A N A L Y T I C A L CHEMISTRY, VOL. 51, NO. 1, JANUARY 1979
portance t o merit further work, for example near known tin Sources a n d in open ocean areas rather t h a n t h e near shore samples analyzed here. T h i s latter oceanographic work has been done in the Eastern Gulf of Mexico with ng L-' amounts of methyltin compounds being found a n d will be published elsewhere. S o m e a t t e m p t s were made (32) t o analyze air samples for tetramethyltin a n d for t h e methyltin compounds in air particulate. Traces of both were found b u t a t quite low concentrations. Further methods development in sample sollection is needed for air analyses for tetramethyltin. Owing t o t h e very low concentrations of tin compounds found in most of t h e environmental analyses, it is important to comment on what was done to establish t h e validity of the method. T h e absence of negative interferences, mainly certain metal cations, was demonstrated by recovery of small amounts of methyltin compounds from natural waters and from urine. Positive interferences from possible volatile organic compounds was found to be nil. T h e exact coincidence of retention times of methyltin hydride peaks from standard compounds with peaks found in environmental samples also supports the identifications made. T h e observation of t h e dual peak for dimethyltin hydride in both standards a n d natural samples also supports identification. T h e only comparison of two methods made was between t h e method described above and a similar one using a dc discharge detector. Urine samples were absorbed in both cases by similar reduction procedures except that in the case of the d c discharge detector. reductions were carried out a t p H 1.5 instead of 6.5. T h e procedure at p H 1.5 gave slightly higher inorganic tin concentrations but barely detectable methyltin peaks because of t h e much poorer detection limit in the case of t h e dc discharge.
ACKNOWLEDGMENT T h e aid of Roy Carpenter, University of Kashington. in assisting in t h e preparation of this manuscript is ackno\\ledged.
19
LITERATURE CITED (1) J. M. Wood, W. P. Ridley and L. J. Dizikes, Science. 197, 4301 (1977). (2) J D Nelson, Jr., H. L. McClain, and R R Colwell, 1972 Proc. Ann. Conf. Marine Techno/. SOC., 8 t h Washington, D.C., (1972) pp 302-312. (3) K. L. Jewett, F. E. Brinckman, and J. M. Beilama, Adv. Chem. Ser.. No. 18, 1975. (4) M. Farnsworth and J. Pekola, Anal. Chem., 26, 735 (1954). (5) H. Teichen and L. Gordon, Anal. Chem., 25, 118 (1953). (6) C. L. Luke, Anal. Chem., 28, 1276 (1956). (7) V. A. Nazarenko, N. V . Lebedevz, and L. I.Vinarova, Zh. Anal. Khim., 28, 1100 (1973). (8) T. Nakara, M. Munemori, and S. Musha, Anal. Chlm. Acta, 62, 267 (1972). (9) K . C. Thompson and D. R. Thomerson, Analyst(London).99, 595 (1974). (10) D. Fleming and R . G . Ide. Anal. Chim. Acta, 83. 67 (1976). (1 1) G. L. Everett, T. S. West, and R. W. Williams, Anal. Chim. Acta. 70, 291 (1974). (12) D. Clark, R. M. Dagnall, and T. S . West, Anal. Chim. Acta, 60, 219 (1972). (13) R. F. Browner and D. C. Manning, Anal. Chem., 44, 843 (1972). (14) 8. M. Patel. R. D. Reeves, R. F. Bowner. C:. J. Molnar. and J. D. Winefordner Appl. Spectrosc., 27, 171 (1973). (15) M. Pinta, "Detection and Determination of Trace Elements", Ann Arbor-Humphrey Science Publishers, Ann Arbor, Mich.. 1970. (16) C. S . Ling and R. D. Sacks, Anal. Chem.. 47, 2074 (1975). (17) P. I . Seinorklin. Hyg. Sanit., 31 (8). 270 (1966). (18) K . Jergen and K . Figge, J . Chromatogr., 109, 89 (1975). (19) V. V Brazhnikov and K. I.Sakodynski. J . Chromatogr., 66. 