Document 8Rn63Z8R5e77105yb79MKZErm

THE PATHOGENIC ACTION OP INHALED MICA Necropsy Findings; Rats MR-582 - H-2857, 2838, 2840, 2864 The pathologic anatomical findings in the four experi ments comprising this study are assembled in Tables 1 to 5. Strict comparison o'f the relative effects recorded for each variant of mica is not possible since dust concentrations varied from 6.6 mg/lit for the mica coated with calcined Ti02, to 8.1 mg/lit for the mica coated with hydrous Tip?, 22,34 mg/lit for the carbon,coated mica and 24.58 mg/lit for the uncoated concord 200/525 mica. Thus, the more prominent effects on the lungs and kidneys observed for the latter two agents may be partly due to the higher dust concentrations employed. However, it seems permissible to infer that the, carbon coated mica had a significantly greater,.,effect on the lungs, to judge by the relative increase in lung weights. In this group the weights of the liver, spleen, and kidneys also showed slight relative preponderance. Another factor to consider is the temporal distribution of these experiments. The two tests with titanium coated mica were concluded during February, 1961, whereas the exposures to the carbon coated and uncoated mica were concluded during May, 1961. During this interval we have seen an appreciable -increase in N37291 2 severity of endemic pneumonitis in the strain of rats currently in experimental use at the Haskell Laboratory. The difference in lung Weights for the rats exposed to the four mica aerosols also matches the severity of symptoms. Thus, slight respiratory impairment was noted in the rats which inhaled the titanium coated mica and those which inhaled the uncoated mica. In the group which inhaled the carbon coated mica the respiratory discomfort was more severe. The kidney, spleen, lymph node and thymus reactions referred to in Tables 1 to 4 may be coincidental findings. Similar abnormalities sporadically occur in rats never exposed to harmful agents. The biological activity of inhaled fibrous silicates cannot be assessed on a fifteen-day basis. While one may infer from the present study that alarming acute pulmonary reactions may not result from the brief single inhalations of low concentrations of the four varieties of mica dust, a thorough investigation extending over one or more years is needed to eliminate the possibility of cumulative pneumoconiotic reaction in human subjects repetitively exposed to the dusts. The pathogenicity of fibrous silicates is also influenced to a marked degree by the length and caliber of the fibrous particles. These factors have not been specified, but need careful review for proper toxicological evaluation of these agents. GWES/ah 5-31-61 G, W. H. Schepers, M.D DUP050041451 liasliell Mo: 2838 Ma te ria l: M ica Coated w ith C alcined. T iO g *Excipient; D ry A ir MR Mo: 582 Test: ALC Ref. N o : E x p e r i m e n t Period; Species; ChRCD Male P rocedure: B u s t I n h a la t io n / ^ H 2-1-61 - Ha? 2 -1 5 -6 1 ________ T. I . S.M.Prosectors: G.. 3 u S U Dose g /lit Cause [ of | [ T e st]I A fte r 1 Death Pulmonary Lesions H +++ == - H= = < CCimnOO va C.i=omn1O>- C^intO- IT 0L0P , -p 1 8 O pmrH 0 <as>) p0H 00 o(GU3 nShS H jg g, PH6I0 ' 0GG CO H 11 11 4" H oo ftl O rl B xs 0 H HO fOt! >min8. nO5 'iOn II * N37291.01 DUP050041452 ra 4J AIDrralH, P, &OVO o i Xo! <"oi m co x! 1 p in frj' &0,} GROSS PATHOLOGY SUMMARY Haskell Ho: 283? Ma te r ia l: M ic a C oated w it h H ydrous T10P* Ex c ip ie n t: D ry M MR Ho: 582 Te s t: ALC Species: nhTMTD M ale Procedure: p a s t I n h a la t lo n / 4 Ref. N o : E x p e r i m e n t Period: 2 -1 -6 1 - 2-15-61 Rat _______ T . 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