defra research project sp1010 - yclf · project overview retained and used the clea framework,...

Category 4 Screening Levels: The Project, The Facts and The Numbers

Camilla Pease & Ed Stutt

Joint Northern Contaminated Land Forum Summer ConferenceBradford, 9 July 2013

Defra Research Project SP1010

Project TeamProject Manager Nicola Harries

Exposure/ uncertainty modelling & risk assessment

Simon Firth

Exposure modelling & risk assessment

Ed Stutt

Toxicology, epidemiology & risk

assessment

Camilla Pease

Toxicology, epidemiology & risk

assessment

Sarah Bull

Uncertainty & risk assessment

Andy Hart

Uncertainty modellingMarc Kennedy

Statistical analysisRoy MacArthur

Technical Lead Mike Quint

Sanity checkSteve Moreby

Cross‐Government Agency Steering GroupDefraDCLGWelsh GovernmentEnvironment AgencyNatural Resources WalesPublic Health England (formerly Health Protection Agency)Food Standards AgencyHomes and Communities Agency

Part 2A legislation (s.78 of EPA 1990)New Statutory Guidance April 2012

Category 4 Screening Levels:• Revised Statutory Guidance (April 2012) states that:

– “New technical tools and advice may be developed and used....to help regulators and others conform to this Guidance.”

– “Tools might be developed to help assessors apply the Category 1-4 approach in relation to specific substances or situations. For example, this might include the development of generic screening levels to help assessors decide when land might be assumed to be in Category 4.”

• Current Soil Guideline Values / Generic Assessment Criteria replaced with more pragmatic (but still strongly precautionary) Category 4 Screening Levels

• Higher simple test for deciding that land is suitable for use and definitely not contaminated

3

What are C4SLs?• Category 4

– Describes land that is clearly not contaminated land– Land where there is ‘no risk or where the level of risk posed is low’

1

2

3

4

Contam

inated

Land

Not con

taminated

Land

Risk

Point above which land is ‘contaminated land’ under Part 2A

C4SLSGV/GAC

Amount of land

• C4SLs are– intended as generic screening values to help show when

land is within Category 4– they describe a level of risk that whilst above ‘minimal’ is

still ‘low’– provide a ‘higher simple test’ for deciding that land is

suitable for use and definitely not contaminated

WP1

WP2

WP3

• To develop a methodology to derive C4SLs for 4 generic land-uses:– Residential– Allotments– Commercial– Public Open Space

• To derive C4SLs for 6 substances:– Benzo(a)pyrene– Cadmium– Arsenic– Benzene– Hexavalent chromium– Lead

Project ObjectivesAug’12

Sep

Oct

Nov

Dec

Jan

Feb

Mar

Apr

May

Jun’ 13

Stakeholder engagement• Stakeholder engagement was built into the project

specification, with stakeholder workshops being incorporated into each Work Package of the research

• Stakeholder workshops held on:– 6th November 2012– 4th February 2013– 2nd May 2013

• Feedback and comments from stakeholders were incorporated and taken into account in the development of the project

Stakeholder Feedback

Project Overview Retained and used the CLEA framework, modified according

to considerations of the underlying assumptions and science, within the context of Defra’s policy background.

Modifications relating to: exposure modelling; toxicological parameters and the setting of toxicological

criteria at a higher than minimal risk (defined as a ‘low level of toxicological concern’ or LLTC); and

considerations in the setting and use of C4SLs.

Developed frameworkto derive C4SL1. Toxicological

assessment2. Derive LLTCs (mg kg‐1

bw day‐1)

4. Use modified CLEA and LLTCs to derive

pC4SLs

5. Use CLEA probabilistically to

explore probability of exceeding LLTC when

representative concentration = pC4SL

7. Is the pC4SL appropriately precautionary?

no

yes

STOPC4SLs suitable for use

(final C4SLs)

6b. Take account of sources of variability and uncertainty that are not quantified by

probabilistic modelling.

