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Br. /. exp. Path. (1986) 67. 113-129 Inhalation and injection studies in rats using dust samples from chrysotile asbestos prepared by a wet dispersion process J.M.G. Davis. J. Addison. R.E. Bolton. K. Donaldson and A.D. Jones The Institute of Occupational Medicine. H Roxburgh Place. Edinburgh F.HR 9SU Received for publicnlion 1 9 April 1985 Accepted for publication 30 July 1985 Summary. Long term inhalation studies and intraperitoneal injection studies in rats were undertaken with a series of chrysotile asbestos dusts. Three dust samples were generated from chrysotile modified by the wet dispersion process (WDC) and one was from unmodified chrysotile. Following a 1 year inhalation period, all the chrysotile samples proved extremely fibrogenie and carcinogenic and there were no .significant differences between the WDC dusts and normal chrysotile. In all experimental groups approximately 25% of animals developed pulmonary carcinomas and in the oldest rats advanced interstitial fibrosis occupied on average lo% of all lung tissue, fn the injection studies all the dust samples produced mesotheliomas in over 90% of animals. Very little chrysotile remained in the lungs of the animals that survived longest following dust inhalation and what there was was present as individual chrysotile fibrils. It is suggested that chrysotile is potentially the most harmful variety of asbestos as shown in these and other animal studies but that it is removed from lung tissue quite rapidly. In the long lived human species this may mean that except where exposure levels are very high and of long duration, chrysotile should be less hazardous than other asbestos types. Keywords: Chrysotile asbestos, wet dispersion process, carcinoma, fibrosis The industrial use of asbestos has been taken in order to examine these effects but shown to result in considerable health risk to most have used either in vitro or injection asbestos workers (Selikoff & Lee 1978). techniques because these require only small Heavy exposure can result in pulmonary amounts of dust which can be specially interstitial fibrosis (asbestosis). bronchial prepared. Long-term inhalation studies carcinoma and mesothelioma. unfortunately require large amounts of While the main commercially used asbes asbestos dust and so far it has not been tos varieties differ markedly in their chemical possible to obtain sufficient size-selected composition, all show considerable potential dusts of any single asbestos type to examine to produce pulmonary disease when inhaled. the effects of fibre length when dusts are It is now believed that the most important inh,aled. As an alternative approach, studies dust factor in disease development may be are continuing in this Institute using such the physical dimension of the fibres, particu asbestos materials as are available that are larly length (Stanton 1972: 1977). Numer likely to produce dust clouds of significantly / ous experimental studies have been under different fibre dimensions.rOne such type of HWBUI0009154 ) imm x ^ 2 _ rt 2. tr ^ SL c? 3 & * - ff ,, v - 3 * 2 -- t 3 f 5-|= 2.3-' 2 1 -3= S. =. n d |____s* 5"!; S^w2. "!!j t 3 o52 c5e""Lr o jA *t~*;-. =.*< o = a'3 5t5 j11 5^ o:.n"|?S- T "**1 '< n ^ s- oS. = a << ^*3 Si 3g ;ji eS onga.1 *g3 i*fS"3 S.<.3w ^33.r*>n*3r o=;. 8 x! f 3^-8 I ?8 e. 1 s sr ssx 3 rr a: |8S 33?"S-5 !: 3 SI 2 i 3 < j 3 =1^5 lhfi\ tl^l 35 8 j Mca M3 B3=-ESQ SS?.,1,1 :t|Jl! %. *> Djol SI S ftS i rme"1 -oo ~ S-:j Sa.S2 s8. 3? 3 3 i! > n 9K n = B 2 3 Hfei I C 3 , 3 8. o 3 er b 2 3 ~1 "~ -- X" S; " v. y. = JJ ^ -i ^ a'SMSR*- < ST ,, 3- = " = fet? 3a- 25^D* *s 3T ~ c'^.re 3ns-^x, ?-r S~ 2 5" 5?.' - '1 1X S 2 Si s h S' a a Table 1. Dust sampling techniques Type of sample Total dust Respirable dust Fibre number Description of sampling equipment Open filter. 50 mm diameter sampling flow rate x Ittres/tnln facing downwards Casella MRE 11 jA gravimetric* dust sampler Vertical elutrlatorf Open filter holder. 