Solvent Syndrome

For nearly 28 years, Patrick (who has requested that his last name be withheld for privacy reasons) serviced typewriters, printers, coin counters and other business machines for a succession of different employers across southern British Columbia. He would pull out parts, soak them with a solvent-based cleanser and then blast them clean with compressed air. He would drop particularly gummy bits into an open tub filled with a mixture of solvents.

For a time, he worked in a small, unventilated storage locker located in one company’s underground parking garage, spending most of the day in a haze of volatile chemicals, floating dust and engine exhaust, notes a decision by the Workers’ Compensation Appeal Tribunal, released on June 12, 2008.

The rags, soaked with lacquer thinner that Patrick carried from job to job, would routinely eat through the bottom of his plastic tool box. He says his boss was “pissed” because he had to replace it every six months or so. Most of the time, he did not use a ventilator or wear gloves, so he often suffered from burning eyes and dry skin. By the late 1990s, he was also beginning to exhibit the classic neurotoxic effects of long-term exposure to the solvents and cleaners he used every day.

“I would get these ‘brain farts’ where I couldn’t focus or pay attention to detail,” Patrick says. It might be just a little mistake, like putting reel number two into slot number three, but when one is fixing gaming machines for the British Columbia Lottery Corporation, that could cause “real bad problems.”

He was also easily distracted, his thoughts scattered and erratic. He would tell his wife a story and, 10 minutes later, tell it again. He was depressed, under stress and quick to anger — often over trivial incidents. “I became a hothead all of a sudden,” Patrick says. The police were called to his home several times to calm loud arguments, and there were episodes of road rage.

His doctor diagnosed him with a neuro-affective disorder due to exposure to organic solvents and cleansers, while a psychiatrist provided a working diagnosis of “personality change (aggressive type) due to solvent exposure.” His deteriorating condition forced him to leave work for good in 2004, shortly after the birth of his third child.

Patrick first applied for workers’ compensation in 1999, but the claim was suspended due to “a lack of medical information.” He reapplied in 2006, but was rejected, and filed an appeal in October 2007. Finally, in June 2008 — after nine years of battling the system — his claim was approved.

These days, Patrick stays home and takes care of his kids, while his wife works. “I have got a big calendar on my fridge and five sheets of paper listing everything I am supposed to do each day of the week,” he says. “When I am doing my exercises and following my routine, things work out okay. But I spent my whole life working on machines. I loved my job, and I miss it.”

Lasting Effects

Patrick’s case is by no means unique. Thousands of workers have suffered the short-term effects of excessive exposure to solvents — giddiness and euphoria for some, apathy and confusion for others — along with diminished powers of concentration and coordination, fatigue, irritation, depression and shifts in mood and personality. It was long believed that these effects were transitory: when the exposures ended, the symptoms went away.

But recent research has shown that many of these cognitive problems can linger for years — even decades. And like Patrick, much of the damage appears to be permanent.

According to a recent study of retired French utility workers, the past use of industrial solvents can be directly linked to lower scores on a series of standardized cognitive tests used to track dementia and Alzheimer’s disease. The findings of the study, Time May Not Fully Attenuate Solvent-Associated Cognitive Deficits in Highly Exposed Workers, were published in the May 2014 issue of Neurology.

“I was surprised by the results. Individuals who had been highly exposed 20, 30 or even 40 years before our testing were still exhibiting symptoms,” says the study’s lead author, Dr. Erika Sabbath, research fellow at the Harvard School of Public Health in Cambridge, Massachusetts. “The neurological effects had not faded away the way we thought they would.”

Of the 2,143 retirees who underwent cognitive testing in 2010 as part of the study, 33 per cent had been exposed to various chlorinated solvents on the job, 26 per cent to benzene and 25 per cent to petroleum solvents. Detailed exposure records collected by their employers, weighted by year and job classification, grouped the retirees into three categories: those who were never exposed to solvents; those who were moderately exposed; and those who were highly exposed from having received a lifetime dose at or above the median range.

The highly-exposed group scored consistently lower — often in the “impaired” range — in tests measuring verbal memory and fluency, immediate recall, psychomotor speed and natural response times, and the completion of more complex tasks requiring concentration. Although all the subjects had been retired for at least 12 years, those with the highest and most recent exposures exhibited impairments “in nearly all the tested domains, rather than only those most frequently associated with solvent exposure,” Dr. Sabbath says.

With people delaying retirement and working well into their 60s and 70s, the neurological implications can be serious.

“These are the ages when subtle cognitive deterioration [associated with aging] typically begins to occur,” Dr. Sabbath says.

Past exposure to solvents will exacerbate these cognitive deficits, “but we don’t know whether cognitive functions decline even more quickly in older workers currently exposed,” she adds, noting that more research is needed.

Mechanics of Deterioration

The brain’s 100 billion neurons are a prime target of a number of toxic agents, including mercury, lead, arsenic, carbon monoxide, several pesticides and industrial solvents. Their profuse receptor and neurotransmitter sites, as well as the complex biochemical pathways linking them, are readily disrupted. Most neurons have limited regenerative capacity, and any losses are usually permanent.

