Neurotoxic Effects from Exposure to Organic Solvents

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Neurotoxic Effects from Exposure to Organic
Solvents
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Organic Solvent
Solvent any substance that dissolves another
substance resulting in a solution. Solvents may
be aqueous (water-based) or organic
(hydrocarbon-based). An organic solvent is
lipophilic and a volatile liquid at room
temperature. Organic solvents are most commonly
used for cleaning, degreasing, thinning.
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Methyl Ethyl Ketone
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Perchloroethylene
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Trichloroethylene (TCE)
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Toluene
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Peripheral Neuropathy
This is not a common consequence of severe
solvent exposure, exceptions being exposure
to n-hexane carbon disulphide methyl-n-butyl
ketone styrene trichloroethylene n-Hexane is
widely used in quick drying rubber cements,
glues, inks and varnishes and may only be
revealed when a material safety data sheet (MSDS)
is obtained from the manufacturer.
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Central Nervous System Effects
Acute Central Nervous System Effects Almost all
volatile lipid-soluble organic chemicals cause
general non-specific depression of the CNS (or
general anesthesia). Beginning with ethyl ether a
number of industrial solvents were used
historically as surgical anesthetics.
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Central Nervous System Effects(continued)
Acute Central Nervous System Effects Clinical
Findings Symptoms and Signs headache, nausea
vomiting, dizziness, light-headedness, vertigo,
disequilibrium, slurred speech, euphoria,
fatigue, sleepiness, weakness, irritability,
nervousness, depression, disorientation, and
confusion loss of consciousness and death (from
respiratory depression) secondarily, an
increase in risk of accident
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Chronic Neurobehavioral Effects Of Exposure To
Organic Solvents
Acute neurobehaviorial effects of solvents have
been long recognized and accepted. Controversy
concerns potential chronic effects including the
reversibility of any such effects. In the 1970s
and early 1980s, a series of case control studies
conducted almost entirely in Scandinavian
countries mostly among painters reported
significant associations between chronic,
irreversible neurobehavioral effects including
dementia and putative workplace exposure to
organic solvents. Some reported a clear dose
response suggesting that current exposure limits
were inadequate to protect against these effects.
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Chronic Toxic Encephalopathy
The described disease entity was labeled as
painters syndrome, or psycho-organic
syndrome or more broadly (solvent -related)
chronic toxic encephalopathy. Characteristic
described features were long-term low to
moderate level solvent exposure, neuropsychiatric
symptoms (fatigue, memory impairment,
concentration difficulties) defects in perceptual
and psychomotor functions tests frank dementia in
severe cases Other features sometimes described
included brain atrophy changes in regional
cerebral blood flow changes in cerebrospinal
fluid proteins
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Chronic Toxic Encephalopathy
Many of these studies were criticized for
purported lack of adequate control of confounding
and inaccurate assessment of exposure. Similar
studies conducted in other countries, especially
the United States, produced much more mixed
results. Because of these concerns, several
important consensus conferences were held in the
early to mid-1980s. While many of the
controversial issues were not resolved, there was
agreement on common nomenclature.
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1985 International Solvent Workshop Classification
Type 1 (the least severe) Characterized by
fatigue, memory impairment, irritability,
difficulty in concentrating, and mild mood
disturbance. This corresponds to the WHO
classification of organic affective syndrome. It
is reversible on removal from exposure.
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Clinical Manifestations and Causes of CNS
ConditionsII. Chronic syndromes
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1985 International Solvent Workshop Classification
Type 2 Symptoms of neurotoxicity and
abnormalities of performance on
neuropsychological testing. Type 2 disorder has
been subdivided into Type 2A sustained
personality or mood change Type 2B impairment in
intellectual function. This level corresponds to
the WHO classification of mild chronic toxic
encephalopathy.
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Clinical Manifestations and Causes of CNS
ConditionsII. Chronic syndromes (continued)
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Clinical Manifestations and Causes of CNS
ConditionsII. Chronic syndromes (continued)
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1985 International Solvent Workshop Classification
Type 3 (most severe) Global deterioration in
intellectual and memory functions
(dementia). This corresponds to the WHO
classification of severe chronic toxic
encephalopathy and is usually irreversible.
