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Environmental Health Perspectives
differed considerably by the use of medical
products containing DEHP and the institution
in which they were patients.
To our knowledge, this study is the first
to describe infants’ exposure to BPA, TCS,
BP-3, MePB, and PrPB. In conjunction with
the previous data collected on phthalates for
the same group of premature infants (Green
et al. 2005; Weuve et al. 2006), our ﬁndings
suggest that infants may be exposed during
critical periods of their development to several
potential reproductive and developmental toxi-
cants at levels higher than those reported for
the general population. However, this was an
exposure study, and we were therefore unable
to explore whether such exposures were associ-
ated with adverse health eﬀects in these infants.
is study is also the ﬁrst to demonstrate that
increasing intensity of DEHP-containing
PVC product use is proportional to exposure
to BPA, as was reﬂected in signiﬁcant eleva-
tions in urinary concentrations of BPA and the
absence of similar elevations in urinary concen-
trations of the other four additional phenols
examined. Concerns related to BPA toxicity as
well as high BPA exposure levels in this sensi-
tive population of low-birth-weight premature
infants may justify using products that do not
contain BPA while not compromising the qual-
ity of medical care. Future research is needed to
establish the source(s) and the potential health
outcomes of these exposures to BPA.
Re f e R e n c e s
Blake MJ, Castro L, Leeder JS, Kearns GL. 2005. Ontogeny of
drug metabolizing enzymes in the neonate. Semin Fetal
Neonatal Med 10:123–138.
Burchell B, Coughtrie M, Jackson M, Harding D, Fournel-Gigleux
S, Leakey J, et al. 1989. Development of human-liver UDP-
glucuronosyltransferases. Dev Pharmacol Ther 13:70–77.
Calafat AM, Needham LL, Silva MJ, Lambert G. 2004. Exposure
to di-(2-ethylhexyl) phthalate among premature neonates
in a neonatal intensive care unit. Pediatrics 113:e429–e434.
Calafat AM, Wong L-Y, Ye X, Reidy JA, Needham LL. 2008a.
Concentrations of the sunscreen agent benzophenone-3
in residents of the United States: National Health and
Nutrition Examination Survey 2003–2004. Environ Health
Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. 2008b.
Urinary concentrations of triclosan in the U.S. population:
2003–2004. Environ Health Perspect 116:303–307.
Calafat AM, Ye XY, Wong LY, Reidy JA, Needham LL. 2008c.
Exposure of the U.S. population to bisphenol A and 4-tertiary-
octylphenol: 2003–2004. Environ Health Perspect 116:39–44.
Cashman AL, Warshaw EM. 2005. Parabens: a review of epide-
miology, structure, allergenicity, and hormonal properties.
Ceccarelli I, Della Seta D, Fiorenzani P, Farabollini F, Aloisi AM.
2007. Estrogenic chemicals at puberty change ER alpha in
the hypothalamus of male and female rats. Neurotoxicol
Center for the Evaluation of Risks to Human Reproduction. 2007.
NTP-CERHR Expert Panel Report on the Reproductive
and Developmental Toxicity of Bisphenol A. Research
Triangle Park, NC:National Toxicology Program.
BPAFinalEPVF112607.pdf [accessed 26 November 2007].
Chapin RE, Adams J, Boekelheide K, Gray LE, Hayward SW,
Lees PSJ, et al. 2008. NTP-CERHR expert panel report
on the reproductive and developmental toxicity of
bisphenol A. Birth Defects Res B Dev Reprod Toxicol
Darbre PD, Harvey PW. 2008. Paraben esters: review of recent
studies of endocrine toxicity, absorption, esterase and
human exposure, and discussion of potential human health
risks. J Appl Toxicol 28:561–578.
Della Seta D, Minder I, Belloni V, Aloisi AM, Dessi-Fulgheri F,
Farabollini F. 2006. Pubertal exposure to estrogenic chemi-Pubertal exposure to estrogenic chemi-
cals affects behavior in juvenile and adult male rats. Horm
de Wildt SN, Kearns GL, Leeder JS, van den Anker JN. 1999.
Glucuronidation in humans—pharmacogenetic and devel-
opmental aspects. Clin Pharm 36:439–452.
Department of Health and Human Services. 2005. Protection
of Human Subjects. 45 CFR part 46. Available: http://
[accessed 23 February 2009].
