f3300 New Sharon Church Road Hillsborough, NC 272778 January 17, 2017May 12, 2014 Tel: (919) 732-7442 Fax: (919) 286-5647

Protocol for Assessing Dermal Exposures While Using Pressurized Sprays, Airbrushing And Drawing With Pastels

Woodhall Stopford, MD, MSPH

Background There is an increasing weight of evidence that the critical measure for determining safety of skin irritants and sensitizers is the quantity of the toxicant per unit of skin area (see attached; Stopford, 2013). ACMI's Toxicology Advisory Board (TAB) has reviewed this evidence and accepts the proposition that the risk of skin sensitization and skin irritation is a function of surface concentration (in units of µg/cm2) of the allergen or toxicant of concern. We have developed data for the quantitative assessment of skin exposures from liquid, solid and paste materials but lack data for exposures from use of pressurized aerosol spray products (spray ), from exposure to associated with air brushing activities, and for skin exposures associated with use of pastels. The TAB has recommended that additional studies be conducted to quantify the range of dermal exposures associated with three different scenarios: (1) using spray paints, (2) airbrushing and (3) drawing with pastels.

Standard approaches to assessing dermal exposures OECD (1997) has developed a guidance document for the conduct of studies that assess dermal exposure to pesticides during their agricultural application, including spray applications. This document recommends either the use of eleven 10x10 cm patches that represent potential exposures to various parts of the body or the use of light weight coveralls as whole body dosimeters. OECD notes that the use of coveralls as a dosimeter overcomes difficulties with extrapolating from small patches to the whole body and gives a more accurate estimate of whole body exposure.

When determining overall skin exposures from exposures to aerosols during spray painting and mixing or application of powders, use of flash spun () suits as whole body dosimeters is acceptable (Rajan-Sithamparanadarajah et al, 2004; Roff et al, 2004(a,b); VanRooij et al, 1994). Aerosols will deposit over the entire body with variation in deposition from one site to the next. The total body deposition measurement makes an assessment of this variation unnecessary. VanRooij et al (1994) found that the use of 10 x 10 cm pads underestimated total dermal exposures by a factor of 4.5 when compared to Tyvek total body dosimeters.

OECD (1997) notes that there should be at least one procedural laboratory recovery sample for each analytical run to account for day-to-day variation and efficiency, and that these spiked samples should cover the range of concentrations anticipated for the field samples. Spiked samples are prepared by pipetting diluted solutions of the material that was aerosolized onto patches, coveralls and gloves (Hughson & Aitken, 2004; Popendorf et al, 1995).

OECD (1997) also recommends that any protective gloves that are worn be analyzed to determine potential exposure to the hands. Hand exposures can be determined by analyzing latex or nitrile protective gloves (van Wendel de Joode B et al, 2005; Fransman et al, 2004)

OECD (1997) notes that skin exposures can also be assessed though hand washing techniques. A double hand washing technique using liquid hand soap (Kimberly-Clark) has been found to have a mean removal efficiency of up to 96% for pesticide removal (Stopford et al, 2003; Brouwer et al, 2000).

Potential skin exposure to paints and powders is usually determined by measuring a metal marker found in the paints or powders. Metals analyzed have included aluminum, copper, chromium, nickel, barium, titanium and boron (Delgado et al, 2004; Rajan- Sithamparanadarajah et al, 2004). The amount of metal deposited on skin equivalents (Tyvek suits or gloves) is compared to the amount of metal found in the or powder to determine exposure in terms of µg of the paint or powder/cm2 of skin. The measurement of deposition on Tyvek suites or gloves gives the maximum potential exposure to skin.

Sampling for aerosol levels will be necessary to assure effective clearing of the model room after each run. Dermal exposures are a function of both exposure to suspended aerosols as well as direct contact activities. Measurements of air concentrations will be necessary to model skin contact and potential absorbed dose associated with the assessed activities (OECD, 1997; Berger-Preiss, 2009; Schneider et al, 1999).

