obtained for each combined collector. If the filter and sorbent are combined
and analyzed together, the applied recovery correction must be statistically the
same for both filter and sorbent over the entire range.

Determination of Breakthrough Volume or Collection Efficiency

Breakthrough Volume-—

To evaluate a sorbent for breakthrough volume, test atmospheres of the analyte
were generated in air of at least 80% relative humidity. The details of

the test atmosphere generator and specific generation techniques are given later
in this section. The sampling rate was based on the pressure drop across the
sampling device, the minimum length of time required for sampling, and the
expected capacity based on past experience.

The test atmosphere was generated at a concentration twice that of the OSHA stan-
dard. For this determination, the time of appearance of the analyte in the
effluent from the front section of the sampling device was monitored.

When possible, online monitoring was used. A set of six samplers was placed in
the sampling chamber, and the concentration of the test atmosphere was measured.
During sampling, the effluent from the sorbent tubes was monitored and compared
with the test chamber concentration. The 5% breakthrough volume is defined to
be when the effluent concentration reaches 5% of the influent concentration. The
test was continued until the effluent concentration was at least one-third of the
influent concentration so that premature breakthrough of one tube due to "chan-
neling" was not mistaken for overloading of the six tubes.

Online detection of the low levels of many substances studied in this program
was not possible. In this case, as when the generated concentration was below
the detection limit of the monitor, the capacity test was conducted using a num-
ber of samplers, each containing a backup section. After sampling began, the
samples were removed, one by one, at regular intervals, and each section analyzed
separately to determine when the amount of material in the backup section was
equivalent to 5% of the amount in the front section.

Once the breakthrough volume was determined, a sampling volume no greater than
two-thirds of the breakthrough volume was recommended. A minimum one-hour sam—
pling period was imposed for TWA determinations.

If the breakthrough volume was sufficient for collection at twice the OSHA stan-
dard at the recommended flow rate and sampling period, method testing was con-
tinued. If not, appropriate steps were taken to improve the method. Reduction
in the sampling rate, increased sorbent volume, and selection of another sorbent
were options.

The testing of filter/sorbent collection media was similar to the procedure
described above for sorbents alone. However, careful observation was made of
the amount collected on filter and sorbent individually over time. Multiple
samplers were used in the capacity tests, and samplers were removed and analyzed
at regular intervals throughout the test. The amounts collected on the filter,
sorbent, and backup sorbent were plotted versus time. The plot frequently
indicated the extent of vapor collected on the filter. It also gave a much

13


The review of a failure report provided an opportunity to take several approaches:
e Accept the report
e Accept the report, make suggestions for future work and encourage
sufficient detail in the report that it was clear why a method

could not be developed or validated

e Accept the report and using the data already generated, write a
Class E method.

The third approach is not one to be criticized since many times a failure report
contained more data than many of the existing Class E methods.

The draft reports were returned with comments and recommendations to SRI or ADL
for incorporating into the final reports.

DISTRIBUTION OF METHODS

Upon receipt of the final methods at NIOSH, the SAMs, SDSs, and BUDs were dis-
tributed as follows:

e Coordinator, NIOSH Manual of Analytical Methods

e Coordinator, NIOSH Manual of Sampling Data Sheets

e Chief, Measurements Support Branch, NIOSH

e Chief, Priorities and Research Analysis Branch, NIOSH

e Clearinghouse for Occupational Safety and Health (NIOSH TIC
and NTIS)

e OSHA

This distribution allowed for a continuous dissemination (approximately every 3
months) of methods throughout the 3-1/2 year contract. Annual dissemination was
accomplished by publishing the methods (SAMs) in the NIOSH Manual of Analytical
Methods, Second Edition. The first three volumes of the methods manual were

published in April 1977; Volume 4, in August 1978; and Volume 5, in August 1979.

All substances in this study were assigned "compound numbers" in 1974 at the

start of the Standards Completion Program, each preceded by the letter "S". The
validated methods (Class B) are published in the NIOSH Manual of Analytical Methods
in order of their corresponding S-number. The proposed methods (Class E) were
each assigned a P&CAM-number and published in the Manual and ordered by their
P&CAM-numbers. Failure reports were identified with the assigned S-number.

