14.1 - L.Leese

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An Agency of the Health and Safety Executive www.hsl.gov.uk An Agency of the Health and Safety Executive

Arsenic speciation in urine using µLC ICP-MS for routine biological monitoring – A two year study

Elizabeth Leese, Jackie Morton and Vikki Carolan

Email – liz.leese@hsl.gsi.gov.uk

ISBM – Wednesday 11th September 2013

An Agency of the Health and Safety Executive

Introduction

• Arsenic & exposure

• Workplace exposure

• µLC-ICP-MS separation technique

• Background Levels study

• 2 year semi-conductor workplace study

Arsenic

• Found in all rock, soil, water and air.

• Ranked – 20th most abundant element in the earths crust

– 14th in seawater

– 12th human body

• Classified as a group 1 carcinogen by IARC – Cancer of the skin, lung, kidney and bladder.

– Vomiting, abdominal pain, weakness, diarrhoea and muscle cramps.

• Exposure – Inhalation

– Ingestion

– Dermal

Species of Arsenic

Monomethylarsonite (MMA3+)

Dimethylarsinite (DMA3+)

Arsenite As3+

Arsenate As5+

Dimethylarsinate (DMA5+)

Monomethylarsonate (MMA5+)

Arsenocholine, AC

Trimethylarsonioacetate Arsenobetaine, AB

Arsenic Exposure

• Environmental & Dietary

– Cigarettes

– Shellfish & Seafood

– Poultry

– Grain e.g. rice

– Red wine / real ale

– Soil and water

Arsenic Exposure Worldwide

http://www.bgs.ac.uk/arsenic/

Arsenic Exposure

• Occupational – Semi Conductor Industry

– Glass Production / Recycling

– Wood Preservation / burning preserved wood

– Pesticide manufacture / application

– Power plants burning arsenic rich coal

– Mining, smelting & landfill

Urinary Arsenic Analysis – Problem 1

• Total Arsenic

– A total element value is not helpful when assessing exposure, because its unable to distinguish dietary arsenic from toxic inorganic arsenic

• Hydride / Extraction techniques

– Difficulty reducing methylated metabolites • Under estimation

– Food & drink containing methylated metabolites

e.g. rice, red wine & seafood • Over estimation

Arsenic Speciation - µLC-ICP-MS

• Allows separation of individual species

• Species of Interest

– Inorganic - As3+ As5+

– Methylated Metabolites – DMA5+ MMA5+

– Dietary – AB.

Separation Technique

ICP-MS

Thermo Scientific XSERIES 2

ESI OneFAST

• 6 port switching value

• 1 ml sample loop

• 50x4mm ID Dionex AG7 column

Mobile Phase A – 2 mM Ammonium carbonate

Mobile Phase B – 70 mM Ammonium carbonate

As5+ MMA

1 µg/L Standard

As5+ MMA

10 µg/L spiked urine

Urinary Arsenic Analysis – Problem 2

• Lack of unexposed Background Reference Values

• NO UK Guidance Values

• Drinking water

– EU 10 µg/L total arsenic

– US & WHO 10 µg/L inorganic arsenic

• Biological Samples

– US BEI 35 µg/L summation of inorganic &

– German BAT 50 µg/L metabolites NO AB

• Population studies from unexposed individuals

Most studies people are asked to abstain from eating shellfish and seafood.

Background Levels Study

• 95 urine samples collected from 53 males and 42 females (>18 years old)

• Not occupationally exposed to arsenic

• Questionnaire returned with urine sample

– Gender / Date of birth

– Smoking habits

– Dietary supplement

– Diet of previous 7 days • Fish Shellfish Seaweed

• Rice Mushrooms Poultry

• Red wine Real ale Bran / germ

Background Levels Results

Health Canada – Human Biomonitoring of Environmental Chemicals in Canada. n= 6400

US NHANES – National Report on Human Exposure to Environmental Chemicals. n=2557

As3+ As5+ MMA DMA AB

HSL n=95

µg/L µmol/mol creatinine

µmol/mol creatinine

95th percentile 0.54 0.99 0.23 0.35 2.37 3.08 12.68 16.08 126.7 174.7

Mean 0.18 0.30 0.06 0.09 0.78 1.33 4.10 7.09 28.69 51.30

µg/L µg/L µg/L µg/L µg/L

Health Canada 95th percentile

4.5 <LOD 3.0 30 110

US NHANES 95th percentile

<LOD 1.10 2.40 16.0 35.0

Background Levels Results µmol/mol creatinine As3+ As5+ MMA DMA AB

Seafood n=66

Mean 0.31 0.09 1.61 8.76 72.06

Range <LOD – 2.3 <LOD – 0.63 <LOD – 13.9 0.9 - 104 0.3 - 1090

NO seafood n=29

Mean 0.29 0.08 0.70 3.31 4.06

Range <LOD – 1.1 <LOD – 0.56 0.2 – 1.9 0.6 – 7.5 0.1 – 47.8

Red wine (NO seafood) n=9

Mean 0.29 0.16 0.81 4.0 4.6

Range 0.07 – 0.54 <LOD – 0.56 0.3 – 1.3 1.9 – 7.5 0.7 – 47.8

NO wine or seafood n =20

Mean 0.29 0.05 0.65 3.02 2.44

Range 0.03 – 1.1 <LOD – 0.31 0.2 – 1.9 0.6 – 5.2 0.1 – 9.8

2 Year Occupational Study

• Semi-conductors

• Pre & Post samples

– Spring

– Autumn

• 91 workers (54 males & 25 females)

• 441 urine samples

– 203 paired pre and post samples

– 35 single samples

2 Year Occupational Study Results

Semi-conductors

n=441 µg/L µmol/mol creatinine

Mean 0.10 0.12 0.11 0.13 0.58 0.72 3.5 4.2 29.6 37.9

95th percentile 0.31 0.39 0.28 0.45 1.48 1.87 11.4 14.1 111.3 162.8

Unexposed Background

n=95 µg/L µmol/mol creatinine

Mean 0.18 0.30 0.06 0.09 0.78 1.33 4.10 7.09 28.69 51.30

95th percentile 0.54 0.99 0.23 0.35 2.37 3.08 12.68 16.08 126.7 174.7

Summary

An arsenic speciation method has been used to establish urinary background levels for five arsenic species in a UK population

A two year semi-conductor occupational study showed workers were not exposed.

• Reproducible

• Low LOQs

• Good external quality assurance (GEQAS)

Thank you

14.1 - L.Leese

Health & Medicine