Question

1. Describe the relationship between dose, route, and duration of exposure to a health hazard and the effect this has on absorption and the possibility of adverse health risks.

Answer 1

Dose is often cited simply as the most important determining factor for whether chemical will cause a harmful reaction. This idea was originally expressed by the Swiss physician Paracelsus (1496-1531): “Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy.”

The relationship between dose and response can be visualized as a simple graph with dose on the x-axis and response on the y-axis. Two important points on a dose response curve that are illustrated in the accompanying figure are the “NOAEL” (No Observed Adverse Effect [or response] Level) and the “LOAEL” (Lowest Observed Adverse Effect Level). These doses are especially important to risk assessors when establishing safe levels of chemicals.

DOSE RESPONSE CURVE LOAEL, NOAEL - LOCAEL = Lowest observed RESPONSE o NOCAEL = no observed effect DOSE Control group

In simplest terms:

Amount x Frequency x Duration = Total dose over a specified period of time. Let’s start with doses of medications because that is easy to understand and explain.

You may consume a 500 mg pill (=amount) of drug “Y” every eight hours (=frequency) for two days (=duration) to reach a total ingested dose of 500 mg x 3 8-hr periods in a day x 2 days = 3,000 mg of “Y”.The internal dose is the amount that stays in your body. This can often be different than the total dose due to elimination (for example in urine). Internal dose is expressed in terms of the amount in the body per kilogram of body weight. If you absorb 50% of the ingested total dose of “Y” and you weigh 60 kg, then your internal dose is 50% x 3,000 mg ÷ 60 kg = 25 mg per kg of body weight. A child absorbing drug “Y” equally well, but weighing only 10 kg the child would experience a larger internal dose of 150 mg per kg of body weight. In reality, while being absorbed, chemical substances can be transformed (metabolized) to facilitate elimination, or incorporated into biochemical pathways, or activated with potentially harmful effects. These processes occurring while the chemical is being taken into the body make calculations of internal dose at any given time more complex.

Exposure is sometimes defined as a measurement of the level at which one encounters any substance. That substance could be a glass of a fine wine or a medication that you ingest or other substances that that you inhale, apply to your skin (for example, a nicotine patch), or inject directly into your bloodstream. Many people are concerned with exposures to chemical substances in food or water, or in the air that you inhale, or in the environment that the skin is exposed to.

Route (or pathway) of exposure is another factor controlling how much of a substance gets absorbed into your body. The main routes of exposure to chemicals in the environment are by ingestion (gastrointestinal), dermal absorption (through skin), and by inhalation (through the lungs). For example, liquid mercury released from a broken thermometer will not be absorbed appreciably from the gastrointestinal tract if it is accidently ingested. Mercury is also not easily absorbed through skin. However, breathing vapors from that spilled mercury could result in a significant internal dose by inhalation.

An acute exposure is one of short duration whereas a chronic exposure is one that is repeated or prolonged for an extended period. Effects of a chemical can be different depending on whether the exposure is acute or chronic. Regulatory agencies often recommend safe exposure levels for multiple exposure durations, including acute and chronic.

People have different characteristics and susceptibilities at different times of their lives and also because of genetic predisposition. Some ethnic groups have greater tolerance to the intoxicating effects of alcoholic beverages. Diet, nutritional status, and amount of stress we are experiencing in our lives can also affect response to chemicals. These individual-specific factors are sometimes determined by level of education and other social and economic factors that impact our personal choices, behaviors, and overall lifestyle. Medications and other chemicals in a person’s body at the same time can sometimes intensify or diminish the response.

In other words, how each of us responds to any given chemical can get complicated! However, fundamental messages here are still that

(1) dose is arguably still the single most important determinant of response

(2) no dose will occur without an exposure.

To summarize some basic relationships of key concepts discussed here: Internal dose of a chemical and an individual’s response to that chemical is dependent upon…

level of exposure
frequency of exposure
route of exposure
fraction absorbed by that route
duration of exposure, and
individual sensitivities

DOSE Exposure Level or Amount Frequency - Route - - fraction absorbed - Duration includes genetos makeup, age, gender, health etc. Individual Response