6c. Take account of other relevant scientific considerations, including background

concentrations, other routes of exposure, and epidemiological evidence

6d. Take account of any social or economic considerations that are thought relevant to setting an appropriate level of precaution

6a. Take account of uncertainties affecting the toxicological assessment

3. Make (and justify) relevant modifications

to CLEA

The CLEA paradigm for ‘minimal risk’

Cs

HCV

SGV

Expo

sure

Pa

ram

eter

s

CLEA model

Is Cs > SGV?

Measured Concentrations

•CLEA fit for purpose: to determine minimal risk values

•What modifications can be made to derive C4SL?

• Review ‘authoritative’ human health/tox guidance

• Follow the principles of defining minimal risk in SR2

• Take the lowest value for the most sensitive effect OR

• A ‘Policy’ decision is taken e.g. to equate to an

existing standard or objective

The CLEA paradigm for ‘low risk’

Cs

LLTC

C4SL

Expo

sure

Pa

ram

eter

s

CLEA model

Is Cs > C4SL?


Review ‘authoritative’ guidanceFollow the general principles in SR2Review the dose response curve for the most sensitive effect(s)N.B. and consider ALL effects where dose‐responses overlap)

Consider modifications to exposure parameters

‘Policy’ inputs/Risk Management Decisions

The new Part 2A Statutory Guidance needs new tools to support the definition of a ‘low risk’ screening level

“Zero risk”

Exposure to the bodyvia mouth, lung or skin

“Minimal risk”

“Low risk”

0

Intake dose of a contaminant

Toxicological Hazard

Level of uncertainty

“Unlikely to be a concern”“ Intake is of low concern”

Does the dataset reflect reality for humans?

Does the prediction of intake from a complex exposure modelreflect reality for humans?

Chemical Specific Assessment Factors – thresholded effectsChemical Specific Margins – non‐thresholded effectsFor carcinogens – parallels approaches in COC G06 guidance Oct 2012

SGV

C4SL

CAT 4CAT 3

SPOSH?Risk = f Hazard x Exposure

Toxicological Assessment1. Collate the Evaluations for the Contaminant as per SR2:

identify all known toxicological hazards; collate HBGVs from relevant authoritative bodies and specify the conditions of Minimal Risk

2. Reviewthe scientific basis of each HBGV.

Choose the pivotal study.

2a) Animal toxicology data2b) Human toxicology/ epidemiology data

3. Are there adequate dose‐effects data

for the chosen pivotal study?

(3b) & (6b) Perform BMD modelling and determine

the mg/kg bw/day that constitutes an X% change in

incidence or response1

and use BMDLX as the POD2

Yes3a) Use NO(A)EL/LO(A)ELas the POD

No

4. Does the critical endpoint exhibit a threshold?

No Yes



2c) Policy choice, with or without a toxicological rationale

Go To 7Yes

6c) Specify an ELCR above 1 in 105 based upon an agreed policy decision

All systemic effects

4b) Derive a CSAF using scientific evidence oruse default UFs

Cancer

7. DEFINE LLTC(units the same as POD)

Consider whether effects address‘harm’ as specified in Part 2A SG

6a) Revert to quantitative animal data (Go to 3) and use qualitative human data to support the outcome using weight of evidence

No

Min Risk

POD

CSAFUF

5b) Thresholdedchemicals

5a) Non‐thresholdedchemicals

4a) Derive a CSM using scientific evidence oruse generic margins

POD

ELCR ‐ LLTC

ELCR 1 in 105

CSMGenericdefault

Green = risk management decision (see text in report)

• Consider lifetime averaging• Consider combined exposures in CLEA for

different routes/impact of bioavailability• Consider using receptor‐specific physiological

parameters


Genericmargin

• LLTC derived using similar framework to SR2 but with additional/refined interpretation:

– Take account of all critical health effects – not just the most sensitive

– Use of BMD modelling to set POD where possible

– Avoid the use of default UFs – use scientifically based chemical specific adjustment factors/margins, where possible

– Consider moving above ELCR of 1 in 100,000 (e.g. 2 in 100,000) for carcinogens with human epidemiological data

– Consider using receptor specific physiological parameters

Advocating - Use BenchMark Dose Modelling to interpret dose-response data whenever data allows

Three ways to Derive an LLTC

Example of Change in Point of Departure for Cadmium

• Cadmium kidney toxicity in human - as indicated by elevated levels of a small protein biomarker β2-microglobin (β2M) in urine.

