Q & A on Introduction to Toxicology
***Q. Is there any difference between LD50 and median lethal dose? Are they just different ways of saying the same thing?
A. No, LD50 is shorthand, another acronym to impress the uninitiated. The "50" should be a subscript, but is often written as I have.
***Q.How is LD50 different from ED50 as it says LD50 is a special case of ED50?
A. The effect may be anything -blindness, loss of hair, or death. Death is only one of the effects that might be tested. The effect under scrutiny is often called the 'endpoint" that is being studied.
*** Q. In the toxicology submodule you refer to a dose that effects 90% of test subjects as ED90, but in the homework you refer to the dose as EC90, are the interchangeable?
A. I should have been consistent. The "D" in "ED" stands for "dose," typically mg / kg of body weight. That is the terminology used for oral and dermal exposure of test animals. For inhalation exposure of land animals or water exposure of aquatic species, the term "EC" is used and it means "effective concentration," typically in ppm or mg / m^3.
*** Q. (Several questions regarding the electronic quiz, question 1, and acute exposure:)
A. Acute vs. chronic refers to the duration of the exposure, not the effect. Regarding the Dartmouth researcher who was exposed to dimethyl mercury that you read about, her exposure was seconds, but the effect, culminating in death, took months. Many acute exposures have a "latency" period before the effects are patent.
In the Law, the exposure specified as a one-time brief exposure to the chemical, and thus acute. The effect is measured at 14 days. Or rather lack of effect, if the animal is not dead before then. (See Blackboard announcement about hints.)
Q. *Question: Is there guidance available in translating toxicity from tests on lab animals to humans, or even to other species? From what I can gather water quality standards are often set based on a certain species (i.e. Cu is acutely toxic to a fathead minnow at 5ug/L, (I just made that up)). I assume that the species that the standard is based on is the species that experiences toxicity at the lowest levels. However, it seems that not all species that could be affected may have been tested and it may be necessary to try and extrapolate to attempt to determine toxicity for a species other than ones listed in the research.
A. That's a popular subject with me. See C:\RAP Web Site\ENVE_651\Module10\Submodule_10B_uncertainty_bio\Submodule_10B_1.htm but animals are not human and one animal species is not like another. In ecological toxicity, one searches for a species that are relevant. See C:\RAP Web Site\EQE_649\Module_08\Submodule8C\Submodule_8C_1.htm
*Q. Are there references that may indicate risks from consumer products? The first thought that comes to mind is the potential risks from radiation that one might be subjected to from the TV and or computer monitors. Are there any "dose" relationships that may be correlated to eyesight degeneration vs. time spent looking at a TV or computer monitor?
A I agree that TV is a hazardous waste, but it's probably not toxic. We'll do a little something on radiation. Yes, the dose-response relation is what we are looking for. Lasers are tested for eyesight deterioration, cataracts, using the rabbit model. Let me not describe the test.
* Q. Is there a way to define the interlink between injury and disease. Like for example injuries that lead to diseases or diseases that make injuries easy to take place(for e.g. diseases that make bones weak so that they break easily).
A.While there are certainly diseases that make injury more likely, they are seldom an interrelationship issue. For example, if an employee had nerve damage and was uncoordinated, it would not matter if the nerve damage was from a workplace chemical exposure or a childhood injury, the employee should not be operating equipment. In a well-regulated work environment, such issues would not come up, so I don't know of any regulations that pertain to that issue.
* Q. The definition of "toxic substance" appears to be very far reaching. Has there been any case law that has excluded this definition from products that produce only occasional and/or limited injury or illness? Example: occasional mild lung irritation from inadvertent inhalation of a cleaning agent. The "injury" in this case would seem very minor and not worthy of labeling the offending cleaner a "toxic substance".
A. In the lesson we learned of a legal definition of "highly toxic" for the purpose of labeling products. That definition only related to laboratory tests with rats. It also presents a definition of "toxic" that says nothing about dose. Everything is toxic in sufficient quantities, isn't it? If the effects of inhaling the detergent were known, it would be toxic and need that label. But most powders can cause irritation when they are inhaled. Point is, that without expressing dose, it is impossible to discuss toxicity.
*Q. To my mind, people who use toxic substances in their work, have to receive better salaries. As far as I know, Ph.D. students of biological faculties in Poland receive only $ 12 additionally per month, and in Ukraine - milk for free… Q. Do you think there is some solution considering this problem?
A. Ouch! In the US that is no long an option. However, some dangerous jobs have traditionally had higher pay, but the employer must make the job reasonably safe. They cannot pay workers to ignore safety regulations.
And. It is a matter of economics. When people are prosperous, they have time and leisure to think about their health and other amenities. When people are working 90 hours a week to feed themselves, they do not have time to worry about 1 part per billion of something in their drinking water.
Q. In sub module 1C, the NOEL was noted at being the no observable effect level. Therefore, I am to assume that any dose higher than the NOEL would produce an effect and everything lower would have no observable effect. Does the no observable effect include long latency periods (such as causing cancer years later???)?
