Dose-Response Analysis for Policy Review

(Total Points = 20, i.e., 20% of the overall grade)

Use the dataset titled “Assignment Excercise_201 Children Study” (already uploaded in
Blackboard)
• Assignment has to be uploaded by the due date.
• Do not forget to write your name.
• This is an individual submission.
In the fourth edition of Guidelines for Drinking-Water Quality in July 2011, the World Health
Organization (WHO) the 400-μg/L drinking-water guideline for manganese (Mn) was
discontinued because this health-based value is well above concentrations of manganese
normally found in drinking water. The WHO no longer considers deriving a formal guideline
value for Mn in water. In response to this controversial decision, scientists are conducting
multiple epidemiological studies to get evidence whether Mn above 400 or 500 µg/L has adverse
neurocognitive health effects in vulnerable populations especially in children. We are conducting
one such study in Bangladesh using a cohort of 201 children aged 7-12 years.
After initial data collection on 201 children, you are doing a preliminary analysis to observe if
there is initial evidence regarding the effects of Mn on child behavioral problems, an indicator of
damage to the central nervous system.
You are hoping that your observation will generate new or additional knowledge on the effects
of Mn in drinking water in children, which may be helpful when the policy makers at EPA and
WHO will review the guideline for Mn in near future.
1) Review two readings (1 and 2; already uploaded in Blackboard) that provide information
about WHO and EPA Drinking Water guidelines respectively regarding water manganese.
What gaps do you observe in the existing scientific literature regarding the chronic
neurobehavioral health effects of manganese? (2 points)
In the EPA literature, there is similar neurological affects in individuals who ingest high
doses of Mn as compared to those who have had high inhalation exposure from work. The
EPA also mentions short-term, chronic exposure and long-term exposure to Mn bringing
about similar neurological damages. In the 2004 WHO study, they stated that drinking water
should not have more then 400micrograms/L of Mn. However there weren’t any evidence
based studies available until 2007 onwards that gave grounds to set a limit for drinking water.
Neither of the literatures identify exactly what dosage would be considered neurologically
harmful.
2) Are there inconsistencies in findings across the two studies? How do you plan to address
these gaps of knowledge using your existing dataset (Excel spreadsheet)? (2 points)
Yes, there are some inconsistencies within the two studies such as at what point does
water Mn become toxic. I plan to address the gaps by taking into account the data
presented but only using the information that is consistent and confirmed within both
 studies, such as there being high concentrations of Mn that exist in water naturally and
anthropologically, and that at very high levels there are neurological effects.
3) How is water Mn (in the existing dataset) converted into categorical variables? From policy
point of view identify two approaches to convert a continuous variable into a categorical
variable and explain the approaches briefly. (2 points)
It is converted into categorical variables by separating the numbers into two groups, low
(300-400and below) and high (500 and above). From the policy point of view, they used a
guideline from the EPA or WHO to classify the water concentration of Mn to be low if it is
either 300/400, or high if levels are 500mg and above. The guidelines depends on what is
reasonable to enforce within the country, especially since Mn may be found naturally at a
higher concentrations in multiple countries.
4) Draw scatterplot to check linear associations of blood manganese with blood lead. Report
correlation coefficients. Interpret your findings. (2 points)

Association Between Blood Mn and Blood Pb

50
45
40
35
30
Blood Pb

25
20
15
10
5
0
0.0 500.0 1000.0 1500.0 2000.0 2500.0 3000.0 3500.0 4000.0
Blood Mn

r=0.12
There is a positive linear relationship between blood manganese and lead in the blood, but it
has a weak relationship.
5) Draw scatterplot to check linear associations of water manganese with academic achievement
in math. Report correlation coefficients. Interpret your findings. (2 points)
 Academic Achievement in relation to WMn
35

30

25

20
Math Score

15

10

0
0.0 500.0 1000.0 1500.0 2000.0 2500.0 3000.0 3500.0 4000.0
Water Mn

r= - 0.245
There is a negative linear relationship between the concentration of water manganese and the
children’s math scores. It has strong statistical significance.
6) Using scatterplots present dose-response analyses to examine the neurobehavioral effects of
water manganese taking the EPA standard for Mn into account. Consider TWO cognitive or
behavioral outcomes while creating graphs and doing your analysis. You are advised to
meaningfully categorize exposure variable(s). (2 points)
The EPA guidelines recommended that potable water manganese concentrations be below
300μg/L seeing as concentrations above this may bring about neurologic side effects.
 Effects of Water Mn on Aggressive Behaviour (EPA)
35

30

25
Aggressive behaviour

20

15

10

0
0.0 500.0 1000.0 1500.0 2000.0 2500.0 3000.0 3500.0 4000.0

Water Mn Concentration

r = 0.5
There is a strong, positive linear relationship between aggressive behaviour in children and the
concentration of water Mn that is consumed.