The SDS reports have a similar chronology as the SAMs in the Methods Manual and
are published in the NIOSH Manual of Sampling Data Sheets. The BUD Reports and
Failure Reports are compiled and published as separate documents.

All publications are available through the National Technical Information Service.

34


Aerosol
\ | a)

Teflon ‘’Venturi”’ Mixer

Dilution Air Slo

—— Viton Gasket

<— Luer Fitting

“ Sample

FIGURE 7 CROSS-SECTIONAL VIEW OF DILUTION AND SAMPLING SECTION
(Branch B)

30


APPENDIX A

This appendix lists all methods validated in this program and gives pertinent
information such as the collection medium, sample treatment procedure, analy-
tical method, and the range over which the method was validated (see Table A-1).
The code designates whether SRI (S) or ADL (A) performed the experimental work
on the substance. The compound numbers were assigned to each substance at the
beginning of the Standards Completion Program, and the methods are arranged
according to their corresponding S-number in the NIOSH Manual of Analytical
Methods.

In addition, proposed (Class E) methods are summarized, each with a corresponding
P&CAM-number that was assigned to it before publication in the Manual. A list
of the substances that failed in the validation effort is also included (see
Table A-2).


Ion-selective electordes were used in the program. Methods were validated based
on this technique for ammonia, hydrogen cyanide, and nitric acid. In addition,
titrations were used for sodium hydroxide and sulfur dioxide.

Other methods were based upon particular characteristics of the analyte. For
example, x-ray diffraction was applied to the analysis of zinc oxide.

SAMPLING METHODS

Industrial hygiene sampling and analysis are used to determine the concentration
of chemicals to which employees are exposed. Collection of a representative sam-
ple is difficult and is best done using personal sampling devices that collect
samples from the employee's breathing zone. Such devices normally consist of a
sample collection device (filter or sorbent tube) worn at the lapel and connected
by flexible tubing to a calibrated sampling pump worn on the belt. Personal sam-
pling pumps that operate in several ranges from 0.01 to 4 L/min are available.
These pumps can collect both short- and long-term samples for evaluation of ex-
posure to ceiling levels and the time-weighted average.

The first consideration is the selection of a sampling medium compatible with

the physical state of the analyte at the levels of interest. The substance may
exist as a gas, vapor, particulate, or combination, depending on the level in a
given atmosphere. At low levels, one compound may exist as a vapor, but at higher
levels it may be primarily particulate. Predictions of vapor concentrations may
be derived from vapor pressure data, if available, but for some substances no
reliable data are available.

A rough guideline was used in this program for determining if a substance exists
as a vapor or particulate (or both) at levels near the OSHA standard. If the
ratio of the equilibrium vapor concentration at 25°C to the standard were between
0.05 and 50, then contribution from both vapor and particulate was considered.

A ratio below 0.05 indicates that the material will probably be particulate;
whereas, if above 50, it will probably be vapor. Frequently, this determination
was made experimentally by generating test atmospheres of the substance near

the standard and collecting samples with particulate/vapor sampling trains.

The sampling devices most commonly used were filters, solid sorbent tubes (char-
coal, silica gel, porous polymers), and midget bubblers and impingers. In terms
of ease and reliability, the first two methods were considered most desirable.
Filters collect particulates and sorbent tubes collect gases and vapors, al-
though there are also indications that some vapors will collect on filters, and
glass wool plugs used to retain sections of sorbent may collect a portion of the
particulates. Some reactive species had to be stabilized at the time of sam-
pling, frequently by trapping them in a suitable solvent in impingers or bubblers
because no reliable alternative procedures were available. These devices are
troublesome to use in the field and were avoided when possible.

Filters

The procedure most commonly used for collection of particulates involves sample
collection with a closed-face 37-mm filter cassette containing a filter sup-
ported by a cellulose backup filter support. The most frequently used filter
materials include mixed cellulose ester (MCE), polyvinyl chloride (PVC), glass

7


cv, pooled coefficient of variation calculated as above based on data
for the 18 analytical (spiked) samples (three groups of six).

Oa derived corrected value for CV, to include precision error due to
the use of desorption efficiency factor, which is an average of six
values.

