Occupational Exposure to Carbon Nanotubes and Nanofibers

Table A–14. Example of uncertainty factor (UF) selection for human-equivalent concentrations torat effect level in MWCNT subchronic inhalation studies †Type of UFPossibleUF valueNOAEL[Pauluhn2010a]LOAEL[Ma-Hock etal. 2009] Rationale1. Animal to humanextrapolation2. Subchronicanimal doseresponsedataused in absenceof chronic data3. Human interindividualvariability forsensitive subpopulation4. LOAEL used insteadof NOAEL5. Modifying factor(e.g., poor dataquality; severeeffect)Up to 10 (4 forTK; 2.5 for TD)[WHO 2005]Up to a factorof 10 [US EPA1994]10 (3.16 eachfor TK and TD)[WHO 2005]Up to a factorof 10 [US EPA1994]Up to a factorof 10 [US EPA1994]2 2 TK: Dosimetry based on estimatedretained lung burden (in Table A–13);additional uncertainty about slowerclearance of CNT (ad hoc TK factor of2).TD: Assume equal average subchronicresponse at equivalent dose in eachspecies (TD factor of 1).2 2 Subchronic data were used, assumingsteady-state lung burden in ratsuncertainty about chronic effects (ad hocUF of 2).5 5 Variability in workers (TK andTD components); factor of 5 fromAschberger et al. [2010].1 3 NOAEL: factor of 1.LOAEL: Responses at LOAEL were“minimal” severity by histopathology[Ma-hock et al. 2009].1 1 Subchronic studies were standard qualityassays, and lung effects were early-stage.Total UF 3,000 ‡ 20 60 OEL is derived as HEC_POD/total UF.Abbreviations: TK—toxicokinetic. TD—toxicodynamic. NOAEL—no observed adverse effect level. LOAEL—lowest observedadverse effect level. POD—point of departure. UF—uncertainty factor.†These UF examples refer to estimates in Table A–13.‡Total uncertainty factor is typically capped at 3,000 [US EPA 1994].138 NIOSH CIB 65 • Carbon Nanotubes and Nanofibers