Research Request – Multiple Chemical Sensitivity and the impact of chlorine on Testosterone production

Is there any research or evidence for the following:

• Has Chemical Sensitivity been linked to the diagnoses listed?
• Have there been any side effects identified from salt water pool exposure
• Has Thermoregulation issues been linked to the diagnoses listed?
• Has prolonged exposure to chlorine been linked to diminished testosterone levels?
• Do diminished testosterone levels result in chemical sensitivity and/or thermoregulation issues?

Diagnoses: ABI, Epilepsy, moderate to severe static encephalopathy, hemiparesis, pan hypopituitarism, cognitive impairment, marked dysarthric speech and intractable nocturnal multi-focal seizures.

Date: 31/08/2020

Requester: Naomi (Senior Technical Advisor TAB/AAT)

Researcher: Jane (Research Team Leader)

Contents

1. What is Multiple Chemical Sensitivity (MCS)? …………………………………………………………………….. 2
2. Has Chemical Sensitivity been linked to the diagnoses listed? ……………………………………………… 4
3. Have there been any side effects identified from salt water pool exposure? …………………………. 4
4. Has Thermoregulation issues been linked to the diagnoses listed? ……………………………………….. 5
5. Has prolonged exposure to chlorine been linked to diminished testosterone levels? ……………… 5
6. Do diminished testosterone levels result in chemical sensitivity and/or thermoregulation issues?
7. References …………………………………………………………………………………………………………………….. 7

Please note: The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice.

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What is Multiple Chemical Sensitivity (MCS)?

Multiple Chemical Sensitivity (MCS) is the most common term used to describe a condition presenting as a complex array of symptoms linked to low level chemical exposures. The underlying mode(s) of action of MCS, i.e., the biological mechanisms by which the chemical sensitivity occurs, remain uncertain [1].

A common theme reported by individuals is experiences of heightened responsiveness to chemicals at extremely low exposure levels. Sufferers identify a remarkably wide and diverse range of chemical, biological and physical factors as symptom triggers. Most commonly, the literature mentions the following as potential triggers of symptoms [2]:

• Carpeting, printing ink, soft plastics, synthetic fabrics
• Chlorinated and fluoridated water
• Cigarette smoke
• Cleaning products
• Electromagnetic field
• Fragranced products such as perfumes, aftershave, and deodorants
• Pesticides
• Pharmaceutical drugs and anaesthetics
• Volatile organic compounds, including paint and solvents

Similarly, the symptoms experienced by individuals from exposures are diverse and involve multiple organ systems. Although non-specific neurological symptoms are common, overall there is no characteristic symptom profile that identifies MCS. Nevertheless, reported symptoms can, in some cases, be debilitating [2].

A study by Ross et al. [3] found that symptoms fell into three groups:

1. Central nervous system
2. Respiratory system
3. Gastrointestinal system

The table below shows the percentage prevalence of symptoms reported by Ross et al [3]:

Symptom	Prevalence (%) #
Headache	55
Fatigue	51
Confusion	31
Depression	30

Multiple Chemical Sensitivity and the impact of chlorine on Testosterone production 2 Page 14 of 335

ndis

Symptom	Prevalence (%) #
Shortness of Breath	29
Arthralgia	26
Myalgia	25
Nausea	20
Dizziness	18
Memory problems	14
Gastrointestinal symptoms	14
Respiratory symptoms	14

The percentage of MCS patients exhibiting a particular symptom

Numerous modes of action have been postulated for MCS. These include immunological changes, respiratory/neurogenic inflammation, limbic sensitisation, elevated NMDA receptor activity, altered metabolism as well as behavioural conditioning and psychological disorders [1].

At this time, worldwide, MCS is not an internationally classified disorder as the illness is not associated with objective medical findings, and mainstream medicine largely has rejected the notion that MCS constitutes a pathophysiological entity [1].

Presently, a diagnosis of MCS is based commonly on self-reported symptoms and chemical exposure histories [1]. The symptom profile of MCS is indistinguishable from other multi-symptom disorders. No laboratory tests currently exist for diagnosing MCS [1]. Different case definitions and the lack of a characteristic symptom profile and objective laboratory biomarkers for MCS have impeded recognition of the disorder as a distinct clinical entity [1].

There are no standardised treatments for MCS. Current treatments advocated for MCS include [1]:

• Dietary changes
• Nutritional supplements
• Detoxification and desensitisation techniques
• Holistic or body therapies
• Prescription medicines
• Behavioural therapies

The most common management regime for MCS is avoidance of agents that trigger symptoms [1].

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Has Chemical Sensitivity been linked to the diagnoses listed?

