Trace amounts of dioxins and dibenzofurans in triclosan

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Triclosan 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) and 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 tetrachlorodibenzofuran, 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 (a) Limit of 4-Chlorophenol and 2,4-Dichloro-phenol, (b) 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 (c) Limit of 2,3,7,8-Tetra-chlorodibenzo-p-dioxin and 2,3,7,8-Tertrachloro-dibenzofuran.
 

Suggested thyroid dysfunction

Structural resemblance between Triclosan and thyroxine has raised concerns about Triclosan interfering with thyroid hormone metabolism in the body, thereby lowering body temperature (Wilson's syndrome), and producing a variety of metabolic imbalances associated with poor thyroid hormone utilization (10).
 

Induction of bacterial resistance

2-Hydroxydiphenyl esters are broad spectrum antibacterial substances that have been used for decades. The cellular target for their antibacterial properties is the enoyl-acyl carrier protein reductase (fabI) component of the type II fatty acid synthetase system. As a result, the fatty acid synthesis is blocked. Resistance mechanisms however include an upregulation of fabI expression and spontaneous missense mutations in the fabI gene. That suggests that their widespread use will predispose for resistant bacterial populations (13, 14).

Reduction of sodium lauryl sulfate skin irritation

Some data indicate a reduction of the irritative potential of sodium lauryl sulfate when used in combination with triclosan (15).

References

08-01-2012 (JRM) -  www.huidziekten.nl