Potential health hazards of a material used in stereolithography and 3D printing

Robert E. Smith

Park University, 8700 NW River Park Drive, Parkville, MO 64152

Advanced Modelling and Simulation 2019, 1, 14–15. doi:10.26705/advmodsim.2018.1.1.14-15
Received 29 May 2018, Published 29 July 2019

Abstract

One of the materials used in stereolithography (STL) is Cyracure® UVR 6105 (Ultraviolet resistant 6105). When cured, or polymerized, it forms a solid material. The major component of the UVR 6105 pre-polymer is 3,4-epoxycyclohexylmethyl-3,4-epoxycyclohexylcarboxylate (ECMECC). It is less mutagenic than bisphenol A diglycidyl ether (BADGE), which has many industrial uses. Both BADGE and ECMECC can be hydrolyzed in reactions catalyzed by esterase enzymes and by acid in gastric fluid. Both BADGE and its hydrolysis product have very solubility in water and low bioavailability. However, the hydrolysis products of ECMECC are partly soluble in water and act as detergents. As a result, they break up the oily globules of ECMECC, forming micelles. This increases the surface area and exposure of ECMECC to esterases and stomach acid. As a result, UVR 6105 is hydrolyzed further, producing mutagenic products that have relatively high bioavailability. So, workers who handle UCR 6105 should always wear gloves and should wash their hands with soap and water afterwards. Moreover, UVR 6105 may not be the best choice for making devices that go into the human body.

Keywords: 3D printing, stereolithography, Cyracure® UVR 6105, epoxies, mutagens, cancer

Introduction

Stereolithography (STL) was used in the Human Genome Project to make plastic models of biopolymers, based on their 3D structures that are in the RCSB Protein Data Bank [1]. Some of these models are used in the Cold Springs Harbor National Laboratory to help teach structural biology. STL is a form of rapid prototyping, or 3D printing. It has improved enough to be used to make 3D models for biomedical applications [2, 3]. This includes personalized devices such as a bioresorbable tracheal splint for an infant who was critically ill [4]. At the same time, 3D models of images of tissues and bones from computed tomography (CT) or magnetic resonance imaging (MRI) enable surgeons to know what to expect before they begin surgery. Models made this way can also be used by medical students and residents to learn how to do difficult surgeries. In addition, 3D models can make it much easier for oncologists to deliver radiotherapy to the precise, proper locations in tumors.

In STL, plastic models are made one layer at a time on a supporting structure that must be removed after printing the model [1, 5]. One of the materials used in STL is Cyracure® UVR 6105 (Ultraviolet resistant 6105) [2, 3, 6]. When cured, or polymerized, it forms a solid material.The major component of the UVR 6105 pre-polymer is 3,4-epoxycyclohexylmethyl-3,4-epoxycyclohexylcarboxylate [6]. UVR 6105 was originally developed as a replacement for another widely-used epoxy pre-polymer, EPON™ 828. Its primary component is the diglycidyl ether of bisphenol A (DGEBA), also known as bisphenol A diglycidyl ether (BADGE). Like most chemicals that have phenyl rings, the polymer it produces degrades (or is bleached) by extended exposure to UV light. In addition, unreacted BADGE can leach out of the polymer and be hydrolyzed to produce bisphenol A, a known toxin and obesogen (which causes obesity) [3, 7]. So, to make cured epoxies that aren’t degraded by lengthy exposure to the sun, UVR 6105 was developed. Since the supports needed to make STL models are removed by hand, most people also appreciated that UVR-6105 was not as mutagenic as BADGE [8].

However, the bioavailability of BADGE is much lower than that of 3,4-epoxycyclohexylmethyl-3,4-epoxycyclohexylcarboxylate and its hydrolysis products [1]. So, UVR 6105 is potentially more toxic that BADGE. Thus, workers should not use their bare hands and fingers to remove the supports from a 3D-printed model made from UVR-6105. This is because if the worker were to touch his or her mouth or eat food before thoroughly washing his or her hands, some of the uncured (unreacted) monomer could enter the blood and reach stomach and liver. It can be hydrolyzed by in a reaction catalyzed by either acid (H+) in gastric fluid or an esterase in liver to produce the metabolites 3,4-epoxycyclohexylmethanol (ECHM) and 3,4-epoxycyclohexanoic acid (ECHHA). ECHM has is more genotoxic that either BADGE or UVR 6105 [8]. The genotoxicity of ECHHA has not been tested, but it does contain an epoxy (oxirane) group that is usually mutagenic.

In addition, it has been suggested that Cyracure® UVR 6105 could be used to make materials for dental applications [9]. However, it might not be wise to put epoxy resins made from it in the mouth or anywhere in the human body. No man-made polymerizations are complete, so there is always some unreacted UVR 6105 that could leach out of the polymer and be hydrolyzed to produce toxic, mutagenic products [3]. Instead, siloranes might be a better choice than Cyracure® UVR-6105 for preparing 3D printed structures for dentistry, bone engineering or any other medical application . They are quite stable to hydrolysis[10].

More details about Cyracure® UVR 6105 and siloranes were presented in two recent books that also describe the use of computer modeling in modern drug development [3,11].

References

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  2. Scalera F, Corcione CE, Montagna F, Sannino A, Maffezzoli A. Development and characterization of UV curable epoxy/hydroxyapatite suspensions for stereolithography applied to bone tissue engineering. Ceram. Int. 2014​, 40, 15455–15462.
  3. Smith RE. Systems Thinking in Medicine and New Drug Discovery, Volume Two (Newcastle upon Tyne, Cambridge Scholars Publishing). 2018.
  4. Hamburg MA, Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development, US FDA, Bethesda, MD, 2013​.
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  6. Voytekunas VY, Ng FL, Abadie MJM. Kinetics study of the UV-initiated cationic polymerization of cycloaliphatic diepoxide resins. Eur. Polym. J. 2008​, 44, 3640-3649.
  7. Cannon JM, Kostoryz E, Russo KA, Smith RE, Yourtee DM. Bisphenol A and its biomaterial monomer derivatives alteration of in vitro cytochrome P450 metabolism in rat, minipig, and human. Biomacromol. 2000​, 1, 656-664.
  8. Kostoryz EL, Smith RE, Chappelow C, Yourtee DM, Glaros AG, Eick JD. In vitro mutagenicity and metabolism of the cycloaliphatic epoxide Cyracure UVR 6105. Mut. Res. 2004​, 563, 25-34.
  9. Palin WM, Fleming GJP, Burke FJT et al. Monomer conversion versus flexure strength of a novel dental composite. J. Dent. 2003​, 31, 341-351.
  10. Eick JD, Smith, R.E., Pinzino, C.S. and Kostoryz, E.L. Stability of silorane monomers in aqueous systems. J. Dent. 2006​, 34, 405-410.
  11. Smith RE. Systems Thinking in Medicine and New Drug Discovery, Volume One (Newcastle upon Tyne, Cambridge Scholars Publishing). 2018.

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