A comparison of the results from intra-pleural and intra-peritoneal studies with those from inhalation and intratracheal tests for the assessment of pulmonary responses to inhalable dusts and fibres

Abstract

The aim of this paper is to compare results from inhalation studies with those from intraperitoneal and intrapleural tests, where available, for a number of fibrous and particulate test materials. The objective is to determine how well intraperitoneal/intrapleural studies predict the pathological responses observed in more standard in vivo studies of pulmonary toxicity, with a particular focus on carcinogenicity. Published toxicity data was obtained for a number of materials including asbestos, wollastonite, MMVFs (including glass fibres, stone wools and RCF), silicon carbide whiskers, potassium octatitanate, quartz, kevlar, polypropylene and titanium dioxide. For some of the fibrous material reviewed, there is conformity between the results of intraperitoneal and inhalation tests such that they are either consistently positive or consistently negative. For the remaining fibrous materials reviewed, intraperitoneal and inhalation tests give different results, with positive results in the intraperitoneal test not being reflected by positive inhalation results. It is suggested that the intraperitoneal test can be used to exonerate a dust or fibre (because if negative in the intraperitoneal test it is extremely unlikely to be positive in either inhalation or intratracheal tests) but should not be used to positively determine that a dust or fibre is carcinogenic by inhalation. We would argue against the use of intraperitoneal tests for human health risk assessment except perhaps for the purpose of exoneration of a material from classification as a carcinogen.

Potassium octatitanate fibers induce persistent lung and pleural injury and are possibly carcinogenic in male Fischer 344 rats

“…To resolve these problems and determine whether further experimentation on the carcinogenicity of POT fibers is warranted, we conducted a short‐term experiment comparing the intensity of early indicators of possible carcinogenicity in rats given POT fibers or non‐fibrous titanium dioxide nanoparticles (nTiO 2 ). We used two types of nTiO 2 , photoreactive anatase (a‐nTiO 2 ) and inert rutile (r‐nTiO 2 ): a‐nTiO 2 is a weak carcinogen in the lung that induces neoplastic development when high doses are given . The major component of these materials is titanium but the shapes (granular particles, short rods, and long needle‐like‐shaped fibers) are different.…”

Review of refractory ceramic fiber (RCF) toxicity, epidemiology and occupational exposure

“…This classification was reaffirmed by a subsequent Working Group meeting in 2001 (IARC, 2002), which concluded that there was sufficient evidence in experimental animals but inadequate evidence in humans for the carcinogenicity of refractory ceramic fibers. Later analyzes, however, indicated that the RCC animal studies were compromised by overload, a factor that has made it difficult to derive accurate estimates of risk by extrapolation of animal study results (Brown et al, 2005;Drummond et al, 2016;Greim et al, 2014;Maxim et al, 2003;NIOSH, 2006;Utell & Maxim, 2010). Notwithstanding limitations of the animal studies, these results prompted Figure 1.…”

“…While the issue of the simultaneous effect of asbestos and other mineral particles needs to be further explored in reality, the hypothesis of a synergistic joint effect needs to be considered. Drummond et al (2016) published a review article that examined the relationship between the results of intra-pleural and intraperitoneal studies with those from inhalation and intratracheal tests for the assessment of pulmonary responses to inhalable dust and fibers. They concluded:…”

Nanomaterials: certain aspects of application, risk assessment and risk communication

“…Moreover, pulmonary fibrosis has been highlighted as an effect of MWCNT exposure (Sharma et al 2016 ; Vietti et al 2016 ). Intraperitoneal injection, described as the most sensitive method for carcinogenicity testing of fibers (Bernstein et al 2001 ; Drummond et al 2016 ) has revealed a relation between curvature and carcinogenic potency of MWCNTs. However, due to its sensitivity this method is useful for hazard identification and studying mechanisms of action, its applicability to risk assessment remains to be established.…”