Toxicology of wear particles of cobalt-chromium alloy metal-on-metal hip implants Part II: Importance of physicochemical properties and dose in animal and in vitro studies as a basis for risk assessment.
The objective of the Part II analysis was to evaluate animal and in vitro toxicology studies of CoCr particles with respect to their physicochemistry and dose relevance to metal-on-metal (MoM) implant patients as derived from Part I. In the various toxicology studies, physicochemical characteristics were infrequently considered and administered doses were orders of magnitude higher than what occurs in patients. Co was consistently shown to rapidly release from CoCr particles for distribution and elimination from the body. CoCr micron sized particles appear more biopersistent in vivo resulting in inflammatory responses that are not seen with similar mass concentrations of nanoparticles. We conclude, that in an attempt to obtain data for a complete risk assessment, future studies need to focus on physicochemical characteristics of nano and micron sized particles and on doses and dose metrics relevant to those generated in patients or in properly conducted hip simulator studies.
Cardno ChemRisk, Aliso Viejo, CA, USA. Electronic address: amy.madl@cardno.com.
Amy K
AK
Madl
Cardno ChemRisk, Aliso Viejo, CA, USA. Electronic address: michael.kovochich@cardno.com.
Michael
M
Kovochich
Cardno ChemRisk, San Francisco, CA, USA. Electronic address: monty.liong@cardno.com.
Monty
M
Liong
Cardno ChemRisk, Brooklyn, NY, USA.
Brent L
BL
Finley
Cardno ChemRisk, San Francisco, CA, USA.
Dennis J
DJ
Paustenbach
University of Rochester, Department of Environmental Medicine, Rochester, NY, USA.
Günter
G
Oberdörster
D000818:Animals; D002858:Chromium Alloys / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D003035:Cobalt / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D010316:Particle Size; D018570:Risk Assessment
D002858:Chromium Alloys; D003035:Cobalt
Cobalt-chromium; Hip implant; Metal-on-metal; Wear debris