Dermal exposure potential is a function of the mass of aerosol available for skin contact as well as non-aerosol exposures during such processes as wiping and filling. Because of increased particle mass and rapid fallout, skin exposures would be expected to increase as the overall particle size (expressed as mass median particle aerodynamic diameter (MMAD)) increases. Measurements for larger particles can be done with monitors developed to cover the ACGIH inhalable particle collection efficiency convention or with 37 mm polystyrene-acrylonitrile open-faced cassettes painted with a conductive to prevent large particle loss to the sampler (Kenny et al, 1997). Once generation of aerosols ceases, particles larger than 10 µm MMAD would be expected to settle from the breathing zone within a couple of minutes: measurements of smaller-sized particles would be important to characterize continued skin exposures during any post aerosol generation activity. Thirty-seven mm closed-face cassettes (CFCs) collect 100% of particles with an aerodynamic diameter of 0.5-10 µm with no losses to the cassette. CFCs have a sharp drop off in efficiency in collecting larger particles, collecting 20% at 20-30 µm and 10% at 40-70 µm with their collection efficiency curves similar to those of the ACGIH thoracic aerosol convention, and they collect a similar mass of particles

2 compared with thoracic particle samplers (Li et al, 2000; Aizenberg et al, 2000; Skaugset et al, 2013).

Model rooms for determining skin exposures during spray activities have ranged from 40 m3 to 60 m3 (Berger-Preiss et al, 2009; Koch et al, 2012; ). Models used for estimating skin exposures to various products usually assume an air exchange rate of one room air exchange per hour (Koch et al, 2012). Model rooms used for determining skin exposures from aerosols are painted with commercial paint (Berger-Preiss et al, 2005). Aerosol generation times range from 6-16 min (Delgado et al, 2004; ). Usual room height is presumed to be 8 ft. (Koch et al, 2012). The post exposure period where sampling continues is usually for a period of 20 min (Berger-Preiss et al, 2005)

Prior studies of exposures from use of spray paints, airbrushing and use of pastels Stopford et al (2002) evaluated the frequency of use of various spray products by graphic artists. Spray were used <1-10 minutes per session with <1-6 sessions per day. Spray fixatives were used 10-30 seconds per application for <1 to 5 times a day. Solvent exposure was measured during spraying of adhesives with trichloroethane levels ranging from 60-400 ppm, n-hexane levels ranging from 360-430 ppm, and acetone was measured at 180 ppm.

Stopford (2003) evaluated charcoal dust exposure to students in a drawing class where drawing activities took place for 155 minutes. Respirable dust exposures were below the detection limits for the study with detection limits ranging from 180-201 µg/m3.

Brock and Stopford (2003) evaluated the characteristics of dust produced when drawing with soft pastels. Dust particles were quite large with only 1.2% being =/<4 µm in mean aerodynamic diameter.

In studies of aerosol generation during use of pastels, spray paints and during airbrushing activities, Stopford (2012) conducted the following activities: pastels: completely fill twelve 700 cm2 artist drawing over 30 min. Brush and remove any settled dust. Average exposure to respirable particulates was estimated to average 0.5 µm/m3 over 24 hours. airbrushing: decorate 6 sheets of artist drawing using a 165 cm2 stencil. Average exposure to respirable particulates associated with airbrushing acrylic paints was estimated to be 0.3 µm/m3 over 24 hours. pressurized aerosol can paints: Completely cover 6 sheets of 700 cm2 artist drawing paper with paint. Average exposure to respirable particulates was estimated to be 3.7 µm/m3 over 24 hours.

Methods Exposure room All studies will be conducted in a 47 m3 room with commercially painted plywood walls and ceilings ventilated at 1 air change per hour. Exhaust fan ventilation rates are adjustable and will be monitored with a hotwire velocimeter. Interior temperature will be

3 maintained at 20 +/- 5o C (EN 14852:2005; Pall, 2013). The exposure room will be exhausted between each experiment. Humidity will be monitored but not controlled.