• Meta analysis of 165 paired datasets from 35 human epidemiology studies

Table 3.1: BMD and BMDL modelling for the total and sub-populations

Total population Caucasians only Over 50, non

occupationally exposed

U 2M >300 g/g creatinine BMR 5 BMR 10 BMR 5 BMR 10 BMR 5 BMR 10

BMD 4.09 4.72 4.65 5.32 5.25 5.73

BMDL 3.68 4.32 3.84 4.53 6.33 5.46

U 2M >1000 g/g creatinine BMR 5 BMR 10 BMR 5 BMR 10 BMR 5 BMR 10

BMD 5.83 6.4 6.8 7.32 6.33 6.77

BMDL 5.39 5.99 5.95 6.51 5.46 5.94

Minimal risk= 4 µg β2M/g creatinine(stated as a BMDL5)

Cadmium in urinevs

β2M in urine

Internal marker of effect: ‘Hybrid approach’ to modelling, including a kinetic modelling stage

POD for LLTC: propose BMDL10

EFSA Evaluation 2009

Oral route: Step 4 Effects are thresholded derive a CSAF

Min Risk LLTC

Uncertainty to account for differences between individuals

Method for defining these ‘adjustment factors’ is from WHO 2005 Median

ilexthPercentAF

Derive Oral LLTC value

POD = BMDL10 of 4.3 µg Cd g-1 creatinine (lowest 95th percent confidence limit)

(marker of renal effect – a 10% extra risk of exceeding the lower cut off threshold of 300 µg β2M/g creatinine in urine)

Using the 90th percentile data, the CSAF is 2.9.

Therefore the LLTCoral is 4.3/2.9 = 1.5 µg Cd/g creatinine.

Using toxicokinetic modelling:

This translates to an intake of 0.54 µg kg-1 bw day-1

Take care not to go higher than 0.54 for a screening level!!!Note - from US ATSDR 2012 evaluation: a HBGV for Bone effects is set at an intake of 0.5 µg kg-1 bw day-1

Cf. HCV = 0.36 µg kg-1 bw day-1

Toxicological Assessment1. Collate the Evaluations for the Contaminant as per SR2:

identify all known toxicological hazards; collate HBGVs from relevant authoritative bodies and specify the conditions of Minimal Risk

2. Reviewthe scientific basis of each HBGV.

Choose the pivotal study.

2a) Animal toxicology data2b) Human toxicology/ epidemiology data



(3b) & (6b) Perform BMD modelling and determine

the mg/kg bw/day that constitutes an X% change in

incidence or response1

and use BMDLX as the POD2

Yes3a) Use NO(A)EL/LO(A)ELas the POD

No

4. Does the critical endpoint exhibit a threshold?

No Yes



2c) Policy choice, with or without a toxicological rationale

Go To 7Yes

6c) Specify an ELCR above 1 in 105 based upon an agreed policy decision

All systemic effects

4b) Derive a CSAF using scientific evidence oruse default UFs

Cancer

7. DEFINE LLTC(units the same as POD)


6a) Revert to quantitative animal data (Go to 3) and use qualitative human data to support the outcome using weight of evidence

No

Min Risk

POD

CSAFUF

5b) Thresholdedchemicals

5a) Non‐thresholdedchemicals

4a) Derive a CSM using scientific evidence oruse generic margins

POD

ELCR ‐ LLTC

ELCR 1 in 105

CSMGenericdefault

Green = risk management decision (see text in report)

• Consider lifetime averaging• Consider combined exposures in CLEA for

different routes/impact of bioavailability• Consider using receptor‐specific physiological

parameters


Genericmargin

Committee on Toxicity reviewed the Framework on 14th May 2013

Draft Minutes from this meeting are now available (seehttp://cot.food.gov.uk/cotmtgs/cotmeets/)

“One Committee Member, who was familiar with contaminated land policy, commented that the broad approach was reasonable.” (para 24)

“Members agreed that the report was good” (para 28)

“The committee agreed that the use of a chemical-specific margin (CSM) approach, which paralleled the margin of exposure (MOE) approach, was appropriate to derive an LLTC for non-threshold chemicals. However, defining an acceptable margin entailed value judgements, and was not purely scientific.”

