This study has been undertaken robustly and the experimental findings are reasonable. Note that the authors study only mice, and draw conclusion only on mice. Their comments on human health are very circumspect

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Expert reaction to new study on triclosan and tumours in mice
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Dr Nick Plant, Reader in Molecular Toxicology at the
University of Surrey, said:
• “This study has been undertaken robustly and the experimental findings are
reasonable. Note that the authors study only mice, and draw conclusion only on
mice. Their comments on human health are very circumspect.
• “As the authors state, it is difficult to assess if the dose that they use in mice is
relevant to human exposure levels, but at a simple examination it appears to be
much higher than I would expect to see in a human. This further complicates
extrapolation to the human situation as we are not comparing equivalent
exposures.
• “However, the authors do not address a key point in their paper, which is whether
the proposed mechanism is conserved across species. The previously reported
effects of triclosan on the nuclear receptor PPARalpha do not impact human
health as the PPARalpha signalling pathway is different between rodents and
humans (and the authors dispute these anyway). In this paper, the authors suggest
that the tumourogenic mechanism is via another nuclear receptor CAR. For this
nuclear receptor there is also a considerable species difference in response, with
chemicals (including carcinogens) acting differently between rodents and man.
• “On this basis, it is not valid to state that the effect of triclosan in mice will occur
in humans as well, indeed the historical body of evidence suggests a species-
dependent effect is more likely. However, as with all new signals, it is important to
examine them and decide if they are biologically plausible in the species of
concern (in this case humans). I would treat this paper as interesting, but would
not see it as the basis for a shift in triclosan use at present. There are simply too
many unanswered questions as to whether the findings are relevant to humans,
and indeed the body of evidence currently suggests that they are not.”
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Dr Oliver A.H. Jones, Lecturer in Analytical Chemistry at
RMIT University Melbourne, said:
• “The results of this study are certainly interesting but I do not think they are a
cause for concern for human health.
• “Firstly the mice used in the study were primed with a tumor promoting
chemical before being exposed to triclosan (which humans would not be) and
the concentrations of triclosan used were much higher than those found in the
environment.
• “It is also worth remembering that mice are not mini humans and what
happens in a mouse liver is often very different from what happens in human
livers, or even in those of other rodents. For example, previous studies on rats,
and hamsters treated with triclosan did not show any tumor formation at all.
Thus the present study, whilst interesting, does not show the full picture.”
• “The results of this study are certainly interesting but I do not think they are a
cause for concern for human health.
• “Firstly the mice used in the study were primed with a tumor promoting
chemical before being exposed to triclosan (which humans would not be) and
the concentrations of triclosan used were much higher than those found in the
environment.
• “It is also worth remembering that mice are not mini humans and what
happens in a mouse liver is often very different from what happens in human
livers, or even in those of other rodents. For example, previous studies on rats,
and hamsters treated with triclosan did not show any tumor formation at all.
Thus the present study, whilst interesting, does not show the full picture.”
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Prof Tony Dayan, Emeritus Professor of Toxicology,
University of London, said:
• “The report describes a sophisticated set of investigations into the molecular biological and
pathological consequences of prolonged exposure of laboratory mice to TCS, culminating in
promotion of the development of liver cancer in mice pre-treated with a powerful cancer-
causing chemical, i.e. tumours occurred more often in mice co-treated with TCS over a long
period.
• “The authors themselves point out that the dose of TCS was very considerably higher than
the average amount that humans might ingest from toothpaste and other products or in
drinking water if the normal procedures of water purification had not removed any that
might have been present in raw water sources. They did not explore whether lower doses
had similar actions nor did they investigate the relevance of the gene changes shown to
human tumour development.
• “High doses of many substances have been shown to act as ‘promoters’ of liver tumours in
experimental animals, including a number that have been sufficiently well studied to show
that the same effect has not occurred in humans, including phenobarbitone, a well known
treatment for certain types of seizures, and certain other medicines.”
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Prof Alan Boobis, Professor of Biochemical Pharmacology,
Imperial College London, said:
• “This is not the first study of the carcinogenicity of triclosan, even in mice.
Previous, guideline compliant, studies have established that triclosan is
carcinogenic to the liver of mice but not to rats or hamsters. The mechanism of
tumour formation has not been established, but it does not involve damage to
DNA (genotoxicity). The present study extends information on the possible
mechanism for liver tumours in mice. This appears to involve initial damage to
the liver, leading to fibrosis which then acts to exacerbate any pro-carcinogenic
incidental or induced DNA damage, by compounds that can interact directly
with DNA.
• “The dose used in the present study was similar to that at which tumours had
been observed previously in mice. Studies in primates showed no hepatic
damage at doses greater than those used in the present study, when
administered for 12 months. Whilst it is possible that the carcinogenic effect in
mice is relevant to humans, it should be noted that mouse liver tumours are
induced by many chemicals, and often they are not relevant to humans. Further
information on the mode of action for the liver tumours observed in the present
study would be necessary to determine the relevance if any for triclosan.
• “Notwithstanding this uncertainty, the tumours in mice are secondary to hepatic
damage, an effect that shows a threshold. Hence, ensuring exposure to triclosan
is below that causing liver damage would be more than sufficient to avoid the
risk of any carcinogenic effects in humans.”
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Prof Sir Colin Berry, Emeritus Professor of Pathology at
Queen Mary University of London, said:
• “Triclosan is metabolised in the liver by sulphation and glucuronidation; i.e.
groups are added to the compound to make it soluble enough to excrete. So this
is work for liver cells (like alcohol) and if you have damaged them, any continued
stimulus to activity will result in growth with increased tumour numbers in
experimental situations where DNA damage has been induced. Tylenol uses the
same mechanisms and would probably act in the same way.
• “Initiation and promotion are long standing concepts in oncogenesis but
anything increasing division rates in liver cells will work – more cirrhotics get
hepatocellular cancer now as we keep them alive longer with their liver nodules
growing.”
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