Introduction to assessment and

management of chemicals

Module 4:
Exposure Assessment
 Exposure assessment

"the process of estimating or measuring the magnitude, frequency, and

duration of exposure to an agent, along with the number and characteristics
of the population exposed. Ideally, it describes the sources, routes,
pathways, and uncertainty in the assessment."

● Who is exposed?

● What are the sources of exposure?

● What is the magnitude, frequency and duration of the exposure?

Who is exposed?
Chemical
- Workers exposure
Vulnerable

- Consumers
- Vulnerable populations
(children, elderly, pregnant beings)
- The environment and non-human animals
Who is exposed?
Chemical
- Workers exposure
Vulnerable

- Consumers
- Vulnerable populations
(children, elderly, pregnant beings)
- The environment and non-human animals
 Children/juveniles are not
smaller versions of adults!

● Rapid metabolism
– Higher consumption of food and water per unit
weight
– Higher inhalation volume per unit weight

● Development
– Immature organ system
– Immature metabolism

● Behavior
– Hand-to-mouth activity, sucking and biting
– Live close to the ground
What are the sources of exposure?

Production

Emission
and
discharge

Release into
Transport and
Recycle the
storage
environment

Disposal Accidents

Use
Sources of exposure

● Point sources (e.g. industrial emission or discharge,

contaminated sites)
● Non-point sources (e.g. ambient air pollution, drinking
water contamination)
● Natural sources (e.g. bedrock minerals)
● Use-related sources (e.g. agricultural run-offs, household
waste)
Environmental fate of chemicals
Exposure time considerations

● Magnitude of exposure

● Duration of exposure
– Acute – immediate effects or within a few hours to a day
– Subchronic - weeks or months
– Chronic – lifelong or a significant part of a lifetime

● Frequency of exposure
– Continuous
– Intermittent

● Timing of exposure
– Critical life stage (e.g., fetal development, childhood, aging)
 Aggregate and cumulative exposure
Aggregate exposure
● combined exposures to a single stressor
across multiple routes and multiple
pathways.
Cumulative exposure
● combined exposure to multiple stressors via
multiple exposure pathways that affect a
single biological target.

https://www.epa.gov/expobox/exposure-assessment-tools-tiers-and-types-aggregate-and-cumulative
To measure or to model,
that is the question!
 Environmental exposure assessment

Monitoring data Modelled data

Chemical analyses in Based on chemical characteristics,

air, water, biota,
production volumes, use patterns, emissions,
sediment, etc.
sources, environmental fate, etc.
Usually worst-case scenario is assumed!

MEC = Measured
Environmental Concentration
PEC = Predicted Environmental
Concentration
 Fig. 2. Comparison of predicted and measured concentrations of the selected compounds at the three investigated
points, calculated by means of the ratio PEC/MEC, by level of prediction accuracy. If 0.5 < PEC/MEC < 2, then the PEC
is acceptable, if PEC/MEC < 0.5, then the PEC is unacceptably low; if PEC/MEC > 2, then the PEC is unacceptably high.

Verlicchi et al. 2014. Comparison of measured and predicted concentrations of selected pharmaceuticals
in wastewater and surface water: A case study of a catchment area in the Po Valley (Italy).
 Calculating PEC

PEC calculation for pharmaceuticals according to the European Medical Agency (EMA)

Maximum daily dose consumed per inhabitants X Fraction of market penetration

PEC =
Amount of wastewater per inhabitants per day x Dilution factor

• Equation lacks of environmentally relevant details, e.g. type of waterbody, degradation of the compound
• Default values are used to achieve an “efficient compromise”
• Possibility to scale up to larger areas, e.g. across national borders
 Calculating PEC

PEC calculation for pharmaceuticals according to the European Medical Agency (EMA)

Maximum daily dose consumed per inhabitants X Fraction of market penetration

PEC =
Amount of wastewater per inhabitants per day x Dilution factor

Examples:

