Additive Manufacturing for Occupational Hygiene: A Comprehensive Review of Processes, Emissions, & Exposures.

This comprehensive review introduces occupational (industrial) hygienists and toxicologists to the seven basic additive manufacturing (AM) process categories. Forty-six articles were identified that reported real-world measurements for all AM processes, except sheet lamination. Particles released from powder bed fusion (PBF), material jetting (MJ), material extrusion (ME), and directed energy deposition (DED) processes exhibited nanoscale to submicron scale; real-time particle number (mobility sizers, condensation nuclei counters, miniDiSC, electrical diffusion batteries) and surface area monitors (diffusion chargers) were generally sufficient for these processes. Binder jetting (BJ) machines released particles up to 8.5 µm; optical particle sizers (number) and laser scattering photometers (mass) were sufficient for this process. PBF and DED processes (powdered metallic feedstocks) released particles that contained respiratory irritants (chromium, molybdenum), central nervous system toxicants (manganese), and carcinogens (nickel). All process categories, except those that use metallic feedstocks, released organic gases, including (but not limited to), respiratory irritants (toluene, xylenes), asthmagens (methyl methacrylate, styrene), and carcinogens (benzene, formaldehyde, acetaldehyde). Real-time photoionization detectors for total volatile organics provided useful information for processes that utilize polymer feedstock materials. More research is needed to understand 1) facility-, machine-, and feedstock-related factors that influence emissions and exposures, 2) dermal exposure and biological burden, and 3) task-based exposures. Harmonized emissions monitoring and exposure assessment approaches are needed to facilitate inter-comparison of study results. Improved understanding of AM process emissions and exposures is needed for hygienists to ensure appropriate health and safety conditions for workers and for toxicologists to design experimental protocols that accurately mimic real-world exposure conditions.ABBREVIATIONS ABS : acrylonitrile butadiene styrene; ACGIH® TLV® : American Conference of Governmental Industrial Hygienists Threshold Limit Value; ACH : air change per hour; AM : additive manufacturing; ASA : acrylonitrile styrene acrylate; AVP : acetone vapor polishing; BJ : binder jetting; CAM-LEM : computer-aided manufacturing of laminated engineering materials; CNF : carbon nanofiber; CNT : carbon nanotube; CP : co-polyester; CNC : condensation nuclei counter; CVP : chloroform vapor polishing; DED : directed energy deposition; DLP : digital light processing; EBM : electron beam melting; EELS : electron energy loss spectrometry; EDB : electrical diffusion batteries; EDX : energy dispersive x-ray analyzer; ER : emission rate; FDM™ : fused deposition modeling; FFF : fused filament fabrication; IAQ : indoor air quality; LSP : laser scattering photometer; LCD : liquid crystal display; LDSA : lung deposited particle surface area; LOD : limit of detection; LOM : laminated object manufacturing; LOQ : limit of quantitation; MCE : mixed cellulose ester filter; ME : material extrusion; MJ : material jetting; OEL : occupational exposure limit; OPS : optical particle sizer; PBF : powder bed fusion; PBZ : personal breathing zone; PC : polycarbonate; PEEK : poly ether ether ketone; PET : polyethylene terephthalate; PETG : Polyethylene terephthalate glycol; PID : photoionization detector; PLA : polylactic acid; PM1 : particulate matter with aerodynamic diameter less than 1 µm; PM2.5 : particulate matter with aerodynamic diameter less than 2.5 µm; PM10 : particulate matter with aerodynamic diameter less than 10 µm; PSL : plastic sheet lamination; PVA : polyvinyl alcohol; REL : recommended exposure limit; SDL : selective deposition lamination; SDS : safety data sheet; SEM : scanning electron microscopy; SL : sheet lamination; SLA : stereolithography; SLM : selective laser melting; SMPS : scanning mobility particle sizer; SVOC : semi-volatile organic compound; TEM : transmission electron microscopy; TGA : thermal gravimetric analysis; TPU : thermo polyurethane; UAM : ultrasonic additive manufacturing; UC : ultrasonic consolidation; TVOC : total volatile organic compounds; TWA : time-weighted average; VOC : volatile organic compound; VP : vat photopolymerization.

Evaluation of the skin-sensitizing potential of gold nanoparticles and the impact of established dermal sensitivity on the pulmonary immune response to various forms of gold.

