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Risk Assessment is another type of causation: predicting whether an exposure, usually in a population rather than a single individual, will increase the risk of developing some adverse health effect, without necessarily determining whether such health effect actually occurs. Risk means that all such exposed individuals are more likely to develop an adverse effect, but it does not mean that any particular individual will or even that the majority of individuals will. Smoking, for example, increases risk of lung cancer from approximately one in 100 to 1 in 10--a signficiant increase. Nevertheless, ninety percent of smokers do not develop lung cancer, even though they are all at increased risk. Risk Assessment is used by regulatory agencies, such as the EPA, to determine how much of a chemical can be released into the environment without causing an unacceptable increase in risk of an adverse effect. 'Unacceptable' is more of a policty decision than a scientific one.
Specific causation analysis can be divided into the following three components:
(1) Hazard Assessment
(2) Exposure Assessment
(3) Health Assessment
(1) Hazard Assessment: what harm can the chemical cause, based on intrinsic toxicity and circumstnaces of exposure, form of chemical (gas, liquid, solid) and susceptibility of individual.
(2) Exposure Assessment how much of the chemical is in a media (air, water, food, soil) available to be taken into the body? Is this a one-time or multiple exposure? Does it occur over a short period of time (acute) or over many months or years (chronic)? How does the length of exposure affect the toxicity of the chemical? How much of the chemical gets absorbed into the body (dose), and where in the body does it end up (distribution and target organ/tissue)?
(3) Health Assessment: what type of health effect develops (or gets exacerbated), and does this occur immediately or after a delay (lag time)? Is this a new effect in the individual or is there a history of this type of problem, made worse by the chemical exposure? Is the individual in a high risk group (in utero, infant, elderly, reduced immune function)? Are there other (alternative) known causes for this problem and were these causes present ?
Hazard Assessment
Other studies have similarly linked manganese fume exposure to Parkinsonism or related syndromes. Ono et al (2002) reported on a 17-year-old man who was a welder, chronically exposed to manganese fumes, showing myoclonic involuntary movement (IVM) primarily in the upper and lower extremities on the right side. T1 MRI’s showed high intensity signals in the globus pallidus. This was identified in the peer reviewed article as the first such reported instance of chronic Mn poisoning, reflected by elevated levels of manganese in the blood and hair, resulting in myoclonic IVM without Parkinsonism (i.e., all previously reported cases were Parkinsonism).
A report in the International Journal of Toxicology (Sadek et al, 2003), entitled, ‘Parkinsonism due to manganism in a welder, describes a more classic case of the ‘cock walk’ syndrome in a 33-year-old welder who had experienced symptoms progressively for two years, including progressive cognitive slowing, rigidity, tremors, slowing of movement and loss of balance leading to falling. The T1-weighted MRI showed increased intensity in the basal ganglia. Testing indicated elevated levels of manganese in both urine and blood. And further inquiry revealed long term welding without use of a respirator. The paper concludes that welding can provide sufficient exposure to result in neurologic impairment.
The scientific and medical literature clearly shows that manganese poisoning is related to the condition called Parkinsonism, and likely either causes it alone or significantly contributes to its etiology. The reason courts have been slow to allow this linkage to be considered by juries—but as the recent decision by Judge O’Malley, of Federal Court in Ohio and appointed to oversee thousands of cases, indicates, is now changing—may be due to the varying collection of symptoms and a number of syndromes other than Parkinsonism. This makes a linkage with chronic manganese poisoning seem vague and difficult to pinpoint. But recent findings such as those at Mayo, which show a consistent profile of brain injury underlying the symptoms, firm up the linkage.
Lead and mercury also cause brain injury, but the issues are distinct in a number of ways. First, neither lead nor mercury have any essential role in the body as does manganese, and so are only considered toxic (and while there may be a concentration at which toxicity does not occur, there is no evidence that there is any concentration at which either of these metals plays any useful or essential role in the body).
Second, while all three chemicals can cause significant effects in adults—and do—the primary concern of mercury and lead is in young children and pregnant women (fetuses), whereas manganese poisoning is more exclusively limited to adult occupational exposure (obviously a potential problem for pregnant women or those of child bearing age who may become pregnant). The levels and timing of effect in prenatal exposures is entirely different and more complex than that in adults, especially in determining the accurate exposure assessment for the fetus.
Third, while both mercury and lead cross the blood brain barrier and also the placenta easily, either in metallic state or as an organo metallic compound (ethyl lead; methyl or ethyl mercury, usually), they do so passively, down a concentration gradient (from high—in the blood—to low—in the brain. Lead may attach to some proteins but this appears to be a minor pathway. As such, these chemicals tend to diffuse through the brain and concentrate in areas of highest fat content—the cerebral cortex. Manganese, as an essential mineral, crosses the blood brain barrier through active transport and is then carried to the parts of the brain where it is used. In poisoning this process for the most part is simply intensified. This explains the localized concentration of manganese in the globus pallidus and in the ….. and the characteristic, particular Parkinsonian type of effects seen in this type of poisoning.
Mercury and lead tend to concentrate in the cerebral cortex and in lower level, chronic poisoning (necessarily lower level to become chronic), affecting various higher end cognitive and behavioral functioning. Mercury, during, neonatal development also appears to disturb the orderly organizational neuronal structures. This produces the different effects seen in mercury and lead poisoning, and between mercury and lead.
