Manuela TiramaniInterzonal workshop “Harmonisation of risk assessment in section toxicology”AGES Vienna 23-24 June 2015

Further developments of EFSA GD on exposure assessment

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THE GD ON NON-DIETARY EXPOSURE: THE WAY SO FAR

EFSA OpEx GD

Pesticide risk assessments must be carried out for all scenarios of nondietary exposure

Different approaches all over EU (justified?)Available data satisfactory?EU harmonisation vs zonal approach

So far, models established over 20 years ago have been the standardsto assess exposure of agricultural operators to PPPs, but they do notreflect current application techniques (� AOEM!)

EFSA was asked by COM to proceed with the preparation of a GuidanceDocument

� Working group

The GD had to include:

•A quality assessment of the available databases•The derivation of regulatory percentiles from the most appropriatedatasets

•The preparation of an operator exposure calculator spreadsheet

The WG basic idea was to establish a first tier exposure assessment

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THE GD ON NON-DIETARY EXPOSURE: THE WAY SO FAR

EFSA OpEx GD

2007EFSA “Project to assess current approaches and knowledge with a view to develop aGuidance Document for pesticide exposure assessment for workers, operators, bystandersand residents”) http://www.efsa.europa.eu/en/scdocs/doc/26e.pdf

2010EFSA Scientific Opinion on preparation of a guidance document on pesticide exposureassessment for workers, operators, bystanders and residents. EFSA Journal2010;8(2):1501

2011Request from European Commission (A working group of risk managers was set up and ameeting took place in Brussels on 11 May 2011 to discuss about the specific questions raised byEFSA opinion)

2013First draft of the GD circulated to MSs for commenting

2013Finalisation of a new model developed by BfR (AOEM)

2013-2014Revision of the first draft (inclusion of new data)

2014 (April-May)Public consultation

2014 (October)PUBLICATION

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• Assessment of the available databases

• Preparation of a calculator

• Basic principles of the Guidance and the annexedcalculator are:

• the transparency of data,

• the traceability of information and

• the reproducibility of the outcomes.

� Only databases for which the working group hadaccess to the raw data and that could becirculated, if requested by third parties, wereconsidered.

ACTIVITIES

EFSA OpEx GD

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TOPICS

EFSA OpEx GD

•Tier approach:•Standardised first tier exposure assessment is available(most scenarios)•Scenarios not covered by standardised methods: themost appropriate ad hoc approach can be followed

•Where a non-standardised higher tier exposure assessmentis adopted, the justification should be clearly documented

•The deterministic methods is still suggested in routine riskassessment for individual PPPs, because of the limitations ofthe currently available data

•The method of risk assessment should be refined forpesticides that are acutely toxic

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EFSA OpEx GD

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• Defines the exposed groups

• Lists and evaluates existing standard models

• Focuses on risk assessment for systemic toxicity (localeffects not covered)

• Does not cover guidance on dermal absorption

• Does not apply to biocides/biological PPPs

• Proposes a tiered approach for exposure assessment

• Evaluates and gives recommendations for a series ofdefault assumptions/values/parameters

MAIN CONTENTS

EFSA OpEx GD

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MAIN CONTENTS

EFSA OpEx GD

Exposed category Database/model

Operator (field) German model

Operator (field) UK POEM

Operator (field) Agricultural operator exposure model (AOEM)

Operator (field) EUROPOEM II

Operator (field) PHED

Operator (field) TNsG Biocides

Amateur ConsExpo

Amateur French data

Operator (greenhouse) Industrieverband Agrar (IVA)—Germany

Operator (greenhouse) Southern Europe

Operator (greenhouse) Dutch

Operator (seed treatment) SeedTropex

Worker EUROPOEM II

Worker German

Worker (fork lift driver, sowing) SeedTropex

Worker Transfer coefficient

Residents and bystanders EUROPOEM II

Residents and bystanders BREAM (Resident and Bystander Exposure Assessment Model)

Residents and bystanders ConsExpo

Residents and bystanders Lloyd and Bell 1983 and 1987 (spray drift values)

Residents and bystanders CRD 2008

Residents and bystanders California EPA

Residents and bystanders Ganzelmeier spray drift data

Residents and bystanders BfR 2008

•Amount and quality of data?

•Availability of data?

•Selection of scenarios based on?

•Driven by scenarios of concern or data availability?

