Download Chemical Mixtures: Parabens and Triclosan

Chemical Mixtures: Parabens and Triclosan
Shakila Balkhi, Simrum Bhullar & Kierah Leverton
Department of Environmental and Occupational Health
California State University, Northridge
ABSTRACT
Part of Endocrine System
Triclosan and parabens are anthropogenic chemicals that are used in personal care products to reduce or prevent bacterial
contamination as well as preserve the product. These chemicals have been introduced into the cosmetic industry to lengthen the Pineal gland (brain)
shelf life of most products.
Pituitary gland (brain) –
These chemicals have not been in use long enough to determine long term health effects and have created an experimental works closely with the
generation within our society. However, animal studies have predicted the chemicals to affect the endocrine system via hormone Hypothalamus.
disruption. Comparison of Triclosan and parabens will examine related mechanisms of actions and similarities between the
chemicals.
Scientific literature was reviewed to determine possible health effects, bioaccumulation, mechanisms of action, and regulations of
the chemicals. Further review of studies determined Triclosan and parabens may have synergistic effects when interacting.
INTRODUCTION
Triclosan is a synthetic antimicrobial agent that is commonly used in a variety of personal care products including make up, soaps,
toothpastes, deodorants, and hand sanitizers. It was first introduced in hospitals in the 1970s for its antimicrobial properties and
production has dramatically increased since. Parabens have been in the market since the 1930s and are the most common
preservatives found in cosmetics and personal care products. Many studies have shown concern with these products causing
endocrine disruption due to their estrogenic properties.
Hormones Produced
Low Exposure Health
Effects
Hormone Regulates
Melatonin
Circadian rhythm and
reproductive hormones.
Adrenal gland stimulation
for hormone production;
maintain healthy body
composition in children
and aids in healthy bone,
muscle mass and fat
distribution; breast milk
production; kidney
function.
Anterior Lobe Hormones:
Adrenocorticotropic
hormone (ACTH),
Follicle-stimulating
hormone (FSH),
Growth hormone (GH),
Luteinizing hormone (LH),
Prolactin, and
Thyroid-stimulating
hormone (TSH). Posterior
Lobe Hormones:
Anti-diuretic hormone
(ADH), and Oxytocin.
High Exposure
Health Effects
Dwarfism (in children); Gigantism (in
Imbalance of internal children); Imbalance
functions of the body. of internal functions
of the body.
Testes (male)
Testosterone
Sperm production; normal Decreased sex drive,
development of male
muscle mass, sperm
characteristics.
count; body hair loss.
Thymus (upper chest)
Thymosin (only until
Production and maturation Development of
puberty – then is inactive.) of T-lymphocytes.
immune system in
early stages of life.
Thyroid (neck)
T3 (tri-iodothyronine) and
T4 (thyroxine).
ROUTES OF EXPOSURE
Triclosan is a common chemical found in toothpaste, mouthwash, deodorants, soaps, textiles, toys,
liquid dishwashing soap and plastic kitchenware. It is known for its antiseptic properties and is
detected in aquatic environments and in food sources (12). The routes of exposure for Triclosan are
through ingestion and dermal absorption. Studies have shown about 6.3% of Triclosan is absorbed into
the human skin just 24 hours after application, in vitro (12).
Parabens are chemicals used as preservatives in pharmaceuticals,
cosmetics, lotions, skin cleansers, hair products (9). They are used to
prevent bacteria growth and have been commonly used since the 1950s.
About 85% of cosmetic products have them (1). The routes of exposure for
parabens are from ingestion, dermal absorption, and inhalation from
contaminated air and dust. Parabens are quickly metabolized in the liver
which results in the distribution of free parabens and adducts of PHBA,
glucuronide, sulfate, and glycine adducts (14).
BIOACCUMULATION AND PERSISTENCE
A high enough concentration of both these chemicals can
cause endocrine system disruption in fish, which can lead to
reproductive and behavioral problems. When animals
consume these poisoned fish, the chemicals bio accumulate
up the food chain and increase in toxicity (1).
Parabens are known xenoestrogens and create excess estrogen in the body by binding to estrogen receptor sites (6).
