Web of Science ®Google Scholar
• Boverhof DR, Ladics G, Luebke B, Botham J, Corsini E, Evans E, et al. (2014). Approaches and considerations for the assessment of immunotoxicity for environmental chemicals: a workshop summary. Regul Toxicol Pharmacol, 68, 96–107.
   PubMed Web of Science ®Google Scholar
• Bruckner JV. (2000). Differences in sensitivity of children and adults to chemical toxicity: the NAS panel report. Regul Toxicol Pharmacol, 31, 280–5.
   PubMed Web of Science ®Google Scholar
• Bushnell PJ (2014). Testing for cognitive function in animals in a regulatory context. Neurotoxicol Teratol. pii:S0892-0362(14)00107-X. doi:10.1016/j.ntt.2014.04.068. [Epub ahead of print]
   Web of Science ®Google Scholar
• Calabrese EJ. (2001). Assessing the default assumption that children are always at risk. Hum Ecol Risk Assess, 7, 37–59.
   Web of Science ®Google Scholar
• Cappon GD, Bailey GP, Buschmann J, Feuston MH, Fisher JE, Hew KW, et al. (2009). Juvenile animal toxicity study designs to support pediatric drug development. Birth Defects Res B Dev Reprod Toxicol, 86, 463–9.
   PubMed Web of Science ®Google Scholar
• Chiou YB, Blume-Peytavi, U. (2004). Stratum corneum maturation. A review of neonatal skin function. Skin Pharmacol Physiol, 17, 57–66.
   PubMed Web of Science ®Google Scholar
• Claudio L, Kwa WC, Russell AL, Wallinga D. (2000). Testing methods for developmental neurotoxicity of environmental chemicals. Toxicol Appl Pharmacol, 164, 1–14.
   PubMed Web of Science ®Google Scholar
• Clewell HJ, Gentry PR, Covington TR, Sarangapani R, Teeguarden JG. (2004). Evaluation of the potential impact of age- and gender specific pharmacokinetic differences on tissue dosimetry. Toxicol Sci, 79, 381–93.
   PubMed Web of Science ®Google Scholar
• Cohen Hubal EA, de Wet T, Du Toit L, Firestone MP, Ruchirawat M, van Engelen J, Vickers C. (2014). Identifying important life stages for monitoring and assessing risks from exposures to environmental contaminants: Results of a World Health Organization review. Regul Toxicol Pharmacol, 69, 113–24.
   PubMed Web of Science ®Google Scholar
• Collinge M, Burns-Naas LA, Chellman GJ, Kawabata TT, Komocsar WJ, Piccotti JR, et al. (2012). Developmental immunotoxicity (DIT) testing of pharmaceuticals: Current practices, state of the science, knowledge gaps, and recommendations. J Immunotoxicol, 9, 210–30.
   PubMed Web of Science ®Google Scholar
• Cory-Slechta DA, Crofton KM, Foran JA, Ross JF, Sheets LP, Weiss B, Mileson B. (2001). Methods to identify and characterize developmental neurotoxicity for human health risk assessment. I: behavioral effects. Environ Health Perspect, 109, 79–91.
   PubMed Web of Science ®Google Scholar
• CPSC (Consumer Product Safety Commission). (2014). Chronic Hazard Advisory Panel on Phthalates and Phthalate Alternatives Final Report (2014). Available online: https://www.cpsc.gov/en/Regulations-Laws–Standards/Statutes/The-Consumer-Product-Safety-Improvement-Act/Phthalates/Chronic-Hazard-Advisory-Panel-CHAP-on-Phthalates/. Accessed August 2014.
   Google Scholar
• Cuzzolin L. (2013). Drug metabolizing enzymes in the perinatal and neonatal period: differences in the expression and activity. Curr Drug Metabol, 14, 167–73
   PubMed Web of Science ®Google Scholar
• 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, 238–56.
   PubMed Web of Science ®Google Scholar
• Dekant W, Colnot T. (2013). Endocrine effects of chemicals: aspects of hazard identification and human health risk assessment. Toxicol Lett, 223, 280–6.
   PubMed Web of Science ®Google Scholar
• DeWitt JC, Peden-Adams MM, Keil DE, Dietert RR. (2012). Developmental immunotoxicity (DIT): assays for evaluating effects of exogenous agents on development of the immune system. Curr Protocols Toxicol, 51, 18.15.1–18.15.14.
   Google Scholar
• DeWoskin RS, Thompson CM. (2008). Renal clearance parameters for PBPK model analysis of early lifestage differences in the disposition of environmental toxicants. Regul Toxicol Pharmacol, 51, 66–86.