Measurement of aerosol exposures in air Air samples will be collected with both closed and open-faced 37 mm cassettes with 5 µm pore-size PVC filters both during runs and prior to each run to assure complete clearing of particulates between runs. These filters have a 99.94% efficiency at collecting particles with a MMAD of 0.3 µm when measured using ASTM Method D2986 (Pall, 2013). Cassettes will be worn by the operator in his breathing zone. Air samples will be drawn at 2 L/min using pumps calibrated before and after each session with an SKC soap film flowmeter. Filters will be weighed within  1.0 g. The flowmeter, stop watches and scales will all be calibrated against NBS or NIST-traceable standards.

Analysis for metals Hand wash samples will be digested by EPA Method 200.2 and gloves, patches and suits by EPA method 3051 (microwave). Metal analyses of the digestates will be performed by EPA method 6010 (ICP). Results will be corrected for blank analyses and will be compared with positive controls to present the results, after correcting to the skin area of a standard man, in terms of mass of paint per unit surface area (in µg/cm2).

For determining skin exposure, the 80th percentile skin area figures for an adult male (Koch et al, 2012; Berger-Preiss et al, 2009) will be used: body: 18720 cm2 hands: 820 cm2

The use of an 80th percentile level will allow results of these studies to be compared with prior published studies of dermal deposition during spray painting and work with powdered materials.

In addition, results will be compared with the 50th percentile skin area for an adult male as a more conservative protective level.

From comparing metal values for the Tyvek suit and gloves for each run with the amount of metal in the test paint (in µg/g), the deposition of paint per unit surface area will be found as follows:

µg metal in test article = gm of paint deposited µg/gm metal in paint

µg paint deposited/ standard surface area for hands or body (in cm2) = µg paint/ cm2 surface area

Protocols Pressurized aerosol can paint studies

4 Pressurized aerosol can paints will be stored in a 20 +/- 1o C. water bath prior to use (EN 14852:2005). Aerosol paint canisters will be temperature equilibrated at 20 +/- 1o C in a water bath (EN 14852:2005) prior to use. Six sheets of 700 cm2 artist paper will be completely painted during testing of each spray paint. Studies will be done in a test room (described above) ventilated at one air change per hour. The operator will remain in the test room for 20 min after completing each painting run. He will wear Tyvek hooded overalls and nitrile gloves. The gloves and suit will be removed after each operation, dried on hangers then placed in plastic sampling . The operator will wear an organic /P100 respirator (3M Model 60921) during spray paint studies. Blanks of gloves and blank Tyvek patches will be collected after each run. Positive controls will be made using a pipette to dispense paint used in each experiment on to gloves and Tyvek patches. Paint will be collected from aerosol paint cans using the method developed by Spray Products, Inc. where a pin hole is placed in the top of the can, the can is allowed to vent for 12 hours then the hole is enlarged for sampling. A minimum of 6 samples will be tested. Spray cans will be weighed to the nearest 0.1 gm before and after each run.

Results will be expressed as potential deposition of paint per cm2 of body surface and hand surface using body and hand surface areas of a standardized man for the calculations (Koch et al 2012). Results will be expressed both as a range and mean of deposition in terms of mass per unit surface area.

Airbrush studies A professional airbrush artist will conduct all airbrush studies and will supply the airbrush and paints used in these studies. Studies will be done in a test room (described above) ventilated at one air change per hour. The operator will wear Tyvek hooded overalls. Acrylic paints containing titanium dioxide will be used for these studies.

A minimum of 6 runs will be conducted using an airbrush to fill in a 165 cm2 stencil on 6 sheets of artist paper over a period of 6-10 minutes. The operator will remain in the exposure chamber for 20 minutes after each run. He will wear a N95 mask during each run.

Blank Tyvek patches will be collected after each run. Positive controls will be made using a pipette to dispense paint used in each experiment onto Tyvek patches.

After each run the operator's hands will be washed using a double washing technique with liquid hand soap (Kimberly-Clark; Stopford et al, 2003; Brouwer et al, 2000). Tyvek suits and hand washes will be analyzed for titanium and results will be expressed as potential deposition of paint per cm2 of body surface and hand surface using body and hand surface areas of a standardized man for the calculations. Results will be expressed both as a range and mean of deposition in terms of mass per unit surface area.