Vie = 7/6 = 1.0801 CV,

Tne derived corrected value of CV; analogous to the desorption efficiency
factor noted above except that this notation is used where the factor
is associated with analytical method recovery (ARM) other than for
solid sorbents.

CV ARM = 1.0801 cv,

wv, pooled coefficient of variation based on the data for the eighteen
generated samples.

Ce coefficient of variation of the sample collection, not including
the variability of the personal sampling pump. The value dependent
on the data from the eighteen analytical and eighteen generated samples.

we = (see "Note" below)

cv, coefficient of variation due to the pump error, assumed to be equal
to 0.05.

Note:

In case CV, S C1, take CVs = 0. Then replace CV} by a pooled estimate
(cvy* ) based on cae and Ws, namely

7 2
*
_ £, WV, + £, CV,

i £, +f,

wanere Fy an and ae are the respective f-values used in the denominators of
Cvy2 an


30 +

de
+

26

20 =P
z
g 15 dL
ao
10 Se
<+— Target Values (CV)
5 +
(0) + i sofa 4
0 0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16

PRECISION (CV)

FIGURE B-1 COMBINATIONS OF CV; AND BIAS WHICH YIELD NET ERRORS (Sampling and
Analysis) OF 25% OR LESS AT LEAST 95% OF THE TIME

B-3


*
APPENDIX B
STATISTICAL PROTOCOL

INTRODUCTION

This appendix gives the steps of a recommended statistical protocol for analysis
of air concentration data for hazardous chemicals. The purpose of the statisti-
cal analysis is to estimate the total precision error of a subject method and
resolve this error into its components due to the sampling method (less pump
error), the analytical method (including error in the desorption efficiency fac-
tor), and an assumed level of pump error.

MAXIMUM NET ERROR FOR UNBIASED METHOD

The present suggested standard for air monitoring accuracy is that the absolute
total error (sampling plus analysis) should be less than 25% in at least 95% of
samples analyzed at the level of the standard. In the case of normally distri-
buted sampling and analysis errors (and no bias), the above requirement implies
that the true coefficient of variation of the total error, denoted by CVy,

should be no greater than 0.128 derived as follows: CVy = 0.25/1.96 = 0.128.

The number 0.128 is the largest true precision for a net error of +25% at the 95%
confidence level. The number of 1.96 is the appropriate z-statistic from the
standard normal distribution at the same confidence level.

However, the estimated values of CVz (denoted by CVp), which are reported by SRI
under the NIOSH contract 210-76-0123, will themselves be subject to appreciable
random errors of estimation. Therefore, the "critical value" not to be exceeded
by an experimental value of CV must be lower than the maximum permissible true
value of CVp which is implied by the wording of the accuracy standard. The maxi-
mum permissible true value of CV; will be referred to as its "target level" and
the required degree of confidence that a subject method meets this accuracy stan-
dard can be obtained by calculating an appropriate [(1 - a) probability level]
upper confidence limit on Vy and obeying the following decision rule:

Rule: Reject the method if the 95% upper confidence limit on CV.
exceeds the target level of CVp. Otherwise, accept the method.

As would be expected, to have the 95% degress of confidence that Cv, does not
exceed its target level, we must also suffer the penalty of sometimes falsely
rejecting "good" methods whose true CV, is satisfacotry, but for which the CVp

*
Reprinted from Documentation of NIOSH Validation Tests, National Institute for
Occupational Safety and Health, Cincinnati, Ohio (DHEW-NIOSH Publication #77-
185), 1977. Available from Superintendent of Documents, U.S. Government
Printing Office, Washington, DC, Order No. 017-033-00231-2.

B-1


GENERATION OF TEST ATMOSPHERES
General

Extensive facilities for preparing synthetic atmospheres were developed at SRI
and ADL for use on this program. These facilities were successfully used for
validating methods to sample and analyze gases, vapors, dusts, aerosols, and
fumes. They consisted basically of a source generator, which introduces test
air containing high analyte concentration into a dilution system, where three
concentration levels are automatically prepared and delivered to sampling cham-
bers. The two main dilution systems are described in this section.

