Occupational exposure limit for silver nanoparticles: considerations on the derivation of a general health-based value

Abstract

With the increased production and widespread commercial use of silver nanoparticles (AgNPs), human and environmental exposures to silver nanoparticles are inevitably increasing. In particular, persons manufacturing and handling silver nanoparticles and silver nanoparticle containing products are at risk of exposure, potentially resulting in health hazards. While silver dusts, consisting of micro-sized particles and soluble compounds have established occupational exposure limits (OELs), silver nanoparticles exhibit different physicochemical properties from bulk materials. Therefore, we assessed silver nanoparticle exposure and related health hazards in order to determine whether an additional OEL may be needed. Dosimetric evaluations in our study identified the liver as the most sensitive target organ following inhalation exposure, and as such serves as the critical target organ for setting an occupational exposure standard for airborne silver nanoparticles. This study proposes an OEL of 0.19 μg/m(3) for silver nanoparticles derived from benchmark concentrations (BMCs) from subchronic rat inhalation toxicity assessments and the human equivalent concentration (HEC) with kinetic considerations and additional uncertainty factors. It is anticipated that this level will protect workers from potential health hazards, including lung, liver, and skin damage.

Keywords: Clearance; dosimetry; occupational exposure; silver nanoparticles; subchronic inhalation.

Figure 1.

Mathematical framework for deriving a health-based occupational exposure limit (OEL) for silver nanoparticles (AgNPs) from in vivo rat inhalation studies. The OEL reflects tissue dosimetry, toxicokinetic adjustments and additional uncertainty factors.

Figure 2.

Benchmark dose (BMD) analysis of significant histopathology endpoints of toxicity in male and female rats after subchronic inhalation of AgNPs (Sung et al, 2009). Dose response curves are modeled as multistage polynomial degree 2 model for dichotomous data. BMDs (black dashed lines) and BMDLs (red dashed lines) are calculated as a 10% change in response relative to control and are indicated as tissue burden (μg silver/organ). BMDs and BMDLs are summarized in Table 2.

Figure 3.

Benchmark dose analysis of significant endpoints of lung inflammation in male and female rats and lung function in male rats from subchronic inhalation of AgNPs (Sung et al, 2008). BMDs (black dashed lines) and BMDLs (red dashed lines) are calculated as a 1 standard deviation change in response relative to control and are indicated as tissue burden (μg silver/organ). BMDs and BMDLs are summarized in Table 2.

Figure 4.

Benchmark dose (BMD) and 95% confidence limit of BMD (BMDL) comparison across endpoints. Histopathological (*starred), functional, and bronchiolar lavage endpoints are indicated across the bottom. BMDs (green diamonds) and BMDLs (blue circles) are indicated as tissue burden (total ng silver/organ). BMDs and BMDLs are summarized in Table 2.

Figure 5.

Dosimetrically adjusted BMC and BMCL comparison across histopathological (*starred), functional, and bronchiolar lavage endpoints. Endpoints are indicated across the bottom of the figure and BMCs (green diamonds) and BMCLs (blue circles) are calculated as aerosol concentration (μg/m³) at the BMDs and BMDLs. BMCs and BMCLs are summarized in Table 2. Sung et al., 2009 reported a NOAEL of 133 (μg/m³) is indicated.