Pastel studies Twelve sheets of artist paper will be filled out completely during testing of each pastel. Studies will be done in a test room (described above) ventilated at one air change per hour. Any free powder on each sheet will be removed by knocking off each sheet and brushing up

5 the settled powder from the 12 sheets with a camel's hair brush using the method developed by Stopford (2012). This would expect to generate exposures to pastel dust in addition to that associated with drawing activities. Pastels will be chosen to have high levels of a metal marker (titanium or cobalt) and will be supplied by manufacturers or distributors. A minimum of 6 runs will be conducted with the operator remaining in the test room for 20 min after each run. Blank Tyvek patches will be collected after each run. Positive controls will be made using a pipette to dispense suspended dust of the pastel used in each experiment onto the Tyvek patches.

After each run hands will be washed using a double washing technique with liquid hand soap (Kimberly-Clark, Stopford wt al, 2003; Brouwer et al, 2000). Tyvek suits and hand washes will be analyzed for the metal of interest and results will be expressed as potential deposition of pastel dust per cm2 of body surface and hand surface using body and hand surface areas of a standardized man for the calculations. Results will be expressed both as a range and mean of deposition in terms of mass per unit surface area.

References Aizenberg V, Grinshpun SA, Willeke K, Smith J, Baron PA. Performance characteristics of the button personal inhalable aerosol sampler. AIHAJ. 2000 May-Jun;61(3):398-404.

Berger-Preiss E, Boehncke A, Könnecker G, Mangelsdorf I, Holthenrich D, Koch W. Inhalational and dermal exposures during spray application of biocides. Int J Hyg Environ Health. 2005;208(5):357-72.

Berger-Preiss E, Koch W, Gerling S, Kock H, Appel KE. Use of biocidal products (insect sprays and electro-vaporizer) in indoor areas--exposure scenarios and exposure modeling. Int J Hyg Environ Health. 2009 Sep;212(5):505-18. doi: 10.1016/j.ijheh.2009.02.001. Epub 2009 Mar 31.

Brock T, Stopford W. Bioaccessibility of metals in human health risk assessment: Evaluating risk from exposure to cobalt compounds. J Environ Management. 2003; 3(5):71N-76N.

Brouwer DH, Boeniger MF, van Hemmen J. Hand wash and manual skin wipes. Ann Occup Hyg. 2000; 44(7): 501-10.

Delgado P, Porcel J, Abril I, Torres N, Terán A, Zugasti A. Potential dermal exposure during the painting process in car body repair shops. Ann Occup Hyg. 2004 Apr;48(3):229-36. Epub 2004 Mar 3.

Fenske RA, Blacker AM, Hamburger SJ, Simon GS. Worker exposure and protective clothing performance during manual seed treatment with lindane. Arch Environ Contam Toxicol. 1990 Mar-Apr;19(2):190-6.

6 Fransman W, Vermeulen R, Kromhout H. Occupational dermal exposure to cyclophosphamide in Dutch hospitals: a pilot study. Ann Occup Hyg. 2004 Apr;48(3):237-44. Epub 2004 Mar 2.

Hughson GW, Aitken RJ. Determination of dermal exposures during mixing, spraying and wiping activities. Ann Occup Hyg. 2004 Apr;48(3):245-55.

Kenny LC, Aitken R, Chalmers C, Fabriès JF, Gonzalez-Fernandez E, Kromhout H, Lidén G, Mark D, Riediger G, Prodi V. A collaborative European study of personal inhalable aerosol sampler performance. Ann Occup Hyg. 1997 Apr;41(2):135-53.

Koch W, Behnke W, Berger-Preiß E, Kock H, Gerling S, Hahn S, Schröder K. Validation of an EDP assisted model for assessing inhalation exposure and dermal exposure during spraying processes. Baua: Research Project F 2137. Dortmund/Berlin/Dresden 2012

Lai CY, Chen CC. Performance characteristics of PM10 samplers under calm air conditions. J Air Waste Manag Assoc. 2000 Apr;50(4):578-87.

