Download Dr. Samantha Champ for BASF on Triclosan: Comments on Proposed Amendments to Rules Governing Health Risk Limits for Groundwater (PDF)

150 years BASF SE, 67056 Ludwigshafen, Germany
MinnesotaDepartmentofHealth
625RobertStreetNorth
P.O.Box64975
St.Paul,MN55164‐0975
Attention:NancyRice
E‐mail:[email protected]
October 01, 2015
Dr. Samantha Champ
E-EMD/HB
Tel. +49 621 6072140
Fax +49 621 606672140
[email protected]
Comments on Proposed Amendments to Rules Governing Health Risk Limits for Groundwater,
Minnesota Rules, Chapter 4717, Part 7500, Part 7850, Part 7860, and Part 7865
Dear Ms Rice,
This submission provides comments to the Proposed Amendments to Rules Governing Health Risk Limits
(HRL) for Groundwater, Minnesota Rules, Chapter 4717, Part 7500, Part 7850, Part 7860, and Part 7865,
as published in the Minnesota State Register Monday 31 August 2015, Volume 40, Number 9, in particular
with respect to the HRL proposed for triclosan.
This document highlights the flaw in the approach used to develop the short term HRL that has been
calculated based on a 20% reduction in tT4 in the rat, following exposure to high levels of triclosan.
In
addition, as the HRL’s for other parameters of exposure (subchronic and chronic) are based on the
outcome of the short-term health risk limit, the inappropriate use of this endpoint is further magnified.
Background
The HRL for triclosan, Section 4717.7865, sets a value of 50 µg/L, based on certain defined endpoints
and based on the Toxicological Summary for Triclosan [Health Based Value for Groundwater , [Health
Risk Assessment Unit, Environmental Health Division, Minnesota Department of Health, Web Publication
Date: August 2014]. With respect to the Toxicological Summary, we note the analysis references as the
“Point of Departure (POD): 7.23 mg/kg-d (BMDL for decreased total thyroxine (tT4) from Zorrilla et al
2009 based on a benchmark response of 20%)”, and as the “Critical effect(s): Decreased serum total
thyroxine (tT4)”. In our view use of these criteria for calculating the HRL is inappropriate.
There are several studies pertaining to the potential effects of triclosan on thyroid function (Kapelari et al.,
2008; Paul et al., 2010a; Paul et al., 2012; Paul et al., 2013). While it has been well established that
exposure to triclosan in rats produces a dose dependent decrease in serum thyroxine (T4), with decreases
in T4 shown in rats exposed to high levels of triclosan, notably this is without any consistent change in the
rat with respect to TSH or triiodothyronine (T3). Also, it is significant that toxicity testing in a variety of
species provides no basis for concluding that triclosan adversely affects thyroid function, male and female
reproductive function, gestation, or postpartum development of offspring. (Morseth, 1988; Christian and
Hoberman, 1992; Schroeder and Daly, 1992a and 1992b; Denning et al., 1992; Piekacz, 1978). There is
BASF SE
67056 Ludwigshafen, Germany
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Hans-Ulrich Engel, Sanjeev Gandhi, Michael Heinz,
Harald Schwager, Wayne T. Smith, Margret Suckale
150 years also considerable evidence that humans are more resistant to changes in circulating thyroid hormones
compared to rats. Unlike rats, humans have robust compensatory feedback mechanisms and extensive
binding capacity, both of which maintain thyroid hormone levels within a homeostatic range. Most
importantly, human studies reveal no evidence that triclosan exposure at relevant doses affects the human
thyroid system. Therefore, use of the rat model data for evaluation of potential human thyroid effects, and
for calculation of a HRL, is overly conservative and inappropriate.
Triclosan and Thyroid Hormone Homeostasis
Research supports that triclosan does not elicit an adverse effect on the human thyroid (Cullinan et al,
2012, Allmyr, 2009, Koeppe, et al, 2013). An adverse thyroid effect such as hypothyroidism has been
defined by the American ThyroidAssociation as decreased free T4 concentrations accompanied by
increased serum TSH concentrations (Surks et al., 1990). This thyroid hormone pattern has not been
seen in any known rat studies, or in any other species administered triclosan even at doses comparable
to those administered in the rat studies discussed above. It has also been suggested that the use of
thyroid weights and histology provide a better assessment of thyroid function because these endpoints are
less sensitive to confounders such as stress and diurnal variations (DeVito et al., 1999). As reviewed by
Rodricks et al. (2010), numerous sub‐chronic and chronic studies in various mammalian species showed
no evidence of thyroid enlargement, thyroid hyperplasia, or effects on reproduction and development after
triclosan exposure. For example, in subchronic studies where thyroid weights and/or histopathological
evaluations were conducted, triclosan did not produce effects on the thyroid at doses as high as 900
mg/kg/day. In addition, chronic studies in rats, mice, hamsters, and baboons showed no effects on thyroid
weight or histopathology at doses of 150 mg/kg/day, 200 mg/kg/day, 250 mg/kg/day, and 300 mg/kg/day,
respectively. In addition, if a state of hypothyroidism were developed, it would also be expected to have
adverse effects on reproduction and development. However, the findings from one- and two-generation
reproductive and developmental studies conducted with triclosan in mice, rats, hamsters, and rabbits found
no adverse effects on reproduction and development (Morseth, 1988; Christian and Hoberman, 1992;
Schroeder and Daly, 1992a and 1992b; Denning et al., 1992; Piekacz, 1978).
Further, a long term clinical study (5 years) by Cullinan et al. (2012) supports that triclosan does not act
as a disruptor of thryroid function in humans. Additionally, a study by Allmyr et al. (2009) complements
the Cullinan study and found that an estimated exposure to 0.01 mg/kg/day of triclosan for 2 weeks in
human volunteers resulted in no changes in thyroid function. Therefore, both short‐term and long‐term use
of triclosan has been shown to not disrupt thyroid function in humans.
Conclusion
Overall, while high levels of triclosan have been shown to alter T4 levels in rats, there has been no evidence
that triclosan induces adverse effects on other thyroid hormones (T3, TSH) or rat thyroid function In
addition, the findings from one- and two-generation reproductive and developmental studies conducted
with triclosan in mice, rats, hamsters, and rabbits found no adverse effects on reproduction and
development. Moreover, even the mild T4 perturbation seen in rats is unlikely to occur in humans due to
the considerable buffering capacity of the human thyroid hormone system vs. that of the rat. Consequently,
as both the stated “Point of Departure” and “Critical Effect(s)” referenced in the Toxicological Summary
are not supported by the state of the science as relevant for human health risk assessment, the HRL for
triclosan should be reconsidered.
150 years Yours sincerely,
BASF SE
Care Chemicals
Regulatory Affairs – Biocides
i.A. Dr. Samantha Champ
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