- Triclosan is a broad-spectrum antibacterial/anti-microbial
agent. It is manufactured in the U.S. by Ciba-Geigy, under their trade
name Irgasan DP300, and by several other manufacturers outside of the U.S..
As a result of its bacteriostatic activity against a wide range of both
gram-negative and gram-positive bacteria it has found increasing and recent
popular use in personal care products, i.e.- toothpaste, deodorant soaps,
deodorants, antiperspirants and body washes, detergents, dish washing liquids,
cosmetics and anti-microbial creams, lotions and hand soaps. It is also
used as an additive in plastics, polymers and textiles to give these materials
antibacterial properties.
-
- Triclosan is a diphenyl ether (bis-phenyl)
derivative, known as either 2,4,4'-Trichloro-2'-hydroxydiphenyl ether or
5-Chloro-2-(2,4-dichlorophenoxy) phenol. It is related in structure to
a number of bis-phenyl polychlorinated and bis-phenyl chlorophenol compounds.
Due principally to the synthesis chemistry of polychloro diphenyl ethers
and phenoxy phenols there is the potential for the formation of small amounts
of unwanted trace by-products which are of concern. Beginning in the early
1970's and into the mid 1980's research revealed that phenoxy herbicides
such as 2,4-D and 2,4,5-T (1,2,3), the major components of Agent Orange,
the bactericide Hexachlorophene (4,5), various chlorophenols, i.e.- pentatchlorophenol,
used in wood treatment (6), certain polychloro phenoxy phenols (7) and
polychloro diphenyl ethers (8) and diphenyl ether herbicides (9) contained
various low levels of polychlorinated dioxins and polychlorinated furans.
-
- Consequently, since triclosan is by
its chemical structure a polychloro phenoxy phenol it is possible that
several polychlorodibenzo-p-dioxins (dioxins) polychloro-dibenzofurans
(dibenzofurans) can be found in varying low level amounts, as synthesis
impurities in triclosan. Their presence or absences is dependent upon the
type and purity of the starting materials used to synthesize triclosan
as well as reaction conditions such as temperature, pressure and the like.
If present, their relative concentrations as impurities can vary from
batch to batch. This raises concerns because of the toxicity of dioxins
and dibenzofurans.
-
- The toxicity of dioxins and dibenzofurans
varies with the position and number of chlorine atoms attached to the aromatic
rings. In general, their toxicity increases with increasing chlorine substitution.
Those dioxins and dibenzofurans that have chlorine atoms at the 2,3 and
7 positions are particularly toxic. Tetrachlorodibenzo-p-dioxin and tetrachlorodibenzo-furan,
which have chlorine atoms at the 2,3,7, and 8 positions, are considered
the most toxic of the dioxins and dibenzofurans (4), with 2,3,7,8-tetrachlorodibenzo-p-dioxin
referred to as one of the most toxic substances known.
-
-
- As a result of the potential for the
formation of dioxins and dibenzofurans as unwanted low level trace by-products
the USP, in Pharmacopeial Form, Volume 22, Number 3, Pharmacopeial Reviews
and subsequently in Pharmacopeial Form, Volume 23, Number 5, In-Process
Revision, has proposed a new monograph for the specific testing of triclosan.
This proposed monograph details the assay and testing of USP triclosan.
In addition to setting product specification standards and procedures to
assay the purity and physical identity of USP triclosan, it also defines
the limits and methods of testing for unwanted trace by-products which
may be present. The proposed tests for these unwanted by-products are (1)
Limit of 4-Chlorophenol and 2,4-Dichloro-phenol, (2) Limit of Triclosan
Related Compound A (1,3,7-trichlorodibenzo-p-dioxin), Triclosan Related
Compound B (2,8-dichlorodibenzo-p-dioxin), 2,8-Dichlorodibenzofuran, and
2,4,8-Trichlorodibenzo-furan, and (3) Limit of 2,3,7,8-Tetra-chlorodibenzo-p-dioxin
and 2,3,7,8-Tertrachloro-dibenzofuran.