Gold nanoparticles (AuNP) are largely biocompatible; however, many studies have demonstrated their potential to modulate various immune cell functions. The potential allergenicity of AuNP remains unclear despite the recognition of gold as a common contact allergen. In these studies, AuNP (29 nm) dermal sensitization potential was assessed via Local Lymph Node Assay (LLNA). Soluble gold (III) chloride (AuCl3) caused lymph node (LN) expansion (SI 10.9), whereas bulk particles (Au, 942 nm) and AuNP did not. Next, the pulmonary immune effects of AuNP (10, 30, 90 µg) were assessed 1, 4, and 8 days post-aspiration. All markers of lung injury and inflammation remained unaltered, but a dose-responsive increase in LN size was observed. Finally, mice were dermally-sensitized to AuCl3 then aspirated once, twice, or three times with Au or AuNP in doses normalized for mass or surface area (SA) to assess the impact of existing contact sensitivity to gold on lung immune responses. Sensitized animals exhibited enhanced responsivity to the metal, wherein subsequent immune alterations were largely conserved with respect to dose SA. The greatest increase in bronchoalveolar lavage (BAL) lymphocyte number was observed in the high dose group - simultaneous to preferential expansion of BAL/LN CD8+ T-cells. Comparatively, the lower SA-based doses of Au/AuNP caused more modest elevations in BAL lymphocyte influx (predominantly CD4+ phenotype), exposure-dependent increases in serum IgE, and selective expansion/activation of LN CD4+ T-cells and B-cells. Overall, these findings suggest that AuNP are unlikely to cause sensitization; however, established contact sensitivity to gold may increase immune responsivity following pulmonary AuNP exposure.

Evaluation of emissions and exposures at workplaces using desktop 3-dimensional printer.

There is a paucity of data on additive manufacturing process emissions and personal exposures in real-world workplaces. Hence, we evaluated atmospheres in four workplaces utilizing desktop "3-dimensional" (3-d) printers [fused filament fabrication (FFF) and sheer] for production, prototyping, or research. Airborne particle diameter and number concentration and total volatile organic compound concentrations were measured using real-time instruments. Airborne particles and volatile organic compounds were collected using time-integrated sampling techniques for off-line analysis. Personal exposures for metals and volatile organic compounds were measured in the breathing zone of operators. All 3-d printers that were monitored released ultrafine and fine particles and organic vapors into workplace air. Particle number-based emission rates (#/min) ranged from 9.4 × 109 to 4.4 × 1011 (n = 9samples) for FFF3-d printers and from 1.9 to 3.8 × 109 (n = 2 samples) for a sheer 3-d printer. The large variability in emission rate values reflected variability from the printers as well as differences in printer design, operating conditions, and feedstock materials among printers. A custom-built ventilated enclosure evaluated at one facility was capable of reducing particle number and total organic chemical concentrations by 99.7% and 53.2%, respectively. Carbonyl compounds were detected in room air; however, none were specifically attributed to the 3-d printing process. Personal exposure to metals (aluminum, iron) and 12 different organic chemicals were all below applicable NIOSH Recommended Exposure Limit values, but results are not reflective of all possible exposure scenarios. More research is needed to understand 3-d printer emissions, exposures, and efficacy of engineering controls in occupational settings.

Insights Into Emissions and Exposures From Use of Industrial-Scale Additive Manufacturing Machines.

BACKGROUND: Emerging reports suggest the potential for adverse health effects from exposure to emissions from some additive manufacturing (AM) processes. There is a paucity of real-world data on emissions from AM machines in industrial workplaces and personal exposures among AM operators. METHODS: Airborne particle and organic chemical emissions and personal exposures were characterized using real-time and time-integrated sampling techniques in four manufacturing facilities using industrial-scale material extrusion and material jetting AM processes. RESULTS: Using a condensation nuclei counter, number-based particle emission rates (ERs) (number/min) from material extrusion AM machines ranged from 4.1 × 1010 (Ultem filament) to 2.2 × 1011 [acrylonitrile butadiene styrene and polycarbonate filaments). For these same machines, total volatile organic compound ERs (µg/min) ranged from 1.9 × 104 (acrylonitrile butadiene styrene and polycarbonate) to 9.4 × 104 (Ultem). For the material jetting machines, the number-based particle ER was higher when the lid was open (2.3 × 1010 number/min) than when the lid was closed (1.5-5.5 × 109 number/min); total volatile organic compound ERs were similar regardless of the lid position. Low levels of acetone, benzene, toluene, and m,p-xylene were common to both AM processes. Carbonyl compounds were detected; however, none were specifically attributed to the AM processes. Personal exposures to metals (aluminum and iron) and eight volatile organic compounds were all below National Institute for Occupational Safety and Health (NIOSH)-recommended exposure levels. CONCLUSION: Industrial-scale AM machines using thermoplastics and resins released particles and organic vapors into workplace air. More research is needed to understand factors influencing real-world industrial-scale AM process emissions and exposures.