   PubMed Web of Science ®Google Scholar
• de Zwart LL, Haenen HE, Versantvoort CH, Wolterink G, van Engelen JG, Sips AJ. (2004). Role of biokinetics in risk assessment of drugs and chemicals in children. Regul Toxicol Pharmacol, 39, 282–309.
   PubMed Web of Science ®Google Scholar
• Dietert RR, Dietert JM. (2007). Early-life immune insult and developmental immunotoxicity (DIT)-associated diseases: potential of herbal- and fungal-derived medicinals. Curr Med Chem, 14, 1075–85.
   PubMed Web of Science ®Google Scholar
• Dorne JL, Walton K, Renwick AG. (2001a). Uncertainty factors for chemical risk assessment: human variability in the pharmacokinetics of CYP1A2 probe substrates. Food Chem Toxicol, 39, 681–96.
   PubMed Web of Science ®Google Scholar
• Dorne JL, Walton K, Renwick AG. (2001b). Human variability in glucuronication in relation to uncertainty factors for risk assessment. Food Chem Toxicol, 43, 1153–73.
   Web of Science ®Google Scholar
• Dorne JL, Walton K, Slob W, Renwick AG. (2002). Human variability in polymorphic CYP2D6 metabolism: is the kinetic default uncertainty factor adequate? Food Chem Toxicol, 40, 1633–56.
   PubMed Web of Science ®Google Scholar
• Dorne JL, Walton K, Renwick AG. (2003a). Human variability in CYP3A4 metabolism and CYP3A4-related uncertainty factors for risk assessment. Food Chem Toxicol, 41, 201–24.
   PubMed Web of Science ®Google Scholar
• Dorne JL, Walton K, Renwick AG. (2003b). Polymorphic CYP2C19 and N-acetylation: human variability in kinetics and pathway-related uncertainty factors. Food Chem Toxicol, 43, 225–45.
   Web of Science ®Google Scholar
• Dorne JL, Walton K, Renwick AG. (2004a). Human variability in the renal elimination of foreign compounds and renal excretion-related uncertainty factors for risk assessment. Food Chem Toxicol, 42, 275–98.
   PubMed Web of Science ®Google Scholar
• Dorne JL, Walton K, Renwick AG. (2004b). Human variability for metabolic pathways with limited data (CYP2A6, CYP2C9, CYP2E1, ADH, esterases, glycine and sulphate conjugation). Food Chem Toxicol, 42, 397–421.
   PubMed Web of Science ®Google Scholar
• Dorne JL, Walton K, Renwick AG. (2005). Human variability in xenobiotic metabolism and pathway-related uncertainty factors for chemical risk assessment: A review. Food Chem Toxicol, 43, 203–16.
   PubMed Web of Science ®Google Scholar
• Dourson ML, Felter SP, Robinson D. (1996). Evolution of science-based uncertainty factors in noncancer risk assessment. Regul Toxicol Pharmacol, 24, 108–20.
   PubMed Web of Science ®Google Scholar
• Dourson ML, Charnley G, Scheuplein R. (2002). Differential sensitivity of children and adults to chemical toxicity: II. Risk and Regulation. Regul Toxicol Pharmacol, 35, 448–67.
   PubMed Web of Science ®Google Scholar
• Edginton AN. (2011). Knowledge-driven approaches for the guidance of first-in-children dosing. Pediatr Anesth, 21, 206–13.
   PubMed Web of Science ®Google Scholar
• Edginton AN, Fotaki N. (2010). Oral drug absorption in pediatric populations. In: Dressman J, Reppas C, Eds. Oral Drug Absorption: Prediction and Assessment, 2nd ed. New York: Informa Healthcare, pp. 108–126.
   Google Scholar
• Edginton AN, Schmitt W, Voith B, Willmann S. (2006). A mechanistic approach for the scaling of clearance in children. Clin Pharmacokinet, 45, 683–704.
   PubMed Web of Science ®Google Scholar
• EFSA. (2011). Scientific Report of EFSA: Overview of the procedures currently used at EFSA for the assessment of dietary exposure to different chemical substances. European Food Safety Authority. EFSA J, 9, 2490.
   Google Scholar
• EFSA. (2013). Scientific Opinion on the hazard assessment of endocrine disruptors: Scientific criteria for identification of endocrine disruptors and appropriateness of existing test methods for assessing effects mediated by these substances on human health and the environment. European Food Safety Authority. EFSA J, 11, 3132.
   Google Scholar
• Firestone M, Moya J, Cohen Hubal E, Zartarian V. (2007). Identifying childhood age groups for exposure assessments and monitoring. Risk Anal, 27, 701–14.
