Toxicity of Particulate Matter Associated with Combustion Processes

Chapter 5

Toxicity of Particulate Matter Associated with Combustion Processes R. F. Henderson

Downloaded by UNIV LAVAL on July 11, 2016 | http://pubs.acs.org Publication Date: May 9, 1990 | doi: 10.1021/bk-1990-0425.ch005

Lovelace Inhalation Toxicology Research Institute, P.O. Box 5890, Albuquerque, NM 87185

Most of the concern for the t o x i c i t y of the atmospheres associated with f i r e s has focused on vapors and gases. Vapors and gases are the components that are known to cause acute t o x i c i t y , and at high concentrations can lead to incapacitation and death. It i s c l e a r , how ever, that the smokes from f i r e s also have p a r t i c u l a t e components in the form of soot and chemical reaction products, such as metallic oxides or ozonolysis prod ucts. The t o x i c i t y of these materials must also be considered.

Factors Influencing T o x i c i t y of Particulate Matter In evaluating the p o t e n t i a l t o x i c i t y of airborne p a r t i c l e s , i t i s important to consider where they w i l l deposit i n the respiratory t r a c t , how long they can be expected to be retained there (or elsewhere i n the body i f the p a r t i c l e s clear from the lungs) and the inherent t o x i c i t y of the p a r t i c l e s . A l l of these considerations are determined by the physical and chemical c h a r a c t e r i s t i c s of the particles. The s i t e of deposition i n the respiratory tract w i l l depend on the aerodynamic diameter of the p a r t i c l e (Figure 1) (1.2). P a r t i c l e s greater than 10 um aerodynamic diameter are not generally considered respirable. P a r t i c l e s i n the 5-10 um range w i l l deposit mainly i n the nasopharyngeal region while smaller p a r t i c l e s w i l l have s i g n i f i cant pulmonary deposition. Recent work indicates that a s i g n i f i c a n t f r a c t i o n of inhaled submicron p a r t i c l e s deposit i n the nose as well as i n the lungs (3.4). Thus, p a r t i c l e size plays a key role i n determining the portion of the respiratory tract that may be a target for t o x i c i t y of the p a r t i c l e . Retention of p a r t i c l e s i n the lung w i l l depend, in part, on t h e i r s o l u b i l i t y i n the milieu of the lung (1). Water soluble s a l t s , such as most chlorides, w i l l clear the lung rapidly, while 0097-6156/90y0425-0048$06.00/0 © 1990 American Chemical Society

Nelson; Fire and Polymers ACS Symposium Series; American Chemical Society: Washington, DC, 1990.


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Toxicity of Particulate Matter

PREDICTED HUMAN DEPOSITION

0.01

0.1

1.0

10

100

M A S S MEDIAN D I A M E T E R - M I C R O N S Figure 1. Effect o f size on particle deposition i n the respiratory (Reproduced with permission from ref. 1. Copyright 1966 Pergamon.)


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insoluble metallic oxides w i l l be retained with half-times of clearance of hundreds of days (2.5). If the p a r t i c l e i s of intermediate s o l u b i l i t y or contains a mixture of soluble and insoluble components, the clearance of the p a r t i c l e or i t s soluble f r a c t i o n w i l l be influenced by the surface area available f o r d i s s o l u t i o n . The larger the surface area per unit mass, the higher the rate of dissolution of the soluble components of the p a r t i c l e s , and the greater the potential for those components to interact with lung tissue. The inherent t o x i c i t y of the p a r t i c l e w i l l depend on i t s chemical composition. For example, a p a r t i c l e of CdCl2 can be expected to be more toxic than NaCl because of the known t o x i c i t y of C d (6). In the case of fibrous p a r t i c l e s , the t o x i c i t y of the mate r i a l w i l l also depend on the size and shape of the f i b e r s , with long, thin fibers being the most toxic (7,8). In summary, the type of airborne p a r t i c l e that i s of most t o x i c o l o g i c a l concern i s one that i s small enough to have s i g n i f i cant deposition in the lung, i s insoluble enough i n the f l u i d s of the lung to be retained in the lung for long periods of time, and i s inherently toxic to the lung tissue.