According to the Journal of Applied Toxicology, Triclosan also exerts estrogenic activities by inducing luciferase activities in an ER
reporter gene assay (7).
This schematic represents the different mechanisms of estrogen signaling:
(8)
I.
Direct genomic signaling pathway- binds the E2 (17-Beta-estrodial) and
ER (estrogen receptor) complex directly to the ERE (estrogen response
element)
II. Indirect genomic signaling pathway- E2-activated ER’s bind DNA through
through protein-protein interactions with transcription factors as their
respective response elements
III. Non-genomic signaling pathway- binds E2 with ER at the plasma
membrane, which activates various protein-kinase cascades and can
lead to changes in gene expression due to phosphorylation of
transcription factors
IV. Ligand-independent signaling pathway- ER activation and target gene
transcription through phosphorylation of ER’s
Triclosan is also found in aquatic and terrestrial environments
through the dumping of consumer products that ultimately
find their to wastewater treatment plants. In addition,
Triclosan persists in anaerobic conditions and is therefore
present in sediment (2).
EFFECTS ON ENDOCRINE SYSTEM
1000 mg/kg/day (11)
The main parts of the endocrine system are the thyroid gland, pituitary gland,
parathyroid glands, adrenal glands, pancreas, testicles (in males), and ovaries (in
females).
Parabens
Bind to estrogen receptors
500,000-fold molar excess (16)
Parabens
Estrogenic Activity
(15)
Triclosan
10¯⁵M (19)
Studies on animals have shown that Triclosan exposure can modulate estrogen
dependent responses (2).
Displaced estradiol from estrogen
receptors
Triclosan
Mouse mammary tumor cells &
Human breast cancer cells.
10¯⁷M & 10¯⁶ respectively (19)
Triclosan
Methyl-, ethyl-, n-propyl-, and nbutyl-paraben
This system helps regulate the body’s physical, neurological, homeostasis, and sexual
development(4).
The table below details the parts of the endocrine system, hormones produced,
hormone regulations, the low exposure health effects, and the high exposure health
effects.
Ovaries (female)
Islet Cells (pancreas)
Parathyroid (neck)
Amount
Increase in Thyroid Hormone
production
Positive association with T3 levels
Inhibited estrogen receptor binding
The endocrine system is a collection of glands that secrete and produce hormones in the
body that regulate the activity of cells and organs. The hormones are released into the
bloodstream and are essentially chemical messengers of the body.
Hypothalamus (brain)
Endocrine Disruption
Methyl- and butyl-paraben
ENDOCRINE SYSTEM
Adrenal Glands (kidneys)
Hyperthyroidism:
Anxiety, rapid
heartbeat, weight
loss, etc.
The mechanisms of EDC’s include chemicals binding to hormone receptors and exerting direct agonist or antagonist actions,
exerting indirect agonist or antagonist actions, or binding to allosteric sites and yielding unexpected effects at low concentrations
(5).
Chemical
Part of Endocrine System
Hypothyroidism:
Fatigue, weakness,
weight gain, etc.
MECHANISMS OF ACTION
The International Journal of Environmental Research and
Public Health found that high levels of Triclosan were found
in 60% of human milk samples, and in 75% of human urine
samples (2).
According to a study done on parabens in surface water and
fish from the greater Pittsburgh area, methyl paraben and butyl
paraben were found in surface waters at concentrations
ranging from 2.2 to 17.3 and 9.2 and 12.0 ppt, respectively (3).
Metabolism
Hormones Produced
Hormone Regulates
Cortisol and sometimes
aldosterone
Cortisol: response to
stress; use of protein,
carbohydrates and fat;
blood pressure and
cardiovascular function;
inflammation.
Anti-diuretic hormone
Heart rate and blood
(ADH),
pressure, body
Corticotropin-releasing
temperature, fluid and
hormone (CRH),
electrolyte balance,
Gonadotropin-releasing
appetite and body weight,
hormone (GnRH), Follicle glandular secretions of the
stimulating hormone
stomach and intestines,
(FSH), luteinizing hormone production of substances
(LH), Growth hormonethat influence the
releasing hormone
pituitary gland to release
(GHRH) and inhibiting
hormones and sleep
hormone (GHIH),
cycles
Oxytocin, Prolactinreleasing hormone (PRH)
or inhibiting hormone
(PIH), Thyrotropin
releasing hormone (TRH):
triggers the release of
thyroid stimulating
hormone (TSH).
