 PARABENS
- WHAT YOU SHOULD KNOW ...
Parabens’ Chemical Identity: Proprietary
name for the methyl, propyl, butyl, and ethyl esters of
p-hydroxybenzoic acid.
Common Names: methylparaben,
propylparaben, ethylparaben, butylparaben.
Parabens are synthetic preservatives that are widely used in cosmetics and
personal care products such as shampoos, conditioners, hair styling products,
make-up, facial masks, skin lotions and creams, and deodorants. Parabens are
typically an ingredient in baby lotions, shampoos, and other personal care
products for infants and children.
Parabens have been known to cause skin irritation, rash,
contact dermatitis, or allergic skin reactions and have
been found to act like the hormone estrogen in laboratory
experiments.
Click on links below.
OBGYN.NET: PARABENS
AND BREAST CANCER
CORNELL UNIVERSITY REPORT: PARABENS FOUND
IN BREAST TUMORS
CORNELL UNIVERSITY REPORT: PARABENS: EVIDENCE
OF ESTROGENICITY AND ENDOCRINE DISRUPTION
NEW SCIENTIST.COM: COSMETIC CHEMICALS FOUND
IN BREAST TUMORS
Breast Cancer
Parabens are found in human breast tumors
Website: www.obgyn.net
March 22, 2004
 2004
MAR 22 - (NewsRx.com & NewsRx.net) -- Parabens are
found intact within human breast tumors, with methylparaben
showing the highest concentration, researchers report.
According to a study from England, "Parabens are
used as preservatives in many thousands of cosmetic, food
and pharmaceutical products to which the human population
is exposed."
"Although recent reports of the estrogenic properties
of parabens have challenged current concepts of their toxicity
in these consumer products, the question remains as to
whether any of the parabens can accumulate intact in the
body from the long-term, low-dose levels to which humans
are exposed. Initial studies reported here show that parabens
can be extracted from human breast tissue and detected
by thin-layer chromatography," wrote P.D. Darbre and
colleagues, University of Reading, School of Animal & Microbial
Science.
"More detailed studies enabled identification and
measurement of mean concentrations of individual parabens
in samples of 20 human breast tumors by high-pressure liquid
chromatography followed by tandem mass spectrometry. The
mean concentration of parabens in these 20 human breast
tumors was found to be 20.6 ± 4.2 ng g-1 tissue.
Comparison of individual parabens showed that methylparaben
was present at the highest level (with a mean value of
12.8 ± 2.2 ng g-1 tissue) and represents 62% of
the total paraben recovered in the extractions," the
researchers stated.
The researchers concluded: "These studies demonstrate
that parabens can be found intact in the human breast and
this should open the way technically for more detailed
information to be obtained on body burdens of parabens
and in particular whether body burdens are different in
cancer from those in normal tissues.
Darbre and colleagues published their study in the Journal
of Applied Toxicology (Concentrations of parabens in human
breast tumours. J Appl Toxicol, 2004;24(1):5-13).
For more information, contact P.D. Darbre, University
of Reading, School of Animal & Microbial Science, Division
of Cell & Molecular Biology, POB 228, Reading RG6 6AJ,
Berks, UK.
Publisher contact information for the Journal of Applied
Toxicology is: John Wiley & Sons Ltd., the Atrium,
Southern Gate, Chichester PO19 8SQ, W Sussex, UK.
The information in this article comes under the major
subject areas of Oncology and Surgery. This article was
prepared by Cancer Gene Therapy Week editors from staff
and other reports. Copyright 2004, Cancer Gene Therapy
Week via NewsRx.com & NewsRx.net.
© Copyright 2004, Cancer Weekly via NewsRx.com & NewsRx.net
Cornell University
Program on Breast Cancer and Environmental Risk Factors (BCERF)
 Website:
http://envirocancer.cornell.edu/Program/programinfo.cfm
Vol. 9 No. 1 "The Ribbon" Winter - 2004
Research Commentary
Five Types of Parabens Detected
Intact in Human Breast Tumors
By Suzanne M. Snedeker, Ph.D.