   PubMed Web of Science ®Google Scholar
• Fluhr JW, Darlenski R, Lachmann N, Baudouin C, Msika P, De Belilovsky C, Hachem JP. (2012). Infant epidermal skin physiology: adaptation after birth. Br J Dermatol, 166, 483–90.
   PubMed Web of Science ®Google Scholar
• Fowles JR, Banton MI, Pottenger LH. (2013). A toxicological review of the propylene glycols. Crit Rev Toxicol, 43, 363–90.
   PubMed Web of Science ®Google Scholar
• Gamboa da Costa G, Loukotková L, Von Tungeln LS, Olson G, Sprando RL, Hattan DG, et al. (2013). Nephrotoxicity of melamine, cyanuric acid, and their combination in newborn F344 rats. Society of Toxicology, Annual Meeting. March.
   Google Scholar
• Gehrs BC, Riddle MM, Williams WC, Smialowicz RJ. (1997). Alterations in the developing immune system of the F344 rat after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: II. Effects on the pup and the adult. Toxicology, 122, 229–40.
   PubMed Web of Science ®Google Scholar
• Ginsberg G, Hattis D, Sonawane B, Russ A, Banati P, Kozlak M, et al. (2002). Evaluation of child/adult pharmacokinetic differences from a database derived from the therapeutic drug literature. Toxicol Sci, 66, 185–200.
   PubMed Web of Science ®Google Scholar
• Ginsberg G, Hattis D, Sonawane B. (2004a). Incorporating pharmacokinetic differences between children and adults in assessing children's risks to environmental toxicants. Toxicol Appl Pharmacol, 198, 164–83.
   PubMed Web of Science ®Google Scholar
• Ginsberg G, Slikker W Jr, Bruckner J, Sonawane B. (2004b). Incorporating children's toxicokinetics into a risk framework. Environ Health Perspect, 112, 272–83.
   PubMed Web of Science ®Google Scholar
• Giordano G, Costa LG. (2012). Review Article. Developmental Neurotoxicity: Some Old and New Issues. ISRN Toxicol. Article ID 814795, doi:10.5402/2012/814795
   Google Scholar
• Godin SJ, Scollon EJ, Hughes MF, Potter PM, DeVito MJ, Ross MK. (2006). Species differences in the in vitro metabolism of deltamethrin and esfenvalerate: Differential oxidative and hydrolytic metabolism by humans and rats. Drug Metabol Dispos, 34, 1764–71.
   PubMed Web of Science ®Google Scholar
• Guzelian PS, Henry CJ, Olin SS. (1992). Similarities and Differences between Children and Adults: Implications for Risk Assessment. Proceedings of the ILSI Conference. Washington DC: ILSI Press.
   Google Scholar
• Heimann G. (1983). Renal toxicity of aminoglycosides in the neonatal period. Pediatr Pharmacol, 3, 251–7.
   PubMedGoogle Scholar
• Hessel EVS, Tonk ECM, Bos PMJ, van Loveren H, Piersma AH. (2014). Developmental immunotoxicity of chemicals in rodents and its possible regulatory impact. Crit Rev Toxicol, Early Online, 1–15, doi:10.3109/10408444.2014.959163.
   PubMed Web of Science ®Google Scholar
• Hillyer MM, Finch LE, Cerel AS, Dattelbaum JD, Leopold MC. (2014). Multi-technique quantitative analysis and socioeconomic considerations of lead, cadmium, and arsenic in children's toys and toy jewelry. Chemosphere. Feb 18. pii: S0045–6535(14)00107-6. doi: 10.1016/j.chemosphere.2014.01.041. [Epub ahead of print]
   Google Scholar
• Hines RN. (2008). Ontogeny of drug metabolism enzymes and implications for adverse drug reactions. Pharmacol Therapeut, 118, 250–67.
   PubMed Web of Science ®Google Scholar
• Hines RN. (2013). Developmental expression of drug metabolizing enzymes: Impact on disposition in neonates and young children. Int J Pharmaceut, 452, 3–7.
   PubMed Web of Science ®Google Scholar
• Hines RN, Sargent D, Autrup H, Birnbaum LS, Brent RL, Doerrer NG, et al. (2010). Approaches for assessing risks to sensitive populations: Lessons learned from evaluating risks in the pediatric population. Toxicol Sci, 113, 4–26.
   PubMed Web of Science ®Google Scholar
• Holladay SD, Smialowicz RJ. (2000). Development of the murine and human immune system: differential effects of immunotoxicants depend on time of exposure. Environ. Health Perspect, 108, 463–73.