f 2

Potential Toxicity of P a r t i c l e s i n Smokes With the above factors i n mind, what can be said about the potential t o x i c i t y of the p a r t i c u l a t e matter i n smokes? Each f i r e w i l l have smoke with a unique composition and t h i s composition w i l l vary with time for a single f i r e . However, some g e n e r a l i t i e s can be noted. Fires can be expected to produce aerosols due to incomplete combustion and the condensation of v o l a t i l e components. Most of these p a r t i c l e s that remain airborne i n smokes w i l l be i n an aerodynamic size range of submicron to micron p a r t i c l e s (9). Thus, the smokes w i l l have respirable-sized p a r t i c l e s and a s i g n i f i c a n t f r a c t i o n of those p a r t i c l e s , i f inhaled, w i l l be deposited i n the deep lung (2.5). Such small p a r t i c l e s w i l l also remain suspended in a i r longer than larger p a r t i c l e s and thus, w i l l pose a potential exposure hazard for a longer period of time. In addition, small p a r t i c l e s have a large surface area per unit mass and, therefore, the potential to adsorb or desorb more associated chemicals than larger p a r t i c l e s . Thus, the soot i n smokes has the potential for carrying various adsorbed toxicants into the deep lung where they may be desorbed. Second, many of the p a r t i c l e s produced, such as soot and metallic oxides, w i l l have low s o l u b i l i t y i n the lung. Thus, once deposited, these p a r t i c l e s w i l l remain i n the lung for long periods of time with a greater potential f o r exerting whatever inherent t o x i c i t y they may have than would soluble p a r t i c l e s (1.5). A l l of these factors must be considered i n evaluating the t o x i c i t y of p a r t i c u l a t e matter i n smokes. Toxicity of Soot from a Controlled Combustion Process One common p a r t i c u l a t e component of smokes i s soot. For the remainder of t h i s paper, the t o x i c i t y of soot w i l l be addressed. Soot results from incomplete combustion of carbonaceous material


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such as wood or f o s s i l fuels. Variations in the t o x i c i t y of soot should depend on the type and amount of chemicals adsorbed to the soot. As a model, the soot produced from a controlled combustion process--the burning of a standard fuel in a d i e s e l engine w i l l be considered. The t o x i c i t y of soot from the exhaust of a d i e s e l engine w i l l then be compared to the t o x i c i t y of pure carbon black, a soot with n e g l i g i b l e adsorbed organic chemicals. Physical/Chemical Characteristics of Diesel Soot. The d i e s e l soot discussed in this paper i s from exhaust generated by a 1980, 5 . 7 - l i t e r Oldsmobile engine operating on a dynamometer using the Federal Test Procedure urban driving cycle and burning a standardized c e r t i f i c a t i o n fuel (D-2 Diesel Control Fuel, P h i l l i p s Chemical Co.) (10,11). The carbon black i s Elftex 12 from the Cabot Corporation. The physical c h a r a c t e r i s t i c s of the two soots are similar. Both types of p a r t i c l e s have volume median diameters of ~ 0.1 um with surface areas per unit mass of AO to 60 m /g (Wolff, et a l . Inhal. Toxicol.. in press). Neither type of soot p a r t i c l e is soluble in the lung. The distinguishing c h a r a c t e r i s t i c of the diesel soot i s that i t contains 10-30% by weight of organic compounds (amount varies with the operating condition of the engine) that are extractable into methylene chloride while pure carbon black has n e g l i g i b l e amounts of extractable organic material. The extractable organic matter associated with the d i e s e l soot has been chemically characterized and i s known to have some biologi c a l a c t i v i t y (Table I) (12). Most of the mass of the material extracted i s i n the form of high molecular weight a l i p h a t i c compounds, probably from unburned fuel and motor o i l . The b a c t e r i a l mutagenic a c t i v i t y , however, i s mainly associated with the aromatic hydrocarbon f r a c t i o n . Highly mutagenic nitroaromatic derivatives would be expected to form from the interaction of aromatic compounds in the fuel with the NO2 formed during the combustion process. Such nitroaromatic compounds have been detected i n d i e s e l fuel treated with NO2 and i n the extracts of soot collected from the exhaust of diesel engines (Table II) (13). Thus, diesel soot contains compounds that can interact with the genetic material, DNA. Organic extracts of diesel soot have also been shown to be carcinogenic i n mouse skin assays (14). The next question i s whether such compounds are available to the lung tissue when diesel soot i s inhaled and deposited in the lung. 2

