Biomonitoring of dermal exposure to cyclosiloxanes from

consumer products using end-exhaled air

Contribution to Parallel Session 10:

Dermal Exposures

Jacqueline W. H. Biesterbos, MSc

Department for Health Evidence, Radboud University Nijmegen Medical Centre, The Netherlands

Introduction

• The use of personal care products (PCPs)1:

• Some with high frequency (e.g. deodorant/day cream)

• Often multiple products are used simultaneously

aggregate exposure to common ingredients

• Contribution to exposure models in the interest of risk assessment

of aggregate exposures

Research Question:

If a consumer applies a personal care product (e.g. day cream) on the

skin, how much of the product is absorbed and becomes available in

the systemic circulation (internal dose)?

1 Biesterbos et al. Food and Chemical Toxicology 55 (2013) 8-17

Study design1

Focus on dermal absorption of cyclic siloxanes (D4/D5)

• ‘Smooth feel’

• Odourless - transparent

• Solvent for active ingredients

D4 D5

Molecular weight 296.6 370.8

Vapour pressure (Pa at 25°C) 140 27

Log P octanol/water 5.10 5.20

Structure

1 Plotzke et al. 2002 Non regulated study: Human dermal absorption of decamethylcyclopentasiloxane (D5)

Study design – Human volunteer study

Study protocol approved regional ethics committee

• Recruitment and informed consent for healthy volunteers

• 10 females and 5 males were included

• Intake:

• Baseline measurement

• End-exhaled air sample

• Urine sample

• Registration of all PCPs used

• Completion of 24-hr diary

Study design – Exposure protocol

• No use of PCPs 24 hours prior to the experiment

• Volunteer and researcher

• Total dose 15 mg/cm2 applied to the forearm during 60 min

• During dermal exposure the treated arms were kept in a fume hood

• Post-exposure filtered air was supplied to breathing zone during 5 h

Experiment: Subject exposed to:

Control No dermal exposure, D5 applied to ‘dummy’ arm

1 D5 (pure substance)

2 Crème containing D4/D5 (commercial product)

3 Deodorant containing D4/D5 (commercial product)

4 Crème and deodorant containing D4/D5 simultaneously

5 D4 (pure substance)

randomized

Study design – Exposure protocol

• Dermal administration

• Prevention and monitoring of inhalation exposure

Study design – Sample collection

• End-exhaled air collected using a Bio-VOC container

• Substances of interest was transferred to a 1/4” x 3.5” stainless

steel absorbent tube filled with Carbograph 2TD 60/80 and

Carbograph 1TD 60/80

Study design – Sample collection

Notes:

• Time-weighted average air concentrations were determined by air sampling

• Exposure in a laboratory environment and post-exposure in an office

• The collection of urine in the first time slot post-exposure was removed later

after D5 appeared to evaporate from the skin into the breathing zone of the

study participant

Study design – Analysis

• Conditioning of adsorption tubes prior to experiment

• ATD tubes: minimum - 4 h at 350 °C

• Mini ATD tubes: 2 hrs at 320 °C + ½ h at 335 °C

• Tubes are loaded with internal standard (13C-D4 and 13C-D5) to monitor recovery

• Analysis by thermal desorption gas chromatography mass spectrometry (TD-GC-MS)

• Detailed method is presented by Gwendolyn Beckmann on poster nr. 10

Tube conditioning unit TD-GC-MS

Preliminary results - Baseline

Median (range) concentration in end-exhaled air (ng/m3): All (N=15): D4 = 6,609 (1,932-44,795) D5 = 3,769 (1,573-44,383) Men (N=5): D4 = 4,318 (2,727-11,830) D5 = 2,272 (1,573-27,073) Women (N=10): D4 = 7,046 (1,932-44,795) D5 = 6,628 (2,121-44,838)

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Preliminary results – Control experiments (N=3)

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Preliminary results – D5 pure substance

V2 - D5 pure substance

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Preliminary results – Crème (only)

V3 - Creme

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Preliminary results – Deodorant (only)

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Preliminary results – Crème and deodorant (combined)

V4 - Creme and deodorant simultaneously

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Summary and discussion of preliminary results

• Significantly elevated levels of D4 and D5 in end-exhaled air were

observed after normal use of PCPs but (for D5) also following 24 h

of no use of PCPs (control experiments).

• We observed a peak of D5 in almost all exposure experiments

occurring at t=90 min, which may be attributed to inhalation

exposure during the first toilet visit (not during subsequent toilet

visits).

• Results so far do not indicate significant dermal uptake of D5

compared to the background following 24 h of no-use of PCPs.

Acknowledgements

Paul Scheepers, Gwendolyn Beckmann, Rob Anzion, Nel Roeleveld, Frans Russel

Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Ad Ragas

Dept Environmental Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands

Martine Bakker, Bas Bokkers and Christiaan Delmaar

National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands

Tatsiana Dudzina and Natalie von Goetz

ETH Zürich, Switzerland

Correspondence:

Department for Health Evidence, Radboud University Nijmegen Medical Centre,

PO Box 9101, 6500 HB Nijmegen, the Netherlands,

phone: +31 24 36 13 728 e-mail: J.Biesterbos@ebh.umcn.nl

This study was financially supported by CEFIC’s LRI