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- Quantex Laboratories is one of the few
laboratories in the U.S. capable of analyzing triclosan for dioxins and
dibenzofurans employing isotope dilution high resolution gas chromatography/mass
spectrometry (HRGC/MS), as required by the proposed USP monograph. For
those requiring the testing and certification of triclosan as meeting the
proposed USP limits for unwanted trace by-products Quantex Laboratories
can perform the three limit tests (1) Limit of 4-Chlorophenol and 2,4-Dichloro-phenol,
(2) Limit of Triclosan Related Compound A (1,3,7-trichloro-dibenzo-p-dioxin),
Triclosan Related Compound B (2,8-dichlorodibenzo-p-dioxin), 2,8-Dichlorodibenzofuran,
and 2,4,8-Trichlorodibenzo-furan, and (3) Limit of 2,3,7,8-Tetrachlorodibenzo-p-dioxin
and 2,3,7,8-tertrachlorodibenzofuran. We can also provide the complete
testing and assay of triclosan as proposed by the USP, for those requiring
the certification of triclosan to USP, which includes the three limit tests,
the assay of triclosan for purity, the testing for heavy metals, physical
identification , melting range and residue on ignition. All analytical
testing is conducted in conformance to cGMP (Good Manufacturing Practices).
-
- References
- 1. Gribble, G. W., Chemistry, Vol.
47, No. 2, 15-18.
- 2. USEPA, Health Assessment Document
for Polychlorodibenzo-p-dioxins,
- EPA-600/8-84-014A.
- 3. Courtney, K.D., Moore,J.A., Toxicology
and Applied Pharmacology,
- Vol. 20, 396.
- 4. Menoutis, J., A Current Overview
of the Occurrence, Toxicity and
- Disposal of 2,3,7,8-Tetrachlorodibenzo-p-dioxin,
11/84, internal
- Givaudan research monogram.
- 5. Kulkarni, S., V., Kowalski, J.,
A., Waste Streams From
- Hexachlorophene Manufacturing Processes,
Final Draft, USEPA, March
- 1984.
- 6. Rappe, C., Bauser, H., R.,Bassharrdt,
H., P., Annuls of the New
- York Academy of Science, 1979, No.
1, 320.
- 7. Nilsson, C., A., Anderson, K.,
Rappe, C., et. al., Journal of
- Chromatography, Vol. 96, 137-147.
- 8. Norstrom, A., Anderson, K., Rappe,
C., Chemosphere, Vol. 1 (1976),
- 21-24.
- 9. Yamagiaki, T., Miyazaki, T., Akilyana,
K., et. al., Chemosphere,
- Vol. 10 ( 1981), 1137.
- 10. USP, Pharmacopeial Form, Volume
22, Number 3, Pharmacopeial Reviews,
- 2287-2291.
- 11. USP, Pharmacopeial Form, Volume
23, Number 5, In-Process Revision,
- 4827-4831.
-
- About the Authors
- Angela I. Parisi-Menoutis has over 24
years of experience in methods
- development and analysis of surfactants,
quaternaries, amines, polyols,
- personal care products, specialty chemicals
and intermediates. She spent 8
- years as an R&D Group Leader with
Lonza, Inc., and prior to that 7 years
- as an analytical chemist with Colgate
Palmolive Company. Her background
- includes extensive expertise in mass
spectral methods development and
- interpretation including analysis by
isotope dilution HRGC/MS.
-
- James Menoutis has over 20 years experience
as an analytical chemist,
- group leader and manager. His experience
includes toxicology, methods
- development and analysis of botanicals,
flavors, fragrances,
- pharmaceuticals, analysis and methods
development for the analysis of
- clinical pharmaceuticals, pesticide residue
analyses, occupational health
- and toxicological analyses and environmental
analytical methods. As a
- research analytical chemist with Givaudan
were he researched dioxin and
- dibenzofuran chemistry in hexachlorophene
and its raw materials. He has an
- extensive analytical background which
includes experience in isotope
- dilution HRGC/MS.
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