   PubMed Web of Science ®Google Scholar
• Holsapple MP, West LJ, Landreth KS. (2003). Species comparison of anatomical and functional immune system development. Birth Defects Res (Part B), 68, 321–34.
   PubMed Web of Science ®Google Scholar
• Ishitobi H, Mori K, Yoshida K, Watanabe C. (2007). Effects of perinatal exposure to low-dose cadmium on thyroid hormone-related and sex hormone receptor gene expressions in brain of offspring. Neurotoxicology, 28, 790–7.
   PubMed Web of Science ®Google Scholar
• Johnsrud EK, Koukouritaki SB, Divakaran K, Brunengraber LL, Hines RN, McCarver DG. (2003). Human hepatic CYP2E1 expression during development. J Pharmacol Exper Therapeut, 307, 402–7.
   PubMed Web of Science ®Google Scholar
• Juberg DR, Borghoff SJ, Becker RA, Casey W, Hartung T, Holsapple MP, et al. (2014). Workshop Report: Lessons learned, challenges, and opportunities: The US Endocrine Disruptor Screening Program. ALTEX, 31, 63–78.
   PubMedGoogle Scholar
• Kameoka S, Babiarz J, Kolaja K, Chiao E. (2014). A high-throughput screen for teratogens using human pluripotent stem cells. Toxicol Sci, 137, 76–90.
   PubMed Web of Science ®Google Scholar
• Kaufmann W. (2003). Current status of developmental neurotoxicity: an industry perspective. Toxicol Lett, 140–141, 161–9.
   PubMed Web of Science ®Google Scholar
• Kimmel CA, Holson JF, Hogue CJ, Carlo GL. (1984). Reliability of experimental studies for predicting hazards to human development. Final Report for Experiment 6015. National Center for Toxicological Research. January.
   Google Scholar
• Kroes R, Renwick AG, Cheeseman M, Kleiner J, Mangelsdorf I, Piersma A, et al. (2004). Structure-based thresholds of toxicological concern (TTC): guidance for application to substances present at low levels in the diet. Food Chem Toxicol, 42, 65–83.
   PubMed Web of Science ®Google Scholar
• Lehman AJ, Fitzhugh OG. (1954). Ten-fold safety factor studies. Assoc Food Drug Officials of the US Quarterly Bulletin, 18, 33–5.
   Google Scholar
• Lewis RW. (2013). Risk assessment of ‘endocrine substances’: Guidance on identifying endocrine disruptors. Toxicol Lett, 223, 287–90.
   PubMed Web of Science ®Google Scholar
• Li A. (2005). Regulatory developmental neurotoxicology testing: data evaluation for risk assessment purposes. Environ Toxicol Pharmacol, 19, 727–33.
   PubMed Web of Science ®Google Scholar
• Llop S, Lopez-Espinosa MJ, Rebagliato M, Ballester F. (2013). Gender differences in the neurotoxicity of metals in children. Toxicology, 311, 3–12.
   PubMed Web of Science ®Google Scholar
• Ludriksone L, Garcia Bartels N, Kanti V, Blume-Peytavi U, Kottner J. (2014). Skin barrier function in infancy: a systematic review. Arch Dermatol Res. Published online 05 March 2014. doi:10.1007/s00403-014-1458-6.
   PubMed Web of Science ®Google Scholar
• Makri A, Goveia M, Balbus J, Parkin R. (2004). Children's susceptibility to chemicals: a review by developmental stage. J Toxicol Environ Health Part B Crit Rev, 7, 417–35.
   PubMed Web of Science ®Google Scholar
• Makris SL, Raffaele K, Allen S, Bowers WJ, Hass U, Alleva E, et al. (2009). A Retrospective Performance Assessment of the Developmental Neurotoxicity Study in Support of OECD Test Guideline 426. Environ Health Perspect, 117, 17–25.
   PubMed Web of Science ®Google Scholar
• Marty MS, Chapin RE, Parks LG, Thorsrud NA. (2003). Development and maturation of the male reproductive system. Birth Defects Res (Part B), 68, 125–36.
   PubMed Web of Science ®Google Scholar
• McCarthy G. (2013). Reaffirmation of the U.S. Environmental Protection Agency's 1995 Policy on Evaluating Health Risks to Children. Memorandum from the Administrator of the US EPA. Oct 31.
   Google Scholar
• Middaugh LD, Dow-Edwards D, Li AA, Sandler JD, Seed J, Sheets LP, et al. (2003). Neurobehavioral assessment: a survey of use and value in safety assessment studies. Toxicol Sci, 76, 250–61.