Generation of test atmospheres by dynamic means was used because of the advan-
tages over static methods. Wall losses through adsorption, which may be a
significant problem in static systems, become negligible in dynamic systems be—
cause the apparatus walls eventually equilibrate with the gas stream. Dynamic
systems are especially appropriate for producing mixtures of compounds subject
to decomposition because the labile products are continuously swept away and
the mixture is continuously replaced.

In addition to the main generation facilities, many special systems were designed
and constructed for use with reactive compounds. Separate systems constructed
exclusively of Teflon and glass were used with reactive substances including
fluorine, mercury, and several amines. Each substance in this program was
generated from a specific source generator, depending on its physical state and
whether it existed as a vapor and/or as an aerosol in the atmosphere at the
desired concentration. Details of the specific source generators used for
individual substances appear in the Backup Data Report for the substance.

Methodology

Aerosols--
Test atmospheres containing aerosols may be conveniently generated by a number
of techniques including:

Spray drying
Atomization
Condensation

Thermal decomposition
Dust dispersion.

Spray drying--Spray drying is applicable to substances that are soluble in a
convenient solvent. This method involves atomizing a solution to form a mist.
Larger particles are removed by impaction. The remaining flow is mixed with
solvent-free air to permit evaporation of solvent from the droplets. Residue
particles of the solute are left behind as the solvent evaporates.

The size of the aerosol particles produced by spray drying is related to the
initial mist particle size by

pe« cM3y,
m

17


CONCLUSIONS AND RECOMMENDATIONS

The completion of this research effort represents a significant accomplishment
by NIOSH, and its contractors, SRI International and Arthur D. Little, Inc.

The Standards Completion Program (SCP) was the first documented attempt by NIOSH
to develop and validate a large number of methods against a set of experimental
and statistical criteria. As an extension of the SCP, this study resulted in

a considerable addition to industrial hygiene sampling and analytical methodology.
Of the 130 substances studied on this Program, methods were developed and vali-
dated for 92 substances. An additional nine methods were deemed useful and may
be validated with further testing. These methods will provide a means by which
worker exposure to specific toxic substances can be determined. The methods
have proven to be precise and accurate under rigorous laboratory testing. Sam-
ple collection media have demonstrated more than adequate collection efficiency
and capacity for the particular substances. Using these methods, collected sam-
ples can be expected to remain stable for at least one week before analysis.

In carrying out this research, we gained a considerable amount of knowledge in
the area of sample collection media, including solid sorbents and filters. This
knowledge was applied to the development of collection media that were more
efficient and convenient to use than bubblers and impingers containing liquid
absorbing solutions. New methods of sample treatment and analysis were also
investigated and incorporated into methods to achieve greater selectivity and
sensitivity. In addition, extensive experience was gained in the generation of
test atmospheres of toxic substances at low concentrations. This has enabled
us to realistically test sampling and analytical methodology under conditions
simulating the industrial environment. Considering the limitations in the scope
of work and on the level of effort which could be expended in developmental work,
much was accomplished in this program.

Notable specific accomplishments include the development of methods utilizing
instrumentation never or rarely used before in NIOSH methods. Without this
instrumentation, validated methods may not have been feasible. For example:

e Plasma emission spectroscopy for hafnium, silver, and tantalum

e Ion chromatography for ammonium sulfamate, formic acid, methyl-
amine, and sodium fluoroacetate

e Gas chromatography with photoionization detection for tetra-
ethyl lead and tetramethyl lead.

e High performance liquid chromatography used more extensively,
20 methods developed

e Polarography for formaldehyde and crotonaldehyde

35


ABSTRACT

To determine the level of exposure of workers to toxic substances, adequate sam-
pling and analytical methods are required for the specific substances. The
objective of this study was to develop and validate methods for sampling and
analyzing 130 substances for which no methods were currently available. This
report summarizes the experimental protocol and methodology used in the method
development and validation effort.

This report was submitted in fulfillment of Contract No. 210-76-0123 by SRI
International and its subcontractor, Arthur D. Little, Inc., under the sponsor-
ship of the National Institute for Occupational Safety and Health.