“It involved an element of risk management, and careful consideration should be given as to how risk assessment and risk management could be brought together without the possibility of misuse. Specific criteria were needed by which to define the levels of margins, supporting the need for a central discussion rather than ad hoc local decisions.”

The Use of Margins POD

Intake level mg/kg/day= LLTC

Margin?Exposure scenario

Does the Committee think that, in the context of cancer, the use of an Excess Lifetime Cancer Risk (ELCR) higher than 1 in 100,000 is appropriate when defining a LLTC using quantitative dose-response modelling (based on human data)?

“The Committee recommended that further advice on this should be sought from the Committee on Carcinogenicity (COC). ELCRs were used by other bodies internationally and so could not be ignored. However, it is a risk management decision to define an acceptable level of risk.”

The Use of Excess Lifetime Cancer Risk – using Human Data only

We have proposed a banding of 1 in 10,000 – 1 in 50,000 as a ‘notional ELCR’ that could constitute ‘low risk’ but this is not agreed and approved at a government level

A consultation with COC is expected later in the year to further explore this proposition

The CLEA paradigm for ‘low risk’

Cs

LLTC

C4SL

Expo

sure

Pa

ram

eter

s

CLEA model

Is Cs > C4SL?


Review ‘authoritative’ guidanceFollow the general principles in SR2Review the dose response curve for the most sensitive effect(s)N.B. and consider ALL effects where dose‐responses overlap)

Consider modifications to exposure parameters

‘Policy’ inputs/Risk Management Decisions

Key pathways/parametersAssessment to determine relative importance of each exposure pathway for the 6 contaminants

• Soil + dust ingestion • Dermal contact outdoors• Inhalation dust indoors• Consumption of homegrown produce• Inhalation vapours indoors

– Each pathway assessed within CLEA for algorithms used, parameter values

– Sensitivity analysis to determine the most significant sources of uncertainty in estimates of ADE (by varying one parameter at a time with reasonable min and max values)

Sensitivity Analysis

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5Body

weight

Body

weight

Height

Height

Exposure frequency soil & dust

Exposure frequency produce

Exposure frequency derm

al in

Exposure frequency derm

al out

Exposure frequency inhalation

inExposure frequency inhalation

out

Hours in

Hours out

Hours out

Skin adherence in

Skin adherence out

Soil ingested

Soil ingested

Inhalation

rate

Exposed skin in

Exposed skin in

Exposed skin out

Exposed skin out

Produce consum

ption rate

Hom

egrown fraction

Hom

egrown fraction

Produce soil loading

Produce soil loading

Soil cla

ySoil sand

Soil organic matter

Soil organic matter

Threshold wind speed

Threshold wind speed

Empirical function

for dust model

Empirical function

for dust model

Soil temperature

Soil temperature

Building footprint

Living

space height

Building pressure differential

Foundation

thickness

Foundation

thickness

Floor crack area

Dust loading factor

Dust loading factor

Average

annual w

indspeed

Average

annual w

indspeed

Air dispersion factor

Air dispersion factor

Fraction

of hard / vegetative

cover

Fraction

of hard / vegetative

cover

Depth to source below

building

Depth to source below

building

Air water partition

coefficie

ntDiffusion

coefficient in air

Diffusion

coefficient in air

Diffusion coefficient in water

Diffusion coefficient in water

Organic carbon

partitio

n coefficient

Organic carbon

partitio

n coefficient

Octanol w

ater partition

coefficie

ntOctanol w

ater partition

coefficie

ntDermal absorption fractio

nDermal absorption fractio

nRelative

bioavailability soil

Relative

bioavailability airborne

dust

Soil‐to‐plant concentration

factor (green

vegetables)


factor (green

vegetables)

Soil‐to‐plant co

ncentration factor (root vegetables)


ncentration factor (root vegetables)