   PubMed Web of Science ®Google Scholar
• Mooij MG, Schwarz UI, de Koning BAE, Leeder JS, Gaedigk R, Samsom JN, et al. (2014). Ontogeny of human hepatic and intestinal gene expression during childhood: age matters. Drug Metab Dispos, 42, 1268–74.
   PubMed Web of Science ®Google Scholar
• M’Rabet L, Vos AP, Boehm G, Garssen J. (2008). Breast-feeding and its role in early development of the immune system in infants: consequences for health later in life. J Nutr, 138, 1782S–90S.
   PubMed Web of Science ®Google Scholar
• Moya J, Phillips L. (2014). A review of soil and dust ingestion studies for children. J Expo Sci Environ Epidemiol Apr 2. doi:10.1038/jes.2014.17. [Epub ahead of print]
   Google Scholar
• NAS. (2014). The National Children's Study 2014: An Assessment. National Academy of Sciences. Washington DC: The National Academies Press, Washington, DC. 182 pp.
   Google Scholar
• Neal-Kluever A, Aungst J, Gu Y, Hatwell K, Muldoon-Jacobs K, Liem A, et al. (2014). Infant toxicology: State of the science and considerations in evaluation of safety. Food Chem Toxicol, 70, 68–83.
   PubMed Web of Science ®Google Scholar
• Nong A, McCarver DG, Hines RN, Krishnan K. (2006). Modeling interchild differences in pharmacokinetics on the basis of subject-specific data on physiology and hepatic CYP2E1 levels: a case study with toluene. Toxicol Appl Pharmacol, 214, 78–87.
   PubMed Web of Science ®Google Scholar
• NRC. (1983). Risk Assessment in the Federal Government: Managing the Process. The National Research Council, National Academy of Sciences. Washington DC: The National Academies Press.
   Google Scholar
• NRC. (1993). Pesticides in the diets of infants and children. The National Research Council, National Academy of Sciences. Washington, DC: The National Academies Press.
   Google Scholar
• NRC (2007). Toxicity Testing in the 21st Century: A Vision and a Strategy. The National Research Council, National Academy of Sciences. Washington, DC: The National Academies Press.
   Google Scholar
• NRC. (2009). Science and Decisions: Advancing Risk Assessment. The National Research Council, National Academy of Sciences. Washington, DC: The National Academies Press.
   Google Scholar
• OECD. (2013). OECD Guidelines for Testing of Chemicals: Full List of Test Guidelines. Organisation for Economic Co-operation and Development. July. Available online: http://www.oecd.org/env/ehs/testing/TG_List_EN_Jul_2013.pdf. Accessed on 12 April 2014.
   Google Scholar
• Olin SS, Sonawane BR. (2003). Workshop to Develop a Framework for Assessing Risks to Children from Exposure to Environmental Agents. Environ Health Perspect, 111, 1524–6.
   PubMedGoogle Scholar
• Piersma AH, Tonk ECM, Makris SL, Crofton KM, Dietert RR, van Loveren H. (2012). Juvenile toxicity testing protocols for chemicals. Reprod Toxicol, 34, 482–6.
   PubMed Web of Science ®Google Scholar
• Price K, Haddad S, Krishnan K. (2003). Physiological modeling of age-specific changes in the pharmacokinetics of organic chemicals in children. J Toxicol Environ Health Part A, 66, 417–33.
   PubMed Web of Science ®Google Scholar
• Quigley R. (2012). Developmental changes in renal function. Curr Opin Pediatr, 24, 184–90.
   PubMed Web of Science ®Google Scholar
• Raffaele KC, Rowland J, May B, Makris SL, Schumacher K, Scarano LJ. (2010). The use of developmental neurotoxicity data in pesticide risk assessments. Neurtoxicol Teratol, 32, 563–72.
   PubMed Web of Science ®Google Scholar
• Renwick AG. (1993). Data-derived safety (uncertainty) factors for the evaluation of food additives and environmental contaminants. Food Addit Contam, 10, 275–305.
   PubMed Web of Science ®Google Scholar
• Renwick AG. (1998). Toxicokinetics in infants and children in relation to the ADI and TDI. Food Addit Contam, 15, 17–35.
   PubMed Web of Science ®Google Scholar
• Renwick AG, Lazarus NR. (1998). Human variability and noncancer risk assessment: an analysis of the default uncertainty factor. Regul Toxicol Pharmacol, 27, 3–20.
   PubMed Web of Science ®Google Scholar
• Rhomberg LR, Goodman JE. (2012). Low-dose effects and nonmonotonic dose-responses of endocrine disrupting chemicals: has the case been made? Regul Toxicol Pharmacol, 64, 130–3.