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• Discriminates between acute and chronic assessments

• Introduces the concept of “Acute Acceptable Operator Exposure Level” (AAOEL) in addition to the AOEL

• Suggests use of 95th percentile for acute assessments

• Suggests use of 75th percentile for chronicassessments

• Introduces resident exposure assessment (limiteddatabase)

MAIN CONTENTS

EFSA OpEx GD

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In particular for:

•Body weights•Breathing rates•Average air concentrations•Hectares treated per day•Exposure durations•Absorption values •Default surface area of body parts

MAIN CONTENTS

EFSA OpEx GD

A further challenge was the analysis and harmonisation of default values to be used in the calculator

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Finally, everything had to be included in a user-friendly calculator!

CHALLENGES: 5

EFSA OpEx GD

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PUBLIC CONSULTATION

EFSA OpEx GD

Comments received on the draft GD per stakeholder category

Stakeholder category Number of Comments

Authority 96 Academia/research 226

Agrochemical industry / ECPA 88 Consultancy 22

Farmers 3 NGOs

Others

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TOTAL 465

The public was invited to submit comments on the draft GD and the attached calculator via an online form available at www.efsa.europa.eu from 1 April 2014 to 20 May 2014. Risk assessors, risk managers, stakeholders and the scientific community were additionally informed via emails about the open public consultation.

Comments of a more general nature as well as very specific comments on the various section of the draft GD were received.

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PUBLIC CONSULTATION - 2

EFSA OpEx GD

Publicconsultation

Maincomments

Sections of the draft GDNumber of Comments

General commentsAbstract 8SummaryTable of contentsBackground as provided by the Commission 9

Terms of reference 8

Assessment 18

1. Introduction 10

2. Background Data 13

3. Definitions of exposed groups 13

4. Overall approach 325. Default values proposed for the assessment 10

5.1. Body weights 10

5.2. Breathing rates 6

5.3. Average air concentrations 7

5.4. Hectares treated per day 17

5.5. Exposure durations 10

5.6. Absorption values -

5.7. Default surface area of body parts 1

6. Methods for first tier exposure assessment 4

6.1. Operator exposure 27

6.2. Worker exposure 16

6.2.1. Dermal exposure of workers 9

6.2.2. Dislodgeable Foliar Residue (DFR) 9

6.2.3. Multiple Application Factor (MAF) 15

6.2.4. Transfer Coefficient (TC) 27

6.2.5. Inhalation exposure of workers 12

7. Resident and bystander exposure 21

7.1.Resident exposure 12

7.1.1. Spray drift 29

7.1.2. Vapour 14

7.1.3. Surface deposits 14

7.1.4. Entry into treated crops 11

7.2.Bystander exposure 8

7.2.1. Spray drift 16

7.2.2. Vapour 9

7.2.3. Surface deposits 10

7.2.4. Entry into treated crops 10

Conclusions

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EFSA OpEx GD

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•So far, models established over 20 years ago (e.g. UK POEM, German model) have been the standards

•A new predictive model for the estimation of agricultural operator exposure has been developed (AOEM, Großkopf 2012) on the basis of new exposure data to improve the current agricultural operator exposure and risk assessment in the EU

•For the assessment of operator exposure, the 75th percentile was considered appropriate (in addition, a model based on the 95th percentile was developed for future use). The model includes application techniques and scenarios for outdoor treatment of low and high crops, by vehicle-mounted/trailed or self-propelled sprayers or by hand-held spray guns and knapsack sprayers

•Further models are available (adapted from EFSA PPR Panel, 2010) covering partly additional scenarios (e.g. granular application)

OPERATOR EXPOSURE

EFSA OpEx GD

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2. DEFAULT PERSONAL PROTECTIVE EQUIPMENT (PPE)

EFSA OpEx GD

Technical control/PPE item Protection factor(by which exposure in absence of protection should be multiplied)

Specific exposure value affected

Protective (chemical resistant) gloves° Operators Liquids 10% Operators Solids 5%Workers Solids 5%

Dermal exposure – hands only

Working clothing or uncertified cotton coverall Operators 10% Dermal exposure – body only

Protective coverall(this is used instead of working clothing/uncertified cotton coverall)

Operators certified protective coverall 5%

Dermal exposure – body only

Hood and visor* Operators 5% Dermal exposure – head only

Hood Operators 50% Dermal exposure – head only

RPE mask type Filter type

Half and full face masks FP1, P1 and similar 25% Inhalation exposure

80% Dermal exposure – head only

FFP2, P2 and similar 10% Inhalation exposure

80% Dermal exposure – head only

°For manual application of granule formulations, the original exposure data were derived considering

the use of PPE (gloves and coverall). For the non-PPE scenario a 100 times higher value is consideredfor hands and body.*Hood and visor are considered in alternative to the RPE