Soil‐to‐ plant concentration

factor (tuber vegetables)


factor (tuber vegetables)


factor (herbaceous fruit)


factor (herbaceous fruit)


factor (shrub

fruit)


factor (shrub

fruit)


ncentration factor (tree fru

it)Soil‐to‐plant co

ncentration factor (tree fru

it)Soil to indoor air correction factor

Soil to indoor air correction factor

Soil‐to‐dust transport factor

Soil‐to‐dust transport factor

Lifetime averaging

Normalise

d change

in GAC

Benzo[a]pyrene

Benzene

Arsenic

Chromium (VI)

Cadmium

Lead

Sensitivity AnalysisMost significant sources of uncertainty in estimates of ADE:

• Body weight (all pathways), Averaging time (all pathways) • Soil and dust ingestion rate • [Dermal contact outdoors]: Exposure frequency outdoors, Skin adherence

outdoors, Maximum exposed skin fraction outdoors, Dermal absorption fraction

• [Vapour and dust inhalation indoors]: Inhalation rate– [Dust inhalation indoors]: Dust loading factor, Soil to dust transport factor– [Vapour inhalation indoors]: Soil to indoor air correction factor, Building

footprint, Living space height• [Consumption of homegrown produce]: Soil to plant concentration factors,

Homegrown fraction

• Proposed modifications to exposure modelling focussed on adjustment of these parameter values

Central tendency values where appropriate

Proposed modifications to exposure assessment

Proposed change in draft WP1 report Change invoked?

Res Allo Comm

Reduce soil ingestion rates for residential and commercial land‐uses

Halve exposure frequencies for children on allotments Reduce soil adherence factors in children for residential land‐use from 1 to 0.1 mg cm‐2

Reduce exposure frequency for dermal contact outdoors for residential land‐use from 365 to 170 days per year

Update vapour inhalation rates to the mean values recommended in USEPA, 2011

Reduce indoor dust loading factors for residential and commercial land‐uses to better reflect likely concentration of PM2.5

Use of central tendency estimates of fruit and vegetable ingestion rates rather than 90th percentiles ½ ½

Reduce the fraction of homegrown produce for residential land‐use

Exclude the quantitative consideration of background exposure from the derivation of C4SLs

Proposals, retained, rejected or modified on the basis of:

• Steering group review• Stakeholder consultation• Lessons learned while developing C4SLs for the 6

substances, e.g. probabilistic modelling to determine whether change would result in C4SLs with appropriate level of precaution

– Modelling for allotments and residential with homegrownproduce showed high probability of exceedances using mean consumption rates

Top 2 approach (i.e. 90P consumption rates for 2 most important produce types)

Proposed modifications to exposure assessment

Receptor-specific LLTC

• Tox criteria are sometimes derived from concentrations in air (AQO or RfC) or drinking water (DWS) – these concentrations are generally recommended for long-term or lifetime exposure with minimal risk

• The conversion to HCVinh and HCVing was based on adult receptor characteristics (e.g. inhalation rate and bodyweight) but calculation of exposure for generation of GAC/SGV is for 0-6 yr old child

• Exposure relative to bodyweight is 2.5 - 3x higher for child than for adult

• Recommended to derive receptor-specific LLTCinh and LLTCing, based on the average bodyweight and ingestion or inhalation rate for a 0-6 yr old child (13.3 kg, 1 litre day-1 and 8.8 m3) for use in residential land use scenario

C4SL CLEA Modification:Use child‐specific exposure assumptions to convert media concentrations totoxicological criteria for residential land‐use, as appropriate, if lifetimeaveraging is not employed.