361 (1972). (201 G.E. Parrls, W. R. Blair, and F. E. Brinckman, Anal. Chem., 49, 378 (1977). (21) T. L. Shkorbatova, 0. A. Kochkin. L.D. Sirak, and T. V. Khavalits. Z h . Anal. Khim., 26, 1521 (1971). (22) R . S. Braman, D. L. Johnson, C. C. Foreback, J. M Ammons, and J. L. Bricker. Anal. Chem , 49. 621 (1977). (23) R. S . Braman and A. Dynako, Anal. Chem.. 40, 95 (1968). (24) R . Herman and C. T. J. Aikemade. "Chemical Analysis by Flame Photometry", Interscience Publishers, New York and London, 1963. (25) W R. S. Garton. Proc. Phys SOC..64. 591 (19511 (26) W. W. Watson and R. Simon, Phys. Rev., 55, 358 (1939). (27) R M. Dagnall, K . C. Thompson, and T S West, Analyst(London). 93, 518 (1968). (28) W A. Aue and H. H. Hill, Jr J . Chromatogr., 70, 156 (1972). (29) H. W. Johnson and F. H. Stross, Anal. Chem., 37, 1206 (1959). (301 J. D. Smith and J D. Burton, Geochim. Cosmochim. Acta , 36,621 (1972). (31) B. L. Oser, Ed., "Hawk's Physiological Chemistry", 14th ed.. McGraw Hill. New York. 1965. p 561. (32) M. A. Tompkins. Ph.D Dissertation. University of South Florida. Tampa, Fla.. 1977. ~
RECEIVEDfor review December 15. 1977. Accepted September 2'7. 1978 LVork supported b j t h e Yational Science Foundation. RANN Program Grant No. AEN 71-13598 A01 a n d AEN 74-11598 A 0 2
Air-Sampling and Analytical Method for 4,4'-Met hylenebis(2-c hloroaniIine) Stephen
M. Rappaport'
and Raul Morales*
Industrial Hygiene Group, Health Division,
Los Alamos
Scientific Laboratory, University of California,
A sampling and analytical method is described for the determination of airborne exposures of individuals to the carcinogen, 4,4'-methylenebis( 2-chloroaniline), known as MOCA. The personal sampler employs a filler to collect particulate MOCA followed by a bed of silica gel to remove the vapors. MOCA is extracted from the sampler stages with methanol and a 10-pL aliquot is injected into an HPLC operating with a reverse-phase system. The UV detector (254 nm) allows quantitation of 3 ng of MOCA corresponding to 0.15 pg/sample. Precision levels were determined to be 9.2% at 1.5 pgkample and 1 4 % at 0.15 pg/sample.
4,3'-Methylenebisi2-chloroaniline),commonly referred to by t h e DuPont tradename. MOCA. is a commercially im'Present address, School o f Public Health, Cniversity of California. Berkeley, C a l i f . 94720. 0003-2700/79/0351-0019$01 O O / O
Los Alamos.
N e w Mexico 8 7 5 4 5
portant curing agent for polymer and epoxv-resin systems containing isocyanates ( 1 1. Production of MOCA in the US. was estimated a t 3.3 million kg in 1972 when an estimated 10000 people were employed in either production or use of this compound ( 2 ) . MOCA has a molecular weight of 267, a density of' 1.44 g / m L at 2 1 "C and a melting range of' 100-109 "C ( I ) . Relevant literature implicates MOCA as being carcinogenic in rats by both oral and subcutaneous administration and in mice by oral administration (9). Malignant tumors in the test animals were found a t several sites including the lung, liver, mammary glands, and mesothelium. These observations led t h e Health Advisory Committee of t h e British Rubber Manufacturers Association to recommend discontinuance (in Great Britain) of the manufacture and use of MOCA in 1971 (.I). T h e Occupational Safety and Health Administration (OSHA) in 1974 promulgated standards for t h e production and use o f MOCA in t h e U.S. ( $ 5 ) . c 1978 American Chemical Society
20
A N A L Y T I C A L CHEMISTRY, VOL. 51, NO. 1, JANUARY 1979
r-l PUR IF IER
1 HUMIDIFIER
SAMPLING CHAMBER
DECONTAMINATION
Figure 1. Schematic diagram of the test-atmosphere generation system
Table I. MOCA Vapor Pressures and CorresDondinaSaturation Air Concentrations (760m m Hg Atmospheric Pressure)
air concentration
temp., "C
vap. press. m m Hg
120
5.4 x 1 0 - 5 ~
100
3.6 X 1.3 x 7.2 x 5.1 X 3.7 x
60 40
30 20 Reference 6 .