A. Very good questions, see above for part of my answer. You observed that the Consumer Product Safety law for "highly toxic" had a definite cut-off time for effects and only mentioned death as an effect. Lawyers, not toxicologists, write this type of definition. I just put it in the lesson to illustrate how those words were used and to get you to think about their meaning. For the definition of "toxic" it had any harmful effect and no cut off time, so any harmful effect at any time would require the toxic label. Of course there are no testing protocols specified, either.
Q. Would the NOEL also be considered the threshold level?
A. We will talk more about NOEL and thresholds. They are often used synonymously, but are not. The NOEL would refer to a particular experiment. These experiments test a series of progressively higher doses, starting with zero dose called the controls. The NOEL would be the highest of the doses that did not demonstrate an effect. Long ago, toxicologists would state a "no effect level." Since the philosophers tell us that any dose must have some effect, the terms "no observable effect " became standard. Sometimes the matter is expanded to "no observable adverse effect (NOAEL), which is more accurate. These terms are common to regulatory toxicologists who have to come up with some definite number. The terms would be meaningless, unless they are coupled with the particular laboratory experiments that were used to determine them. For chemicals suspected of being carcinogens, those protocols would specify observations for the lifetime of the animals.
A threshold would be the largest dose that produced no effect. It is a scientific concept that is not tied to any particular experiment, but would be stated for a particular animal species and other protocols. There is much scientific debate if carcinogens have thresholds. We will discuss this.
Q. What are the criteria for "effects" when an experiment is done to determine the NOEL up to EC90? What if different individuals within a species show different effects?
A. This is part of the reason that the choice of animal species is so important. Some strains of lab animals are inbred and most of the individuals will show the same effect. Other strains are outbred and there will be more variation in effect. You can also see why the choice of an "endpoint" is so critical. This is why death is such a convenient endpoint.
Q. When comparing the acute influence of higher doses of radiation (but not lethal) and chronic effect of lower doses, is it correct to ask what is better to the human organism?
Usually when reproductive system is a target to some poisonous substances there is a risk of increase in mutations in the next generations. Sometimes physicians or scientist predict the percentage of such a risk. 4. What methods they use to do it?
A. The effects of high doses of radiation are fairly well known, unfortunately. For lower chronic doses, we have to compare what we get from contamination or the workplace with "naturally occurring" radiation. If the dose is small relative to the naturally occurring, , we might ignore it.
Q. Also, am I right to conclude that reversible effects are reversed once exposure has stopped? Do irreversible effects include effects that require intense medical treatment such as chemotherapy (in other words, are does reversible effects include only those effects which would naturally reverse on their own once exposure has ended? Blurry vision might revert back to normal vision after exposure whereas cancer may not be reversible if medical treatment is not seeked and even if it was it still might result in death or may eliminate someone's ability to reproduce.)
A. Again, reversible and irreversible are very general concepts. The effects would have to reverse sometime in the future and not be permanent. Similar to the questions if a seven-day test is chronic or acute, for an adverse effect that slowly reversed itself for years, you would better presenting that explicitly rather than trying to decide if it is reversible or irreversible. We will discuss cancer in much greater detail soon.
Q. Is the effective dose affecting 10% of the population meaning any type of observable effect except death.
A. You would include death as an "effect." Its just that death is such an easily observed endpoint, it is often specified and the LD is often used. Obviously ED is not very descriptive, unless you specify the effect.
Q "toxic" and "highly toxic" are both defined in terms of human illness or death, but the homework question referred to the results of a rat test. Can you infer a chemical is toxic if rats are affected, or does there have to be direct proof that humans will suffer?
A. In this case the law of the land defined the terminology required to warn humans of the hazard in terms of animal testing. Almost all toxicology testing is done in animals and the choice of the correct "animal model" is most important. We will deal much more with this issue in a few weeks.
Q. If, in Environmental Engineering "sticking to ethics" is given a lot of importance then how would one defend the cruelty imparted to animals used for studying the affects of various "poisons"?
A. Animal testing is an important issue. Economics dictates minimizing animal testing, if in vitro testing will suffice. The animal quarters where I did my graduate work were better than my graduate student offices, better ventilation and climate control. Strict adherence to animal welfare controls is an important part of experimental procedures. If animals are stressed they may produce anomalous experimental results. I have never witnessed or heard of any cruel or base treatment of laboratory animals, other than what was required by the experiments. As a practical matter, whole animal testing is required for all foods, drugs, and cosmetics that people will be exposed to, in order to determine if they are "poisons" or better put, what the harmful dose is. It would be irresponsible to purposefully expose consumers without prior animal testing. For persons whose moral system puts humans on a higher plane than animals, I do not perceive any moral issues with testing animals. (A person who took pleasure in hurting mammals is rare, and this type of behavior upsets other people, so it is anti-social.)
On the other hand, persons whose moral system puts animals and humans on the same plane might have problems with animal testing. Biomedical research is probably not a good career choice for persons with this ethic.