• POSresi - Grassed Area Close to Housing

Public Open Space

Public Open Space• Scenario 1, POSresi:

– Grassed area of up to 0.05 ha and a considerable proportion of this (up to 50%) may be bare soil

– Predominantly used by children for playing and may be used for activities such as a football kickabout

– Sufficiently close proximity to home for tracking back of soil to occur, thus indoor exposure pathways apply

• Adaptations to CLEA ‘resi without h/g produce’ – ingestion rate 75 mg.day-1 (approximately 50:50 ratio between

ingestion of soil and soil-derived dust (USEPA, 2011 & EA, 2009c). )

– older children as the critical receptor on basis that they will use site most frequently (AC 4-9)

POSpark – Park Type Open Space

Public Open Space• Scenario 2, POSpark:

– Public park (>0.5 ha), predominantly grassed and may also contain children’s play equipment and border areas of soil containing flowers or shrubs (75% cover)

– Outdoor exposure pathways only (no tracking back)• Based on adaptation of the CLEA allotment land use

scenario for receptor characteristics:– Female child age classes 1-6– Soil ingestion rate of 50 mg.day-1 [based on proportion (~50%) of

daily ingestion rate (100 mg.day-1) assigned to ingestion of soil outdoors (USEPA, 2011)]

– Occupancy period outdoors = 2 hours.day-1

– Exposure frequency of 170 days.year-1 for age classes 2-18 and 85 days.year-1 for age class 1

Probabilistic exposure modelling

3. Revise set of deterministic inputs for Modified CLEA

4. Use Modified CLEA to back‐calculate proposed C4SL

(soil concentration that leads to exposure = LLTC)

5. Use Probabilistic CLEA to estimate probability of exceeding LLTC when

representative concentration = C4SL

6. Is the proposed C4SL appropriately precautionary?

no

yes

STOPC4SL is suitable for use

6 a – d. Other considerations

1 + 2. Derive LLTC

Uncertainty• How precautionary are the C4SL?• How likely is the occurrence of significant harm at a

given soil concentration (e.g. the SGV or C4SL)?– How confident are we that significant harm would not occur at the

health based guideline value (e.g. HCV or LLTC?)– How confident are we in our exposure estimates?

• We have addressed this using:– Probabilistic modelling (Monte Carlo analysis) of CLEA exposure

estimates– Qualitative appraisal of

uncertainties in derivation of LLTC and residual uncertainties in exposure modelling 0

0.10.20.30.40.50.60.70.80.9

1

0.00001 0.0001 0.001 0.01 0.1 1

Cum

ulat

ive

Prob

abili

ty

ADE (mg kg-1(bw) d-1)

• Tables used to qualitatively assess residual uncertainties• Qualitative evaluation of magnitude of uncertainty based

on expert judgement

• Example (for benzene):

Qualitative appraisal of uncertainty

Parameter Evaluation

Estimation of indoor air concentrations using Johnson and Ettinger model for UK building stock. The CLEA model uses the J&E model which is likely to over‐estimate the indoor air concentration of benzene in a large proportion of UK building stock. The extent of over‐estimation is anticipated to be up to several orders of magnitude.

/ +++

Further considerations• May need to consider wider context when setting the

C4SL for a particular substance, e.g.:– Background soil concentrations– Background exposure from non soil sources– Epidemiological evidence– Socio-economic considerations, e.g. the cost and proportionality

in setting C4SLs so low as to always be exceeded• Sense check on whether there could be odour,

phytotoxicity or visual acceptability issues or acute risks at the C4SL

Provisional C4SLSubstance pC4SL with changes to exposure parameters and LLTC (mg.kg-1)

(SGV or GAC shown in brackets for comparison) Residential Allotments Commercial POSresi POSpark

With home grown prod.

Without home grown

prod.

Arsenic 37 (32) 40 49 (43) 640 (640) 79 168

Benzene 0.87 (0.33) 3.3 0.18 (0.07) 98 (95) 140 230

Benzo(a)pyrene (as a surrogate marker for genotoxic PAHs)

5.0 (1.0) 5.3 5.7 (2.1) 76 (14) 10 21

Cadmium 26 (10) 149 4.9 (1.8) 410 (230) 220 880

Chromium (VI) 21 (4.3) 21 170 (2.1) 49 (35) 23 250

Lead 86 – 210 (450*)

130 - 330 (450*)

34 – 84 (450*)

1100 – 6000 (750*) 270 - 760 580 - 1400

GAC from Nathanail et al., 2009 shown * Former SGV now withdrawn

Provisional C4SLs - BaP

Normal background concentrations = 3.6 mg/kg (urban area)