Table I.

Extractable Organic Matter in Diesel Soot

Fractions from LH-20 Chromatography High MW a l i p h a t i c hydrocarbons Aromatic hydrocarbons & derivatives Polar compounds

Mass (%) 58 19 23

Bacterial Mutagenicity 7 81 12

SOURCE: Data from Bechtold et al. (72).


(%)

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FIRE AND POLYMERS Table I I .

a

Relative Intensity of Normalized Mass Spectra C A B D i l u t i o n Tunnel Fuel F i l t e r Extract Sediment Extract Aromaties + N 0 New Engine

Compounds

2

Naphthalene NO2 Biphenyl-N02 Fluorene-N02 Phenanthrene NO2 Dinitrobiphenyl Pyrene NO2 Dinitrofluorene


MS/MS Analysis of Nitroaromatics

+ +++

+ ++ ++ ++

+++ + +

+

SOURCE: Data from Henderson et al. (13). A n a l y s i s of nitroaromatics found by treating d i e s e l f u e l with NO2 (column A) compared to nitroaromatics found i n extracts of f i l t e r s of exhaust from a d i e s e l engine (column B) or i n extracts of d i e s e l soot deposited in a d i l u t i o n tunnel of an animal exposure system (V3). a

B i o a v a i l a b i l i t y of Soot-Adsorbed Organic Chemicals. If the organic compounds adsorbed to soot are available f o r d i r e c t interaction with the DNA of the lung or i f the compounds are available f o r metabolism to DNA-reactive compounds by lung microsomal enzymes, the potential genotoxicity of the d i e s e l p a r t i c l e s could be s i g n i f i c a n t , p a r t i c u l a r l y i n view of the persistence of the insoluble soot p a r t i c l e s in the lung. In one study performed i n v i t r o . ^C-benzo(a)pyrene (BaP), a t y p i c a l aromatic compound produced i n combustion processes, was adsorbed onto d i e s e l soot and the a b i l i t y of lung or l i v e r microsomes to f a c i l i t a t e removal of the l^C-BaP was observed (Figure 2) (15). Transfer of BaP from the soot to the microsomes was found to be dependent on the l i p i d content of the microsomes with greater amounts of BaP found i n association with the more l i p i d lung microsomal fractions than with the l i v e r microsomes. After two hours of incubation, the amount of BaP transferring from the soot to the microsomes leveled o f f at approximately 3% of the BaP o r i g i n a l l y on the soot, and of that, only 1-2% was metabolized (Table I I I ) . This indicates that soot-adsorbed chemicals are not readily available to the lung, but that microsomes or the l i p i d s i n the milieu of the lung may f a c i l i t a t e a very slow removal of a small f r a c t i o n of the chemicals. This slow removal, however, could be s i g n i f i c a n t over a long period of time. 1

Acute T o x i c i t y of Diesel Soot. The acute t o x i c i t y of d i e s e l soot deposited i n the lung i s low compared to that of toxic p a r t i c l e s such as Ga20 (16) or nickel s a l t s (17,). In rats that had s i m i l a r lung burdens of d i e s e l soot or Ga203 (0.5-0.6 mg/g lung), there was no evidence of an inflammatory response to the soot, as evaluated by bronchoalveolar lavage, while there was a strong inflammatory response to the Ga203 (18.19). Less than 0.5 mg/g lung of Ni3S2, 3