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•Exposure of workers must be estimated for activities that involve contact with treated crops. Such contact may occur when workers re-enter treated areas after application of a PPP

•The underlying studies for the worker exposure model show a high level of uncertainties in terms of quality and reliability of data

•For the exposure calculator, the longer term exposure was only considered

•The main routes of exposure during post-application activities are dermal and inhalation, and the sources of exposure are contact with foliage, soil and possibly dust.

•Oral exposure may occur secondarily to dermal exposure, through hand to mouth transfer. It is generally assumed to be negligible in comparison with that via skin and inhalation

•The level of resultant exposure (for a given activity) depends on the amount of residue on foliagethe intensity of contact with the foliage the overall duration of contact

WORKER EXPOSURE

EFSA OpEx GD

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•Inhalation exposure may be to vapour and/or airborne aerosols (including dust)

•After outdoor application of PPPs and after the spray solution has dried, there will be more rapid dissipation of vapour and aerosols, leading to lower inhalation potential than from indoor treatments (where the inhalation route is a relevant route for re-entry workers), such as those made to crops grown in glasshouses

•Worker exposure estimates for the inhalation route after outdoor applications are only necessary in exceptional cases (e.g. for volatile substances)

•The default value for time of exposure should be taken as eight hours for harvesting and maintenance type activities and two hours for crop inspection and irrigation-type activities

•The initial DFR in a first tier assessment should assume 3 µg active substance/cm2 of foliage/kg a.s. applied/ha

•If no data are available on the degree of dissipation, it may be assumed that active substances will dissipate with a half-life of 30 days

WORKER EXPOSURE

EFSA OpEx GD

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•The transfer of residues

from the plant surface to

the clothes or skin of the

worker has to be taken

into account

•It is determined by the

nature and duration of the

activity during re-entry.

Therefore, it is possible to

group various crop

habitats and re-entry

activities.

TC (cm2/h) = PDE

(mg/h)/DFR (mg/cm2)

Table 1: Transfer coefficients (TCs) (modified from EUROPOEM II (2002) considering US EPA, 2012; for both outdoor and indoor scenarios)

Crop Nature of task (a)

Main body parts in contact with foliage

TC (cm2/h), total potential exposure

TC (cm2/h) assuming arms, body and legs covered (workwear; bare hands)

TC (cm2/h), covered body (workwear) and gloves (PPE)

Applicable for the following crops

Vegetables Reach/pick Hand and body

5 800 2 500 580 Brassica vegetables, fruiting vegetables, leaf vegetables and fresh herbs, legume vegetables, bulb vegetables

Tree fruits Search/reach/ pick

Hand and body

22 500 4 500 2 250 Citrus, cane fruits, oilfruits, pome fruits, stone fruits, tree nuts

Grapes (b) Harvesting and other activities (e.g. leaf pulling and tying)

Hand and body

30 000 10 100 No justified proposal possible (data missing)

n.a.

Strawberries Reach/pick Hand and forearm

5 800 (c) 3 000 750 Berries and other small fruit, low

Ornamentals Cut/sort/ bundle/carry

Hand and body

14 000 5 000 1 400 Ornamentals and nursery

Golf course, turf or other sports lawns

Maintenance Hand and body

5 800 2 500 580 n.a.

General (c) Inspection, irrigation

Hand and body

12 500 (d)

7 500 (e) 1 400 (d) No justified

proposal possible

Cereals, grassland and lawns, hops, oilseeds, root and tuber vegetables, sugar beets, etc.

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•Limited dataset

•Four pathways of exposure are considered (EFSA PPR Panel, 2010):spray drift (at the time of application)vapour (may occur after the PPP has been applied)surface depositsentry into treated crops

•Summing all the exposure pathways, each one being conservative (considering high percentiles of exposure), would result in an overly conservative and unrealistic result. This is particularly true for bystanders, considering that it is extremely unlikely that all exposures occur together. However, for residents, it might be appropriate to sum up the mean exposures from each pathway, where available

•For estimating exposure from surface deposits, ground sediments based on drift for application in orchards are taken from Rautmann/Ganzelmeier; for arable crops, respective data are from the BREAM project.