Background
Parabens have been used as preservatives since the 1920s. Chemically, parabens
have a simple structure. They consist of a 6-member carbon ring with a hydroxyl
group on one side (-OH) of the ring and a side chain called an alkyl ester
on the opposite side of the ring. The side chains can be of varying lengths.
Parabens are used to prevent the growth of bacteria in a wide range of consumer
products, including a variety of foods and pharmaceutical drugs. The most
prevalent use has been as a preservative in cosmetics, including facial and
body cosmetics, skin care products, shampoos and conditioners, sunscreens,
underarm products (antiperspirants and deodorants), colognes and perfumes,
and soaps, including liquid hand soap. One of the most widely quoted sources
of information on use, exposure and safety of the four most commonly used
parabens was published in 1984 in a report authored by Elder (1). This report
estimated that parabens were used in over 13,200 different cosmetic products.
Parabens have been widely accepted and used because of
past reports of their effectiveness as preservatives, low
cost, and rapid excretion from the body (both human and
animal testing). However, recently some scientists have
raised concerns that further assessment of parabens may
be needed. This is based on recent evidence from over a
dozen scientific studies indicating that several types
of parabens can bind to the estrogen receptor and can cause
estrogen-like responses when tested in laboratory animals
or in a variety of tissue culture assays (see http://envirocancer.cornell.edu/Bibliography/Bibliography.cfm
under Endocrine Disruption Bibliographies). In whole-animal
studies, the estrogenic effects of parabens were not seen
when fed to the animals, but only when applied to or injected
under the skin. But, these were short-term, high-dose studies.
Little to no information exists on whether use of products
with low levels of parabens over many years results in
accumulation of parabens in body tissues and whether there
are or are not any health effects associated with use of
paraben-containing consumer products.
Overview
The study by P. Darbre and colleagues (2) was conducted to assess whether any
of the six parabens commonly used in consumer products in Europe could be
detected in human breast tumors. The names of the parabens studied were:
methylparaben, ethylparaben, propylparaben, isobutylparaben, butylparaben
and benzylparaben. The prefix (e.g. “methyl”) indicates the name
of the side-chain structure of each paraben. In this study, 20 samples of
human breast tissue were obtained from patients undergoing surgery at the
Edinburgh Breast Unit in Scotland, UK. The samples were frozen, and then
tumors were minced and homogenized to help break up the tissue. Solvents
were used to extract the parabens from the tumor sample, followed by the
use of thin-layer chromotography to isolate any of the parabens present in
the samples. Another method called high-pressure liquid chromatography with
mass spectrometry was used to identify the type and the concentration of
each paraben. For each batch of samples, a blank was included that had no
tumor tissue, which was run through the same extraction and detection procedure.
The authors were surprised that the blank was not zero, but had some parabens.
The authors thought parabens in the hand soap used by technicians or in the
detergent used to clean the glassware may have contaminated the laboratory
equipment. Blank values were subtracted from sample paraben values to correct
for this problem. At least one type of paraben was detected in 19 out of
20 tumors. Methylparaben was the most commonly observed paraben (18/20) and
was detected at the highest average level.
Commentary
This study is the first report of the detection of parabens in human breast
tumors. The authors are careful to point out that the results of this study
do not show that any of the parabens caused breast cancer in these women.
This study is not evidence of cause and effect. The study did show that five
of the six parabens widely used in consumer products can be detected intact
(not changed or metabolized) in human tissues. This is an important initial
finding, but more research is needed to see if exposure to parabens does
or does not affect breast cancer risk.