Particle and vapor emissions from vat polymerization desktop-scale 3-dimensional printers.

Little is known about emissions and exposure potential from vat polymerization additive manufacturing, a process that uses light-activated polymerization of a resin to build an object. Five vat polymerization printers (three stereolithography (SLA) and two digital light processing (DLP) were evaluated individually in a 12.85 m3 chamber. Aerosols (number, size) and total volatile organic compounds (TVOC) were measured using real-time monitors. Carbonyl vapors and particulate matter were collected for offline analysis using impingers and filters, respectively. During printing, particle emission yields (#/g printed) ranged from 1.3 ± 0.3 to 2.8 ± 2.6 x 108 (SLA printers) and from 3.3 ± 1.5 to 9.2 ± 3.0 x 108 (DLP printers). Yields for number of particles with sizes 5.6 to 560 nm (#/g printed) were 0.8 ± 0.1 to 2.1 ± 0.9 x 1010 and from 1.1 ± 0.3 to 4.0 ± 1.2 x 1010 for SLA and DLP printers, respectively. TVOC yield values (µg/g printed) ranged from 161 ± 47 to 322 ± 229 (SLA printers) and from 1281 ± 313 to 1931 ± 234 (DLP printers). Geometric mean mobility particle sizes were 41.1-45.1 nm for SLA printers and 15.3-28.8 nm for DLP printers. Mean particle and TVOC yields were statistically significantly higher and mean particle sizes were significantly smaller for DLP printers compared with SLA printers (p < 0.05). Energy dispersive X-ray analysis of individual particles qualitatively identified potential occupational carcinogens (chromium, nickel) as well as reactive metals implicated in generation of reactive oxygen species (iron, zinc). Lung deposition modeling indicates that about 15-37% of emitted particles would deposit in the pulmonary region (alveoli). Benzaldehyde (1.0-2.3 ppb) and acetone (0.7-18.0 ppb) were quantified in emissions from four of the printers and 4-oxopentanal (0.07 ppb) was detectable in the emissions from one printer. Vat polymerization printers emitted nanoscale particles that contained potential carcinogens, sensitizers, and reactive metals as well as carbonyl compound vapors. Differences in emissions between SLA and DLP printers indicate that the underlying technology is an important factor when considering exposure reduction strategies such as engineering controls.

Inhalation exposure to three-dimensional printer emissions stimulates acute hypertension and microvascular dysfunction.

Fused deposition modeling (FDM™), or three-dimensional (3D) printing has become routine in industrial, occupational and domestic environments. We have recently reported that 3D printing emissions (3DPE) are complex mixtures, with a large ultrafine particulate matter component. Additionally, we and others have reported that inhalation of xenobiotic particles in this size range is associated with an array of cardiovascular dysfunctions. Sprague-Dawley rats were exposed to 3DPE aerosols via nose-only exposure for ~3h. Twenty-four hours later, intravital microscopy was performed to assess microvascular function in the spinotrapezius muscle. Endothelium-dependent and -independent arteriolar dilation were stimulated by local microiontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). At the time of experiments, animals exposed to 3DPE inhalation presented with a mean arterial pressure of 125±4mmHg, and this was significantly higher than that for the sham-control group (94±3mmHg). Consistent with this pressor response in the 3DPE group, was an elevation of ~12% in resting arteriolar tone. Endothelium-dependent arteriolar dilation was significantly impaired after 3DPE inhalation across all iontophoretic ejection currents (0-27±15%, compared to sham-control: 15-120±21%). Endothelium-independent dilation was not affected by 3DPE inhalation. These alterations in peripheral microvascular resistance and reactivity are consistent with elevations in arterial pressure that follow 3DPE inhalation. Future studies must identify the specific toxicants generated by FDM™ that drive this acute pressor response.

Taking stock of the occupational safety and health challenges of nanotechnology: 2000-2015.

Engineered nanomaterials significantly entered commerce at the beginning of the 21st century. Concerns about serious potential health effects of nanomaterials were widespread. Now, approximately 15 years later, it is worthwhile to take stock of research and efforts to protect nanomaterial workers from potential risks of adverse health effects. This article provides and examines timelines for major functional areas (toxicology, metrology, exposure assessment, engineering controls and personal protective equipment, risk assessment, risk management, medical surveillance, and epidemiology) to identify significant contributions to worker safety and health. The occupational safety and health field has responded effectively to identify gaps in knowledge and practice, but further research is warranted and is described. There is now a greater, if imperfect, understanding of the mechanisms underlying nanoparticle toxicology, hazards to workers, and appropriate controls for nanomaterials, but unified analytical standards and exposure characterization methods are still lacking. The development of control-banding and similar strategies has compensated for incomplete data on exposure and risk, but it is unknown how widely such approaches are being adopted. Although the importance of epidemiologic studies and medical surveillance is recognized, implementation has been slowed by logistical issues. Responsible development of nanotechnology requires protection of workers at all stages of the technological life cycle. In each of the functional areas assessed, progress has been made, but more is required.

