Jacques Dunnigan

Health risk of chrysotile revisited

Abstract This review provides a basis for substantiating both kinetically and pathologically the differences between chrysotile and amphibole asbestos. Chrysotile, which is rapidly attacked by the acid environment of the macrophage, falls apart in the lung into short fibers and particles, while the amphibole asbestos persist creating a response to the fibrous structure of this mineral. Inhalation toxicity studies of chrysotile at non-lung overload conditions demonstrate that the long (>20 µm) fibers are rapidly cleared from the lung, are not translocated to the pleural cavity and do not initiate fibrogenic response. In contrast, long amphibole asbestos fibers persist, are quickly (within 7 d) translocated to the pleural cavity and result in interstitial fibrosis and pleural inflammation. Quantitative reviews of epidemiological studies of mineral fibers have determined the potency of chrysotile and amphibole asbestos for causing lung cancer and mesothelioma in relation to fiber type and have also differentiated between these two minerals. These studies have been reviewed in light of the frequent use of amphibole asbestos. As with other respirable particulates, there is evidence that heavy and prolonged exposure to chrysotile can produce lung cancer. The importance of the present and other similar reviews is that the studies they report show that low exposures to chrysotile do not present a detectable risk to health. Since total dose over time decides the likelihood of disease occurrence and progression, they also suggest that the risk of an adverse outcome may be low with even high exposures experienced over a short duration.

An assessment of the fibrogenic potential of very short 4T30 chrysotile by intratracheal instillation in rats.

Three groups of five rats each received, respectively, a single intratracheal instillation of saline (control), 5 mg of UICC chrysotile B asbestos, and 5 mg of a preparation of very short chrysotile fibers (4T30, 100% less than 8 micron) isolated by a sedimentation procedure. At various intervals after the treatment (1 to 60 days), assessment of lung morphology was performed on each animal. Although the two types of chrysotile fibers have similar chemical composition, structure, and surface charge, the lung tissue reaction differed considerably. Lungs of animals exposed to UICC chrysotile B showed significant pathological alterations as early as 7 days following treatment. The lesions were localized in and around terminal bronchioles and consisted of inflammatory cells, fibroblasts and collagen deposition which distorted and obstructed small airways. Reaction to very short 4T30 chrysotile fibers was quite distinct. Seven days after treatment, lungs of these animals showed alveolar and interstitial accumulation of inflammatory cells. The alveolitis persisted 60 days after treatment and no fibrosis was apparent. It appears that very short 4T30 chrysotile fibers are much less fibrogenic than UICC chrysotile B and that intratracheal instillations in rats may represent a useful mean of rapidly assessing the fibrogenic potential of various dusts. These observations support the concept that fiber length is an important factor for fibrogenicity of asbestos.

Rat lung reactivity to natural and man-made fibrous silicates following short-term exposure

The inflammatory and fibrogenic potential of three naturally occurring and two man-made industrial minerals were compared. Groups of five rats each received respectively a single intratracheal instillation of saline (control), UICC chrysotile B asbestos, short chrysotile 4T30, attapulgite, xonotlite (a calcium silicate), and Fiberfrax (an aluminum silicate) at doses of 1, 5, and 10 mg. One month after the treatment, assessment of lung morphology and bronchoalveolar lavage were performed on each animal. Under these conditions, UICC chrysotile B at all doses tested (1, 5, and 10 mg) induced fibrotic lesions in bronchiolar tissues while short chrysotile 4T30 (1, 5, and 10 mg) caused focal accumulation of inflammatory cells in the alveolar structures but no apparent fibrosis. Compared to these positive reactions with different fibrogenicity, xonotlite caused minimal inflammatory reactions detectable only at high dose (10 mg) and by bronchoalveolar analysis. By contrast, the rat lung reacted more significantly to attapulgite and Fiberfrax although the tissue reaction differed considerably for these two materials. While attapulgite, at doses up to 10 mg caused minimal reactions characterized by mononuclear cell infiltration mainly in the alveolar structures, Fiberfrax at 1 mg and higher caused significant granulomatous reactions and the appearance of early fibrosis. Overall the order of lung biological reactivity observed for the various silicates was xonotlite much less than attapulgite less than short chrysotile 4T30 less than Fiberfrax less than UICC chrysotile B. These observations indicate that Fiberfrax, attapulgite, and, to a lesser extent, xonotlite are biologically active within the time span studied and potentially deleterious for lung tissue.

Improvements of the Anson assay for measuring proteolytic activities in acidic pH range

Abstract This paper proposes a modification of the classic Anson assay [Anson, M. L. (1939) J. Gen. Physiol. 22, 79–89] for proteolytic enzymes which are active in the acidic pH range; it abolishes many of the constraints common to this widely used method. The present procedure allows for: (i) the control of zymogen activation; (ii) the measurement of the hydrolyzed products on a very wide concentration range, due to their extended direct proportionality to both the incubation time and the enzyme concentration; (iii) the possibility to perform the assay at any given pH between 1.3 and 5.0 with minimal interference from ionic strength; (iv) a very simple conversion of the absorbance into proteolytic units, allowed by a better choice of TCA concentration. The method offers good sensitivity and is compared in detail to the original method and its various modifications.

