Translational toxicology in setting occupational exposure limits for dusts and hazard classification – a critical evaluation of a recent approach to translate dust overload findings from rats to humans

Table 5 Interspecies lung responses ^a following long-term or chronic inhalation exposure to GBS

Species
Rat	Mouse	Hamster	Primate/human
Likelihood for developing particle overload (slow lung clearance)
+++	+++	+	Not determined*
Alveolar macrophage participation
Active (accumulation in alveolar ducts)	Active (accumulation in alveolar ducts)	Extensive (rapid clearance)	Not as extensive (translocation to interstitial sites)
Pulmonary (neutrophilic) inflammation
+++	+++	+	+
Epithelial and interstitial cell proliferation
+++	+	(+)	(+)
Septal fibrosis
+++	+	(+)	(+)
Anatomical location of retained particulates
Primarily alveolar (some increased translocation at overload)	Primarily alveolar (some translocation at overload)	Rapid clearance	Primarily interstitial
Lung tumours following chronic exposure
Yes	No	No	No

^aSeverity low +, moderate ++, high +++, or questionable (+), reprinted with permission from ([34], p. 52)**.
*This should be + (see p. 53 in [34]) because particle overload is typified by an impairment in alveolar particle clearance (see p. 1 and 4 in [34]).
**There may be a variance of opinion about the extent/degree of some of the endpoints in the table (e.g., alveolar macrophage participation, septal fibrosis) and there is continuing research to refine these findings.

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