6. Epidemiological Toxicology Flashcards
What are the different methods used to identify a hazard?
- Epidemiology
- Toxicology
- In vitro tests
- Structure-activity analyses
What is epidemiology?
The study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in defined populations.
The word epidemiology means “the study of what is upon the people”
epi – upon, among
demos – people/district
logos – study, word, discourse
What is environmental epidemiology?
Concerned with determining how environmental exposures impact human health. It seeks to understand how various external risk factors may predispose to or protect against disease, illness, injury, developmental abnormalities, or death.
What are the limits of what epidemiological studies can prove? Why?
- Epidemiological studies can only go to prove that an agent could have caused, but not that it did cause, an effect in any particular case. You can say “associated with”. Different than in animal studies that can prove causation.
- Because correlation is not causation. These studies can have confounding factors. Can try to reduce the amount of confounding factors by limiting variability by restricting studies to a subgroup or using regression models.
What are confounding factors? Whats an example?
Occur when the study and control populations differ with respect to factors which might influence the occurrence of the disease.
For example, smoking might be a confounding factor and should be considered when designing studies for lungs and lung disease.
What are the different types of Bias Errors?
- Selection bias
- Information bias
- Recall bias
What is selection bias?
when the study group is not representative of the population from which it came.
What is information bias?
when study subjects are misclassified as to disease or exposure status.
What is recall bias?
individuals are asked to remember exposures or conditions that existed years before.
What is probability and how is it calculated?
The likelihood that something will happen (%).
Probability = (# of positive events) / (# of positive events + # of negative events).
What are odds and how is it calculated? What is the odds ratio, how is it calculated, and when is it used?
- Odds: The likelihood that something will happen compared to the likelihood that it will not happen.
Odds = (# of positive events) / (# of negative events) - Odds ratio: It is a ratio or proportion of odds.
OR = Odds that the diseased were exposed / Odds the controls were exposed
Used for case control studies (incidence of past exposure).
What is the relative risk and how is it calculated? When is it used?
(RR) is is the ratio of probabilities expressed as a %.
Relative risk (RR) = Probability of getting disease if exposed / probability of getting disease if not exposed.
Used for Cohort studies and clinical trials.
What happens if the RR=1, if its >1, if the OR=1, if its >1?
If RR or OR is equal to 1 then there is no difference between the groups. If they are more than one then it is harmful.
What is a confidence interval? What if it’s above 1? below? crosses 1?
The confidence interval indicates the level of uncertainty around the measure of effect expressed as an odds ratio. Confidence intervals are used because a study recruits only a small sample of the overall population so by having an upper and lower confidence limit we can infer that the true population effect lies between these two points. Most studies report the 95% confidence interval (95% CI).
If the confidence interval crosses 1 (e.g. 95%CI 0.9-1.1) this implies there is no difference between arms of the study because 1 means there is no effect. If the intervals are above 1 then it means there is a significant increase in effect, if they are less than 1 then there is a significant decrease in effect.
What are the different epidemiology types? What do you need in order to carry out a study?
You must have an ethics approval in order to carry out the study and in order to publish it.
- Experimental: The researcher intervenes and then observes what happens
- Observational: The researcher studies - but does NOT alter what occurs
What is the typical flow & conditions of an experimental epidemiological trial? (L6S14)
It needs to be randomized, blinded, and all the confounding factors need to be considered.
All the steps with a * means there is a potential for introducing bias in the step.
- Recruit participants
- Select participants to do the study on
- Allocation: separate the participants into an intervention group and a control group.
- Expose one group to the intervention and don’t expose the other.
- Follow up
- Outcome + Data collection
- Analysis
Explain an experimental epidemiological trial done with canned beverages. Why is it an experimental trial?
Recruited 60 people and randomly split them into 3 groups of 20 to test the effect on the systolic BP after consuming 2 canned beverages: CC indicates 2 canned beverages; CG, 1 canned and 1 glass bottled beverages; GG indicates 2 glass bottled beverages.