10." 10-*Q 10-6b 10-6b
ppb 71 47 17 9.5 6.7 4.9
ng/ni3 780 5 20 190 100 73 53
Obtained by extrapolation of data
(log Vap. Press. vs. l / T ) in Ref. 6.
It is significant that t h e OSHA standards did not contain provisions for monitoring work places to determine airborne exposures t o MOCA, apparently because reliable methods of air sampling a n d analysis were unavailable. MOCA can be present in t h e air as an aerosol, a vapor, or a combination of t h e two. I n operations where it is packaged or transferred in bulk, it would be generated primarily as a n aerosol (dust). During compounding, MOCA is heated t o approximately 1 2 1 "C t o melt and mix it with t h e formulation ( I ) and would be generated as a vapor. I n either case, it is expected that some of t h e physical state not initially formed could ultimately be produced. Given t h e relatively low vapor pressure of MOCA ( 6 ) ,it is likely t h a t highest exposures would involve inhalation of aerosols. Table I lists vapor pressures and corresponding air concentrations ( a t saturation) between 20 a n d 120 O C . Maximum vapor concentrations t h a t could be encountered would be between 53 ng/m3 (20 "C) a n d 780 ng/m3 (120 "C) at 760 m m H g atmospheric pressure. Although several air-sampling a n d analytical procedures for MOCA have been reported, all have significant shortcomings which make their application for routine use difficult. Meddle and Wood (7) described a colorimetric method for the determination of isocyanates in t h e presence of MOCA. This method suffers from the disadvantages t h a t the bubbler used does not trap all aerosols quantitatively and that the analytical procedure is not sufficiently specific for MOCA. Yasuda (8) used a sampling t u b e packed with Gas-Chrom S t o collect MOCA vapor by adsorption. T h e sampler, however, was not evaluated for t h e collection of aerosols. Using a flame-ionization detector (FID), Yasuda reported a detection limit for MOCA of 2 ng/pL with a 1-pL injection. We were unable to obtain satisfactory reproducibility a t this low level and also
found t h a t standard solutions produced chromatograms with spurious peaks when Yasuda's recommended solvent, acetone, was used. Linch e t al. (9) employed a two-stage sampler consisting of a membrane filter followed by an absorbing liquid t o collect both aerosol a n d vapor phases of MOCA. Analysis consisted of the FID gas chromatography of the trifluoroacetyl derivative of MOCA with a reported detection limit of 2 ng/FL for a 4-pL injection. T h e disadvantages of this procedure include the use of liquids for a field sampler and the necessity of derivatization. T h e purpose of the work described here was to develop and evaluate a method for t h e determination of MOCA in air so that exposures of individuals working with this compound may be monitored. T h e sampler utilizes a filter followed by a section of silica gel to collect both aerosol and vapor phases. T h e analytical method is based on a high-performance liquid chromatographic ( H P L C ) procedure.
