PARABENSASPRESERVATIVESUENO FINE CHEMICALS INDUSTRY LTD.

WHAT ARE PARABENS?
Preservatives are added to food, cosmetic, and pharmaceutical products toprevent decomposition due to bacterial action.
Among preservatives, the Parabens are the most commonly usedbecause of their low toxicity to humans and their effective antimicrobial activity,especially against molds and yeasts.
The Parabens are esters of p-hydroxybenzoic acid.
The Parabens are Methylparaben, Ethylparaben, Propylparaben, utylparaben.
Frequency use of preservatives in cosmetic formulations in 2005
8000
7000
60005000
4000
3000
2000
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ButEtheProhMePSteinberg, D.C., 2005 Preservatives Use :Frequency Report and Registration,
Cosmetics & Toiletries,121(7), 65-69 (2006)

PARABENS’
MICROBACTERIAL EFFECTS

Escherichia coli IFO 3972 :METHYL＋PROPYLPARABEN (2:1) 0.1%

Staphylococcus aureus
IFO 13276 :METHYL＋PROPYL PARABEN(2:1) 0.1%

Candida albicans ATCC 10231 :METHYL + PROPYL PARABEN(2:1) 0.05%

Left : without Parabens
Right :with Parabens
Pseudomonas aeruginosa IFO
13275 :METHYL＋PROPYL PARABEN(2:1) 0.2%

Aspergillus niger ATCC 16404 :METHYL+PROPYL PARABEN(2:1) 0.05%

PARABENS’
MICROBACTERIAL EFFECTS
Minimum Inhibitory Concentration of Parabens (%)
MIC
Microorganism
MPEPPPBP

Aspergillus niger ATCC 10254

0.1

0.04

0.02

0.02

Penicillium digitatum ATCC 10030

0.05

0.025

0.00630.0032

Candida albicans ATCC 10331

0.1

0.1

0.01250.0125

Saccharomyces cerevisiae ATCC 9763

0.1

0.05

0.01250.0063

Bacillus subtilis ATCC 6633

0.2

0.1

0.025

0.0125

Bacillus cereus var. mycoides ATCC 6462

0.20.10.01250.0063

Molds

YeastsBacteria

MP:Methylparaben
EP:Ethylparaben
PP:Propylparaben
BP:Butylparaben

Aalto,T.R., Firman,M.C., Rigler,N.E.,
p-Hydroxybenzoic acid esters as preservatives Ⅰ,
J.Am.Pharm.Assoc.Sci.Ed.,42,449-457 (1953)

USES IN COSMETICS
Parabens have been successfully used in cosmetics for more than 80years.
The use of Paraben, alone or in combination
with other compounds, is well suited for thepreservation of cosmetics.
In most cosmetics, Parabens are used atvery low levels ranging from 0.01 to 0.3%.
http://www.cfsan.fda.gov/~dms/cos-para.html
U.S. Food and Drug Administration, August, 2006

The product containing Parabens may be used on an occasional or aconsistent basis and their use may extend product life.

USES IN FOODS
Under FDA regulation,
Methylparaben andPropylparaben are generally
recognized as safe (GRAS)
when used as chemicalpreservatives in foods, with ause limit of 0.1% for each.

They are used in processed vegetables, baked goods, fats andoils, seasonings, sugar substitutes, and frozen dairy products inconcentrations up to 0.1%.
Elder, R.L. , et al., Final Report on the Safety Assessment of Methylparaben, Ethylparaben,
Propylparaben, and Butylparaben, Journal of The American College of Toxicology,
3(5), 147-209 (1984)

USES IN
PHARMACEUTICALSParabens were first used in pharmaceutical products in 1924.
Since then, they have been incorporated as preservatives in a variety ofpharmaceutical formulations.

Combinations of Parabens are
more effective as preservativesthan individual esters.

