Document ID: chunk:federal_register_of_legislation:F2013C00288:reg:9:p5
Version: federal_register_of_legislation:F2013C00288
Segment Type: reg
Provision Reference: reg 9 (pt 5/7)
Character Range: 2229954–2232916

ATSDR (2008) with the main difference being the application of the BMD model.
                                                            No oral guideline value was provided.
Health Canada (2008)  RfC = 0.00005 mg/m3                   RfC derived based on most sensitive benchmark dose analysis associated with neurotoxicological effects in an occupational inhalation study. A range of RfCs were derived that varied from 0.000050.00014 mg/m3. The range derived is consistent with values derived from ATSDR and WHO.
ATSDR (2008)          Interim oral value of 0.16 mg/kd/day  No oral MRLs have been derived by ATSDR; however they provide an interim guidance value of 0.16 mg/kg/day based on a tolerable upper intake level of 11 mg/day.
                      Inhalation MRL = 0.0003 mg/m3         Chronic inhalation MRL derived on the basis of a benchmark concentration (at the lower 95% confidence limit for the level of manganese exposure expected to result in 10% response rate) BMCL10 (adjusted for continuous exposure) of 0.03 mg/m3 associated with neurobehavioural effects in an occupational study and an uncertainty factor of 100.
US EPA (IRIS 2012)    RfD = 0.14 mg/kg/day                  RfD (last reviewed in 1993) based on a NOAEL of 0.14 mg/kg/day associated with CNS effects in a number of dietary human studies and an uncertainty factor of 1. US EPA also notes that individual requirements for and effects associated with manganese exposure may be highly variable and that some individuals may consume more than 10 mg/day of manganese without any cause for concern.
                      RfC = 0.00005 mg/m3                   RfC (last reviewed in 1993) based on the same study considered by ATSDR (2008), however US EPA considered the LOAEL (HEC) of 0.05 mg/m3 and applied an uncertainty factor of 1000.

As manganese toxicity via inhalation has been shown to be more significant than via oral intakes, it is reasonable that quantitative values for inhalation exposures are significantly lower than for oral exposures. Based on the available data, an oral threshold value of 0.16 mg/kg/day as derived by ATSDR (2008) is based on the most recent detailed review of manganese toxicity. It is noted that the basis for the value is consistent with the upper range of manganese intake considered by US EPA (IRIS 2012), NHMRC (2011) and WHO (2011, if the additional uncertainty factor of 3 were not considered for exposures from soil (based on increased bioavailability from water)).
The quantitative values available for the assessment of inhalation exposures are all essentially based on the same critical study (with the exception of Health Canada), with the main difference being the approach used to quantify a threshold value from the study data (using different benchmark dose models or not using a benchmark dose model), and consideration of uncertainty factors. The air guideline value derived by WHO (1999) is recommended based on the use of