Durando M, Kass L, Piva J, Sonnenschein C, Soto AM, Luque
EH, et al. 2007. Prenatal bisphenol A exposure induces
preneoplastic lesions in the mammary gland in Wistar
rats. Environ Health Perspect 115:80–86.
European Union. 2003. European Union Risk Assessment
Report: 4,4’-Isopropylidenediphenol (Bisphenol A).
European Union. Available: http://ecb.jrc.it/DOCUMENTS/
nolareport325.pdf [accessed 12 April 2008].
European Union. 2008. Updated European Risk Assessment
Report 4,4´-Isopropylidenediphenol (Bisphenol-A).
Environment Addendum of February 2008 (to be read in con-
junction with published EU RAR of BPA, 2003 for full details).
European Union. Available: http://ecb.jrc.it/documents/
phenola_add_325.pdf [accessed 20 August 2008].
Food and Drug Administration. 2001. Safety Assessment of
Di(2-ethylhexyl)phthalate (DEHP) Released from PVC
Medical Devices. Rockville, MD:Center for Devices and
Radiological Health, U.S. Food and Drug Administration.
[accessed 11 August 2003].
Gioiosa L, Fissore E, Ghirardelli G, Parmigiani S, Palanza P.
2007. Developmental exposure to low-dose estrogenic
endocrine disruptors alters sex differences in exploration
and emotional responses in mice. Horm Behav 52:307–316.
Gonzalez H, Farbrot A, Larko O, Wennberg AM. 2006.
Percutaneous absorption of the sunscreen benzophe-
none-3 after repeated whole-body applications, with and
without ultraviolet irradiation. Br J Dermatol 154:337–340.
Goodman JE, Witorsch RJ, McConnell EE, Sipes IG, Slayton TM,
Yu CJ, et al. 2008. Weight-of-evidence evaluation of repro-
ductive and developmental effects of low doses of bisphe-
nol A. Crit Rev Toxicol; doi.org/10.1080/10408440802157839
[Online 16 October 2008].
Gray GM, Cohen JT, Cunha G, Hughes C, McConnell EE,
Rhomberg L, et al. 2004. Weight of the evidence evaluation
of low-dose reproductive and developmental effects of
bisphenol A. Hum Ecol Risk Assess 10:875–921.
Green R, Hauser R, Calafat AM, Weuve J, Schettler T, Ringer
S, et al. 2005. Use of di(2-ethylhexyl) phthalate-containing
medical products and urinary levels of mono(2-ethylhexyl)
phthalate in neonatal intensive care unit infants. Environ
Health Perspect 113:1222–1225.
Health Canada. 2008. Draft Screening Assessment for Phenol,
4,4´-(1-methyl-ethylidene) bis-(Bisphenol A). Chemical
Abstracts Service Registry Number 80-05-7. Available: http://
batch2_80-05-7_en.pdf [accessed 12 September 2008].
Ho SM, Tang WY, de Frausto JB, Prins GS. 2006. Developmental
exposure to estradiol and bisphenol A increases sus-
ceptibility to prostate carcinogenesis and epigenetically
regulates phosphodiesterase type 4 variant 4. Cancer Res
Hornung RW, Reed LD. 1990. Estimation of average concentra-
tion in the presence of nondetectable values. Appl Occup
Environ Hyg 5:46–51.
Howdeshell KL, Hotchkiss AK, Thayer KA, Vandenbergh JG,
vom Saal FS. 1999. Environmental toxins: exposure to bis-
phenol A advances puberty. Nature 401:763–764.
Jansen PLM, Mulder GJ, Burchell B, Bock KW. 1992. New
developments in glucuronidation research: report of a
workshop on “Glucuronidation, Its Role in Health and
Disease.” Hepatology 15:532–544.
Jones RD, Jampani HB, Newman JL, Lee AS. 2000. Triclosan: A
review of effectiveness and safety in health care settings.
Am J Infect Control 28:184–196.
Kang JH, Kondo F, Katayama Y. 2006. Human exposure to bis-
phenol A. Toxicology 226:79–89.
Laviola G, Gioiosa L, Adriani W, Palanza P. 2005.
D-amphetamine-related reinforcing effects are reduced in
mice exposed prenatally to estrogenic endocrine disrup-
tors. Brain Research Bulletin 65:235–240.
