Environ. Sci. Technol. 4984, 18, 808-810
organic sulfate, the reaction occurred either during sampling or shortly after sampling was completed (Table 11). (4) Analysis of the dilute “OB solutions from test 1, runs 9 and 11, detected only minor quantities of three transition metals: Cr (1 pg/m3), Mn (1pg/m3), and Ni (16 pg/m3). The values for all metals were the same for both the 160 and 188 “C samplers and represent only 0.02-0.6% of the total particulate catch. Overall, the results indicate that the Alundum ceramic thimble and the Reeve Angel 934AH filter may be suitable substitutes for reference method 5 when coal-fired power plant stacks with temperatures near the 160 “C sampling temperature specified in the regulations (2) are sampled. They also show that these two in-stack filters should not be used at scrubber-equipped sources and that borosilicate glass-fiber filters should not be used at either source. Finally, until the required improvements to the probe temperature profile and temperature control are made, it seems prudent to report method 5 particulate results from these plants at two temperatures: after ambient desiccation and after heating for 3-24 h at the sampling temperature specified in the regulation. While this approach would not completely compensate for errors in the probe and filter sampling temperatures, it could identify instances where an unusually high or low particulate value (in a series of tests) was caused by an undetected malfunction or calibration error in the heating systemts). Of course, if this approach was used, the filter should be conditioned before use at the highest temperature at which the sample will be conditioned. Registry No. SO2, 7446-09-5; H2S04, 7664-93-9; alumina,
10,85-88. (2) U.S. Environmental Protection Agency. Code of Federal Regulations, Title 40, Part 60, Subparts D and Da. (3) U.S. Environmental Protection Agency. Code of Fereral Regulations, Title 40, Part 60, Appendix A, Reference Methods. (4) Peters, E. T.; Adam, J. W. “Evaluation of Stationary Source Particulate Measurement Methods: Gas Temperature Control During Method 5 Sampling”; U.S. Environmental Protection Agency: Research Triangle Park, NC, 1979; EPA-600/2-79-115, Vol. 111, (available from the National Technical Information Service, Springfield, VA, as Report P B 300336). (5) Peters, E. T.; Adams, J. W. “Sulfur Oxides Interaction with Filters Used for Method 5 Stack Sampling. Workshop Proceedings on Primary Sulfate Emissions from Combustion Sources: Measurement Technology”; U.S. Environmental Protection Agency: Research Triangle Park, NC, 1978; EPA-600/9-78-020a, Vol. I, pp 199-202 (complete report available from the National Technical Information Service, Springfield, VA, as Report P B 287436). (6) Barton, S. C.; McAdie, H. G. Environ. Sci. Technol. 1970, 4, 769-770. (7) Hamil, H.; Thomas, R. “Collaborative Study of Particulate Emission Measurements by EPA Methods 2,3, and 5 Using Paired Particulate Sampling Trains (Municipal Incinerators)”; U.S. Environmental Protection Agency: Research Triangle Park, NC, 1976; EPA 600/4-76-014 (available from National Technical Information Service, Springfield, VA, as Report P B 252-028/6). (8) Mitchell, W. J.; Midgett, M. R.; Suggs, J. C. atom. Environ. 1979, 13, 179-182.
1344-28-1.
Literature Cited (1) Mitchell, W. J.; Midgett, M. R. Environ. Sci. Technol. 1976,
Received for review July 29,1983. Revised manuscript received May 10,1984. Accepted May 16,1984. This work was supported through EPA Contract 68-02-3737.
NOTES Linear Correlation between Photolysis Rates and Toxicity of Polychlorinated Dibenzo-p-dioxins Andrew Mamantov U.S. Environmental Protection Agency, Offlce of Pestlcldes and Toxic Substances, Washington, DC 20460
rn Linear correlations have been detected between the photolysis half-lives of polychlorinated dibenzo-p-dioxins (in n-hexadecane solution) and (a) the LD50 values (of guinea pigs and chick embryo, r = 0.98) and (b) the relative biological potency values (derived from ED50 values, rat hepatoma cell, r = -0.7 to -0.8). These correlations are surprising in view of the wide disparity between a photolysis reaction and a biological end point. It is difficult to avoid considering the possibility of a common or related reactive intermediate in the photolysis reaction and the biological end point.
Introduction The polychlorinated dibenzo-p-dioxins (PCDDs) are members of the large class of halogenated aromatic com808
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pounds. The mechanism of biological activity and toxicity of the PCDDS has not been entirely elucidated (1). Other halogenated aromatic compounds, structurally related to the PCDDs, include the polyhalogenated biphenyls, biphenyl ethers, dibenzofurans, azobenzenes, azoxybenzenes, and naphthalenes which also elicit varying degrees of toxicity. This has led several groups of investigators to postulate a similar mechanism of toxicity for these compounds (1-3). It is generally accepted that PCDDs bind to a biological receptor, a hepatic cytosolic protein in the cytoplasm of the target cells. This complex is transported into the nucleus where it activates a set of genes representing the locus. These genes aryl hydrocarbon hydroxylase (A”) produce messenger RNAs that direct the synthesis of cytochromes P-450 and P-448.
