The Debate on Carcinogenicity of Permanent Hair Dyes: New Insights
Published in: Critical Reviews in Toxicology, Volume 37, Issue 6 July 2007 , pages 521 - 536
Authors: Hermann M. Bolt; Klaus Golka
Affiliation: Leibniz Research Centre for Working Environment
and Human Factors, Dortmund, Germany
Abstract
Oxidative
(permanent) hair dyes contain one or several “primary intermediates”
(e.g., p-phenylenediamines, p-aminophenols) and “couplers” (e.g.,
m-aminophenols, m-hydroxyphenols). In the presence of peroxide, the primary
intermediate(s) and the coupler(s) undergo a chemical reaction to form colored
oligomers. In the 1970s a number of aromatic amines used in oxidative hair dyes
were identified as mutagenic and/or carcinogenic in rodents after lifetime oral
administration. In response, regulatory action was taken, and some hair dye
ingredients were banned in the European Union. Although recent results suggest
that the main “primary intermediate” of oxidative hair dyes, p-phenylenediamine,
has a weak genotoxic potential in vitro, it was not mutagenic in a mixture with
nonmutagenic couplers, if tested under conditions comparable to those of practical
use. Under conditions of use of permanent hair dyes, between 0.1 and 0.5% of
the applied p-phenylenediamine may be absorbed through the skin. Acetylation
in the skin is a key metabolic step for the primary intermediates p-phenylenediamine
and p-aminophenol. Because of the involvement of aromatic amines, the discussion
on the carcinogenicity of hair dyes in humans has been focused on urothelial
cancer. Numerous epidemiological studies have investigated the risk of bladder
cancer associated with the profession as a hairdresser, as well as the risk
to consumers of hair dyes. Although some earlier studies suggested an overrepresentation
of bladder cancer in male hairdressers, the majority of modern studies do not
show an increase in relevant bladder cancer risk for professional or personal
use of oxidative hair dyes. Today, there seems to be no relevant bladder cancer
risk from the use of oxidative hair dyes. Such a conclusion can be derived from
new toxicokinetic and metabolism investigations and is in general accordance
with current epidemiological data. Human urothelial cancers, chemically induced
by aromatic amines, have typical latency times often longer than 20 years. Since
earlier exposures could have an impact decades later, the possibility of bladder
cancer in hairdressers having intensively worked with permanent hair dyes during
earlier decades (prior to the 1980s) should be taken into account.
Keywords: Carcinogenicity; Genotoxicity; Hairdressers; Hair Dye Consumers; Hair Dyes; p-Aminophenol; p-Phenylenediamine; Skin Absorption; Urothelial Cancer