Pharmaceutical A
Max. daily dose consumed per inhabitants: 4000 mg
Fraction of market penetration: 0.01
Amount of wastewater per inhabitants per day: 200 L
Pharmaceutical B
Dilution factor: 10
Max. daily dose consumed per inhabitants: 30 µg
 Calculating PEC

PEC calculation for pharmaceuticals according to the European Medical Agency (EMA)

Maximum daily dose consumed per inhabitants X Fraction of market penetration

PEC =
Amount of wastewater per inhabitants per day x Dilution factor

Examples:

4000 𝑚𝑔 × 0.01 40 𝑚𝑔
PEC (A) = = 2000 𝐿= 0.02 mg/L Fraction of market penetration: 0.01
200 𝐿 × 10
Amount of wastewater per inhabitants per day: 200 L
30 µ𝑔 × 0.01 0.3 µ𝑔
PEC (B) = = = 0.00015 µg/L Dilution factor: 10
200 𝐿 × 10 2000 𝐿
 Tools and resources for estimating
environmental exposure

• OECD – Compilation of environmental exposure models

• OECD – Emission scenario documents (ESD)
• EUSES – The EU System for Evaluation of Substances
• FOCUS – EU Forum for Co-ordination of pesticide fate models with
access to simulation models and scenarios for plant protection
products
• Chesar - ECHA Chemicals Safety Assessment and Reporting tool
• US EPA ExpoBox – Exposure Toolbox
Human exposure assessment - Monitoring

Personal Biomonitoring
• Questionnaires • Absorbed dose
• Diaries • Body burden
• Air filters • Target tissue concentration
• Food baskets • Biologically effective dose
• Duplicate diets
Human exposure assessment - Modelling

Media concentration x Exposure factors

https://www.epa.gov/expobox
Exposure factors

Examples

•Body weight
•Inhalation rates
•Skin surface area
•Intake of water and selected liquids
•Ingestion of fruits, vegetables, meats, dairy
products, fats, fish, shellfish, grains, home-
produced foods, total dietary intake, and human
milk
•Ingestion of soil and dust
•Activity factors
•Consumer products
•Building characteristics

https://www.epa.gov/expobox/about-exposure-factors-handbook
Exposure and dose

● Potential dose
– amount that gets into the mouth or nose
● Applied dose
– amount at the absorption barrier (e.g., respiratory tract) that can be absorbed by the
body.

● Internal dose
– the amount that gets past the absorption barrier (skin layer, lung, gut wall) and into
the blood
– amount of the contaminant that can interact with organs and tissues to cause
biological effects.
● Biologically effective dose
– amount of chemical that interacts with the internal target tissue or organ
The ”ADME” concept

Toxicokinetics:
“What does the body do with the chemical?”

Absorption
Distribution
Metabolism
Excretion

Toxicodynamics:
“What does the chemical do to the body?”

Interaction between a substance and the body

that result in a toxic effect.
Example: Exposure to a chemical in
drinking water

Adult Child
Concentration in water 0.1 mg/l 0.1 mg/l
Drinking water consumption 2 l/day 1 l/day
Body weight 60 kg 10 kg
Calculation (0.1 x 2)/60 (0.1 x 1)/10
Exposure to chemical (=dose) 0.0033 mg/kg bw per day 0.01 mg/kg bw per day
Exposure ratio

𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛×𝑐𝑜𝑛𝑡𝑎𝑐𝑡 𝑟𝑎𝑡𝑖𝑜×𝑒𝑥𝑝𝑜𝑠𝑢𝑟𝑒 𝑑𝑢𝑟𝑎𝑡𝑖𝑜𝑛

exposure per body area =
𝑏𝑜𝑑𝑦 𝑤𝑒𝑖𝑔ℎ𝑡×𝑎𝑣𝑒𝑟𝑎𝑔𝑖𝑛𝑔 𝑡𝑖𝑚𝑒

Concentration = the amount of chemical in the exposure medium (e.g. g/L)