Not subject to U.S. Copyright. Published 1984 by the American Chemical Society
Table I. Linear Regression Analysis between Photolysis Half-Lives and LDso Values of PCDDS
PCDD
(1) 2,3,7,8 (2) 1,2,3,7,8 (3) 1,2,3,6,7,8 (4) 1,2,3,4,6,7,8
LDSO guinea pig,” chick,* rglkg &egg 0.6-2.0‘ 3.1 70-100‘ 7180
0.007 0.003 0.12 1.61
71/Zr
min
56.8 456 379 1800
“Correlation coefficient r = 0.98; slope m = 0.21; intercept b = = 0.98; m = 960; b = 260. CAveragevalues of 1.3 and 85 290. used in analvses.
The induction of hepatic AHH activity and other related monooxygenase activities requires that the halogenated aromatics have certain structural characteristics. Certain geometric requirements seem to be important in yielding electronic parameters leading to effective noncovalent interactions. The binding of halogenated aromatics to the receptor is most effective if the substrate is generally planar. If chlorinated, it should contain four lateral chlorines arranged in approximately a 3 X 10 A box, whereas if its brominated, three lateral bromines are sufficient, arranged in about a 3 X 10 A triangle or box (3). The incumbrance area of the substrate, defined as the surface of the smallest rectangular envelope of a planar molecule drawn proportionally to molecular dimensions, has also been implicated in determining toxic potential. For example, the incumbrance area parallelograms are of similar size for TCDD, 3,3’,4,4/,5,5/-hexachlorobiphenyl, and 3,4-benzopyrene, being 93.0, 95.9, and 110.5 A2, respectively (4). The presence of a correlation between molecular polarizability and induction of cytochromes P-448 and P-450 in PCBs suggests that polarizability may be an important electronic parameter determining toxicity. Besides the magnitude of polarizability, the preferred mean orientation of the induced dipoles about the longest molecular distance appears to be important. The latter would be indicative of the site of the critical receptor (3). The dependence of binding on the polarizability of halogenated aromatics has led to the postulation of a binding mechanism involving charge transfer, and this may alter the conformation in the receptor protein(s). Steroids are known to form charge-transfer complexes, and it has also been suggested that polynuclear aromatic hydrocarbons sterically resemble steroid hormones in order to be carcinogenic. Even though some of these molecules may not be, strictly speaking, structural analogues, the common electronic molecular basis for this hypothesis is the similar net polarizability of these planar and nonplanar molecules (3).
Results In accordance with the assumption that polarizability is an important electronic factor determining the biological activity of PCDDs, it has been found that 2,3,7,8-TCDD binds noncovalently to protein which, in turn, would imply that a reactive intermediate is not involved (5). The present results show the existence of a linear correlation between the photolysis rates (6) and the LD50 and ED50 values of PCDDS (7-9). It has been suggested previously that the photoactivity of 2,3,7,8-TCDDmay relate to some property which is also responsible for its biological activity (6). Table I presents the PCDDs for which both the LD50 values and the photolysis rates are known. A linear regression analysis of the photolysis half-life ( r l I 2 )values (in
Table 11. Linear Regression Analysis between Photolysis Half-Lives and Relative Biological Potency (RBP)”of PCDDs (in Rat) PCDD
RBP
2,3,7,8 1,39798 1,2933 1,2,3,4,6,7,8,9 1,2,3,7,8 1,2,3,6,7,8 1,2,3,4,6,7,8 1,2,3,4,6,7,9 1,2,3,4,6,7,8,9 1,2,3,6,7,9 1,2,3,7,8 1,2,3,6,7,8
100 1.3 0.030 0.028 9.4 0.825 0.4 O.OIBd O.OMd 0.00022d 2.88 1.078
min 56.8 153 653 1460 456 379 1800 3300 1460 764 456 379
r, m, bb -0.77, -0.32, 2.6”
-0.69, -0.22, 2.6e -0.81, -0.32, 2 . 6 -0.81, -0.35, 2.6h -0.70, -0.23, 2.6’ -0.84, -0.34, 2.Q
“log vs. log RBP. correlation coefficient; m, slope; b, intercept. ‘First seven cases are experimental points. dProjected value; cf. ref 6. eExperimental and projected values, 10 points. f Omission of projected 1,2,3,6,7,9-HCDD value from footnote e; cf. text. fImproved average values; cf. text and ref 6. hUsing two improved averaged values from footnote g plus other five experimental values. ‘Inclusion of projected values into footnote g, 10 points. Omission of projected 1,2,3,6,7,9-HCDD value from footnote P: cf. text. J
solution) vs. the LDmvalues yields a correlation coefficient, r, of 0.98 for guinea pigs (7) and chick embryos (8). Table I1 lists the PCDDs for which both the relative biological potency (RBP of 2,3,7,8-TCDD = 100) values (derived from ED, values and “projected” values from inverse linear regression analyses (9))and solution photolysis rl12 values are known. A linear regression analysis of the log rl12vs. log RBP values yields the results shown in Table 11. Using only the experimental RBP values yields an r = -0.77, whereas inclusion of the projected RBP numbers gives r = -0.69. Furthermore, the RBP value of 1,2,3,7,8-PCDDand 1,2,3,6,7,8-PCDDare averaged values of three and four experiments, respectively. Each of these cases contained one extreme outlying experimental RBP value in comparison to the others (12-fold for the former and 14-fold for the latter). If the outliers are omitted from the calculated average values, the correlation coefficients are obviously improved. This improvement yields, in the case of only the experimental RBP values (7 points), r = -0.81, and, for experimental plus projected RBP values (10 points), r = -0.70. Omission of the projected 1,2,3,6,7,9HCDD RBP value from the analysis improves the correlation to r = 4.84. The photolysis r1/2used in this analysis isomer pair corresponds to the 1,2,3,6,7,9/1,2,3,6,8,9-HCDD and the r 1 / 2 for 1,2,3,8-TCDD corresponds to the 1,2,3,7/1,2,3,8-TCDD isomer pair.