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INCUBATION TIME (hr) Figure 2. Bioavailability of soot-adsorbed benzo(a)pyrene (BaP). The transfer of C - B a P from diesel soot to microsomes was measured. Microsomal protein (0.5 mg) was incubated at 37 * C with the [ C]-benzo(a)pyrene-coated diesel particles. ( 0 ) lung microsomes and 0.2 m M N A D P H ; ( O ) lung microsomes; ( A ) liver microsomes with 0.2 m M N A D P H ; ( A ) liver microsomes; ( • ) 0.5 mg albumin; ( • ) buffer (0.15 M phosphate buffer, p H 7.7, containing 3 m M M g C l and 0.1 m M E D T A ) . The presence of N A D P H , a cofactor necessary for BaP metabolism, did not affect the transfer of BaP from the soot. (Reproduced with permission from ref. 15. Copyright 1988 Elsevier.) 1 4

14

2


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Table I I I . ( C)Benzo(a)pyrene Metabolites Formed i n Incubation Medium and on Diesel P a r t i c l e s 8

BaP Metabolites 9,10-diol 7,8,9,10-tetrol 3-hydroxy B(a)P

Free BaP Medium (%) 33.3-42.4 12.8-14.0 ND 44.8-52.7

ND = not detected. [14)BaP-coated d i e s e l p a r t i c l e s or I C]BaP were incubated at 37°C with l i v e r microsomes (1 mg protein) and 0.2 mM NADPH f o r 1 h. The data indicate the percent of the BaP present as parent compound or as individual metabolites i n each of the fractions. SOURCE: Reprinted with permission from ref. 15. Copyright 1988 Elsevier. a


P a r t i c l e - Associated BaP P a r t i c l e (%) Medium (%) ND ND ND ND ND 1.2-1.5 100 98.5-98.8

14

NiS04 and NiCl2 i n s t i l l e d into rat lungs also produced an inflammatory response (17). However, analysis of bronchoalveolar lavage f l u i d from rodents exposed to d i e s e l exhaust containing 3.5 mg soot/m , 7 h/day for 2, 12 or 17 days indicated no i n f l u x of inflammatory c e l l s (20). Thus, the d i e s e l soot, at lung burdens of 0.5 mg/g lung, does not produce an acute inflammatory response. 3

Chronic Toxicity of Inhaled Diesel Soot i n Animal Studies. Numerous studies on the chronic t o x i c i t y of inhaled d i e s e l engine exhaust have been reported. Studies conducted i n the United States (Nationa l Institute of Occupational Safety and Health, Environmental Protection Agency, Southwest Research Institute, General Research Laboratories, Lovelace Inhalation Toxicology Research I n s t i t u t e ) , i n Germany (Fraunhofer Institute for Aerosol Research), Switzerland (Batelle-Geneva Research Institute) and Japan (Japan Automobile Institute) have been summarized i n the proceedings of an internat i o n a l meeting on the subject (14). One of the studies at the Fraunhofer Institute c l e a r l y i n d i cated that the t o x i c i t y resulting from chronic inhalation of d i e s e l engine exhaust was due to the p a r t i c u l a t e component of the exhaust and not the gases (21). Rats were exposed by inhalation over most of t h e i r l i f e span to f i l t e r e d or u n f i l t e r e d d i e s e l exhaust. Exposures were 19 h/day, 5 days/wk with soot concentrations of 4 mg/m . A l l of the measures of t o x i c i t y determined, including decreases in body weight, alveolar clearance, and various measures of lung function, as well as the induction of lung tumors, were observed only i n animals exposed to the u n f i l t e r e d exhaust. In a study conducted at the Lovelace Inhalation Toxicology Research Institute (ITRI), rats were exposed for up to 30 months, 7 h/day, 5 days/wk, to d i e s e l exhaust containing 0, 0.35, 3.5, or 7.1 mg soot/m of a i r . The d i e s e l engine exhaust was generated as indicated i n the section of t h i s paperon "Physical/Chemical Characteristics of Diesel Soot." The lowest exposure concentration, 0.35 mg soot/m , i s d i r e c t l y relevant to some occupational exposures and i s 10 to 100 times higher than any current or anticipated environmental exposures. Observations of the animals were made at 6-mo intervals and included measures of dosimetry (mg soot/g lung), 3