EXPERIMENTAL Production of Controlled Test Atmospheres. The dynamic system used for the generation of aerosols of MOCA has been reported (10). All components were made of stainless steel. glass, o r Teflon. The system produced polydisperse aerosols with mass-median aerodynamic diameters of 1.7 pm and geometric standard deviations of -1.7 in a range of air concentrations between 2 and 200 pglm". The aerosol, produced at a volumetric flow rate of 14 L/min, was diluted with an additional 185 L/min of air as shown in Figure 1. Dilution air was purified by passing it through 10 kg of 5 A molecular sieve at 0 " C followed by a high-efficiency particulate-air (HEPA) filter. Air was humidified to the desired level (0 9 5 2 % R.H.) by passing it over the surface of a heated water bath and brought to the desired temperature (25-40 0.2 "C) in a heated zone prior to entering the sampling chamber. The chamber, shown in Figure 2, could accommodate up to 10 samplers inserted through valved ports which were designed to prevent contamination of the area. Samples were collected from a zone of homogeneous aerosol concentration, temperature, and humidity. Environmental conditions were continuously monitored, as follows: the relative aerosol concentration by a forward light-scattering photometer (Model JM-4000, Virtis Corp., Gardiner, N.Y.); temperature and humidity by an indicator (Model 400C, General Eastern Corp., Watertown. Mass.); and the air-flow rate by a mass-flow meter (Model AHL-10, Teledyne Hasting-Raydist, Hampton, Va.). Prior to entering the mass flow meter, MOCA was removed from the air stream by a HEPA filter followed by a canister of activated coconut charcoal. All generation and air transfer operations involving MOCA were carried out in a ventilated glove box to minimize contamination of the surrounding environment and exposure to personnel. A protocol outlining the facilities and health practices f o r the investigation has been reported ( 1 1).
-
*
*
ANALYTICAL CHEMISTRY, VOL. 51, rtiAFFLEG E X n A U S T e - = \
IRECORDER 1
xhill F 3 R W A s G LIG-T SCATTERING PHCT3h'E T E R
j
I '
l
'
\
Figure 2. Air sampling chamber
Air Sampling. The air sampler used for collecting MOCA is shown in Figure 3. It consisted of two Pyrex-glass tubes containing an 8-mm glass-fiber filter (Type A-E, Gelman Instrument Co., .4nn Arbor, Mich.) followed by 50 mg of 30/60-mesh silica gel (G.C. Grade, D-08. 720-760 m2/g. 4.3 g/cm3, Applied Sciences Laboratories. State College, Pa.). The filter and silica gel sections of the sampler were selected on the basis of their high collection efficiencies and capacities for aerosols (12) and aromatic-amine vapors (131,respectively. Teflon rings held the filter in place. The silica gel was retained by Teflon rings supporting 100-mesh stainless steel screens. The probe containing the sampler was inserted through the O-ring seals in one of the chamber's sampling ports. A one-hole rubber stopper connected to a plastic tube was inserted into the flared end of the probe for sampling. The flow rate was controlled by a critical orifice a t either 0.2 or 0.8 L/min. The sampling method was evaluated by collecting groups of samples (4 or 5 samples per group) for test atmospheres of uniform air concentration and varying conditions of temperature and relative humidity. By comparing the air concentrations indicated by these sample groups, it was possible t o infer whether the environmental conditions affected the precision and accuracy of
NO. 1, JANUARY 1979
