Overview of exposure assessment methodological issues for epidemiological studies on - PowerPoint Presentation

Slide1

Overview of exposure assessment methodological issues for epidemiological studies on pesticides

Hans

Kromhout

Institute

for Risk Assessment Sciences

Utrecht University

2

Farmers (used to be)

Conservative

Stable: career and residency

Knowledgeable

Well-informed (by extension workers)

Fond of their

work

So what’s the problem when we want to study their agricultural exposure?

3

Nature of exposures in agriculture

Seasonal

Often outdoors

Highly variable

Type of agent and

exposure

Biological

, chemical and

physical

Individual agents (active ingredients)

Intensity

, duration and frequency

4

Given nature of exposures in agriculture and potential for misclassification

It is a miracle we

find any

exposure-response relation

at all

5

How bad is it

?

Based on inhalation exposure database

(Kromhout et al. Annals

Occup

Hyg

1993):

Individuals working outdoors in intermittent process have on average:

Day-to-day

concentrations vary up to a factor 150

Between-worker averages vary up to a factor 10

Individual

working indoors in intermittent process have on average:

Day-to-day concentrations vary up to a factor 90

Between-worker averages vary up to a factor 10

6

How bad is it?

Based on dermal exposure

database

(Kromhout

& Vermeulen, Annals

Occup

Hyg

2001

):

For re-entry workers exposed to pesticides

on average

:

Day-to-day concentrations vary up to a factor 10-40

No between-worker differences in average exposure

For sheep dippers:

Day-to-day concentrations vary up to a factor 300

Between-worker averages vary up to a factor 30

Huge differences between body parts!!!

7

Fruit growers exposed to

Captan

during re-entry

Captan

in NL 1991 and 1992

Type

N

K

bw

R.95

ww

R.95

Inhalation

154

108

3.1

541

Dermal wrist

188

133

17.3

143

Dermal hands

182

128

45.1

65.3

8

Relative contributions of main tasks

and routes to exposure

to

Captan

(

de Cock et al. 1996)

Farmer

Son

Wife

Farmer

Son

Wife

Growing season

Inhalable exposure

Dermal exposure

Application

4%

1%

0%

6%

2%

0%

Re-entry

95%

98%

91%

84%

87%

47%

Home

1%

1%

9%

10%

11%

53%

Harvesting season

Inhalable exposure

Dermal exposure

Application

2%

<1%

0%

3%

<1%

0%

Re-entry

97%

99%

98%

89%

93%

84%

Home

<1%

<1%

2%

7%

5%

17%

Total amount

81

88

33

440

468

211

9

Consequences for

epidemiological research

Generic questions possible in general population based studies (case-control) resulting in considerable contrast between exposed and non-exposed

Studies within agriculture suffer from lack

of contrast

and lack of accuracy and precision

Using measurements will not necessarily result in more accurate exposure assessment since:

Mixed exposure situations

Large variability (not enough data available)

Good modelling practices needed

10

Used Methods

Self-reports

Expert-assessment

Job-exposure matrices

Crop-exposure matrices

Algorithms (determinants of exposure)

11Self-reports versus expert assessment

c

ase-control

neuroblastoma

(Daniels et al. 2001)

Very low prevalence

(3.8

%

fathers,

0.7%

mothers)

Fathers

an OR of 1.5 (0.7-3.4) (comprehensive

OH

review)

Self-reports

substantially higher: 7.5% and 3.4%, but 49% of fathers and 80% of mothers were unlikely to have been exposed;

showed no

relation with outcome

Exposure

classification based on job title showed opposite patterns; mothers an OR of 3.2 (0.9-11.7)

Standardized

and validated

questions

focussing

on determinants needed

12

JEMs

For the general population we need exposure assessment to be very specific because of the low prevalence: only individuals with a high probability of exposure should be assigned exposure to pesticides

As long as we make the exposure axis not to specific we will be fine

For agricultural cohorts we will need more detailed job and agent axes Crop Exposure Matrices

13

CEMs

Crop exposures rely often on registration data

But multiple pesticides can be used on a specific crop

Also same pesticide can be used on multiple crops

Results in a very sensitive method, but given the high prevalence within agricultural studies this shouldn’t be too problematic

However it will result in (heavily) correlated exposures

14

Agricultural

Health Study

Algorithm

(

Dosemeci

et al. 2002)

So will semi-quantitative methods as

elaborated

by

Dosemeci

work?

Algorithm scores

appear to provide a reasonably valid measure of exposure intensity

(Coble 2005); but appeared

marginally predictive

of forearm

captan

exposure and did

not predict air, hand rinse or urinary THPI

exposures (Hines 2008); improved algorithm(Coble 2011)

Re-entry exposure component (with most likely a longer duration) has to be included (Negatu 2016)

We cannot

change anything about the

mixed and highly variable

exposure environment of the

applicator

15Conclusions

If you are looking for positive results when studying chronic effects of

pesticides

exposures, go for the case-control design and study the general

population. (You will need large studies)

We will only find meaningful relationships between

pesticides

exposures and chronic

health effects

if we know how to deal with the inherent large temporal and spatial variability in these exposures

16Thank you very much

for

your attention!