Estrogen/Progesterone
Insulin and glucagon
Parathyroid hormone
Female System
Blood glucose levels
Calcium regulation
Low Exposure Health
Effects
Cortisol: Fatigue,
stomach upset,
dehydration and skin
changes.
Aldosterone: Drop in
blood pressure.
Imbalance of internal
body functions.
High Exposure
Health Effects
Cortisol: Cushing’s
disease (fatigue,
weight gain, weak
muscles, etc)
Imbalance of internal
body functions.
Urinary concentrations (9)
1,000,000-fold molar excess (15)
REGULATIONS
Regulations for Triclosan and parabens are minimal and are currently under review within several governments. The European
Union and Canada currently have regulations for parabens. However, within the United States the Cosmetic Ingredient Review
concluded that they were safe in cosmetic products up to 25%. Triclosan is currently not regulated within the US and is under
further review.
Country
Methyl- and Ethyl-Paraben
Propyl- and Butyl Paraben
Triclosan
European Union
8g/kg of product (21)
Max total [] 1.9g/kg (21)
0.3% (20)
Canada
USA
0.3% (22)
Up to 25% (23)
0.3% (22)
Up to 25% (23)
0.3% (22)
Not regulated
CONCLUSION
Drawing conclusions for the chemicals is challenging because they have not been in existence long enough to conclude they are
harmful. However, through literature review these chemicals act using similar mechanisms of action that lead to conclusions of
the two acting synergistically. Both Triclosan and parabens mimic pro-estrogenic activities ultimately having an effect on the
endocrine system. Further studies need to be conducted in order to determine chemical exposure safety.
However, the novelty of the chemicals and their constant use has created an experimental generation for our current society.
Taking a preventative approach to these chemicals is recommended as studies have shown them to have harmful effects to
animals.
REFERENCES
Low bone density
Hyperglycemia
Hypoglycemia
Osteoporosis
(12) Calafat, Antonia M, Xiaoyun Ye, Lee-Yang Wong, John A Reidy, and Larry L Needham. "Urinary Concentrations of
(1) Good, Kate. "The Disturbing Environmental and Health Impact of Pouring Personal Care Products Down the Drain."
Triclosan in the U.S. Population: 2003-2004." Environmental Health Perspectives, 116.3 (2008): 303-307.
One Green Planet. N.p., 30 Jan. 2015. Web. 03 Dec. 2015.
(2) International Journal of Environmental Research and Public Health (ISSN 1660-4601; CODEN: IJERGQ; ISSN 1661-7827 (13) Durán-Álvarez, J C, B Prado, D González, Y Sánchez, and B Jiménez-Cisneros. "Environmental Fate of Naproxen,
Carbamazepine and Triclosan in Wastewater, Surface Water and Wastewater Irrigated Soil - Results of Laboratory Scale
for printed edition) is an interdisciplinary, open access journal published monthly online by MDPI.
Experiments." The Science of the Total Environment, 538 (2015): 350-362.
(3) Rez, Lara, Conrad Volz, Drew Michanowicz, Kyle Ferrar, Charles Christian, Diana Lenzner, and Talal El-Hefnawy. "A
Study of Parabens and Bisphenol A in Surface Water and Fish Brain Ti." Ecotoxicology 22.4 (2013): 632-41. Ssue from the (14) Pycke, BFG, LA Geer, M Dalloul, O Abulafia, and RU Halden. "Maternal and Fetal Exposure to Parabens in a
Multiethnic Urban US Population." Environment International, 84 (2015): 193-200.
Greater Pittsburgh Area. 13 May 2013. Web. 03 Dec. 2015.
(4) Paulsen, Lisa. "The Health Risks of Chemicals in Personal Care Products and Their Fate in the Environment." 2015. MS. (15) Byford, J.R, L.E Shaw, M.G.B Drew, G.S Pope, M.J Sauer, and P.D Darbre. "Oestrogenic Activity of Parabens in MCF7
Human Breast Cancer Cells." Journal of Steroid Biochemistry and Molecular Biology, 80.1 (2002): 49-60.