the method. In one experiment the relative humidity was maintained a t 0% and groups of samples were collected from the chamber at 25,30,35, and 43 "C. The second experiment utilized a constant 30 "C and relative humidities of 0, 30, 60, and 90%. In both experiments. samples were drawn at 0.8 L/min and the average mass of MOCA collected was 1.5 pg/sampler. Two additional groups of samples were collected at 30 "C and 60% R.H., at flow rates of 0.2 and 0.8 L/min, respectively. The average mass of MOCA, for these samples, was 0.15 pg/sampler. Analysis. The filters and silica gel sections of the samplers challenged with MOCA were placed in separate 1-mL glass vials with ground-glass tops. One-half mL of reagent grade methanol was added; each vial was shaken intermittently for 1 h and centrifuged for 10 min in a clinical centrifuge. Ten pL of each solution was injected into an HPLC (Model ALC 202/401, Waters Associates, Milford, Mass.) factory equipped with a U6K injector and a UV-photometer at 254 nm. MOCA eluted from the 4.0 mm X 30 cm p-Bondapak CI8 column (Waters Associates) in 4 min a t a flow rate of 1.3 mL/min (1200 psi) of 812 ( v / v ) acetonitrile/water. The column, at ambient temperature (22 "Cj, yielded 1350 theoretical plates for MOCA. Peak areas were determined by multiplying the height of the peak by its width at half height. At 0.04 AUFS, 3 ng of MOCA could easily be quantitated as shown in Figure 4, which depicts chromatograms from calibration solutions (4A) and a filter extract (4B). The detection limit for MOCA was 0.15 ng at a signal to noise ratio of 2 to 1. Samples were analyzed by calibration with an analytical standard which \vas prepared by the purification of technical-grade MOCA (mp 105-107 "C, Aldrich Chemical Co., Milwaukee, LVis.). Purification involved the extraction of MOCA from cyclohexane by 0.05 K H,SO, followed by the addition of 3 N NaOH bringing the solution to pH 8-9 and reextraction with 9 / 1 ( v / v ) cyclohexanelethyl acetate. The dried MOCA residue had a mp of 109-1 10 "C. Comparative chromatograms of technical grade and purified MOCA revealed that peaks of impurities resolved from the main ingredient had been substantially diminished (Figures 5A and 5B). A typical calibration curve of methanolic solutions of the purified MOCA is shown in Figure 6. The efficiency with which MOCA was extracted from filters and silica gel was tested by spiking these matrices with 10 /iL of methanolic solution and determining the recovery after 21 days of storage at either 5 or 24 "C. Groups of samples were spiked at three levels, i.e., 0.155.0.310, and 1.55 fig which corresponded t o the range of masses extracted from samples collected in the chamber. In air sampling experiments. MOCA was found only on the filter portions of these samplers indicating that there was G L A S S F I B E R FILTER
( 8 - mm d i a m l
\ 50 mg SILICA G ( 3 0 1 6 0 mesh) TEFLON SEALS
FLON S E A L S
-mm o d x6-mm
I
d
I
PYREX G L A S S
( 3 0 - m m x 6 4 - m m o d x 4 - m m i.d.) /-STAINLESS STEEL S C R E E N (I00 mesh) P L A S T I C CAP S E A L
(6 4 - m m I d x 8 - m m o d
,170-mm x I O - m m o d x 8 - m m
'FLARED Figure 3. Probe containing sampler stages
21
I
d )
)
22
ANALYTICAL CHEMISTRY, VOL. 51, NO. 1, JANUARY 1979 36C
-
I
-
40y
2
3
4
5
'WIPL
Figure 6. Calibration curve for purified MOCA. conditions were as in Figure 4 0
1
2
3 min
4
3.0ng
0
3
4
5
rnin Figure 4. Representative chromatograms of calibration solutions (A) and filter extract (B). Column: 4.0 m m X 30 c m g-Bondapak C,8, Mobile phase: Acetonitrile/water (812) at 1.3 mL/min. Detector: UV at 254 n m and 0.04 AUFS
Table 11. Air Concentrations Indicated by Samples Collected from Atmospheres of Varying Temperature and Humidity rel. mean concn, rel. std. no. expt. temp., hum., dev., % "C % samples pg/m' no. 1 25 0 5 54.6' 9.56 30 0 4 47.8' 5.79 35 0 4 48.7' 7.13 0 5 45.8' 17.2 43 2 30 0 4 48.2' 3.17 30 30 5 44.6' 6.32 30 60 5 44.1' 4.17 5 47.5' 9.89 30 90 3 30 60 5 3.6b 11 30 60 4 8.4C 18 Flow rate a Flow rate 0.8 L/min, 1 . 5 pgisample. Flow rate 0 . 2 Limin, 0 . 8 L/min, 0.15 pgisample. 0.15 pg/sample. -
-
3
rnindtes
Chromatographic
5
METHANOL
n
1
6
minutes
Figure 5. Representative chromatograms of technical grade MOCA (A) and purified MOCA ( 8 ) . Chromatographic conditions were as in Figure 4. Detector: UV at 254 n m and 0.08 AUFS
insufficient vapor t o be detected under the experimental conditions.