For instance, this study did not show if levels of the
parabens in breast tumors were any different from nearby
normal breast tissue in these women. Also, this study did
not include any women without breast cancer. To evaluate
breast cancer risk, a study would need to compare levels
of parabens in women with breast cancer (cases) to women
of similar age without breast cancer (controls). This study
was very small, with only 20 tumor samples. A larger, case-controlled
study would be needed to more fully evaluate whether parabens
do or do not affect breast cancer risk. This study did
have some other problems, such as the contamination of
the blank samples mentioned above. Another problem reported
was in the analytical method. An important way to measure
the ability to accurately detect the chemical includes
adding (spiking) a known amount of paraben to a sample
to see how much of the known amount can be recovered from
the sample. For instance, if you add 100 units, you would
like to have a high recovery of over 90%. In this study,
the recoveries of added paraben averaged just under 50%.
Hence, the method used to extract the parabens from the
sample needs to be improved.
This study has received attention in the popular press
because the authors are interested in exploring the hypothesis
of whether estrogenic parabens used in underarm products
(like deodorants and antiperspirants) increase breast cancer
risk. This study did not test this hypothesis. The results
did show that intact parabens can be detected in human
tissue. It did not however, make any attempt to find out
the source of the parabens. The women who donated the tumor
samples were not interviewed. In fact, no reports of their
age or tumor status were included in this study. No information
on other factors that may have influenced their breast
cancer risk, or information on past use or patterns of
use of products with parabens was obtained. It is not known
if the major exposure was due to the parabens from food
or via topical application of a certain type or a variety
of personal care products.
Better studies are needed of whether or not long term
use of paraben-containing consumer products affect human
tissue levels. Given the ubiquitous nature of paraben use
in consumer products and recent evidence of the estrogenicity
of parabens, I would agree with other scientists who have
called for a reassessment of the safety of parabens. Most
of the risk assessments conducted on the safety of parabens
were done before it was known that parabens can act as
an environmental estrogen and before it was known that
levels are detectable in human tissue. A recent study on
the safety of propylparaben does acknowledge the estrogenicity
of this chemical, but does not fully explore possible human
health risks (3). More recent data is needed to update
the 1984 study by Elder, which is one of the few reports
estimating exposure to parabens from food, drug and cosmetic
products. While use of parabens is widespread, product-to-product
use is variable. In a survey of products in my own bathroom
and kitchen, I found a type of paraben listed as an ingredient
in liquid hand soap, two hand lotions, one out of three
shampoos (the “natural” brand was the one with
the paraben), one out of two hair conditioners, and three
out of five sunscreens (including two made for use by children),
but in none of the three antiperspirants that my family
uses.
At this point in time we do not have information on whether
or not paraben-containing products are used at a level
that affects human health. But, research indicating that
several parabens can act as weak environmental estrogens
and the preliminary results of this study do support the
need for more vigorous research in this area. Unlike other
environmental contaminants, use of personal care products
represents a choice made by the consumer and a choice by
the manufacturer who determine the ingredients of the product.
1) Elder, RL. Final report on the safety assessment of
methylparaben, ethylparaben, propylparaben and butylparaben,
Journal of the American College of Toxicology, vol. 3,
pp. 147-209, 1984.
2) Darbre, PD, A Aljarrah, WR Miller, NG Coldham, MJ Sauer
and GS Pope, Concentrations of parabens in human breast
tumors, Journal of Applied Toxicology, vol. 24, pp. 5-13,
2004.
3) Soni, MG, GA Burdock, SL Taylor, NA Greenberg, Safety
assessment of propyl paraben: a review of the published
literature (Review), Food and Chemical Toxicology, vol.
39, pp. 513-532, 2001.
Cornell University
Program on Breast Cancer and Environmental Risk Factors (BCERF)
Website: http://envirocancer.cornell.edu/Program/programinfo.cfm
 Established
in November 1995, BCERF is devoted to the investigation
of risk factors for breast cancer. Since established risk
factors (gender, advancing age, early menarche, late menopause,family
history, and late age of first birth) account for less
than half of all breast cancers, there is concern that
environmental factors may play an important role in this
disease. BCERF is critically evaluating the scientific
information on pesticides, other chemicals, and diet and
the relationship of these factors to breast cancer risk.
This translational research allows for the synthesis and
interpretation of a wide range of research on these environmental
factors, and whether they may affect breast cancer risk.