Using C4SLs• Suggested approach:

– Like SGVs, C4SLs are generic screening values and should be used in the same way (i.e. understand the methodology underpinning their derivation and their limitations)

– Overall guidance outlined in “Using SGVs” should be followed (signposts detailed guidance in CIEH/CL:AIRE and US EPA documents)

– They can be used as part of a GQRA for assessing risks to human health from long-term exposure to soil contamination for common scenarios/pathways

– They can be used to help determine whether a site is within Category 4 for human health

– Statistical guidance based on detailed review of CIEH/CL:AIRE by Fera statistician

Next Steps• Final research reports submitted to Defra for consideration by

Steering Group - 7th June 2013

• Peer review process– Committee on Toxicology – 14th May 2013 – supportive of the

scientific approach, recommended centralised C4SL derivations http://cot.food.gov.uk/pdfs/drcotmin14may13.pdf.

– Peer review of final reports

• Publication on Defra website (“the 12-week publication window should commence from the end of the peer review process”) of:– Final reports– COT minutes– Anonymised stakeholder comments and feedback– Policy view (e.g. companion document)

Thank you

The Human Health Issues for Lead

Lead - Collate Health Based Guidance Values (HBGVs) from relevant authoritative bodies

Withdrawn

If a guidance value for contaminated land is defined based upon a toxicological evaluation, it will be setting a new international precedent.Language used – reference value or action standard etc.

A) ALL Routes HBGVoral Unit UF used PoD Endpoint

US EPA 10 µg Pb/dL bloodDevelopmental Neurotoxicity

Health Canada 10 µg Pb/dL bloodDevelopmental Neurotoxicity

US ATSDRDevelopmental Neurotoxicity

WHO/JECFA 10 µg Pb/dL bloodDevelopmental Neurotoxicity

UK CLEA 2002 10 µg Pb/dL bloodDevelopmental Neurotoxicity

US CDC 2012 5 µg Pb/dL bloodDevelopmental Neurotoxicity

No MRL has been set

Policy Action Standard (June 2012) – based on blood lead levels measured in populations of US children

A ‘DO NOT CITE’ CCME draft Nov 2012 is now using 5 µg/dL

Choice of pivotal study/endpointNeurobehavioural effects in children

Chronic kidney effects in adultsEffects on blood pressure in adults

N.B. Overlapping dose‐response curves

All effects had available datasets conducive to BMD modelling as described in EFSA (2010)

i) Neurobehavioural effects (IQ deficits) – dose‐response data in Lanphear et al., 2005; Original BMD modelling for EFSA 2010 Opinion ‐ by Budtz‐Jorgensen (2010)

ii) Cardiovascular effects (hypertension) in adults – dose‐response data in fourseparate studies (reported in EFSA 2010 Opinion)

(Glenn et al. 2003; Nash et al., 2003; Vupputuri et al., 2003; Glenn et al., 2006).

iii) Renal effects (estimated glomerular filtration rates eGFRs) in adults – dose‐response data in Navas‐Acien et al., (2009).

Biokinetic Modelling of Lead Intakes• Used to convert blood lead concentration to an intake dose• IEUBK used to assess relationship between intake, uptake

and blood lead for 0 to 7 yr old child• Carlisle & Wade and USEPA Adult Lead Methodology (ALM)

used to assess relationship between intake, uptake and blood lead for adult

IEUBK results

0.48

Provisional C4SLs – Lead

Low level of concern for all effects?N.B. No UF has been applied

All of the toxicological quantitative evaluations for the three critical effects measured to date:

NeurobehaviouralChronic kidney diseaseCardiovascular effects

suggest no threshold, and there could be real health concerns to be investigated further in populations of children and adults exposed to blood lead levels higher than 5 µg dL‐1.

Conclusion

Blood Level5 µg/dL

Measureable Health Effects in Human

Exposure to soil Pb innormal life

Evidence good

Evidence lacking

?

High uncertainty in CLEA model + kinetic models

defra research project sp1010 - yclf · project overview retained and used the clea framework,...

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