Leakey JEA, Hume R, Burchell B. 1987. Development of multiple
activities of UDP-glucuronyltransferase in human liver.
Biochem J 243:859–861.
Murray TJ, Mafﬁni MV, Ucci AA, Sonnenschein C, Soto AM.
2007. Induction of mammary gland ductal hyperplasias and
carcinoma in situ following fetal bisphenol A exposure.
Reprod Toxicol 23:383–390.
National Toxicology Program. 2008. NTP-CERHR Monograph
on the Potential Human Reproductive and Developmental
Effects of Bisphenol A. Available: http://cerhr.niehs.nih.
gov/chemicals/bisphenol/bisphenol.pdf [accessed 3
Negishi T, Kawasaki K, Suzaki S, Maeda H, Ishii Y, Kyuwa S,
et al. 2004. Behavioral alterations in response to fear-
provoking stimuli and tranylcypromine induced by perina-
tal exposure to bisphenol A and nonylphenol in male rats.
Environ Health Perspect 112:1159–1164.
Palanza P, Howdeshell KL, Parmigiani S, vom Saal FS. 2002.
Exposure to a low dose of bisphenol A during fetal life or
in adulthood alters maternal behavior in mice. Environ
Health Perspect 110:415–422.
Ryan BC, Vandenbergh JG. 2006. Developmental exposure to
environmental estrogens alters anxiety and spatial mem-
ory in female mice. Hormones and Behavior 50:85–93.
Schlumpf M, Cotton B, Conscience M, Haller V, Steinmann B,
Lichtensteiger W. 2001. In vitro and in vivo estrogenicity of
UV screens. Environ Health Perspect 109:239–244.
Taylor JK. 1987. Quality Assurance of Chemical Measurements.
Chelsea, MI:Lewis Publishers.
Timms BG, Howdeshell KL, Barton L, Bradley S, Richter CA,
vom Saal FS. 2005. Estrogenic chemicals in plastic and
oral contraceptives disrupt development of the fetal
mouse prostate and urethra. Proc Natl Acad Sci USA
U.S. Environmental Protection Agency. 2008. 5-Chloro-2-(2,4-
dichlorophenoxy)phenol (Triclosan): Risk Assessment for
the Reregistration Eligibility Decision (RED) Document.
Case No 2340. DP Barcode 343544. PC Code: 054901.
Washington, DC:U.S. Environmental Protection Agency.
Vandenberg LN, Hauser R, Marcus M, Olea N, Welshons WV.
2007. Human exposure to bisphenol A (BPA). Reprod
vom Saal FS, Hughes C. 2005. An extensive new literature
concerning low-dose effects of bisphenol A shows the
need for a new risk assessment. Environ Health Perspect
Weber DJ, Rutala WA. 2006. Use of germicides in the home
and the healthcare setting: is there a relationship between
germicide use and antibiotic resistance? Infect Control
Hosp Epidemiol 27:1107–1119.
Weuve J, Sanchez BN, Calafat AM, Schettler T, Green RA,
Hu H, et al. 2006. Exposure to phthalates in neonatal
intensive care unit infants: urinary concentrations of
monoesters and oxidative metabolites. Environ Health
Ye XY, Bishop AM, Reidy JA, Needham LL, Calafat AM. 2006a.
Parabens as urinary biomarkers of exposure in humans.
Environ Health Perspect 114:1843–1846.
Ye XY, Bishop AM, Reidy JA, Needham LL, Calafat AM. 2007.
Temporal stability of the conjugated species of bisphenol
A, parabens, and other environmental phenols in human
urine. J Expo Sci Environ Epidemiol 17:567–572.
Ye XY, Kuklenyik Z, Bishop AM, Needham LL, Calafat AM.
2006b. Quantification of the urinary concentrations of
parabens in humans by on-line solid phase extraction-
high performance liquid chromatography-isotope dilution
tandem mass spectrometry. J Chromatogr B Anal Technol
Biomed Life Sci 844:53–59.
Ye XY, Kuklenyik Z, Needham LL, Calafat AM. 2005. Automated
on-line column-switching HPLC-MS/MS method with peak
focusing for the determination of nine environmental phe-
nols in urine. Anal Chem 77:5407–5413.