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Clinical Manifestations and Causes of CNS
ConditionsIII. Severe chronic toxic
encephalopathy (dementia)
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Chronic Toxic Encephalopathy
At a scientific meeting in Montreal in 1990, the
following summary statement was presented A
critical review gives convincing evidence that
long-term occupational exposure to solvents may
lead to chronic disorders of the nervous system
in man. Firstly, studies independent of each
other indicating a chronic disorder by far
outnumber the few studies which do not indicate
an effect. Secondly, the non-confirming studies
do not differ in scientific quality from the
other studies compensating for quantity. Thirdly,
quantitative and qualitative differences in
solvent exposure may explain differences in study
results.
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Chronic Toxic Encephalopathy
More recently (1994), a review has been carried
out by Edward Baker at the CDC, Atlanta, of
research performed since 1985. This review found
a consistency between the studies and with
studies published before 1985 and demonstrated
short-term memory and psychomotor functional
damage as well as a dose-response relationship.
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Chronic Toxic Encephalopathy
The neurobehavioral effects noted in this review
were solvent-exposed workers demonstrate
decrements in short-term memory and psychomotor
functions in most studies there was a
dose-response relationship the neurobehavioral
defects are similar to those seen in heavily
exposed solvent workers and those with pronounced
neurobehavioral dysfunction due to solvent abuse.
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Critical Issues in Assessing Studies Of
Neurotoxic Effects of Organic Solvents
1. To which specific agent or combination of
agents are the study subjects potentially
exposed? 2. What are the levels of exposure to
these agents? Is reliable quantitative data
available? How and with what confidence were
exposure levels estimated? Are the levels of
exposures sufficient to reasonably expect that
they could produce the outcomes being evaluated?
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Critical Issues In Assessing Studies Of
Neurotoxic Effects Of Organic Solvents
3. What is the overall study design? If the
study is cross-sectional or case control (as
opposed to prospective within inception cohort)
are issues of selection bias addressed
adequately? Also, are the solvent exposed and
solvent unexposed comparable with respect to
confounding exposures prior to and during the
period of employment? 4. Which domains of
neurobehavioral response are reported as been
affected by exposure? Is their consistency in
the pattern of the affected domains across
various studies?
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Chronic Solvent Toxic Encephalopathy
Diagnosis of Chronic Solvent Toxic
Encephalopathy Like all occupationally-related
conditions the following procedures are necessary
to make an occupationally-related diagnosis of
chronic solvent toxic encephalopathy 1. A
careful occupational history and possibly
including a workplace visit and measurement of
the environmental hazard.
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Chronic Solvent Toxic Encephalopathy
2. A careful clinical history noting any
temporal relationship between exposure and
symptoms and utilizing the 1985 International
Solvent Workshop Classification.
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Type l and 2 disorders are the most likely to be
reported among solvent-exposed workers. Type 3
disorders have largely been restricted to
individuals who have abused solvent-containing
products (by deliberately inhaling organic
solvent vapors for their euphoric
properties). For example, persons who abusively
inhaled toluene almost daily for 1-7 years showed
evidence of severe, multifocal CNS damage with
cortical, cerebellar, and brain stem atrophy,
electrophysiologic abnormalities, and
neuropsychologic deficits (Lazar et al. 1983).
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Chronic Solvent Toxic Encephalopathy
3. Measurement of central nervous system
impairment with objective changes in
neuro-psychological tests carried out by a
clinical psychologist with experience in testing
solvent-affected workers.
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Chronic Solvent Toxic Encephalopathy
4.Other investigations such as EEG, evoked
potentials, electroneuro-myography, computed CT,
MRI etc. 5.The exclusion of other causes for
chronic neurotoxic effects. The diagnosis should
thus be made on an assessment of a range of
investigations and a final consensus rather than
on any one particular result.