Food and Chemical Toxicology 50 (2012) 4236–4237
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Food and Chemical Toxicology
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Letter to the Editor
Comment on ‘‘Lack of androgenicity and estrogenicity of the
three monomers used in Eastman’s Tritan™ copolyesters’’ by
Osimitz et al. (2012)
Osimitz et al. (in press) in their paper ‘‘Lack of androgenicity
and estrogenicity of the three monomers used in Eastman’s
Tritan™ copolyesters.’’ report data from various in vitro and
in vivo assays to characterize the androgenic activity (AA) and
estrogenic activity (EA) of three chemicals used as monomers in
the production of a family of copolyester plastics (Tritan). Several
specific and general aspects in the uncorrected on-line proof of this
paper are debatable and/or incorrect.
With respect to a specific aspect
In referring to results of our recently published paper (Yang et
al., 2011) using the MCF-7 assay to assess the EA of various mono-
mers used to make plastic polymers, Osimitz et al. (2012) state:
‘‘. . .the MCF-7 assay has shown positive results with compounds that
do not bind directly to estrogen receptors but still induce cell prolifer-
ation (Jones et al. 1998)’’.
However, we explicitly state several times (Yang et al., 2011)
that any putative estrogenic stimulation of MCF-7 cell proliferation
was always confirmed by inhibition with the ER antagonist, ICI
182,780. This confirmation is also shown graphically in Figure 1
of our paper.
With respect to general aspects
1. When testing monomers, it is best to choose the most sensitive
and accurate tests appropriate for the types and use of materi-
als (in this case, chemicals which will come into direct contact
with food). The in vitro test chosen by Osimitz et al. for EA
detection, a BLYES yeast transactivation assay, is between 50
and 200 times less sensitive (Sanseverino et al., 2005, 2009;
Yang et al., 2011; Gordon et al., 2004; ICCVAM, 2011) than
the two assays which have either been validated or qualified
for validation by ICCVAM/NICEATM for EA, specifically MCF-7
and BG-1 assays. Hence, a conclusion that Osimitz et al. (in
press) have shown ‘‘strong evidence for the lack of an
androgenic or estrogenic potential of DMT, CHDM, TMCD, and
TPA’’ is premature without using tests which are more sensitive
and appropriate for food-contact materials.
2. It is not appropriate, whatever the sensitivity or accuracy of
tests showing a lack of EA of monomers, to extrapolate on
whether finished products made in part from those monomers
would not release chemicals having EA. Osimitz et al. (in press):
0278-6915/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.fct.2012.06.038
‘‘The point is often made that the leached component of polymers
may present endocrine hazards. Because polyester oligomers fol-
lowed by monomers make up the bulk of what leaches out of plas-
tics into the environment and or into foods that may come into
contact with the plastic, and because the functional groups of the
oligomers are the same as the monomers, the data within this
manuscript indicate that the finished polymer would also not be
anticipated to be androgenic or estrogenic’’.
That is, plastic products are made from both monomers and
additives, all of which can leach from the finished product in
nanomolar to picomolar (ppm-ppb) amounts, at which levels
many estrogenic chemicals show strong biological activity,
especially in fetal or juvenile mammals (see, for example,
Patisaul et al., 2006, 2009). In fact, ‘‘Tritan’’ refers to a family
of 27 different plastic resins that have different formulations
of polymers and additives, supplied in pellet form suitable for
manufacturing plastic products. The plastic resins differ in
composition and have different additives (e.g., antioxidants,
UV stabilizers, release agents, lubricants, antistatic, and viscos-
ity modifiers), depending on their intended use (Eastman,
2009), many of which can have EA (Yang et al., 2011). More-
over, in common consumer use, plastic articles made from such
resins are subjected to a variety of stresses (e.g., UV light, micr-
owaving, heat, thermal cycling, dishwashing) that can cause
the polymer or the additives to break down or react to form
chemicals other than the original monomers (Kim et al.,
1990, Grosstete et al., 1999, Colin and Verdu, 2006) or additives
and form leachable chemicals with EA (Yang et al., 2011) –
none of which were examined in this study.
References
Colin, X. and Verdu, J. 2006. Polymer Degradation during Processing, C. R. Chimie 9.
Gordon, J.D., Chu, A.C., Chu, M.D., Denison, M.S., Clark, G.C., 2004. Detection of
estrogen receptor endocrine disruptor potency of commonly used
organochlorine pesticides using the LUMI-CELLä bioassay, organohalogen
compounds. Dioxin 66, 169–174.
Grossetete, T., Rivaton, A., Gardette, J.L., Hoyle, C.E., Ziemer, M., Fagerburg, D.R.,
Clauberg, H., 1999. Photochemical degradation of poly (ethylene
terephthalate)-modified copolymer. Polymer 41, 3541–3554.
ICCVAM. 2011. Validation of the BG1Luc Estrogen Receptor Transcriptional
Activation Test Method, available at http://iccvam.niehs.nih.gov/methods/
endocrine/PeerPanel11.htm (last accessed 3/7/2012).
Kim, H., Gilbert, S.G., Johnson, J.B., 1990. Determination of potential migrants from
commercial amber polyethylene terephthalate bottle wall. Pharmacol. Res. 7,
176–179.
Osimitz, T.G., Eldridge, M.L., Sloter, E., Welsh, W., Ai, N., Sayler, G.S., Menn, F., Toole,
C., in press. Lack of androgenicity and estrogenicity of the three monomers used
in Eastman’s Tritan™ copolyesters. Food Chem. Toxicol., http://dx.doi.org/
10.1016/j.fct.2012.02.010.
Patisaul, H.B., Fortino, A.E., Polston, E.K., 2006. Neonatal genistein or bisphenol-A
exposure alters sexual differentiation of the AVPV. Neurotoxicol. Teratol. 28,
111–118.
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Patisaul, H.B., Todd, K.L., Mickens, J.A., Adewale, H.B., 2009. Impact of neonatal ⇑
exposure to the ERa agonist PPT, bisphenol-A or phytoestrogens on George Bittner
hypothalamic kisspeptin fiber density in male and female rats. CertiChem, Inc., 11212 Metric Blvd., Suite 500,
Neurotoxicology 30, 350–357. Austin, TX 78758, USA
Sanseverino, J., Eldridge, M.L., Layton, A.C., Easter, J.P., Yarbrough, J., Schultz, T.W., ⇑ Tel.: +1 512 339 0550.
Sayler, G.S., 2009. Screening of potentially hormonally active chemicals using
bioluminescent yeast bioreporters. Toxicol. Sci. 107 (1), 122–134.
E-mail address: gbittner@certichem.com
Sanseverino, J., Gupta, R.K., Layton, A.C., Patterson, S.S., Ripp, S.A., Saidak, L., Stuart Yaniger
Simpson, M.L., Schultz, T.W., Sayler, G.S., 2005. Use of Saccharomyces cerevisiae
PlastiPure, Inc., 11212 Metric Blvd., Suite 600,
BLYES expressing bacterial bioluminescence for rapid, sensitive detection of
estrogenic compounds. Appl. Environ. Microbiol. 71 (8), 4455–4460. Austin, TX 78758, USA
Yang, C., Yaniger, S., Jordan, V.C., Klein, D., Bittner, G., 2011. Most plastic Tel.: +1 512 637 4386x212.
products release estrogenic chemicals. Environ. Health Perspect. 119 (7),
989–996.
Available online 29 June 2012