Setting Occupational Exposure Limits for Chemical Allergens--Understanding the Challenges.

Chemical allergens represent a significant health burden in the workplace. Exposures to such chemicals can cause the onset of a diverse group of adverse health effects triggered by immune-mediated responses. Common responses associated with workplace exposures to low molecular weight (LMW) chemical allergens range from allergic contact dermatitis to life-threatening cases of asthma. Establishing occupational exposure limits (OELs) for chemical allergens presents numerous difficulties for occupational hygiene professionals. Few OELs have been developed for LMW allergens because of the unique biological mechanisms that govern the immune-mediated responses. The purpose of this article is to explore the primary challenges confronting the establishment of OELs for LMW allergens. Specific topics include: (1) understanding the biology of LMW chemical allergies as it applies to setting OELs; (2) selecting the appropriate immune-mediated response (i.e., sensitization versus elicitation); (3) characterizing the dose (concentration)-response relationship of immune-mediated responses; (4) determining the impact of temporal exposure patterns (i.e., cumulative versus acute exposures); and (5) understanding the role of individual susceptibility and exposure route. Additional information is presented on the importance of using alternative exposure recommendations and risk management practices, including medical surveillance, to aid in protecting workers from exposures to LMW allergens when OELs cannot be established.

Characterization of phagolysosomal simulant fluid for study of beryllium aerosol particle dissolution.

A simulant of phagolysosomal fluid is needed for beryllium particle dissolution research because intraphagolysosomal dissolution is believed to be a necessary step in the cellular immune response associated with development of chronic beryllium disease. Thus, we refined and characterized a potassium hydrogen phthalate (KHP) buffered solution with pH 4.55, termed phagolysosomal simulant fluid (PSF), for use in a static dissolution technique. To characterize the simulant, beryllium dissolution in PSF was compared to dissolution in the J774A.1 murine cell line. The effects of ionic composition, buffer strength, and the presence of the antifungal agent alkylbenzyldimethylammonium chloride (ABDC) on beryllium dissolution in PSF were evaluated. Beryllium dissolution in PSF was not different from dissolution in the J774A.1 murine cell line (p = 0.78) or from dissolution in another simulant having the same pH but different ionic composition (p = 0.73). A buffer concentration of 0.01-M KHP did not appear adequate to maintain pH under all conditions. There was no difference between dissolution in PSF with 0.01-M KHP and 0.02-M KHP (p = 0.12). At 0.04-M KHP, beryllium dissolution was increased relative to 0.02-M KHP (p = 0.02). Use of a 0.02-M KHP buffer concentration in the standard formulation for PSF provided stability in pH without alteration of the dissolution rate. The presence of ABDC did not influence beryllium dissolution in PSF (p = 0.35). PSF appears to be a useful and appropriate model of in vitro beryllium dissolution when using a static dissolution technique. In addition, the critical approach used to evaluate and adjust the composition of PSF may serve as a framework for characterizing PSF to study dissolution of other metal and oxide particles.

An evaluation of employee exposure to volatile organic compounds in three photocopy centers.

Personal and area samples from three copy centres were collected in thermal desorption tubes and analyzed using gas chromatography-mass spectrometry. Real-time personal total volatile organic compounds (TVOC) were measured using a data-logging photoionization detector. Fifty-four different VOCs were detected in the area samples. The maximum concentration measured was 1132.0 ppb (toluene, copy center 3, day 1). Thirty-eight VOCs were detected in the personal samples and concentrations ranged from 0.1 ppb (1,1-biphenyl, p-dichlorobenzene, propylbenzene, styrene, and tetrachloroethylene) to 689.6 ppb (toluene). Real-time TVOC measurements indicated daily fluctuations in exposure, ranging from <71 to 21,300 ppb. The time-weighted average exposures for the photocopier operators on days 1 and 2 were 235 and 266 ppb and 6155 and 3683 ppb, in copy centers 2 and 3, respectively. Personal exposure measurements of individual VOCs were below accepted occupational standards and guidelines. For example, the maximum concentration was 0.3% of the permissible exposure limits (toluene, copy center 3). Exposures were highest in copy center 3; this is likely due to the presence of offset printing presses. It is concluded that photocopiers contribute a wide variety of VOCs to the indoor air of photocopy centers; however, exposures are at least 100 times below established standards.