PARABEN’S SAFETY
The safety has been proven by various studies (in vivo tests) as stated below :・acute chronic and subchronic toxicity studies
・carcinogenesis studies
・reproduction toxicity studies
・absorbing, metabolizing, and excreting studies
・skin stimulating test
・photo-contactsensitization and phototoxicity studies
In 1974, the Joint FAO/WHO Expert Committee on Food Additives （JECFA）
recommended the group Acceptable Daily Intake (ADI) for the methyl-, ethyl-,
propyl-esters of p-hydroxybenzoic acid as 0-10 mg/kg body weight/day(JECFA,1974).
Methylparaben

Propylparaben

Acute Toxicity (LD50)

2-8g/kg＜2-8g/kg＜

Mutagenicity(Bacterium)

Negative

Negative

ADI

0-10mg/kg

0-10mg/kg

TOPICS ―Parabens, underarm cosmetics, and breast cancer(1)The link between the use of underarm cosmetics and breast cancer
has been promoted through a number of publications by Dr.Darbre andDr.Harvey.
About this problem;
Dr.Darbre et al. answered the question from the consultants of theCosmetic, Toiletry, and Fragrance Association (CTFA), ‘nowhere in themanuscript was any claim made that the presence of parabens had
caused the breast cancer, indeed the measurement of a compound ina tissue cannot provide evidence of causality.’
Golden,R., Gandy,J., Letters to the Editor, Journal of Applied Toxicology, 24,297-306 (2004)

TOPICS ―Parabens, underarm cosmetics, and breast cancer(2)It is the opinion of the Scientific Committee on Consumer Productsof European Commission (SCCP) that, in the light of the present
knowledge, there is no evidence of demonstrable risk for thedevelopment of breast cancer caused by the use of parabencontaining underarm cosmetics.
SCCP/0874/05, Opinion of the Scientific Committee on Consumer Products on Parabens, underarm cosmetics and breast
cancer, adopted by written procedure on 28 January 2005

The Cosmetic Ingredient Review (CIR) Expert Panel concluded thatParabens are safe as used in cosmetics in the safety assessment.
Final Report of the Cosmetic Ingredient Review Expert Panel, Amended Safety Assessment of Methylparaben,Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben, June13,2006

Paraben is well known to exist in natural products. Also, we have been using
Paraben all over the world for preservative of cosmetics, foods and pharmaceutical
additives for a long time, taking advantage of its characteristic.
The chemical name of paraben is "p-hydroxybenzoic acid ester".
Paraben is made by a chemical synthesis, however, it has its advantages forsafety, efficiency and cost performance. Due to these reasons, this product canbe used widely for many products. Once paraben is absorbed in a body, itdisintegrates easily and changes into "p-hydroxybenzoic acid" which is ametabolite of paraben, and will be excreted immediately 1).
As for the paraben or p-hydroxybenzoic acidare classified as polyphenol in plants. Inaddition, it has been well known that they areincluded in many vegetables and fruits(typical of berries) 2-5) for a long time.

In recent years, antibacterial and/or antioxidative effect in vegetable or plantoil (ex. carrot, tomato, rapeseed oil, olive oil) receives great attention, andthese products are known to include paraben and p-hydroxybenzoic acid 6-9).
As we have explained, there are many reports of the paraben or p-hydroxybenzoic
acid in plants. In our everyday life, we have many opportunities to touch or to eat
parabens, and we have used antibacterial or preservative effects of paraben since
early times.
Paraben is a good example that we manufacture certain products in natural
products through chemical synthesis, and apply this product in human life.
References
1 Soni, M.G. Food and Chemical Toxicology. 2005, 43: 985-1015.
2 Tomaszewski, M. Bull. Acad. Polonaise Sci. 1960, 8: 61-65.
3 Schmidtlein, H. J Chromatogy. 1975, 115: 123–128.
4 Baardseth, P. Food Chemistry. 1978, 3 (1): 43-46.
5 Schäfers, F. I. Journal of Chromatography, 1982, 240 (2); 21:387-396.
6 Mandal, S. Physiological and Molecular Plant Pathology. 2007, 1(4-6): 201-209.
7 Kang Y. H. J Agric Food Chem. 2008, Sep.24; 56(18): 8558-64.
8 Siger, A. Journal of Food Lipids 2008, 15: 137–149.
9 Salta, F. N. Food Sci Tech Int. 2007, 13 (6): 413-421.

CONCLUSION
The Parabens are the most commonly used preservatives because of their
low toxicity to humans and their effective antimicrobial activity, especiallyagainst molds and yeasts.
Parabens have been studied by a lot of researchers and its safety has been
confirmed from numerous test results.
Parabens are observed and approved by official organizations all over theworld.
Therefore, we can conclude people can safely use products that contain
parabens.