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Mercury and madhatters: Implications of dose response. Dosage and Effect. As indicated in the last lecture, the impact of trace elements on human health depends on dosage. But the manner in which the human body acquires these elements can complicate the understanding of effect.

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Presentation Transcript
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Mercury and madhatters:

Implications of dose response

slide2

Dosage and Effect

As indicated in the last lecture, the impact of trace elements on human health depends on dosage.

But the manner in which the human body acquires these elements can complicate the understanding of effect.

For example, does the dose involve high concentration exposure over a short period of time, or low concentration exposure over long periods of time. How do these effects differ ?

The effects of short-term, high concentration dosage are often readily apparent. But effects of long-term, low concentration dosage are sometimes obscure.

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Dosage and Effect

Also, effects of exposure to toxic elements can vary within populations depending on the age and health condition of individuals

For example a low dose of a particular element may have profound effects on infants, children, and the elderly…

…whereas the same dose may be relatively benign among adults.

Also, certain people can be predisposed to adverse reactions to certain elements (e.g. a person predisposed to cancer is more likely to contract cancer due to exposure to carcinogenic substances than a person who is not).

But the general symptoms are relatively consistent within population

slide4

The case of mercury

Issues related to exposure to mercury illustrate well the complexity of these factors. Mercury occurs in a variety of forms, but is always toxic in high concentrations.

  • Elemental mercury (pure mercury)
  • in liquid form, a shiny, silver-white, liquid metal that “beads”
  • In vapour form, a clear, colourless gas
  • Inorganic mercury compounds (mercury combined with chlorine, oxygen or sulphur)
  • -occurs as crystals (e.g. cinnabar HgS)
  • Organic mercury compounds (mercury combined with organic molecules)
  • -e.g. methylmercury
  • -concentrated in high amounts in large,
  • carnivorous fish near top of food chain
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Sources of mercury

Mercury occurs in a surprising variety of stuff !

Natural sources of mercury (elemental form or as mercury compounds): volcanoes, hot springs, weathering products of of some minerals in rocks.

Elemental mercury associated with human activity: thermometers, electrical switches, fluorescent lights, thermostats, barometers, batteries, dental fillings. About 80 % of elemental mercury released into the atmosphere is linked to fossil fuel combustion in power plants, mining, smelting, and solid waste incineration.

Inorganic mercury compounds associated with human activity: pigments (such as tattoo dyes), vaccines, medicines (as a preservative, for example), skin bleaching creams, disinfectants or antiseptics, paints* and pesticides. Use of mercury in paint phased out in 1991.

Organic mercury compounds: most common is methylmercury (produced by activities of microbes- but source of mercury often human-related) . Taken up by living things and concentrated up food chain.

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How does mercury affect human health ?

On a basic level, mercury causes a net loss of nerve tissue (due to degeneration of nerve tissue and prevention of normal nerve development – gets in the way of the way proteins bind).

In turn, nerve damage is reflected in abnormal functioning of nerve-controlled processes (both physical and mental).

Kidney damage: long term exposure can lead to eventual kidney failure and death (due to inability of kidneys to remove waste products).

Other effects: possible effects on fertility, birth defects, cancer- but less well documented than above

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Minamata Disease

We have already looked at the consequences of short-term exposure to high concentrations of mercury. Remember, Minamata disease was found to be linked to ingestion of mercury-contaminated fish in Japan.

Again, the symptoms of mercury poisoning were acute (and long-lasting) due to irreparable nerve damage

(including intrauterine victims)

slide8

Madhatter Syndrome

The “Mad hatter” character in Lewis Carroll’s Alice in Wonderland (1865) is not as whimsical as one might think

Most people associate the phrase “mad as a hatter” Alice in Wonderland, but was in use well before this work.

For example, Thomas Chandler Haliburton (writer from Nova Scotia) in The Clockmaker (1836) wrote: “Father he larfed out like anything; I thought he would never stop—and sister Sall got right up and walked out of the room, as mad as a hatter”

In this case, “mad” appears to refer to anger. But the term was more commonly used to indicate insanity.

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An interesting aside:

Lewis Carroll (1832-1898), was, in real life, the Oxford Mathematics Lecturer (1855-81), the Reverend Charles Lutwidge Dodgson.

His pseudonym reflects the derivation of his Christian names

Lewis Ludovicus Lutwidge

Carroll Carolus Charles

Alice’s Adventures in Wonderland and later Through the Looking Glass written for Alice Liddell.

Alice Liddell (in 1859- age 7)

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Anyhoo…What do hats have to do with mercury ?