Cytotoxic effects of aramid fibres on rat pulmonary macrophages: comparison with chrysotile asbestos.

Aramid fibres have been proposed as a substitute for many asbestos uses. Although dimensional characteristics of aramid fibres vary with the type of application, some of the commercial grades proposed contain fibres whose geometry is clearly in a range where biological reactivities have been reported for other natural or man-made fibres. We wish to report that short aramid fibres, when tested on cultures of rat pulmonary alveolar macrophages (PAMs), induce the commonly recognized signs of a cytotoxic effect, that is: leakage of cytoplasmic and lysosomal marker enzymes, concomittant with a decreased ATP cell content.

The hemolytic activity of chrysotile asbestos fibers: A freeze-fracture study☆

Short asbestos fibers isolated by a sedimentation procedure have a strong hemolytic activity. In the presence of ferritin particles, hemolysis by chrysotile fibers is inhibited at least during the first 10 min. Freeze-fracture studies show that after 20 sec or 2 min of contact between the fibers and the RBC membrane, the intramembranous particles remain randomly distributed over the whole surface of the P-face. On the E-face of the asbestos-treated red blood cell membranes, the number of intramembranous particles is significantly reduced. With the transmission electron microscopy, it is not possible to resolve the trilaminar structure of the ghost membrane around the deeply buried asbestos fibers. It is postulated that the membrane defects brought about by asbestos are caused by the adsorption of one membrane constituent, possibly phospholipids, on the chrysotile fibers.

The adsorption of polyaromatic hydrocarbons on natural and chemically modified asbestos fibers.

Many reports indicate that the carcinogenic (genotoxic) potential of benzo[a]pyrene (B[a]P) may be enhanced several-fold by the promoter (epigenetic) effect of asbestos particles. This promoting effect could be related to the fact that when B[a]P is adsorbed onto the particles, there is a resulting enhanced transport and uptake of the carcinogen into microsomial membranes. These in vitro data bear relevance to the epidemiological studies which indicate an association between exposure to inhaled asbestos dusts and the high incidence of pulmonary cancers in smokers. Using HPLC, it has been observed that B[a]P has great affinity for natural asbestos fibers, and that chemical modification of natural chrysotile with POCl3 results in the complete loss of this adsorption potential of chrysotile for benzo[a]pyrene.

Asbestos-derived zeolites as water-retaining materials in soils

Asbestos-derived zeolites, when added to soil, are found to be capable of retaining water for longer periods of time. Textural properties (micropore diameter and percent of “larger” pores) are probably important factors because they may determine the level of water storage within the zeolite particles during the wetting phase. These zeolite materials do not exhibit any in vitro cytotoxicity.

Induced conversion of aluminium silicate fibers into mullite and cristobalite by elevated temperatures: a comparative study on two commercial products

Abstract Aluminium silicate fibers (ALF) are used in a variety of industrial products, including as a substitute for asbestos in insulation materials. Although many studies evaluating the thermal resistance of these compounds have been made, conflicting results were sometimes obtained on the conversion of these amorphous silicates into mullite and cristobalite. For our study, two types of ALF were selected: type I (Triton Kaowool®, Normal grade) and type II (Fiberfrax®; High Specific Area “HSA” grade). These two silicate fibers differ mainly in the percentage of impurities such as iron, titanium, sodium and potassium oxides. As observed by X-ray diffraction, differential thermal analysis and infrared spectroscopy, our results show that both types of ALF are transformed into mullite at 1016°C and 990°C respectively for the type I and type II fibers. With the type I ALF, when heated at 1050°C, the quantity of mullite increased with time. No trace of cristobalite was detected even after a 4 weeks heat treatment at 1050°C. However, for the type II ALF which are richer in oxide impurities, two conversion steps were observed: (a) as with the type I fibers, the quantity of mullite increased with time; (b) after 64 h at 1050°C, the second crystallization step into cristobalite started and increased after the 4 weeks heat treatment. These results indicate that the level of oxide impurities can accelerate the conversion of mullite into cristobalite. Considering the known danger associated with the inhalation of cristobalite, these finding indicate that different ALF might have new biological activities when subjected to elevated temperatures for long periods of times.

Response to Murray M. Finkelstein, letter to the editor re Bernstein et al: Health risk of chrysotile revisited. Crit Rev Toxicol, 2013; 43(2): 154–183

Consultant in Toxicology, Geneva, Switzerland, Faculty of Science, University of Sherbrooke, Sherbrooke, QC, Canada, Center for Toxicology and Environmental Health, Little Rock, Arkansas, USA, Toxicology Services, Rutland, UK, Academia Nacional de Medicina México, Mexico City, Mexico, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico, Independent Toxicologist, Haslemere, UK, and Llandough Hospital, Penarth, UK