82

Magnehelic Gauge

_] HEPA Filter

Dilution Air Main Line
Aerosol
Dilution Air — —+ a _-—_]
A B c
Sample Ports
© AN A \’
To CFO and 1
Pressure { , Vacuum Pump |
au ge | |
1 | |
Sample { { |
Manifold

i

To Vacuum Pump

FIGURE 5 ADL AEROSOL DILUTION AND SAMPLING SYSTEM


better indication of the ratio of particulate to vapor than any test over one
time interval.

Collection Efficiency--

In evaluating the efficiency of particulate collection by a filter, test atmo-
spheres were generated as described above for the testing of sorbent capacity.
Six collectors with appropriate backup collectors (filters and/or bubblers) were
tested long enough for the substance of interest to be detected on the backup
collector, if present. If a detectable amount of the analyte were found in the
backup collector, the sampling device was modified to include a backup collector
or an alternate collecting medium was selected. If the presence of vapor were
a possibility, the test atmosphere concentration was at the OSHA standard or
lower because vapor would be more prevalent at the lower levels. Extended sam-
pling periods were sometimes necessary to obtain enough sample for determination.
Sufficient sample was collected so that an amount equivalent to 5% to 10% of a
sample collected at 0.5 times the OSHA standard could be detected on the backup
collector. This was to ensure that an unacceptable bias did not exist that
would invalidate the method.

Generation and Collection of Samples

Test atmospheres were generated at three known concentration levels. A set of
six samples was collected from each test atmosphere and analyzed by the pre-
scribed analytical method. Test atmosphere concentrations at 0.5, 1, and 2
times the OSHA standard were generated (within 25%). Samples were collected
at the recommended flow rate and sampling period. This part of the validation
procedure tested the overall sampling and analytical method for precision and
accuracy.

Independent Method of Determining Test Air Concentration

For most of the materials in this program, the determination of a "true" test
air concentration constituted a significant part of the study. Direct measure-
ment was the obvious method of choice, but this was not feasible for many sub-
stances. Determination of nonreactive gases and vapors was accomplished using
the techniques of delivery rate calibration, such as syringe drive and permeation
tubes.

The measurement of reactive gases and vapors, not suitable for direct determin-
ation by use of delivery rate information, was often achieved by collecting and
analyzing them by an accepted alternative method, frequently one not amenable to
industrial hygiene sampling. For example, collecting parallel samples on a
solid sorbent and in a bubbler, followed by analysis by GC and HPLC allowed
assessment of the accuracy of the method under test. However, confidence in
the alternative method first had to be established by appropriate testing.

The determination of test concentrations of dusts, aerosols, and especially mix-—
tures of both aerosol and vapor was considerably more difficult. The choice

of an independent method for these materials must be made carefully. Use of a
less reliable method to assess accuracy may result in failure to validate an
acceptable procedure. The method most often used for these compounds was to use
an alternative method of collection and compare the results with the results
obtained by the validation method, This was most frequently used for particulates

14


Vaporization--The vaporization method simply involves contacting a flowing air
stream with a liquid or solid so that the stream may pick up vapor from the con-
densed phase. Typically, gas dispersion bottles are used to produce vapors of
liquids. More complex equipment must be used to produce completely saturated
gas streams. Temperature and flow rate over the condensed phase may be used

as control parameters for varying the vapor concentration.

The vaporization method is applicable from the parts-per-billion level to several
percent concentration range. Usually, mixtures prepared by this method are
analyzed by an alternative analytical method to determine concentration rather
than being computed from vapor pressure data.

Permeation--Permeation tubes offer a third method for the preparation of vapor-
air mixtures of known concentration. The substance of interest is sealed in
liquid form inside a tube of some polymeric material, such as Teflon. Vapor
produced by the liquid permeates through the walls and is picked up by an air
stream passing over the tube.

The quantity of vapor delivered by a permeation tube, q, is given by

P,-P
_ 17 ‘2
q DSA (4-2 )

where D is the diffusion constant of the vapor through the polymer, S is the
solubility constant of the gas in the polymer, A is the surface area of the

tube, Py and Po are, respectively, the total pressures on the outside and in-
side of the tube walls, and L is the wall thickness. Because D, S and P are
temperature dependent, the rate of delivery can be varied by varying the tempera-
ture of the tube. Usually the concentration of the vapor mixture produced by
this technique is determined from the weight loss of the tube and the flow rate
of the stream passing over it.