   PubMed Web of Science ®Google Scholar
• Rodriguez W, Roberts R, Murphy D. (2001). Adverse drug events in children: The US Food and Drug Administration Perspective. Curr Therap Res, 62, 711–23.
   Web of Science ®Google Scholar
• Rogers JM, Ellis-Hutchings RG, Grey BE, Zucker RM, Norwood J Jr, Grace CE, et al. (2014). Elevated blood pressure in offspring of rats exposed to diverse chemicals during pregnancy. Toxicol Sci, 137, 436–446.
   PubMed Web of Science ®Google Scholar
• Routledge PA. (1994). Pharmacokinetics in children. J Antimicrob Chemother, 34, 19–24.
   PubMed Web of Science ®Google Scholar
• Saghir SA, Marty MS, Zablotny CL, Passage JK, Perala AW, Neal BH, et al. (2013). Life stage-, sex-, and dose-dependent dietary toxicokinetics and relationship to toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D) in rats: implications for toxicity test dose selection, design, and interpretation. Toxicol Sci, 136, 294–307.
   PubMed Web of Science ®Google Scholar
• SCCNFP. (2002). Position statement on the calculation of the margin of safety of ingredients incorporated in cosmetics which may be applied to the skin of children. Scientific Committee on Cosmetic Products and Non-food products intended for Consumers. Adopted by the SCCNFP during the 19th Plenary meeting of 27 February 2002.
   Google Scholar
• SCCS. (2012). The SCCS's Notes of Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation, 8th Revision. SCCS/1416/11. Scientific Committee on Consumer Safety. Adopted 11 December, 2012.
   Google Scholar
• Schardein JL, Keller KA. (1989). Potential human developmental toxicants and the role of animal testing in their identification and characterization. Crit Rev Toxicol, 19, 251–339.
   PubMed Web of Science ®Google Scholar
• Schardein JL, Schwetz BA, Kenel, MF. (1985). Species sensitivities and prediction of tetratogenic potential. Environ Health Perspect, 61, 55–67.
   PubMed Web of Science ®Google Scholar
• Scheuplein R, Charnley G, Dourson M. (2002). Differential sensitivity of children and adults to chemical toxicity. I. Biological basis. Regul Toxicol Pharmacol, 35, 429–47.
   PubMed Web of Science ®Google Scholar
• Sheets LP. (2000). A consideration of age-dependent differences in susceptibility to organophosphorus and pyrethroid insecticides. Neurotoxicol, 21, 57–64.
   PubMed Web of Science ®Google Scholar
• Smialowicz RJ, Williams WC, Copeland CB, Harris MW, Overstreet D, Davis BJ, Chapin RE. (2001). The effects of perinatal/juvenile heptachlor exposure on adult immune and reproductive system function in rats. Toxicol Sci, 61, 164–75.
   PubMed Web of Science ®Google Scholar
• Smith JN, Hinderliter PM, Timchalk C, Bartels MJ, Poet TS. (2014). A human life stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: Development and validation. Regul Toxicol Pharmacol, 69, 580–97.
   PubMed Web of Science ®Google Scholar
• Spielmann H. (2005). Predicting the risk of developmental toxicity from in vitro assays. Toxicol Appl Pharmacol, 207, 375–80.
   PubMedGoogle Scholar
• Stahlmann R. (2003). Children as a special population at risk – quinolones as an example for xenobiotics exhibiting skeletal toxicity. Arch Toxicol, 77, 7–11.
   PubMed Web of Science ®Google Scholar
• Strolin Benedetti M, Whomsley R, Baltes EL. (2005). Differences in absorption, distribution, metabolism and excretion of xenobiotics between the paediatric and adult populations. Expert Opin Drug Metab Toxicol, 1, 447–71.
   PubMed Web of Science ®Google Scholar
• Sulemanji M, Vakili K. (2013). Neonatal renal physiology. Semin Pediatr Surg, 22, 195–8.
   PubMed Web of Science ®Google Scholar
• Teeguarden JG, Hanson-Drury S. (2013). A systematic review of Bisphenol A “low dose” studies in the context of human exposure: A case for establishing standards for reporting “low-dose” effects of chemicals. Food Chem Toxicol, 62, 935–48.
   PubMed Web of Science ®Google Scholar
• Tilson H. (2000). Neurotoxicity risk assessment guidelines: Developmental neurotoxicity. Neurotoxicology, 21, 189–94.
   PubMed Web of Science ®Google Scholar
• Tonk EC, Verhoef A, Gremmer ER, Van Loveren H, Piersma AH. (2013). Developmental immunotoxicity in male rats after juvenile exposure to ethanol. Toxicology, 309, 91–9.