RESULTS AND DISCUSSION Data from the collection of air samples are given in Table 11. Two observations which were obvious outliers were excluded from analysis. T h e first two experiments were designed to test the effects of temperature and humidity.
-
-
respectively. Basically, the procedure involved the comparison of air concentrations obtained from groups of samples collected from environments varying only in temperature or humidity. Any difference in concentration. more than that predicted by chance. would be registered as an effect. T h e analytical procedure used was t h e one-way analysis of variance (ANOVA). testing the null hypothesis: no significant difference in mean levels for the indicated air concentrations. An assumption of this procedure is that sample variances are homogeneous; t h u s Bartlett's Chi-square Test ( I d ) was performed and showed no evidence of significant heterogeneity among variances of either data set. Application of the AKOVA showed no significant difference in air concentrations among samples collected between 25 and 43 "C (F:3,14 = 2.41: p = 0.110) or between 0 and 90% R.H. (F:l,15 = 2.09; p = 0.144). Thus. there is no evidence that either temperature or humidity significantly affected the method. T h e precision of the method was determined at two levels. 1.3p g and 0.15 pg per sample, by pooling relative standard deviations of groups of samples listed in Table 11, i.e., those from experiments 1 and 2 and those from experiment 3. Bartlett's Chi-square Test showed no heterogeneity of variance in either case. T h e pooled estimates of t h e relative standard deviations were 9 . 2 7 ~at 1.5 pcg/sample (37 samples) and 1.1'70 a t 0.15 pg/sarnples (9 samples). If these methods were applied to field sampling, using pumps with a precision of ~ T cthe , combined relative standard deviations should be 10% at -1.5 pg/sample.
-
A N A L Y T I C A L CHEMISTRY, VOL. 51, NO. 1, JANUARY 1979 T a b l e 111. Extraction Efficiencya of F i l t e r s and Silica Gel
CONCLUSIONS
MOCA from
amt.
MOCA
no.
added,
samples
pg
0.155 0.155 0.155 0.155
5 5
0.310
1 4
0.310 0.310 0.310 1.55 1.55 1.55 1.55 a A f t e r 21
3
5 3 4 1 4
3 7
temp,
matrix filter filter silica silica filter filter silica silica filter filter silica silica
gel gel
gel gel
"C
5 24 5 24 5 24 5 24 5 24
gel gel
5
24
23
mean recovery, %
std. dev.,
88 91 97
1.8 2.7
87
4.6
86 90 91 96 97 96 90 89
---
%
3.0
8.7 2.3 2.6 --1.8 3.6 2.9
d a y s of storage.
I3 mm G L A S S FIBER F LTER IGELMAN TYPE A - E ) 14mm 1 ~ 6 4 m m o d I
50 mg SILICA GEL, 30/60 MESH TEFLON SEAL 14-mm o d 1 2 m m 1 %
PLASTIC C A P !6-mm i d I
Figure 7. Prototype personal sampler suggested for field use
Results of t h e extraction experiment are shown in Table
111. Overall, MOCA may be extracted from either silica gel or filters a t -91% efficiency after 21 days of storage (97f 67% after one day). T h e r e is no apparent difference in extraction efficiency between the filters and silica gel or for samples stored a t 5 or 24 "C. Furthermore, since 21 days had elapsed between the times of addition and extraction of MOCA, samples may be considered to be adequately stable under typical storage conditions. Interference studies with various amines were conducted a n d t h e following were found to have retention times close enough to t h a t of MOCA to interfere with the analysis using t h e described H P L C and extraction methods: 4,4'-diamino-3,3'-dimethylbiphenyl, 1- and 2-naphthylamine, A'methylaniline, 3,3'-dichlorobenzidine, 2- a n d 3-chloro-4methylaniline, and 4-aminotoluene. T h e following aromatic amines, at one-half the concentration of a MOCA solution ( 5 n g / p L ) did not interfere: aniline, 2- and 3-chloroaniline, 4,4'-methylenedianiline, and benzidine.