EnviroChem Endocrine Disruption
Series
Parabens: evidence of estrogenicity and endocrine disruption
This bibliography is provided as a service to our readers.
It is compiled from the entries in the BCERF Environmental
Risk Factors Bibliographic Database.
We will make every effort to update this bibliography.
If you have comments on this bibliography, or have a suggestion
of a reference you would like us to review for inclusion
in the bibliography, please send this information via email
to: breastcancer@cornell.edu
This bibliography is arranged topically.
The topics include:
Parabens levels
in breast tumors
Risk assessments
and potential exposure to parabens
Studies demonstrating
an estrogen-mimic effect of parabens
Parabens’ adverse
effects on male reproduction
Parabens
levels in breast tumors
Darbre, P. D., Aljarrah, A., Miller, W. R., Coldham, N. G., Sauer, M. J., and
Pope, G. S. (2004). Concentrations of parabens in human breast tumors. Journal
of Applied Toxicology 24, 5-13.
Harvey, P. W. (2003). Parabens, oestrogenicity, underarm
cosmetics and breast cancer: a perspective on a hypothesis
(editorial). Journal of Applied Toxicology 23, 285-288.
Harvey, P. W., and Everett, D. J. (2004). Significance
of the detection of esters of p-hydroxybenzoic acid (parabens)
in human breast tumours (editorial). Journal of Applied
Toxicology 24, 1-4.
Risk
assessments and potential exposure to parabens
Elder, R. L. (1984). Final report on the safety assessment of methylparaben,
ethylparaben, propylparaben and butylparaben. Journal of the American College
of Toxicology 3, 147-209.
Soni, M. G., Burdock, G. A., Taylor, S. L., and Greenberg,
N. A. (2001). Safety assessment of propyl paraben: a review
of the published literature. Food and Chemical Toxicology
39, 513-532.
Studies
demonstrating an estrogen-mimic effect of parabens
Blair, R. M., Fang, H., Branham, W. S., Hass, B. S., Dial, S. L., Moland, C.
L., Tong, W., SHi, L., Perkins, R., and Sheehan, D. M. (2000). The estrogen
receptor relative binding affinities of 188 natural and xenochemicals: structural
diversity of ligands. Toxicological Sciences 54, 138-153.
Byford, J. R., Shaw, L. E., Drew, M. G., Pope, G. S.,
Sauer, M. J., and Darbre, P. D. (2002). Oestrognic activity
of parabens in MCF7 human breast cancer cells. Journal
of Steroid Biochemistry and Molecular Biology 80, 49-60.
Darbre, P. D., Byford, J. R., Shaw, L. E., Hall, S., Coldham,
N. G., Pope, G. S., and Sauer, M. J. (2003). Oestrogenic
activity of benzylparaben. Journal of Applied Toxicology
23, 43-51.
Darbre, P. D., Byford, J. R., Shaw, L. E., Horton, R.
A., Pope, G. S., and Sauer, M. (2002). Oestrogenic activity
of isobutylparaben In vitro and In vivo. Journal of Applied
Toxicology 22, 219-226.
Inui, M., Tetsuya, A., Takenaka, S., Inui, H., Nakazawa,
M., Ueda, M., Watanabe, H., Mori, C., Iguchi, T., and Miyatake,
K. (2003). Effects o f UV screens and preservatives on
vitellogenin and choriogenin production in male medaka
(Oryzias latipes). Toxicology 194, 43-50.
Kang, K.-S., Cho, S.-D., and Lee, Y.-S. (2002). Additive
estrogenic activities of the binary mixtures of four estrogenic
chemicals in recombinant yeast expressing estrogen receptor.
Journal of Veterinary Science 3, 1-5.
Lemini, C., Silva, G., Timossi, C., Luque, D., Valverde,
A., and Gonzales-Martinez, M. (1997). Estrogenic effects
of p-hydroxybenzoic acid in CD1 mice. 130-134.