3

3


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microdosimetry (level of DNA adducts), clearance of secondarily introduced tracer p a r t i c l e s from the lung, inflammatory responses, immune responses, respiratory function and histopathology. The gaseous and p a r t i c u l a t e contents of the d i e s e l exhaust are shown in Table IV (22).

Table IV.

3

P a r t i c l e s (mg/m ) C0 (%) CO (ppm) Hydrocarbons (ppm) NO2 (ppm) NO (ppm)


2

Diesel Exhaust

Control (Air-Exposed) 0.01 0.2 1 3 0 0

Composition

Low 0.35 0.2 3 4 0.1 0.7

Medium 3.5 0.4 17 9 0.3 6

HiRh 7.1 0.7 30 13 0.7 10

SOURCE: Data from Henderson et al. (13). The accumulation of p a r t i c l e s i n the lung with time (Figure 3) indicated that there was a greater lung burden i n animals exposed to the two higher exposure levels than would be expected based on the deposition and clearance rates observed in the low level-exposed rats (23). This suggested that chronic exposure to the high levels of p a r t i c l e s had impaired the normal clearance mechanisms of the lung. This hypothesis was confirmed by studies on the a b i l i t y of the soot-laden lungs to clear inhaled * C s - l a b e l e d fused aluminos i l i c a t e p a r t i c l e s (FAP) from the lungs (Figure 4). The two high level-exposed groups of animals cleared the secondary p a r t i c l e s with a half-time twice that of the control and low level-exposed rats (23). There was a detectable response of the lung to the inhaled d i e s e l soot only at the two highest exposure concentrations. The inflammatory response detected in the bronchoalveolar lavage f l u i d was exposure concentration-dependent and, in general, increased with time of exposure and increasing lung burden (Figure 5) (22). Part of the soot was cleared to the lymph nodes; these s i t e s had i n creased t o t a l c e l l s and increased antigen-specific antibody forming c e l l s i n response to subsequent immunization (24). Respiratory function changes were consistent with development of dust pneumoconiosis at the two higher exposure concentrations (25). The histopathology observations indicated a progressive inflammatory, p r o l i f e r a t i v e and f i b r o t i c lung disease in animals exposed at the two higher concentrations, with a small but s i g n i f i c a n t increase in tumors (Table V) (11). In summary, these life-span studies in rodents suggest that large quantities of d i e s e l soot deposited in the lung are toxic. However, there was no life-span shortening at any l e v e l of exposure. For noncarcinogenic endpoints there appeared to be a threshold relationship with no s i g n i f i c a n t responses at the low exposure concentration and progressive alterations of many parameters at the higher exposure concentrations when lung burdens 13



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0

6

12

18

24

MONTHS OF EXPOSURE Figure 3. Accumulation of diesel soot in lungs exposed to diesel engine exhaust containing 0.35, 3.5, or 7.0 mg soot/m . Lung burdens at the lower exposure concentration did not exceed 1.0 mg/g lung (Data from ref. 23). 3

Figure 4. Clearance of Cs-fused aluminosilicate particles from lungs of rats exposed to diesel exhaust (Data from ref. 23). 134


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1600 HIGH MEDIUM — o — LOW -^>— CONTROL o

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Toxicity of Particulate Matter Associated with Combustion Processes

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