•Dermal and oral absorption percentages should be taken from the toxicological evaluation. For the dermal absorption percentage (resulting from contact with the spray solution) used for resident and bystander exposure assessment, the value for the in-use dilution should be used, and, for contact with drift deposits, the higher of the two values should be used

RESIDENT AND BYSTANDER EXPOSURE

EFSA OpEx GD

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•In principle, residential exposure should be based on the 75th percentile estimates.

• However, summing the individual 75th percentile exposures does not seem appropriate, whereas summing the means does seem reasonable for assessing repeated exposure

•Both the 75th percentile and mean values need to be calculated for each residential exposure (currently only available for spray drift and drift deposit), the 75th percentile will be assessed separately and the means will be summed up (each calculated exposure is likely providing a conservative estimate, therefore the final resident exposure should be the sum of the mean values of each exposure pathway).

RESIDENT EXPOSURE – SPRAY DRIFT

EFSA OpEx GD

Method of application (distance from sprayer)

These values are the 75th percentiles for residents (assuming average breathing rates for inhalation exposures)

Dermal (mL spray dilution/person) Inhalation (mL spray dilution/person) Adults Children Adults Children

Arable/ground boom sprayer 2 m 0.47 0.33 0.00010 0.00022 5 m 0.24 0.22 0.00009 0.00017 10 m 0.20 0.18 0.00009 0.00013 Orchard/broadcast air assisted applications (a) 2–3 m n.a. n.a. n.a. n.a. 5 m 5.63 1.689 0.0021 0.00164 10 m 5.63 1.689 0.0021 0.00164

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•In principle, residential exposure should be based on the 75th percentile estimates.

• However, summing the individual 75th percentile exposures does not seem appropriate, whereas summing the means does seem reasonable for assessing repeated exposure

•Both the 75th percentile and mean values need to be calculated for each residential exposure (currently only available for spray drift and drift deposit), the 75th percentile will be assessed separately and the means will be summed up (each calculated exposure is likely providing a conservative estimate, therefore the final resident exposure should be the sum of the mean values of each exposure pathway).

RESIDENT EXPOSURE – SPRAY DRIFT

EFSA OpEx GD

Method of application(distance from sprayer)

These values are the mean values (assuming average breathing rates for inhalation exposures)

Dermal (mL spray dilution/person) Inhalation (mL spray dilution/person)

Adults Children Adults Children

Arable/ground boom sprayer

2 m 0.22 0.18 0.00009 0.00017

5 m 0.12 0.12 0.00008 0.00014

10 m 0.11 0.10 0.00007 0.00011

Orchard/broadcast air assisted applications(a)

2–3 m n.a. n.a. n.a. n.a.

5 m 3.68 1.11 0.00170 0.00130

10 m 3.68 1.11 0.00170 0.00130

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SERI = (VC × IR × IA)/BWwhere:SERI = systemic exposure of residents via the inhalation route (mg/kg bw per day)VC = vapour concentration (mg/m3)IR = inhalation rate (m3/day)IA = inhalation absorption (%)BW = body weight (kg)

•For moderately volatile compounds (vapour pressure ≥ 0.005 Pa and < 0.01 Pa)

an adult value of 15 µg/m3

× 0.23 m3/day/kg × 60 kg = 3.45 µg/day/kg × 60 kg = 207 µg/day

a child value of 15 µg/m3

× 1.07 m3/day/kg × 10 kg = 16.05 µg/day/kg × 10 kg = 160.5 µg/day.

•For compounds with low volatility (vapour pressure < 0.005 Pa)

an adult value of 1 µg/m3

× 0.23 m3/day/kg × 60 kg = 0.23 µg/day/kg × 60 kg = 13.8 µg/day

a child value of 1 µg/m3

× 1.07 m3/day/kg × 10 kg = 1.07 µg/day/kg × 10 kg = 10.7 µg/day

RESIDENT EXPOSURE – VAPOUR

EFSA OpEx GD

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SERD = (AR × D × TTR × TC × H × DA)/BWwhere:SERD = systemic exposure of residents via the dermal route (mg/kg bw/day)AR = application rate (mg/cm2) (consider MAF, if necessary)D = drift (%) (if multiple applications have to be taken into account, a lower percentile could be considered for risk refinement)TTR = turf transferable residues (%) (for products applied in liquid sprays, 5 %, and for products applied as granules, 1 % (these values come from data obtained using the Modified Californian Roller Method (Fuller et al., 2001; Rosenheck et al., 2001) and represent the upper end of the range from a number of studies with different compounds))TC = transfer coefficient (cm2/h) (default values of 7300 cm2/h for adults and 2600 cm2/h for children are recommended, TC values take into account minimal protection from clothes)H = exposure duration (hours) (a default value of two hours is recommended by US EPA, 2001)DA = dermal absorption (%)BW = body weight (kg)