   PubMed Web of Science ®Google Scholar
• Touw DJ, Westerman EM, Sprij AJ. (2009). Therapeutic drug monitoring of aminoglycosides in neonates. Clin Pharmacokinet, 48, 71–88.
   PubMed Web of Science ®Google Scholar
• US EPA. (1987). The Risk Assessment Guidelines of 1986. EPA/600/8–87/045. Office of Health and Environmental Assessment, US Environmental Protection Agency. Washington DC. August 1987.
   Google Scholar
• US EPA. (1995). Policy on Evaluating Health Risks to Children. Available at http://www2.epa.gov/sites/production/files/2014-05/documents/1995_childrens_health_policy_statement.pdf. Accessed 10 October 2014.
   Google Scholar
• US EPA. (1996). Food Quality Protection Act (FQPA) of 1996. US Environmental Protection Agency. Washington DC. Available at http://www.epa.gov/opp00001/regulating/laws/fqpa/. Accessed 5 March 2014.
   Google Scholar
• US EPA. (1998a). Guidelines for Neurotoxicity Risk Assessment. 630/R-95/001F. Risk Assessment Forum, US Environmental Protection Agency. Washington, DC.
   Google Scholar
• US EPA. (1998b). Health Effects Test Guidelines, OPPTS 870.6300, Developmental Neurotoxicity Study, EPA 712-C-98–239. Office of Prevention, Pesticides, and Toxic Substances, US Environmental Protection Agency, Washington, DC.
   Google Scholar
• US EPA. (2002). Final Report: A Review of the Reference Dose and Reference Concentration Processes. EPA/630/P-02/002F. Risk Assessment Forum, US Environmental Protection Agency Washington DC. December 2002.
   Google Scholar
• US EPA. (2005). Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants. EPA/630/P-03/003F. Risk Assessment Forum, US Environmental Protection Agency Washington, DC. November 2005.
   Google Scholar
• US EPA. (2006). A framework for assessing health risks of environmental exposures to children. EPA/600/R-05/093F. US Environmental Protection Agency. National Center for Environmental Assessment. Washington, DC. September.
   Google Scholar
• US EPA. (2008). Child-Specific Exposure Factors Handbook (Final Report). EPA/600/R-06/096F. US Environmental Protection Agency. Washington, DC.
   Google Scholar
• US EPA. (2011a). Exposure Factors Handbook Edition (Final). EPA/600/R-09/052F. US Environmental Protection Agency. Washington, DC.
   Google Scholar
• US EPA. (2011b). Recommended Use of Body Weight 3/4 as the Default Method in Derivation of the Oral Reference Dose. EPA/100/R11/0001. US Environmental Protection Agency. Washington, DC.
   Google Scholar
• US EPA. (2011c). Endocrine Disruptor Screening Program for the 21st Century: (EDSP21 Work Plan). The Incorporation of In Silico Models and In Vitro High Throughput Assays in the Endocrine Disruptor Screening Program (EDSP) for Prioritization and Screening. Office of Chemical Safety and Pollution Prevention. US Environmental Protection Agency. Washington, DC. September 30.
   Google Scholar
• US EPA. (2012). 2012 Edition of the Drinking Water Standards and Health Advisories. EPA 822-S-12-001. Office of Water. US Environmental Protection Agency. Washington, DC. April.
   Google Scholar
• US FDA. (2011). Guidance for Industry Reproductive and Developmental Toxicities: Integrating Study Results to Assess Concerns. Center for Drug Evaluation and Research (CDER), US Food and Drug Administration. Washington DC. September.
   Google Scholar
• Vahter M, Akesson A, Liden C, Ceccatelli S, and Berglund M. (2007). Gender differences in the disposition and toxicity of metals. Environ Res, 104, 85–95.
   PubMed Web of Science ®Google Scholar
• Vos JG, DeKlerk A, Krajnc EI, Van Loveren V, Rozing J. (1990). Immunotoxicity of bis(tri-n-butyltin)oxide in the rat: Effects on thymus- dependent immunity and on nonspecific resistance following long-term exposure in young versus aged rats. Toxicol Appl Pharmacol, 105, 144–55.
   PubMed Web of Science ®Google Scholar
• Walthall K, Cappon GD, Hurtt ME, Zoetis T. (2005). Postnatal development of the gastrointestinal system: A species comparison. Birth Defects Res (Part B), 74, 132–56.
   PubMed Web of Science ®Google Scholar
• Weiss CF, Glazko AJ, Weston JK. (1960). Chloramphenicol in the newborn infant: a physiological explanation of its toxicity when given in excessive doses. N Engl J Med, 262, 787–94.