25 mm filter diameter In Getman head facing downwards sartorius membrane filter and nudepore polycarbonate membrane filter * Dunmore el el. (1964)t Walton (1954). * Dodgson & Whittaker (1973). Asbestosis Research Council (1971). || Walton & Beckett (1977). Sampling period The full 7 h exposure The full 7 h exposure At least 1 full day Of the order of 1 min Analysis gravimetric gravimetric Infra-red spectroscopy* counting iirnl sizing of fibres by phase contrast optical mlcroscope|| x 600 sizing of fibres by electron micro scopy x itMinn oc f | a. f 1 %St VOI -n HWBUI0009155 tori Table 2. Mass and fibre number concentrations for the dust clouds generated from wet dispersed chrysotile products and standard chrysodle textile yam Dust" Exposure WDCyam Factory WDC Chrysotile yam Exp. WDC Exp. WDC (Reversed daylight) Type of measurement Respirable dust concentration mg/m** (Means of daily estimations--see text) Casella MRE 113A (Incorporating a horizontal elutriator) Vertical elutriator gravimetric gravimetric gravimetric fibres/ml Infra-red absorption spectroscopy 3.6 3-5 3.6 3-6 3-7 2.8 3.6 3o 3-7 4-4 3-5 3-3 4-7 3-8 3-4 i Total dust concentration mg/m"1 Fibre number 'Snatch' samples on membrane filters. Counted by phase contrast opticnl micnwcnpy. Mean of too samples 4-6 4-8 4-3 5-7 S-6 T 679 468 428 108 ri; ?? s 2 IT $. n in Cr. HWBUI0009156 m L HWBUI0009157 Table j. Mean levels of pulmonary Hbroslj produced by wet dispersed chrysolite duns and dust from ehrysoclle textile yam (ranges in brackets) lime after start of exposure tmonth?} Noe.xoafmraintsed iVrihmnrhlnhir fibrosis Intemltliii rihrnsb 1l 1S 37-19 Factory WDC Chrysolite yam 44 1$ iH.f> r 1.1 -- ir7-3-xo.4M7.H-n.oi 0.1 * 0.3 11.8 10-0.51 (0-1.1Ml.l4-4n.f1M iH<i,5\ .9-lX.fU1-M979-XI.9--l Ih.J 15-h -- (fi.3-ii.3Mtr.fi-zt.si <0-4.9} (ti.|t->M'hi i(H>j.8i M>-.}.7< 1 Kip. WDC Kip. WDC Kcversed Daylight Cmind" CentmU 68 17-39 17-19 J7-19 4 f1 18.1 18.7 -- UI1.K- |1.}I 111.9-18.7} it 9#* tt1.4b-it.7i 1. t H.f -- O t.l-lN.hl Uh.o-iK.S) i t t* III.S <i*.f* t-li.i it ti.S !*>-. }--------- . ^rwv^'WM^iiii:tiwallfclliiiiii<.......... <;-W(| \) " 3 is 3-a a. 3 re Sore !3a ."~'r=eF sre : s * : ;g3 s S E23 ~ re 3 Ooo r tT - 1 B 1 ^ re re ore 5% 2 fg. 8.1 8 8"S'3 P5 " c -- 00 CO re ?L E 3o ,, Sof 32 00 3 "3 y? JM ^ t3 O3- 52 OpW* ?m 55-5 =:0 3 3 . 8. ^ | ?i>" ii; as?* tg sr 4 2 jo E. ?re ST 3. 2re -- 5 o w g -5 " S, , Z* p* -3us re <O<' Es E 2. re <'< %. ; cos: II R iol s voj - ~ *, 9S_-> 2sf;K=ilre l~aFe sin Spao; ^ *o 5T m 9S 2 =* re 3 J8 re 3 * o c ? s-sr2 ^ a c S. ESS g-gE e, 1 So?3* 5 =reP W3 3re r3e Sre. r52e * m cr. "re9 . 2 *> 3 si: 3 !r - o ss - 5" -5re-s- 3 "< 5" s oa .as-*3E' =^rX~erq--5o31 scre3- Co k S *B-t 53 1 S 2 S 2. 3 90 1 l||j!s?5SIe8s .2=",33 " Si. K S-W " 0-2 = g 2 ?r =3 g 2 S' ||l |?= 2. 9 o = 3 " 2 5 re 3 83- Sre . f3it 3^;! --= 5 3?-3s 2a to re re TOS <r3e O3 a 5* 3< 3 C g- 5" =1 " If S 2n- 3i w mg-5f0t e, 3 80 --: Sn sre 3e | , s -* sr 0 c-oq ar Bj3iC e res 1 ?!" arR 330 3-i"-52. --5ft^ c3--r ---- 3 A S 8|g B C 2 IJffi ?5 C re o^j. acr SCre' 2= SM. 3 o'=" 3 : 3 3 to g : re 3 O" .. it Ce -- " E S e~3 ; 5"=". E IM;: vt c -<- n 3. a;i Ijs I s Ifi. 3 0 2.^" 3 1 ? If-- -- ^ =Tv2 ?J3a =e " _ ST S 7! ? 1 S -i 3 a; < t 1-3 = s.; "r- = ; < O re S5i "Ci O 8 !,= n H. J.5! SI . M> f-i. Ms e 3 ? 3i = ~9 < HWBUI0009158 yam** Pulmonary tumours and mesotheliomas produced by wet dispersed chrysotile dusts and dust from standard chrysotile textile No. of rats examined Adenomas Total carcinomas Adenocarcinomas Squamous carcinomas Mesotheliomas WDC yam 41 *3 7 6 O Factory WDC lI 10 3 0 Chrysotile yam 42 <3 1 Exp. WDC 43 10 5 3 4 Exp. WDC (Reversed Daylight) 37 5 12 5 7 1 Controls 1 39 s T 1 O 2 25 O O 0 O O g ? rti a. HWBUI0009159 i Table s- Numbers of tumours occurring at sites other than lung " Number of rats examined Organ System Digestive/peritoneal Urinogenita! Endocrine Musculo, skeletal and Integumentary Reticuloendothelial/ vascular Totals WDC yarn 41 SM tI f 4r i2 1 66 Factory WDC 44 BM 2 II l! 12 3 39 Chrysolite yam 42 BM 2 r 3> t4 3 5 xo B. benign: M. malignant Exp. WDC 43 8M 13 3 3 5I 0f 12 5 Exp. WDC (Reveraxi Daylight) 37 BM r s ti 44 2 68 Controls 1 39 BM i3 2 H2 5 3 7 15 Controls 2 *5 UM l 1 '3 l 4 HWBUI0009160 ) I=s e s O^ ^ OQ trs ^J ~ | g) U GO 9jl U 99ce . N ^ 3 3S5C I *$ N '& ^ ri 1 2 ( V HWBUI0009161 Jo -J 1 HWBUI0009162