Felt hats (e.g. top hats) were all the rage in the 1800s

Early manufacturers used beaver fur, which matted well in its natural state

As beaver fur was becoming scarce (and was very expensive), hat manufacturers started making hats from cheaper fibres, such as rabbit fur.

These cheaper fibres did not mat as well as beaver fur, so were chemically treated to enhance matting ability

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Hat-making, cont’d

The hair was shaved off the animal skin to make a crude felt.

The felt was then boiled in boiling acid to harden the felt.

For added matting, the felt was brushed with a solution of mercurous nitrate

Process was called “carroting”- referring to the tendency of the mercury compound to colour the hat orange.

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Finishing processes included steaming and ironing the hat to shape it. Workers in the hat factories (“hatters”) working in poorly ventilated workshops would breathe in the mercury compounds and accumulate the metal in their bodies.

The disease that uniquely afflicted hatters became known as mad hatter’s syndrome

Physical Symptoms:

trembling (hatter’s shakes)

lurching gait

loosening of teeth

lair loss

loss of co-ordination

slurred speech

drooling

Mental Symptoms:

irritability

loss of memory

depression

anxiety

inability to think clearly

hallucinations

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The problem that won’t go away

The use of mercury compounds in hat-making was phased out by the mid-1900s, but does this mean everything is o.k. ?

Not necessarily

Sediments in rivers near Danbury Connecticut, once the “hat-making capital” of the world in the 1800s (56 factories), have been found to contain 67,000 parts per billion mercury (compared to accepted level of 20,000 ppb).

While normally buried “out of sight, out of mind,” storms and floods can remobilize sediments and release mercury into river water, and ultimately to Long Island Sound where it can taken up by plankton and fish.

So while threat of mercury poisoning may be insignificant on a day-to-day basis, it may be higher on the long term.

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Is mercury poisoning a modern phenomenon ?

One might think that, with all this use of mercury in modern times,that mercury poisoning is limited to the modern day.

But there are signs that the toxicity of mercury has been appreciated for some time.

For example, In Roman times, criminals were sentenced to work in cinnabar mines (cinnabar was widely used as a pigment in the ancient world)

This was obviously a death sentence.

Interestingly, Pliny described the symptoms of mercury poisoning in the first century AD.

Cinnabar (HgS)

So much for learning from the past, huh ?

slide15

Does mercury threaten the average person in low doses ?

Problem is, unlike the previously examined cases of mercury poisoning that were characterized by acute symptoms, symptoms of low-level exposure to mercury can be obscure.

In many cases, mercury is one of many elements in a person’s environment that may produce adverse symptoms (so difficult to pinpoint the cause of symptoms)

We are in the earliest stages of understanding human response of low dose exposure.

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Health problems commonly blamed on mercury

(but which have not yet been proven to be linked to mercury)

Mercury Amalgam Fillings

Mercury binds effectively with silver and gold

Silver or gold powder are mixed with tin or tin/copper alloy

and mercury (the mercury allows the mixture to be molded

into the cavity over an extended period of time).

Amalgam hardens and assumes a permanent shape.

The resulting amalgam supposedly has good chemical stability in the mouth, adheres well to tooth enamel, and has a high compressive strength

But some dispute about possible health effects.

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Health problems commonly blamed on mercury

(but which have not yet been proven to be linked to mercury)

Mercury Amalgam Fillings

  • Health problems claimed to be linked to the use of mercury amalgam “fillings” include:
  • emotional problems (depression, anxiety, irritability),
  • neurological disorders (facial twitches, muscle spasms, epilepsy)
  • - cardiovascular problems (rapid heart rate, chest pains),
  • - arthritis,
  • - allergies,
  • - digestive problems (ulcers, regional ileitis)
  • - immunologic disorders (e.g. leukemia, mononucleosis).
  • Is this a “straw man” effect, or are low doses of mercury responsible ?
  • Anyone’s guess right now- need long-term studies (so far, inconclusive)
slide18

Health problems commonly blamed on mercury

(but which have not yet been proven to be linked to mercury)

Mercury and Autism

There has also been much talk about the link between mercury and autism

Thimerosal, a mercury-based preservative used in some vaccines, is under fire for an apparent increase in the incidence of autism among children after being given the MMR vaccine (measles-mumps-rubella).

But interestingly, a recent study in Denmark (the first country to ban thimerosal in 1992) indicated a continued increase in autism diagnoses after the ban (consistent with the rest of world)

Due to mercury, or simply better diagnosis of autism ?

Again, this is still under debate – the added concern here is the level of risk imposed by not immunizing children (so arguments are very heated right now).