Conclusion The mechanisms of both toxicity and photolysis of halogenated aromatics are still far from being understood. The nature of the reactive inermediate(s) formed in the photolytic reaction has not been elucidated. It has been suggested that a reactive intermediate may not be involved in the mechanism of toxicity of 2,3,7,8-TCDD. The correlations between the photolysis rates of the PCDDs and the LD50 values are quite good. The correlations between photolysis rates and relative biological potency values are admittedly not as satisfactory. Nevertheless, the significance of these correlations must be viewed in the light of the wide disparity between the two types of reactions, on one hand, photolysis and, on the other hand, two biological end points. It is difficult to avoid the intriguing possibility of common or related reEnviron. Sci. Technol., Vol. 18, No. 10, 1984
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active intermediate(8) in the two types of reaction mechanisms. This would mean that for photolysis and toxicity common molecular electronic requirements must exist. The common electronic requirements would be influenced by the structural and geometric characteristics of the reactive molecular species in the two types of reactions. The possibility of the generation of a reactive intermediate related to a photolytidy excited molecule suggests a novel link between these two types of reaction mechanisms. Registry No. 2,3,7,8-Tetrachlorodibenzo-p-dioxin, 1746-01-6; 1,3,7,8-tetrachlorodibenzo-p-dioxin, 50585-46-1;1,2,3,8-tetrachlorodibenzo-p-dioxin, 53555-02-5; 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, 3268-87-9; 1,2,3,7,8-pentachlorodibenzo-p-dioxin, 40321-76-4; 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin, 57653-85-7; 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 35822-46-9; 1,2,3,4,6,7,9-heptachlorodibenzo-p-dioxin, 58200-70-7; 1,2,3,6,7,9-hexachlorodibenzo-p-dioxin, 64461-98-9.
Literature Cited (1) Safe, S.Chemosphere 1983,12,447-451. (2) Rawls, R. L. Chem. Eng. News 1983,61 (23)37-48. (3) McKinney, J.; McConnell, E. In ”Chlorinated Dioxins and Related Compounds: Impact on the Environment”; Hut-
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zinger, 0.; Frei, R. W.; Merian, E.; Pocchiari, F., Eds; Pergamon Press: Oxford, England, 1982;Vol. 5, pp 367-381. (4) Arcos, J. D.;Argus, M. F. In “Chemical Induction of Cancer”; Academic Press: New York, 1974;Vol. IIA, pp 302-337. (5) Poland, A.; Glover, G. Cancer Res. 1979,39, 3341-3344. (6) Nestrick, T. J.; Lamparski, L. L.; Townsend, D. I. Anal. Chem. 1980,52,1865-1874. (7) Bradlaw, J. A.; Garthoff, L.H.; Hurley, N. E.; Firestone, D. Food Cosmet. Toxicol. 1980,18,627-635. (8) Verrett, M. J.; quoted by Bradlaw, J. A.; Casterline In “Halogenated Biphenyls, Terphenyls Naphthalenes, Dibenzodioxins and Related Products”; Kimbrough, R. D., Ed.; Elsevier/North-Holland New York 1980;p 161. (9) McConnell, E. E.;Moore, J. A. (a) Toxicol. Appl. Pharmacol. 1978, 44, 335-356; (b) EPA-RPAR on Pentachlorophenol. Fed. Regist. 1978,43 (2021,48454. Received for review October 3,1983.Revised manuscript received January 30, 1984. Accepted July 12, 1984. The views and conclusions expressed in this report are solely those of the author and do not necessarily represent those of the U.S. Environmental Protection Agency.