The brain is also an “energy hog”, demanding 20 per cent of the entire body’s energy budget and 15 per cent of its cardiac output. As a result, solvents in the bloodstream reach and cross the blood-brain barrier and, once there, tend to bioaccumulate in the lipid-heavy neurons.

While behavioural symptoms may appear long before any physiological damage becomes apparent, the brains of solvent abusers may provide an intriguing glimpse into the damage these chemicals cause.

A large autopsy study co-authored by Dr. Marc Del Bigio, Canada research chair in developmental neuropathology at the University of Manitoba in Winnipeg, showed that inhaling high levels of the powerful solvent toluene over several years could severely damage the white matter of the brain — the same part that is attacked in multiple sclerosis, except the damage in the latter case is caused by inflammation rather than a toxic exposure. These masses of tiny axon fibres provide electrical connections between the nerve cells of the brain and are covered by myelin, a whitish insulating material.

According to the study, Brain Damage in a Large Cohort of Solvent Abusers, published in Acta Neuropatholica in April 2010, of the 75 brain samples stained and examined, 16 showed “well-established” atrophy of the brain’s white matter — a condition known as leukoencephalopathy — with patchy losses of the myelin sheathing and the appearance of abundant macrophages.

Another six autopsied samples showed early signs of brain damage, including the rare macrophages, but without the obvious myelin loss, “suggesting that some recovery is possible in mild forms,” Dr. Del Bigio says.

“As the myelin is damaged, the body must clean up the mess,” he explains. “Macrophages are the cells that act like a ‘garbage disposal,’ picking up damaged material and helping to recycle it.” Their appearance in an autopsy examination is a marker that some kind of damage has occurred.

When the myelin insulation is partially destroyed, nerve cells cannot communicate efficiently and brain signals are slowed. Some experiments in rats indicate that nerve cells might also be lost, although Dr. Del Bigio thinks that the methods of analysis in autopsy cases might not be sensitive enough to detect subtle damage.

The most severe cases often exhibit evidence of neurological or psychiatric disease, including tremors and shakiness, impaired memory, poor balance and coordination, depression and, in the worst cases, dementia and spinal-cord damage, also known as paraplegia.

While it is difficult to extrapolate the neurological effects suffered by addicts to the lower levels seen in the workplace, the brain damage appeared to be duration-dependent and could be detected within a few years of abusing solvents.

“In our study, we saw the earliest evidence of damage in a 15-year-old child who had been known to sniff glue,” Dr. Del Bigio says. Although occupational concentrations are lower, workers may also be chronically exposed to a more complex mix of solvents over a much longer period.

New Face of Exposure

“Neurotoxicity, chronic fatigue, multiple chemical sensitivity and the ever-present mental-health problems in the workplaces — this is the ‘modern face’ of occupational medicine,” says Dr. Douglas Hamm, an occupational medicine specialist practising in Victoria.

“Many of the ‘big smokestack’ workplace problems are largely over,” he says. “But these more complex conditions have all arisen since the formation of the workers’ compensation system. It does not know how to address them.”

Dr. Hamm, who was one of the first to recognize Patrick’s neurological symptoms, sees these cases on a regular basis. But he says many of his colleagues shy away from solvent-related and other occupational neurological claims.

“The long, drawn-out battles before a [workers’ compensation] tribunal are so time-consuming and, too often, so frustrating,” Dr. Hamm says. “It is particularly challenging to try to untangle the neurological damage caused by solvent exposure from a lot of other background noise, like mood disorders or general cognitive decline.”

A whole spectrum of effects is associated with solvent exposure. In the paper, The Nervous System — Target Organ into the Twenty-First Century, Dr. Hamm notes that the World Health Organization (WHO) recognizes three progressive levels of central-nervous-system dysfunction:

• Organic Affective Syndrome: the short-term effects on mood, motivation, memory and concentration are reversible and do not show up on neuropsychological tests;

• Mild Chronic Toxic Encephalopathy: memory and psychomotor problems are more persistent, while mood, personality and behavioral abnormalities are common; and

• Severe Chronic Toxic Encephalopathy: intellectual impairments and personality changes begin to interfere with social and occupational functioning, while the more severe symptoms are usually irreversible.

“While it can be hard to define the milder neurological effects, like minor variations in mood, the diagnosis becomes easier in the more flagrant cases,” Dr. Hamm explains.

Path of Resistance

Even if one gets a diagnosis of some kind of solvent-related, neuro-affective disorder or chronic toxic encephalopathy, there are “many more roadblocks” to obtaining compensation for a neurologically damaged worker, says Maryth Yachnin, staff lawyer with the Industrial Accident Victims Group of Ontario in Toronto.

