In the wake of germophobia: the use and misuse of antibacterial agents

Next time you buy an antibacterial hand soap, think about the antibacterial agent lasting in the environment for decades..Giving reign to resistant bacterial strains

Hand sanitizers and antibacterial hand soaps gained overnight fame, any starlet would covet, after the swine flu epidemic. The most common active ingredient found in the house hold soap bar or hand-wash is Triclosan (TCS), has been in use for over 40 yrs and is the perpetrator behind the claim of 99.9% effectiveness in killing germs. Its first use being in the 70s for surgical scrubs. It has been a decade since its potential as a hazardous environment pollutant began to be scrutinized by environment protection agencies. However, that is not the only black mark against its use, as its potential and multi pronged negative effects on human physiology are being ascertained by scientists worldwide.

Triclosan effects on calcium ion release: reduced muscle contraction

Emerging data shows that TCS, at a concentration close to that has been found in human blood, urine and breast milk can alter physiology in several types of animal models. The latest report demonstrates its inhibitory effects on contraction in voluntary (skeletal) and involuntary (cardiac) muscle. ‘Structurally TCS is related to non dioxin like organic pollutants, that are known neurotoxins. We have been interested in them for over 15 yrs,’ explained Dr. Isaac N. Pessah, University of California, Davis, U.S., when asked how their interest had alighted on TCS.

To move muscles, of the heart (involuntary) or  while lifting a weight or simply walking or sitting (voluntary), muscle cells receive an electrical signal sent by a nerve cell to instigate contraction. Then the cell membrane of the muscle cell gets depolarized and calcium ions are released into the cytosol, causing the required contraction and the movement. This is called excitation- contraction (EC) coupling . Any dysregulation of EC coupling can cause slower or less powerful contraction of the heart, frozen movements or in fact  inability to move, or hold things.

Mice exposed to a variety of doses  of TCS  had reduced heart function, including reduced cardiac output (how much blood flows out of the heart) and lower left ventricular end diastolic volume. A 25% or 1/4th reduction in cardiac output is seen in mice treated with the highest dose of 25mg/kg of TCS.

Next, the effects of TCS on skeletal muscle that regulate body movement was tested using  a standard test , known as the grip strength test. In this test mice are allowed to hold on to a metal mesh wire using all four limbs, the mesh is attached to a meter that estimates the force of the grip. Treatment with TCS reduced the grip strength of the same mice to about 18% of what it was prior to treatment. Finally, to test its effects on animals that are the directly affected by aquatic pollutants, the fat head minnow was used.  Larval fathead minnows were exposed to TCS in their swimming water for 7 d at different concentrations. There was significant reduction in swimming ability in almost all concentrations used.

Experiments with rodent cardiac and skeletal muscle cells showed that TCS impairs excitation –contraction coupling by causing a depression in release of calcium ions that bind physically to muscle proteins called actin to cause contraction. Prolonged exposure to TCS can lead to complete loss of calcium ion release. This has serious implications for heart failure in humans. Further experiments using radiolabelled TCS indicated that it binds to specialized Ryanodine receptors that regulate calcium ion flow and  therefore cause inhibition of calcium ion release.

Hormonal changes by Triclosan

The use of TCS is not restricted to just personal care products. Dr. Caren Helbing, University of Victoria, British Columbia said, “Triclosan is used in many medical devices such as heart valves for example, local concentrations around heart tissue could actually be higher than what is measured systemically. Additionally, triclosan is being incorporated in children’s high chairs, many types of fabrics etc that do not necessarily provide any benefit, but increase environmental hazard.” Her laboratory has shown the effect of TCS exposure on regulation of thyroid hormone in the bull frog in 2006. In 2009 and 2010 laboratories associated with the US Environmental Protection Agency demonstrated that exposure to triclosan causes abnormal sex hormone regulation and reduction in thyroid hormone levels in both male and female rats.

However, as hormonal physiology has significantly diverged between rodents and humans, that data could not be used to afford a government regulation or ban on consumer products. Musle contraction on the other hand is a highly conserved mechanism. “EC coupling is a fundamental mechanism by which muscle regulate contraction in all species. So what we find in mice should be relevant to the human condition,” said Dr. Pessah adding, “of course this need further investigation.” Their lab will pursue the effects of long term exposure to TCS as prolonged disruption of EC coupling can lead to heart failure. Their current results were published in Proceedings of National Academy of Sciences in August 2012.

TCS and related compounds are known to persist in the environment for decades as they are degraded  slowly.  A recent survey carried out by the Arizona State University (ASU), U.S., partnering with the U.S. federal government in the fresh water bodies of Minnesota. found presence of TCS and the related triclocarban (TCC) in all the water sources tested and the soil/ sedimentation tested positive here as well.  The study was conducted by the laboratory of Dr. Rolf Halden at ASU and was published in the Journal of Hazardous Materials, August 2012.

Long term presence in the environment may cause the increase of resistant bacterial strains that are potentially more aggressive human pathogens.

Even so, consumer companies do not abide this scientific data and await government regulation. “Unilever currently uses triclosan in a limited number of products. These products provide real benefits to consumers and we are in line with regulatory limits worldwide, including EU cosmetic directive,” said a spokesperson from Hindustan Unilever, which has popular products like lifebuoy hand soap and bathing soap. “We will continue to monitor and review the situation for triclosan and take part in the research for a better understanding of the potential risk associated with these applications,” he said.

There is an alternate reality. “An expert panel, convened by the US FDA in 2005, found that TCS does not provide any benefit to the average consumer. This new research from Dr. Pessah’s lab only adds to the extensive body of literature on potential human health risks and documented environmental pollution from widespread use of the antimicrobial triclosan,” said Dr. Halden, who was part of the 2005 committee “It is time to curtail triclosan use back to clinical and hospital uses, where its application can be reasonably justified,” he said in summation.

The US FDA is scheduled to come up with a directive for future use of TCS this winter. In the meanwhile, Dr. Halden and Dr. Helbing agree that limiting consumer usage of antibacterial agents is the best way to handle these pollutants.

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