Connecticut College. Digital Commons @ Connecticut College. 2015. Web. 3 Dec. 2015.
(5) Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from The Endocrine Society R. (16) Routledge, Edwin J, Joanne Parker, Jenny Odum, John Ashby, and John P Sumpter. "Some Alkyl Hydroxy Benzoate
Preservatives (Parabens) Are Estrogenic." Toxicology and Applied Pharmacology, 153.1 (1998): 12-19.
Thomas Zoeller, T. R. Brown, L. L. Doan, A. C. Gore, N. E. Skakkebaek, A. M. Soto, T. J. Woodruff, and F. S. Vom Saal
(17) Blair, RM, H Fang, WS Branham, BS Hass, SL Dial, CL Moland, WD Tong, LM Shi, R Perkins, and DM Sheehan. "The
Endocrinology 2012 153:9, 4097-4110
(6) Barton-Schuster, Dalene. "Elevated Estrogen Levels Linked to Toxins in Body Care Products." Natural Fertility Infocom. Estrogen Receptor Relative Binding Affinities of 188 Natural and Xenochemicals: Structural Diversity of Ligands."
Toxicological Sciences, 54.1 (2000): 138-153.
N.p., n.d. Web. 03 Dec. 2015.
(18) K.L, Pedersen, Pedersen S.N, Christiansen L.B, B Korsgaard, and P Bjerregaard. "The Preservatives Ethyl-, Propyl- and
(7) Huang H., Du G., Zhang W., Hu J., Wu D., Song L., Xia Y. and Wang X. (2014), The in Vitro estrogenic activities of
Butylparaben Are Oestrogenic in an in Vivo Fish Assay." Basic & Clinical Pharmacology & Toxicology, 86.3 (2000): 110-113.
Triclosan and triclocarban, J. Appl. Toxicol., 34, pages 1060–1067. DOI: 10.1002/jat.3012
(19) Gee, R. H, A Charles, N Taylor, and P. D Darbre. "Oestrogenic and Androgenic Activity of Triclosan in Breast Cancer
(8) Peter Vrtačnik, Barbara Ostanek, Simona Mencej-Bedrač, Janja Marc*. The many faces of estrogen signaling.
Cells." Journal of Applied Toxicology, 28.1 (2008): 78-91.
Biochemia Medica 2014;24(3):329-42. http://dx.doi.org/10.11613/BM.2014.035
(20) SCCS (Scientific Committee on Consumer Safety), Opinion on triclosan, ADDENDUM to the SCCP Opinion on Triclosan
(9)Koeppe, ES, KK Ferguson, JA Colacino, and JD Meeker. "Relationship Between Urinary Triclosan and Paraben
Concentrations and Serum Thyroid Measures in NHANES 2007-2008." Science of the Total Environment, 445 (2013): 299- (SCCP/1192/08) from January 2009, 22 March 2011
(21) SCCS (Scientific Committee on Consumer Safety), Opinion on parabens, 14 December 2010, revision of 22 March 2011
305.
(10) Taxvig, C, Vinggaard, AM, Hass, U, Axelstad, M, Boberg, J, Hansen, PR, et al. “Do parabens have the ability to interfere (22) http://www.hc-sc.gc.ca/cps-spc/cosmet-person/labelling-etiquetage/ingredients-eng.php#a4.7 Health
Canada/Consumer Product Safety/Safety of Cosmetic Ingredients. Web 26 Nov. 2015.
with steroidogenesis?” Toxicol Sci, 106 (2008): 206-1
(11) Vo, Thuy T.B, Yeong-Min Yoo, Kyung-Chul Choi, and Eui-Bae Jeung. "Potential Estrogenic Effect(s) of Parabens at the (23) http://www.fda.gov/cosmetics/productsingredients/ingredients/ucm128042.htm FDA/Cosmetics/Parabens Web. 27
Nov. 2015
Prepubertal Stage of a Postnatal Female Rat Model." Reproductive Toxicology, 29.3 (2010): 306-316.