“If you are seeking compensation for a bad back, you don’t need reams of epidemiological evidence and recent scientific studies,” Yachnin says. “It is still possible to be successful, but these are some of the hardest cases to win, because the standard of evidence is so high.”

In addition, there can be a long delay before the symptoms become debilitating, and evidence of past exposure is very hard to reconstruct. In most cases, workplace levels were not quantified or assessed at the time the exposures began. “You are lucky if every couple of years, somebody took one or two readings, and that was probably in some other area of the plant,” Yachnin says.

Finally, it can be a challenge to present evidence of neurological effects if one is relying on the testimony of a worker who suffers from memory loss, confusion and other cognitive deficits.

“They can have good days and bad days,” she suggests. “One day, they are describing incidents and recalling details, but the next, there can be a lot of problems. They may not be consistent in reporting their symptoms or their work history, which can undermine credibility.”

As is often the case in workers’ compensation cases, there can be a wide and confusing disparity in individual sensitivities to a particular chemical agent, complicated by such confounding factors as sex, age, marital status, body mass index, smoking, alcohol consumption and an individual’s “cognitive reserves”.

According to epidemiological data from the study of a large cohort of French utility workers — this time focusing on whether the association between occupational solvent exposure and cognition vary by education level — it appears that those who had graduated from high school tended to perform significantly better on a battery of cognitive tests than those who had not, even though their exposure histories were otherwise very similar.

Within the less-educated group, there was a strong dose-response relationship between lifetime exposure to each of the workplace solvents and “poor cognition”. However, no such relationship could be detected among those with secondary education.

The authors suggest that the denser neural networks associated with education — the so-called cognitive reserves — “masked or delayed expression of changes in the brain” that followed occupational solvent exposures.

“Early education is an extremely effective way — a broad shield, so to speak — for protecting your cognitive abilities against both known and unknown toxic exposures and other factors,” Dr. Sabbath says.

An individual’s cognitive reserves depend, in part, on genetics and, in part, on the regular “workouts” the brain gets. Resiliency to neurotoxic assault might depend on “how much reading you do, how much education you have, how much travelling you do or how interesting a job you have,” explains Dr. Christopher Friesen, clinical neuropsychologist and director of the Niagara Neuropsychology Service in Grimsby, Ontario. All these activities build up the connections in the brain. The stronger the brain is wired, the more resilient it will be to the debilitating and combined effects of old age and solvent exposure.

For example, someone may have scored in the 50th percentile — almost right in the middle — on one of the standard cognitive tests his or her entire life, but once that person has been overexposed to some neurotoxic solvent, the score drops down to the 16th percentile. That is still in the lower end of the average range, but processing speed, memory and attention continue to decrease slowly, decade by decade, as one ages.

“Later in life, you will be at a disadvantage, and it is not going to take long before the effects of aging are going to be noticeable and you are going to be functionally impaired,” Dr. Friesen says.

Science of Brain Plasticity

Although one cannot travel back in time to repeat high school, there are steps that can be taken following brain damage — regardless of whether it is caused by solvent exposure, injury or disease — to ameliorate the symptoms, slow cognitive deterioration and maintain independence.

“The hottest topic in neuroscience today is brain plasticity. It is not about growing new neurons, but making better connections,” Dr. Friesen says.

To date, exercise has been shown to be the strongest, most effective method of preventing further cognitive decline. But the kind of exercise is important. Rather than spending time on a treadmill staring at a blank wall, Dr. Friesen recommends learning a new dance.

“Dancing is not only good aerobic exercise; it engages your memory as you learn the steps, your emotions, your timing, your auditory senses,” he says. “There are social connections as you coordinate with your partner and even pleasurable sensations as you interact with the music.”

Changes can also be made to diet and lifestyle. Smoking, overall weight, diabetes and high cholesterol are all vascular factors that affect the amount of blood reaching the brain. “What is good for the heart is good for the brain,” Dr. Friesen adds.

Finally, there is brain training. “There are no guarantees that cognitive training will work for everyone,” he notes. “The research is mixed, but there is some evidence that these exercises can slow down the cognitive declines related to aging.”

A number of computer-based brain-training programs on the market offer puzzles, quizzes and other mental challenges. Working with a doctor or neuropsychologist, an individual would select the specific ones that match the particular cognitive deficits with which one is struggling.

“You have to be willing to do the work, three or four times a week, for, say, six weeks,” Dr. Friesen advises. “After that, if you are seeing some benefit, then continue.”

While one can delay the progression of the damage and learn coping mechanisms to compensate for mood swings or memory loss, “the scary thing is there isn’t a whole lot you can do to reverse the cognitive deterioration once it begins to show,” Dr. Sabbath says. “That is why prevention is really important.” Improved personal protective equipment, substituting dangerous solvents with less toxic alternatives and implementing engineering or administrative controls to isolate solvent-based processes are all “very doable,” she adds.

“Prevention is really straightforward,” Dr. Sabbath says. “Simply pulling on a respirator can help protect your mental capacity.”

William M. Glenn is a writer in Toronto.

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