Okubo, T., Yokoyama, Y., Kano, K., and Kano, I. (2001).
ER-dependent estrogenic activity of parabens assessed by
proliferation of human breast cancer
Pedersen, K. L., Pedersen, S. N., Christiansen, L. B.,
Korgaard, B., and Bjerregaard, P. (2000). The preservatives
ethyl-, propyl- and butylparaben are oestrogenic in an
in vivo fish assay. Pharmacology & Toxicology 86, 110-113.
Routledge, E. J., Parker, J., Odum, J., Ashby, J., and
Sumpter, J. P. (1998). Some alkyl hydroxy benzoate preservatives
(parabens) are estrogenic. Toxicology and Applied Pharmacology
153, 12-19.
Vinggaard, A. M., Kroner, W., Lund, K. H., Bolz, U., and
Peterson, J. H. (2000). Identification and quatification
of estrogenic compounds in recycled and virgin paper for
household use as determined by an in vitro yeast estrogen
screen and chemical analysis. Chemical Research in Toxicology
13, 1214-1222.
Parabens’ adverse
effects on male reproduction
Fisher, J. S., Turner, K. J., Brown, D., and Sharpe, R. M. (1999). Effect of
neonatal exposure to estrogenic compounds on development of the ducts of rat
testis through puberty to adulthood. Environmental Health Perspectives 107,
397-405.
Kang, K.-S., Che, J.-H., Ryu, D.-Y., Kim, T.-W., Li, G.-X.,
and Lee, Y.-S. (2002). Decreased sperm number and motile
activity on the F1 offspring maternally exposed to butyl
p-hydroxybenzoic acid (butyl paraben). Journal of Veterinary
Medical Science 64, 227-235.
Oishi, S. (2002a). Effects of butyl paraben on the male
reproductive system in mice. Archives of Toxicology 76,
423-429.
Oishi, S. (2002b). Effects of propyl paraben on the male
reproductive system. Food and Chemical Toxicology 40, 1807-1813.
Prepared by Suzanne M. Snedeker, Ph.D.
Sun block
18 April 01
Gender-bending chemicals that mimic the effect of oestrogen
are common in sunscreens, warns a team of Swiss researchers
who have found that they trigger developmental abnormalities
in rats.
"We need to do more tests to see how they might be
affecting people," says Margaret Schlumpf from the
Institute of Pharmacology and Toxicology at the University
of Zurich, Switzerland.
Researchers know that chemicals which behave like oestrogen
can cause health problems. They can have a dramatic effect
on animals, for example turning fish into hermaphrodites.
Some researchers claim that hormonally active chemicals
from the urine of women taking the birth control pill are
already swamping the environment, and may be causing a
decline in sperm counts.
Uterine growth
Schlumpf and her colleagues tested six common UV screening chemicals used in
sunscreens, lipsticks and other cosmetics. All five UVB screens -benzophenone-3,
homosalate, 4-methyl-benzylidene camphor (4-MBC), octyl-methoxycinnamate
and octyl-dimethyl-PABA - behaved like oestrogen in lab tests, making cancer
cells grow more rapidly.
Three caused developmental effects in animals. Only one
chemical - a UVA protector called butyl-methoxydibenzoylmethane
(B-MDM) - showed no activity.
One of the most common sunscreen chemicals, 4-MBC, had
a particularly strong effect. When the team mixed it with
olive oil and applied it to rat skin, it doubled the rate
of uterine growth well before puberty. "That was scary,
because we used concentrations that are in the range allowed
in sunscreens," Schlumpf says.
Nobody knows if doses are high enough to create problems
for people, says Schlumpf.
Low levels
" Evidence that they're a real health concern is still lacking," says
Richard Sharpe from the Medical Research Council's Reproductive Biology Unit
in Edinburgh. But he adds, "It's not good news that we are lathering ourselves
with creams with hormonal activity."
The Cosmetic Toiletry & Perfumery Association, which
represents sunscreen manufacturers in Britain, replies
that the levels found by Schlumpf are well below anything
that would cause an effect after a single application.