The permeation tube methods are used to prepare mixtures with concentrations in
the part per billion to hundreds of parts per million range. Dimethylmercury
was generated using a permeation tube for validation of the alkyl mercury method.

Chemical reaction--Chemical reaction methods are convenient for very reactive
substances not readily available in a stable form. Two examples are

(1) generation of stibine by injection of an aqueous solution of
potassium antimony tartrate and sodium borohydride into dilute
sulfuric acid, and

(2) preparation of cyclopentadiene by passing the dimer through
a tube furnace.

Main Dilution/Sampling System

SRI International--

The system for generating and collecting samples of vapor, inorganic/organic
particulate, dusts, and fumes consists basically of a sample generator, a mixing
and dilution section, and three sampling chambers. Samples are generated at a
concentration 2 times the OSHA standard, serial dilutions are made to 1 and 0.5

20


e Precision 1. Three analytical recovery sets (above).
The total CV pooled from three groups of
6 samples must be less than 0.07.

2. Three sets of six samples each were col-
lected from test atmospheres.

The total CV pooled from three groups of six
samples must be less than 0.105 (including
allowance of 0.05 for error due to the sampling
pump.

e Accuracy Three sets of six samples were collected from
test atmospheres. The mean concentration deter-
mined by the test procedure must be within 10%
of the "true" concentration at each of three
test levels. In addition, precision and uncor-
rected bias must be such that, in combination,
they do not exceed the 25% rule stated above
(see Figure B-1, Appendix B).

These are the minimum criteria used to determine acceptability. In addition,
the method for each compound was evaluated for possible defects that might occur
in field sampling situations, either by additional laboratory testing or by
reference to literature.

Bartlett's test for homogeneity of variances was applied to the coefficients of
variation at 0.5, 1, and 2 times the OSHA standard for samples collected from
test atmospheres. If Bartlett's test was passed, it was feasible to pool the co-
efficients of variation to calculate CV,. All data were subjected to Grubb's
test to determine if one point in a set of data should be rejected as being an
outlier.

The precision of the analytical method was assessed using the analytical recovery
data. The pooled coefficient of variation of (cv,) was calculated.

Precision and accuracy of the total sampling and analytical method were evalu-
ated using the results from three sets of analytical recovery tests, the three
sets of samples collected from test atmospheres, the breakthrough tests, and
the storage stability tests. The pooled coefficient of variation (CV,) for the
three sets of samples collected from test atmospheres was calculated. To obtain
a measure of the accuracy of the method, the mean value of the concentration
found by analysis at each level was compared with the value for the "true" con-
centration determined by the independent method.

The total coefficient of variation (CV,,) was calculated using the pooled CV.

for three sets of analytical samples aiid the pooled cv, for the three sets of
samples collected from test atmospheres.

16


Aerosol
|
ee

<3— Teflon ‘Venturi’ Mixer
ma

Dilution Air

sss wy F
Re RRS Viton Gasket
ca wes

| en ae

| — Sample Probes

Luer Fitting

4

\ Sample

FIGURE 6 CROSS-SECTIONAL VIEW OF DILUTION AND SAMPLING SECTION
(Branches A and C)

29


during sample collection. The Girard T derivatives of the aldehydes were stud-
ied extensively and methods were validated based upon formation of the Girard T
derivative of acetaldehyde, formaldehyde, and furfural. A bubbler containing
Girard T reagent in an aqueous solution at a controlled pH was used to collect
samples. Since the Girard T derivatives are positively charged species that
exhibit UV absorptivity, different analytical approaches were feasible.

Polarographic methods of analysis of the derivatives of formaldehyde and croton—
aldehyde were developed. Analysis by HPLC was later considered in order to
achieve greater resolution between the individual aldehydes and potential inter-
ferences. Methods validated using HPLC analysis include acetaldehyde and fur-
fural. Tests indicated that HPLC analysis may be applicable to the Girard T
derivatives of other aldehydes such as formaldehyde, propionaldehyde, and
benzaldehyde.