T h e method developed for the collection and analysis of MOC.4 in air has several advantages over those previously reported. For example, samples can be injected into t h e H P L C within 6 min of each other. The analysis is conducted a t ambient temperature, t h u s minimizing the possibility of degradation of MOCA at gas chromatographic temperatures, and there is no need for derivatization. T h e sensitivity of the procedure is 3 to 10 times greater t h a n t h a t reported by Yasuda or Linch. The quantitation limit of the method is 0.3 n g / p L or 150 ng/sample. Assuming t h a t 48 L of air are sampled (0.2 L / m i n for 4 h) the minimum air concentration that could be measured is 3 pg/m3. T h e method is insensitive to changes in temperature and humidity and samples are stable for a minimum of 3 weeks under normal conditions. T h e sampler is a small device, employs no liquids and is amenable to personal monitoring. I t quantitatively traps MOCA either as an aerosol or a vapor. A prototype sampler employing a commercially available filter holder is shown in Figure 7 . It has essentially the same geometry and collection characteristics as those employed in this investigation. ACKNOWLEDGMENT T h e authors gratefully acknowledge t h e assistance of Donald Gettemy, Robert Hermes, and Claudine Kasunic who performed many of the sampling and analytical procedures. LITERATURE CITED (1) J. D. Ryan, "MOCA a Diamine Curing Agent for Isocyanate-Containing Polymers", duPont Chemicals for Elastomers, Trade Bulletin, 197 1 (2) 'Final Ruies Set for Carcinogens", Chem. andEng. News. 52. 12 (1974). (3) "IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man' , Vol. 4, International Agency for Research on Cancer, Lyon. France, 1974, pp 65-71. (4) G. Parkes. British Rubber Manufacturers Association, Health Advisory Committee, Bulletin No. 6, 8, and 9 (1971). ( 5 ) Occupational Safety and Health Administration, Fed. Regist., 39, 2355 1 (1974). (6) Elastomers Chemicals Department, E.I. du Pont de Nemours and Company, private communication. (7) D.Meddle and R. Wood, Analyst. (London), 95, 402 (1970). (8) S . K. Yasuda, J . Chromatogr. 104, 283 (1975). (9) A. L. Linch, G. O'Conner, J. Barnes, A. S. Killian, and W. E. Neeld. A m . Ind. Hyg. Assoc. J , , 32,802 (1971). (10) S. M. Rappaport and D. J. Gettemy. A m . Ind. Hyg. Assoc. J . , 39, 287 ( 1978). (1 1) S. M. Rappaport and E. E. Campbell. Ant. Ind. Hyg. Assoc. J . , 37, 690 (1976). (12) D. A. Lundgren and T. C. Gunderson, A m . Ind. Hyg. Assoc. J , , 36, 866 (1975). (13) G. Wood and R. Anderson, A m . Ind. Hyg, Assoc. J , , 36,538 (1975). (14) R . Bethea, B. Duran and T Baullion. "Statistical Methods for Engineers and Scientists", Marcel Dekker, New York. 1975, pp 247-251
RECEIVED for review June 19. 1978. .iccepted October 2, 1978. LVork supported by the National Institute for Occupational Safets and Health and performed at the Los Alamos Scientific Laboratory operated under the auspices of the U.S. Dep a r t m e n t of E n e r g y , C o n t r a c t KO. LV-7405-ENG-36 (NIOSH; LASL Agreement IA-74-35).