Contact ratio = amount of medium in contact with the human body (e.g. L/cm2)
Exposure duration = time during which the person is in contact with the chemical (e.g. hours)
Body weight = body weight over the averaging time (e.g. kg)
Averaging time = period of time of exposure relevant for the health risk characterization (e.g. days)
Example: Ingestion

𝐶𝑚𝑒𝑑𝑖𝑢𝑚 × 𝐼𝑛𝑔𝑅 × 𝐸𝐹 × 𝐸𝐷
𝐴𝐷𝐷 =
𝐵𝑊 × 𝐴𝑇

ADD = Average daily potential dose (mg/kg-day)

Cmedium = Concentration of contaminant in medium (e.g. mg/L, mg/g)
IngR = Ingestion rate (e.g. L/day, g/day)
EF = Exposure frequency (days/year)
ED = Exposure duration (years)
BW = Body weight (kg)
AT = Averaging time (days)

https://www.epa.gov/expobox/exposure-assessment-tools-routes-ingestion
 Childhood exposure to lead in soil and dust

𝐶𝑠𝑜𝑖𝑙 + 𝑑𝑢𝑠𝑡 × 𝐶𝐹 × 𝐼𝑅𝑠𝑜𝑖𝑙 + 𝑑𝑢𝑠𝑡 × 𝐸𝐹 × 𝐸𝐷

𝐴𝐷𝐷 𝑠𝑜𝑖𝑙 + 𝑑𝑢𝑠𝑡 𝑖𝑛𝑔 =
𝐵𝑊 × 𝐴𝑇
1 × 0.001 × 100 × 365 × 4
𝐴𝐷𝐷 𝑠𝑜𝑖𝑙 + 𝑑𝑢𝑠𝑡 𝑖𝑛𝑔 =
15.6 × 1,460

𝑚𝑔
𝐴𝐷𝐷 𝑠𝑜𝑖𝑙 + 𝑑𝑢𝑠𝑡 𝑖𝑛𝑔 = 𝟎. 𝟎𝟎𝟔𝟒 𝑝𝑒𝑟 𝑑𝑎𝑦
𝑘𝑔
ADD soil + dust ing = Early childhood average daily dose from ingestion of soil and dust (mg/kg per day);
C soil + dust = concentration of contaminant in soil and dust (1 mg/g);
CF = conversion factor of 0.001 g/mg;
IR soil + dust = intake rate of soil and dust (100 mg/d);
EF = exposure frequency (365 d/yr);
ED = exposure duration (4 years);
BW = average body weight (15,6 kg);
Adapted from
AT = Time (4 years, in days = 1,460).
US EPA Child-Specific Exposure Factors Handbook
Summary

● Exposure can be estimated by using monitoring data or through modelling

● Exposure scenarios and models are available for a range of situations
● Modelling-based approaches can assist in
– building knowledge about the environmental distribution of chemicals
– exposure situations
– dose estimations
● Available generic exposure assessment methods and models help obtain
insights into environmental and human chemical exposure
● Further work is needed to elucidate
– aggregated exposures to the same chemical, across sources
– cumulative exposures across chemicals
– exposure from products (e.g. consumer articles)
References and resources
EPA ExpoBox
https://www.epa.gov/expobox

EFSA (2022) Guidance on the assessment of exposure of operators, workers, residents and bystanders in risk assessment of
plant protection products
https://www.efsa.europa.eu/en/efsajournal/pub/7032

OECD (2012) Descriptions of existing models and tools used for exposure assessment
https://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=ENV/JM/MONO(2012)37&doclanguage=en

OECD emission scenario documents

https://www.oecd.org/chemicalsafety/risk-assessment/introductiontoemissionscenariodocuments.htm
https://www.oecd-ilibrary.org/environment/series-on-emission-scenario-documents_23114606/datedesc#collectionsort

ECHA: Guidance on Information Requirements and Chemical Safety Assessment - Concise Guidance (Part D) and In Depth
Guidance (Chapters R.12-R-18)
https://echa.europa.eu/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment
Thank you for your attention!