A study by the association, not yet published, shows no
effect from these chemicals in rats. But, it adds, "If
levels are increasing [in the environment] then we're aware
something would have to be done soon."
Breast milk
That day may be here since 4-MBC and other sunscreen chemicals have been shown
to accumulate in fish from lakes where people swim.
More worryingly, they have been found in breast milk at
levels of nanograms per kilogram of fat - about the same
as other known environmental contaminants. Schlumpf worries
that the large amount of sunscreen used by bathers, especially
children, could dramatically increase this exposure.
Schlumpf says the other 25 or so chemicals used in sunscreens
should also be tested for hormonal activity, and she will
be looking more closely at 4-MBC to see if the offspring
of exposed rats develop health problems.
For the moment, she isn't advising people to ditch sunscreens
completely, but suggests that sunblocks like zinc oxide
might make a healthier alternative.
More at: Environmental Health Perspectives (vol 109, p
239)
Cosmetic chemicals found in
breast tumours
12 January 04
NewScientist.com news service
Website: NewScientist.com
Preservative chemicals found in
samples of breast tumours probably came from underarm
deodorants, UK scientists have claimed.
Their analysis of 20 breast tumours found high concentrations
of para-hydroxybenzoic acids (parabens) in 18 samples.
Parabens can mimic the hormone estrogen, which is known
to play a role in the development of breast cancers. The
preservatives are used in many cosmetics and some foods
to increase their shelf-life.
"From this research it is not possible to say whether
parabens actually caused these tumours, but they may certainly
be associated with the overall rise in breast cancer cases," says
Philip Harvey, an editor of the Journal of Applied Toxicology,
which published the research.
"Given that breast cancer is the largest killer of
women and a very high percentage of young women use underarm
deodorants, I think we should be carrying out properly
funded, further investigations into parabens and where
they are found in the body," Harvey told New Scientist.
Chemical cousins
The new research was led by molecular biologist Philippa Darbre, at the University
of Reading. She says that the ester-bearing form of parabens found in the
tumours indicates it came from something applied to the skin, such as an
underarm deodorant, cream or body spray. When parabens are eaten, they are
metabolised and lose the ester group, making them less strongly estrogen-mimicking.
"One would expect tumours to occur evenly, with 20
per cent arising in each of the five areas of the breast," Darbre
told New Scientist. "But these results help explain
why up to 60 per cent of all breast tumours are found in
just one-fifth of the breast - the upper-outer quadrant,
nearest the underarm."
However, Chris Flower, director general of the Cosmetic,
Toiletry and Perfumery Association, challenged the study's
findings. "There are almost no deodorants and body
sprays that contain parabens," he says. "Although
they are in most other creams and cosmetics, the safety
margin is huge and they would not have any effect on enhancing
growth of new tumours."
Darbre replies that deodorants and antiperspirants have
only stopped containing parabens in the last few months
and that the tumours she studied occurred prior to this.
A small survey by New Scientist of three British high
street shops and one supermarket found deodorants in each
that contained parabens, although most of these products
did not. However, many other products used under the arm
commonly contained parabens, such as body sprays, hair
removal creams and shaving gels. Body lotions, face creams,
cleansers and shampoos also frequently contained parabens.
Skin deep
Previously published studies have shown that parabens are able to be absorbed
through the skin and to bind to the body's estrogen-receptors, where they
can encourage breast cancer cell growth. But Flower maintains that the amount
of parabens absorbed by the skin is very low and the parabens are "metabolised
by the skin cells to produce products that have no estrogenic activity".
Darbre's research did not look at the concentrations of
parabens in other areas of the breast or body tissues and
Harvey cautions that the significance of the chemicals
in tumour tissue should not be over-interpreted.
Darbre says she has not used cosmetic products, including
underarm deodorants, for eight years. She recommends that
other women do the same "until their safety can be
established".
Journal reference: Journal of Applied Toxicology (vol
24, p5)
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