Girard T derivatives of chloroacetaldehyde, crotonaldehyde, and acrolein were
not stable or quantifiable. Alternative methods were developed based upon the
derivative formed by reaction of crotonaldehyde with hydroxylamine, and the for-
mation of the hydrate of chloroacetaldehyde.

Organoleads

Methods for sampling and analysis of tetraethyl lead and tetramethyl lead were
developed based on collection of XAD-2, desorption with pentane, and analysis by
gas chromatography with a photoionization detector. The photoionization detector
was used because of a much higher selectivity for organoleads over alkanes than
that available with the flame ionization detector. This was necessitated because
of the low standards for these compounds.

A larger amount of XAD-2 was required for tetramethyl lead because of its much
higher volatility. It is quite likely that both could be collected simultane-
ously with the larger sorbent tube.

Others

Attempts were made to develop general methods for mercaptans, amines, alcohol-
amines, and nitroalkanes. However, results were not satisfactory. A method

was developed and validated for n-butyl mercaptan based upon collection with a
sorbent tube containing Chromosorb 104, and analysis by gas chromatography.

The sorbent did not have adequate capacity to collect methyl or ethyl mercaptan.
The amines and alcoholamines were difficult to analyze by GC, the preferred

method which incorporated derivatization of the collected sample. Sensitivity

and precision were very poor for some amines. Jon chromatography proved a

more efficient and sensitive analytical method than GC for methylamine. The
nitroalkanes gave inconsistent storage stability results on various solid sorbents.

LABORATORY TESTS
Calibration Curve
Once an analytical method was selected, optimum conditions were established to

achieve maximum selectivity and sensitivity of the compound of interest. For
example, in GC or HPLC the analyte must be well separated from the solvent peak

aay


Acetaldehyde

Acetic acid

Acrolein

Acrylamide

Alkyl mercury compounds
Allyl glycidyl ether
2-Aminopyridine
Ammonia

Anmonium sulfamate
Anisidine (ortho & para isomers)
Antimony & compounds
ANTU

Azinphos, methyl

Benzoyl peroxide
Boron trifluoride
Bromine
n-Butylamine
n-Butyl mercaptan

Cadmium fume

Carbon dioxide

Carbon monoxide

Chlordane

Chlorine

Chloroacetaldehyde

alpha~Chloroacetophenone

o-Chlorobenzylidene
malonoitrile (OCBM)

Chlorodiphenyl, 42% Cl

1-Chloro-1-nitropropane

Chloropicrin

Chloroprene

Cobalt metal fume & dust

Copper fume

Crag herbicide

Crotonaldehyde

Cyclopentadiene

2,4-D

Demeton

Dibrom

Dibutyl phosphate

1,2-Dichloro-5, 5-dimethy1-
hydantoin

Dichlorodifluoromethane

Dichloromonof luoromethane

Dichlorotetrafluoroethane

Diethylaminoethanol

Diisopropylamine

Dimethylphthalate

Dinitrobenzene (all isomers)

Dinitro-o-cresol

Dinitrotoluene

Diphenyl

Dichlorvos (DDVP)

Table 1

List of Substances

Endrin
Ethanolamine
2-Ethoxyethanol
Ethyl chloride
Ethylenediamine
Ethyl mercaptan

Ferbam

Fluorides in dust
Fluorine
Fluorotrichloromethane
Formaldehyde

Formic acid

Furfural

Furfuryl alcohol

Hafnium
Heptachlor
Hydrogen cyanide
Hydroquinone

Iodine
Iron oxide fume

Malathion
Maleic anhydride
MAPP (methyl acetylene/
propadiene mix)
Mercury
Methoxychlor
Methyl acetylene
Methylamine
Methyl chloride
Methylcyclohexanol
Methylcyclohexanone
Methyl formate
Methyl isocyanate
Methyl mercaptan
Methyl methacrylate

Nitric acid
Nitric oxide
p-Nitroaniline
Nitroethane
Nitromethane
Nitrogen dioxide
1-Nitropropane