Li SN, Lundgren DA, Rovell-Rixx D. Evaluation of six inhalable aerosol samplers. AIHAJ. 2000 Jul-Aug;61(4):506-16.

OECD. Guidance Document for the Conduct of Studies of Occupational Exposures to Pesticides During Agricultural Applications. OCDE/GD(97)148. 1997.

Pall Life Sciences (2013). Filtration Products for Air Monitoring and Sampling. http://www.pall.com/pdfs/Laboratory/08.1868_Air_Monitoring_SS.pdf

Popendorf W, Selim M, Lewis MQ. Exposure while applying industrial antimicrobial pesticides. Am Ind Hyg Assoc J. 1995 Oct;56(10):993-1001.

Rajan-Sithamparanadarajah R, Roff M, Delgado P, Eriksson K, Fransman W, Gijsbers JH, Hughson G, Mäkinen M, van Hemmen JJ. Patterns of dermal exposure to hazardous substances in European union workplaces. Ann Occup Hyg. 2004 Apr;48(3):285-97.

Roff M, Bagon DA, Chambers H, Dilworth EM, Warren N. Dermal exposure to electroplating fluids and metalworking fluids in the UK. Ann Occup Hyg. 2004(a) Apr;48(3):209-17.

Roff M, Bagon DA, Chambers H, Dilworth EM, Warren N. Dermal exposure to dry powder spray paints using PXRF and the method of Dirichlet tesselations. Ann Occup Hyg. 2004(b) Apr;48(3):257-65.

Schneider T, Vermeulen R, Brouwer DH, Cherrie JW, Kromhout H, Fogh CL. Conceptual model for assessment of dermal exposure. Occup Environ Med. 1999 Nov;56(11):765-73.

7 Skaugset NP, Ellingsen DG, Notø H, Jordbekken L, Thomassen Y. Intersampler field comparison of Respicon(R), IOM, and closed-face 25-mm personal aerosol samplers during primary production of aluminium. Ann Occup Hyg. 2013 Oct;57(8):1054-64. doi: 10.1093/annhyg/met025. Epub 2013 Jun 22.

Stopford W, Miller JS, Smith KN, Bosserman W. Solvent Exposure to Graphic Artists. Submitted to CPSC. http://duketox.mc.duke.edu/graphicartiststudy.doc. 2002.

Stopford W. Risk assessment for exposure to respirable dusts generated from used of chalks and pastels. http://duketox.mc.duke.edu/pasteldust.doc. 2003.

Stopford W, Turner J, Cappellini D. Determination of the magnitude of clay to skin and skin to mouth transfer of phthalates associated with the use of clays. http://duketox.mc.duke.edu/polymerclayresults2.pdf. 2003.

Stopford W. Aerosol production during the use of art and craft materials. http://duketox.mc.duke.edu/ARTDUST4.doc. 2012.

Stopford W. Quantitative Risk Assessment of Skin Sensitizers and Irritants. http://duketox.mc.duke.edu/QRA%20Skin%20Sensitizers%20and%20Irritants9.doc. 2013.

VanRooij JGM, Maassen LM, Bodelier-Bade MM, Jongeneelen FJ. Determination of skin contamination with exposure pads among workers exposed to polycyclic aromatic . Appl. Occup. Environ. Hyg. 9: 693-9, 1994.

van Wendel de Joode B, Vermeulen R, van Hemmen JJ, Fransman W, Kromhout H. Accuracy of a semiquantitative method for Dermal Exposure Assessment (DREAM). Occup Environ Med. 2005 Sep;62(9):623-32.

Williams R, Suggs J, Rodes C, Lawless P, Zweidinger R, Kwok R, Creason J, Sheldon L. Comparison of PM2.5 and PM10 monitors. J Expo Anal Environ Epidemiol. 2000 Sep- Oct;10(5):497-505.

8