Effects of Water Mn concentration on Attention (EPA)

50

45
40

35

30
Attention

25
20
15

10
5

0
0.0 500.0 1000.0 1500.0 2000.0 2500.0 3000.0 3500.0 4000.0

Water Mn Concentration
r = 0.46
There is a strong positive relationship between water manganese concentration and the ability to
pay attention.
7) Using scatterplots present dose-response analyses to examine the neurobehavioral effects of
water manganese taking the WHO standard for Mn into account. Consider TWO cognitive or
behavioral outcomes while creating graphs and doing your analysis. You are advised to
meaningfully categorize exposure variable(s). (2 points)
The WHO guidelines suggested that the concentration of water manganese be limited to
400μg/L. Drinking water above this concentration has been associated with neurological
changes.

Effects of Water Mn on being Anxious/Depressed (WHO)

25

20

15
Anxious/Depressed

10

0
0 500 1000 1500 2000 2500 3000 3500

Water Mn Concentrations

r = 0.46
The graph indicates a strong, positive relationship between water manganese concentrations
and being anxious or depressed.
 Effectts of Water MN on WithdrawnDepressed(WHO)
18

16

14
Withdrawn/Depressed

12

10

0
0.0 500.0 1000.0 1500.0 2000.0 2500.0 3000.0 3500.0 4000.0
Concentration of Water Mn

r=0.63
There is a strong positive relationship between water manganese concentration and the
effects of being withdrawn or depressed.
8) Using bar graphs present dose-response analyses to examine the neurobehavioral effects of
water manganese taking the EPA standard for Mn into account. Consider TWO cognitive or
behavioral outcomes while creating graphs and doing your analysis. (2 points)
Based on the ingestion of water Manganese concentration, within the low exposure group,
the average number of children who display aggressive tendencies is 7.4, whereas within the
high exposure group there is an average of 12.7, as represented in the graph below. . This
was calculated based on the EPA’s guideline that Mn water concentration below 300μg/L is
 low while anything above that can be considered high.

Dose-Response Relationship Between Mn

Concentration and Aggressive Behaviour
10.0

8.0
6.0

4.0
2.0

0.0
Low exposure mean High exposure mean

Based on the ingestion of water Manganese concentration, within the low exposure group,
the average number of children who display attention problems is 11.2, whereas within the
high exposure group there is an average of 21.5, as represented in the graph below. This was
calculated based on the EPA’s guideline that Mn water concentration below 300μg/L is low
while anything above that can be considered high.

Dose-Response Relationship Between

Mangancese Concentration and Attention
Problems
10.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
Low exposure mean High exposure mean

9) Using bar graphs present dose-response analyses to examine the neurobehavioral effects of
water manganese taking the WHO standard for Mn into account. Consider TWO cognitive or
behavioral outcomes while creating graphs and doing your analysis. (2 points)
Based on the ingestion of water Manganese concentration, within the low exposure group,
the average number of children who display attention problems is 9.1, whereas within the
high exposure group there is an average of 11.7, as represented in the graph below. This was
 calculated based on the WHO’s guideline that Mn water concentration below 400μg/L is low
whereas above that number can be considered high.

Dose-Response Relationship Between Mn

Concentrations and Anxious/Depressed
10.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
Low exposure mean High exposure mean

Based on the ingestion of water Manganese concentration, within the low exposure group,
the average number of children who display attention problems is 11.2, whereas within the
high exposure group there is an average of 21.5, as represented in the graph below. This was
calculated based on the WHO’s guideline that Mn water concentration below 400μg/L is low
while above that number can be considered high.

Dose-ResponseRelationship Between Mn
Concentrations and being Withdrawn/Depressed
10.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
Low exposure mean High exposure mean

10) What policy recommendation would you convey to the policy makers (e.g., those who are in
EPA) based on your dose-response analysis (Q6-Q9)? Do we need additional experimental
studies to generate more scientific evidence for convincing policy makers to re-consider Mn
standard? Why or why not? (2 points)
Based on the data collected, it seems that the higher the dosage of Mn ingested, the more we see
Mn induced toxicity. Therefore, I would recommend to WHO that they reduce their guidelines
for the safely tolerable amount of water Mn to match that of the EPA. I do believe there is need
for more scientific study on this matter to convince policy holders/makers because although there
were some measurements and evaluations done within the study by the EPA, there was also a lot
of self-reported data/information within the EPA article that could not be quantified or trusted
enough for evidence based research.