The pathogenesis of MCS is unknown pathogenesis. No research could be sourced supporting a direct link between the onset of MCS and:

• Head trauma/acquired brain injury
• Moderate to severe static encephalopathy
• Hemiparesis
• Pan hypopituitarism
• Cognitive impairment (memory problems and confusion are symptoms of MCS)
  • MCS often is associated with subjective cognitive complaints, but neuropsychological reviewers of MCS have concluded that there is no evidence of cognitive deficits [4, 5].
• Marked dysarthric speech
• Intractable nocturnal multi-focal seizures

A single case study has reported co-existing MCS and epilepsy [6]. However, the patient (a 23-year old female) reported that symptoms of MCS preceded the onset of epilepsy. MCS symptoms began at age 1 (gastrointestinal symptoms and/or change in body temperature induced by the smell or ingestion of causative chemicals) and started to suffer partial seizures at age 17. The delivery of the anti-epileptic drug Levetiracetam improved recurrent symptoms of MCS. The authors note that further randomised trials are required to confirm the efficacy of this treatment.

There is an overlap in symptomology and clinical findings between MCS, fibromyalgia and chronic fatigue syndrome which are also conditions which are medically unexplained [7]. One study found that a diagnosis of fibromyalgia and chronic fatigue syndrome are common among MCS patients (75% and 85% respectively) [7].

Have there been any side effects identified from salt water pool exposure?

A saltwater pool is an alternative to a traditional chlorine pool. Although you don’t add chlorine tablets to a saltwater pool, it does still contain chlorine. It just has a smaller amount that’s generated through the filter system.

Since chlorine is still present in the pool (just at a lower level), there are still the negative side effects associated with chlorinated pools [8]. These include but aren’t limited to the chlorine smell, irritation to the swimmers eyes and lungs, and bleaching of swimsuits and pool covers. Prolonged exposure to chlorine, especially to children, can lead to “swimmers lung” and

Multiple Chemical Sensitivity and the impact of chlorine on Testosterone production

asthma. Since the levels of chlorine are lower than that of a traditionally chlorinated pool, these side effects are minimized.

Some blog posts have suggested that saltwater can reduce skin inflammation and calm the immune system, however, this is just opinion rather than scientific fact.

4. Has Thermoregulation issues been linked to the diagnoses listed?

Several aetiologies related to endocrine imbalances may cause decreased heat production. These include hypopituitarism/panhypopituitarism, hypoadrenalism, and hypothyroidism. Other causes include severe malnutrition or hypoglycemia and neuromuscular inefficiencies seen in the extremes of age [8, 9].

A variety of causes may also be associated with impaired thermoregulation, but, generally, it is associated with failure of the hypothalamus to regulate core body temperature. This may include Panhypopituitarism which is due to inadequate or absent production of the anterior pituitary hormones. It is frequently the result of other problems that affect the pituitary gland and either reduce or destroy its function or interfere with hypothalamic secretion of the varying pituitary-releasing hormones [8, 9].

5. Has prolonged exposure to chlorine been linked to diminished testosterone levels?

Rodent studies have demonstrated that at high doses several chlorination by-products among the haloacetic acids (HAAs) and haloacetonitriles (HANs) and trihalomethanes (THMs) can damage the testes and disrupt spermatogenesis [10-13]. Although there is a widespread human exposure to these potential toxins, to date, only two epidemiological studies have assessed their possible impact on testicular function.

Investigating a small cohort of healthy volunteers, Fenster et al. (2003) [14] found that exposure to THMs in tap water was associated with decreased sperm mobility but these findings were not confirmed by Luben et al. (2007) [15]. However, these two studies addressed the risks via the consumption of drinking water.

Only a single cross-sectional study could be located that investigated the associations between testicular hormones at adolescence and the exposure to chlorination by-products when attending chlorinated swimming pools [16].

• 361 school male adolescents (aged 14–18 years) in Belgium who had visited swimming pools disinfected with chlorine or by copper-silver ionization.

— Multiple Chemical Sensitivity and the impact of chlorine on Testosterone production — Page 17 of 335

• Parental questionnaire to determine time spent in chlorinated pools (indoor and outdoor), height and body weight and the collection of a blood sample.
• Adolescents having attended indoor chlorinated pools for more than 250 h before the age of 10 years or for more than 125 h before the age of 7 years were:
  • 3x more likely to have an abnormally low serum inhibin B and/or total testosterone than their peers who never visited this type of pool during their childhood (odds ratio, 95% CI, 2.83, 1.06–7.52, p = 0.04 and 3.67, 1.45–9.34, p = 0.006, respectively)
  • Same association wasn’t see for free testosterone

Limitations

1. Potential for individual characteristics to influence results such as height, weight, breast fed as a child, parental smoking, difference in percentage/time spent at indoor and/or outdoor chlorinated pools which were all significantly different between the 3 included groups of adolescents
2. Testosterone level continues to change up until the age of 17 (mean age 15.5) which means lifetime testosterone levels may not be impacted
3. Tanner stage (sexual maturity rating) or the testes size were not measured
4. Sample size was moderate in size. Larger sample may elicit different results

6. Do diminished testosterone levels result in chemical sensitivity and/or thermoregulation issues? No research could be sourced which supports a link between diminished testosterone levels, the onset of MCS and/or thermoregulation issues.