   PubMed Web of Science ®Google Scholar
• Wetmore BA, Allen B, Clewell HJ III, Parker T, Wambaugh JF, Almond LM, et al. (2014). Incorporating population variability and susceptible subpopulations into dosimetry for high-throughput toxicity testing. Toxiol Sci doi:10.1093/toxsci/kfu169. [Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• WHO. (1974). Toxicological evaluation of certain food additives with a review of general principles and of specifications. In: 17th Report of the Joint FAO/WHO Expert Committee on Food Additives, Report No. 539. World Health Organization. Geneva, Switzerland, June 25-July 4, 1973. Available at: http://www.inchem.org/documents/jecfa/jecmono/v05je90.htm. Accessed 5 March 2014.
   Google Scholar
• WHO. (1986). Environmental Health Criteria 59: Principles for evaluating risks from chemicals during infancy and early childhood: the need for a special approach. World Health Organization/International Programme on Chemical Safety. Geneva, Switzerland.
   Google Scholar
• WHO. (1994). Environmental Health Criteria No. 170: Assessing Human Health Risks of Chemicals: Derivation of Guidance Values for Health-based Exposure Limits. International Programme on Chemical Safety, World Health Organization. Geneva.
   Google Scholar
• WHO. (2001). Guidance Document for the Use of Data in Development of Chemical-Specific Adjustment Factors (CSAF) for Interspecies Differences and Human Variability in Dose/Concentration Response Assessment. International Programme for Chemical Safety, World Health Organization: Geneva.
   Google Scholar
• WHO. (2012). Harmonization Project Document No. 10. Guidance for Immunotoxicity Risk Assessment for Chemicals. World Health Organization/International Programme on Chemical Safety. Geneva, Switzerland.
   Google Scholar
• Willhite CC, Ball GL, McLellan CJ. (2008). Derivation of a bisphenol A oral reference dose (RfD) and drinking-water equivalent concentration. J Toxicol Environ Health B Crit Rev, 11, 69–46.
   PubMed Web of Science ®Google Scholar
• Wolf CR, Smith G. (1999). Cytochrome P450 CYP2D6. IARC Sci Publ, 148, 209–29.
   PubMedGoogle Scholar
• Wolterink G, Piersma AH, van Engelen JGM. (2002). Risk assessment of chemicals: What about children?. RIVM Report 613340005/2002. Bilthoven, Netherlands.
   Google Scholar
• Wolterink G, van Engelen JGM, van Raaij MTM. (2007). Guidance for assessment of chemical risks for children. RIVM Report 320012001/2007. Bilthoven, Netherlands.
   Google Scholar
• Wood SL, Beyer BK, Cappon GD. (2003). Species comparison of postnatal CNS development: Functional measures. Birth Defects Res (Part B), 68, 391–407.
   PubMed Web of Science ®Google Scholar
• Wu S, Blackburn K, Amburgey J, Jaworska J, Federle T. (2010). A framework for using structural, reactivity, metabolic and physicochemical similarity to evaluate the suitability of analogs for SAR-based toxicological assessments. Regul Toxicol Pharmacol, 56, 67–81.
   PubMed Web of Science ®Google Scholar
• Yolton K, Cornelius M, Ornoy A, McGough J, Makris S, Schantz S. (2014). Exposure to neurotoxicants and the development of attention deficit hyperactivity disorder and its related behaviors in childhood. Neurotoxico Teratol, 44, 30–45.
   PubMed Web of Science ®Google Scholar
• Yoon M, Campbell JL, Andersen ME, Clewell HJ. (2012). Quantitative in vitro to in vivo extrapolation of cell-based toxicity assay results. Crit Rev Toxicol, 2, 633–52.
   Web of Science ®Google Scholar
• Zar T, Graeber C, Perazella MA. (2007). Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dialysis, 20, 217–9.
   PubMed Web of Science ®Google Scholar
• Zoetis T, Tassinari MS, Bagi C, Walthall K, Hurtt ME. (2003). Species comparison of postnatal bone growth and development. Birth Defects Res (Part B), 68, 86–110.
   PubMed Web of Science ®Google Scholar
• Zoetis T, Hurtt ME. (2003a). Species comparison of anatomical and functional renal development. Birth Defects Res (Part B), 68, 111–20.
   PubMed Web of Science ®Google Scholar
• Zoetis T, Hurtt ME. (2003b). Species comparison of lung development. Birth Defects Res (Part B), 68, 121–4.
   PubMed Web of Science ®Google Scholar
• Zosel A, Egelhoff E, Heard K. (2010). Severe lactic acidosis after an iatrogenic propylene glycol overdose. Pharmacotherapy, 30, 219–24.
   PubMed Web of Science ®Google Scholar