Bisphenol A is the major can lining material. So the CC would in theory have more risk. They found there was an associated increase in systolic BP. by about 4.5 mm Hg after drinking from the 2 cans.
It’s experimental because the researcher is manipulating the independent variable (exposure to the BPA through cans) in order to observe the dependent variable (effect on blood pressure).
What are the different types of epidemiology observational studies?
- Cohort
- Cross-sectional survey
- Case control
What is a cohort study? State the present and the future.
A cohort (group) of individuals with exposure to a chemical and a cohort without exposure are followed over time to compare disease occurrence.
Present: exposure
Future: disease
What are the different types of cohort studies? explain them.
- Prospective:
At the time that I start looking, I don’t know the outcome. I will see effect later. I know one group was exposed and one wasn’t, and I’m going to look at what the outcome is after the exposure. - Retrospective:
Looking at the end result (disease or not) and go backwards to see what the difference was between the groups.
Explain the 2 different types of cohort studies by using the following study: Does in utero exposure to 13-cis retinoic-acid (accutane) adversely affect pregnancy outcome? Why is this a cohort study?
Cohorts: 154 human pregnancies with fetal exposure to isotretinoin (exposed) were compared to all infants born in Atlanta in 1982 (not exposed).
Outcomes:
- Retrospective: 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants.
- Prospective: 36 of the 154 pregnancies. The outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 malformed infants.
Conclusion: Isotretinoin exposure was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5). Usually the relative risk is 3%.
This is a cohort study because there are 2 groups: the exposed group (to accutane) and the non exposed group, the researcher does not have control over this variable. Then the researcher can observe the difference between the 2 groups either before the effect happens (prospective) or after the effect happens (retrospective).
Explain the study: Does pre-natal and early childhood BPA exposure contribute to the development of obesity in children?
What are the possible confounding factors?
What kind of study is this and why?
BPA was measured in urine samples from pregnant women and children (at ages 3 and 5). Fat mass index (FMI) was assessed at ages 5 and 7.
Urinary BPA concentrations were positively associated with the child age 7 FMI (β = 0.31 kg/m2; 95% CI: 0.01, 0.60, p = 0.04). Therefore there was a relationship between BPA exposure and obesity.
Possible confounding factors:
The pregnant women could have been exposed to perfluorinated compounds too rather than just BPA, the mother could have a fast-food diet type, the children could have had a bad diet.
This is a prospective cohort study because they had no control over the independent variable (exposure to BPA), but the researcher then observed the effects of this exposure on children’s obesity (dependent variable) years later.
What is a cross-sectional study? What is the present and future?
All factors (exposure, outcome, and confounders) of a population are measured simultaneously (at one specific point in time).
Present: Disease and exposure
Future: -
Explain the study: Exposure of Young Men in Montreal to PBDEs (flame retardants) and Phthalates (plasticizers) and Reproductive Function. What kind of study is it and why?
153 healthy young men living in the greater Montreal area were exposed to polybrominated diphenyl ethers and phthalates therefore we studied their hormonal balance and semen quality.
How:
- A questionnaire
- Measured urinary phthalate metabolites
- Levels of PBDE in hair (to see when they were exposed)
- Took hormonal measurements
- Tested for semen and sperm chromatin quality
Results:
- Each 10-fold increase in BDE-47 (major flame retardant) was associated with lower TSH (thyroid funtion) levels (-17.3%; 95% CI: -31.5, 0.0; p = 0.05).
- BDE-47 exposure was also associated with a decrease in sperm concentration (-19.7%; 95% CI: -36.8; 2.0; p = 0.07) and motility (- 25.5%; 95% CI: -44.5, 0.1; p = 0.05).
- Trends towards decreases in these parameters were also observed in association with exposure to BDE-100 and the sum of BDE-47, -99, and -100 (∑3BDEs).
- Overweight men were more sensitive than men with a normal BMI to the endocrine disruptive effects of PBDEs.
- There were no differences with exposure to high phthalate levels vs low levels.
This is a cross sectional study because the exposure to PBDEs and Phthalates, their outcome (thyroid, sperm), and the confounders were all measured and observed at the same point in time.