References

• National Industrial Chemicals Notification and Assessment Scheme. Multiple Chemical Sensitivity: Identifying Key Research Needs; National Industrial Chemicals Notification and Assessment Scheme, Australia; Office of Chemical Safety and Environmental Health, Australia. OCSEH: Canberra, Australia. 2010. Retrieved from http://www.sacfs.asn.au/download/MCS_Draft_Report_Feb_2010_PDF.pdf
• Department of Health and Ageing, Government of South Australia. A review of the Multiple Chemical Sensitivity (MCS) Guidelines for South Australian Hospitals 2010. Retrieved from https://www.sahealth.sa.gov.au/wps/wcm/connect/ff826a004f0e15b79823fe9ea2e2f365/MCS+hosp+Guideline+Review+report+2016.FINAL.pdf?MOD=AJPERES&ACHEID=ROOTWORKSPACE-ff826a004f0e15b79823fe9ea2e2f365-n5hB6SU
• Ross GH. History and clinical presentation of the chemically sensitive patient. Toxicology and Industrial health. 1992 Jul;8(4):21-8.
• Bolla KI. Use of neuropsychological testing in idiopathic environmental testing. Occupational medicine (Philadelphia, Pa.). 2000;15(3):617-25.
• Labarge AS, McCaffrey RJ. Multiple chemical sensitivity: a review of the theoretical and research literature. Neuropsychology Review. 2000 Dec 1;10(4):183-211.
• Kakisaka Y, Jin K, Fujikawa M, Kitazawa Y, Kato K, Nakasato N. Levetiracetam improves symptoms of multiple chemical sensitivity: Case report. The Journal of Medical Investigation. 2017;64(3.4):296-8.
• Ziem G, McTamney J. Profile of patients with chemical injury and sensitivity. Environmental Health Perspectives. 1997 Mar;105(suppl 2):417-36.
• Darress, A. Salt Pools: Fact and Fiction. 2016. Retrieved from https://clearcomfort.com/blog/salt-pools-fact-fiction/#:~:text=Since%20chlorine%20is%20still%20present,of%20swimsuits%20and%20pool%20covers
• Aminoff, Michael J., and Josephson, S. Andrew. Aminoff’s Neurology and General Medicine. 5th ed., 2014.
• Children’s Hospital of Philadelphia. Panhypopituitarism in Children. 2020. Retrieved from https://www.chop.edu/conditions-diseases/panhypopituitarism-children
• Abdel-Nahab MH. (2003) Testicular toxicity of dibromoacetonitrile and possible protection by tertiary butylyhydroxyquinone. Pharmacol Research 47, 509–515.
• Linder RE, Klinefelter GR, Strader LF, Suarez JD, Roberts NL & Dyer CJ. (1994) Spermatotoxicity of dibromoacetic acid in rats after 14 daily exposures. Reprod Toxicol 8, 251–259.
• Linder RE, Klinefelter GR, Strader LF, Narotsky MG, Suarez JD, Roberts NL & Perreault SD. (1995) Dibromoacetic acid affects reproductive competence and sperm quality in male-rat. Fundam Appl Toxicol 28, 9–17.

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Multiple Chemical Sensitivity and the impact of chlorine on Testosterone production

14. Linder RE, Klinefelter GR, Strader LF, Suarez JD & Roberts NL. (1997) Spermatotoxicity of dichloroacetic acid. Reprod Toxicol 11, 681–688.
15. Fenster L, Waller K, Windham G, Henneman T, Anderson M, Mendola P, Overstreet JW, Swan SH. Trihalomethane levels in home tap water and semen quality. Epidemiology. 2003 Nov 1:650–8.
16. Luben TJ, Olshan AF, Herring AH, Jeffay S, Strader L, Buus RM, Chan RL, Savitz DA, Singer PC, Weinberg HS, Perreault SD. The healthy men study: an evaluation of exposure to disinfection by-products in tap water and sperm quality. Environmental health perspectives. 2007 Aug;115(8):1169–76.
17. Nickmilder M, Bernard A. Associations between testicular hormones at adolescence and attendance at chlorinated swimming pools during childhood. International journal of andrology. 2011 Oct;34(5pt2):e446–58.