Children’s object to mouth transfer should be calculated using the following equation:

SOEO = (AR× D× DRP× IgR× OA)/BW

Children’s hand to mouth transfer should be calculated using the following equation:

SOEH = (AR× D× TTR× SE× SA× Freq× H× OA)/BW

RESIDENT EXPOSURE – SURFACE DEPOSIT

EFSA OpEx GD

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Entry into treated crops is based on exposure from activities such as walking in treated fields for adults.

The method used should be the same as for workers, with the same DFR and a TC based on data for inspection activities (75th percentile: 7500 cm2/h, mean: 5980 cm2/h) , and with a 15-minute exposure TC values are only available for adults. A factor of 0.3 has been applied to the adult TC for children re-entering treated crops

For entry onto treated lawns (two hours of inhalation), exposures should be calculated in the same way as surface deposits (see above), but using a deposition percentage of 100 %

For children, all the pathways of exposure to surface deposits are relevant. Currently, for adults, object to mouth and hand to mouth transfer of surface deposits are considered less important and are not considered in the exposure calculator

For turf treatments, the calculation of exposure to drift fallout is not relevant when bystanders/residents are exposed when entering treated areas directly; the exposure calculation should consider a 100 % surface deposit for people entering treated lawns directly

RESIDENT EXPOSURE – ENTRY INTO TREATED CROPS

EFSA OpEx GD

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Exposures for bystanders should be assessed in the same way as for residents, except that dermal and inhalation exposures to spray drift should be taken as the 95th

percentile values derived from the underpinning datasets

However, the four estimated exposures will be kept separated because, based on the available data, the WoGconsiders that it is unlikely and unrealistic that all the different exposures from the different pathways will occur contemporaneously in the case of bystanders using a probability of 95 %.

For surface deposits, the transfer coefficients should be replaced with 14 500 cm2/h for adults and 5 200 cm2/h for children (short-term exposure of 15 minutes, recommended by US EPA 2001), and the frequency of infant hand to mouth activity should be 20 events per hour (95th percentile of the range of values from 0 to 70).

BYSTANDER EXPOSURE

EFSA OpEx GD

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PERSPECTIVES

EFSA OpEx GD

Data gaps

The WoG highlights the following specific data gaps:

•Operator:Seed treatment exposure scenarios, greenhouse exposure scenarios, home and allotment garden exposure scenarios and other minor scenarios are not covered by the Guidance.Water-soluble bags: the exposure deriving from ML activities is assumed to be 10 % of the corresponding formulation; however further data are needed.Less experienced operators: no data are available to model these cases (but operators and workers have to be trained)

•Use of PPEA lot still needs to be done for an appropriate application of the proposed factors at the post-marketing level.

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PERSPECTIVES

EFSA OpEx GD

Data gaps

•Workers

Available data are not reliable enough to proceed with the acute

exposure assessment (in particular with regard to the TC and DFR

values); further collection/production of data on specific TC and

DFR values is needed to produce more realistic exposure

assessments.

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PERSPECTIVES

EFSA OpEx GD

Data gaps

•Residents/bystanders

Limited dataset!!

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PERSPECTIVES

EFSA OpEx GD

EU Projects: e.g. BROWSE

EU organisations: EFSA (e.g. surveys to define representativescenarios, literature search for relevant published papers)

MSs: national initiatives to address specific scenarios (onexposure, on te use of PPE, etc…)

Industry: field studies to address specific scenarios, to refinethe current ones

Academia: field studies integrating exposure and healt data(see EFSA activity on epidemiology)

Greenhouse: BfR activity

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ACKOWLEDGMENTS

EFSA OpEx GD

Members of the EFSA working group

•Claudia Grosskopf (BfR, Germany)

•Paul Y Hamey (CRD, UK)

•Kyriaki Machera (BPI, Greece)

•Sabine Martin (BfR, Germany)

•Walter Steurbaut (University of Ghent, Belgium)

•Jane Richardson (EFSA)

•Manuela Tiramani (EFSA)