Oxalic acid

Paraquat
Pentachlorophenol

Perchloromethyl mercaptan

p-Phenylenediamine
Phosdrin
Phosphine

Phosphorus pentachloride

Phosphorus yellow
Pyrethrum

Picric acid

Pival

Quinone

Ronnel
Rotenone

Silver, metal and soluble
compounds

Sodium fluoroacetate

Sodium hydroxide

Stibine

Strychnine

Sulfur dioxide

Sulfur hexafluoride

Sulfur monochloride

Sulfuryl fluoride

2,4,5-T

TEDP

TEPP

Tantalum

Tetraethyl lead
Tetramethyl lead
Thiram

Tin, organic compounds
2,4-Toluenediisocyanate
Trinitrotoluene

Vanadium, V205 dust
Vanadium fume

Warfarin

Zinc oxide fume


of 2 times the OSHA standard is generated, no dilution air is added to the 2S
dilution line--0.017 cu m/min is simply allowed to flow through this line--and
0.050 cu m/min of dilution air is added to the 0.050 cu m/min and 0.017 cu m/min
of main line mixture admitted to the 1S and 0.5S dilution lines, respectively.

All materials which the vapor may contact before collection are 316 and 304
stainless steel. A glass heater is included where the liquids are added to the
main line. Shutoff ball valves are placed in the dilution lines to allow their
independent operation and the calibration of air flows. The main line has a
2.54-cm (1 in) 0.D., and the dilution lines are 1.90-cm (0.75 in) 0.D. Diameters
were chosen to give turbulent flow with an approximate minimum Reynolds number
of 3000.

Air supply--Air from the house compressor is treated by passing it sequentially
through a cotton filter, a silica gel bed, a charcoal bed, and a high efficiency
glass fiber filter for removal of water, hydrocarbons and particulate. This air
is then connected to a manifold containing six takeoff ball valves. The pres-
sure (20 psig) at the manifold is maintained with a Nullmatic Moore 40H50 regu-
lator and monitored with an Ashcroft 0-60 psig test gauge. The air supply is
used for each of the dilution system connections as well as for the flame ioni-
zation detector monitor flame and "zero" air.

Sample collection manifold--Sample flow through the sampling devices connected
to the dilution lines is established by connecting each device by means of a
short piece of flexible tubing to a CFO which is connected to a 1.27 cm (0.5 in)
0.D. vacuum manifold. Each dilution line has a separate manifold which derives
its vacuum from a Model 0322 Gast vacuum pump. The orifices are jewel orifices
pressed into a threaded Teflon rod. One end of the rod is screwed into a tee on
the manifold, and the other has a hose tabulation fitting connected to it. The
orifice is protected from plugging by a piece of 100-mesh stainless steel screen.

Vent System--All excess vapor-laden air is collected via a 3.8l-cm (1.5 in) PVC
manifolding system where it is passed through a 0.3 x 0.3 x 0.6-m charcoal bed.
Flow is established by means of a pressure blower on the exit side of the char-
coal bed, and it is vented to the laboratory hood exhaust.

Monitors--To provide a ready check on operating conditions, several gauges or
monitors have been included in the system. Dwyer Magnehelic gauges monitor the
pressure on the main line and each of the dilution lines. A 0-10 cm H20 gauge
is used on the main line (setpoint 8 cm) and 0-2 cm H20 gauges are used for the
dilution lines. The purpose of these latter gauges is to provide a check
against possible back pressure developing in these lines which would affect the
dilution ratios.

The flame ionization detector (FID) is used to determine the time at which the
main line concentration has reached equilibrium and to monitor the concentration
level during breakthrough studies and sample collection.

Arthur D. Little, Inc. Aerosol System--

The dilution and sampling system used to produce the appropriate aerosol test
atmospheres is shown schematically in Figure 5. Basically, the system consists
of a main horizontal line into which aerosol and dilution air are introduced

and three vertical dilution and sampling sections which branch off the main line.

26


23

FIGURE 3 SRI SAMPLE GENERATION SYSTEM FOR VAPORS AND PARTICULATES


We finally extend our thanks to Grace A. Fannin who kept many of the NIOSH
staff appraised of the status of the methods and distributed the methods for
review and dissemination.

viii


ACKNOWLEDGMENTS

The authors would like to acknowledge the staff members at SRI International,
Arthur D. Little, Inc., and the National Institute for Occupational Safety and
Health for their efforts in contributing toward the overall success of this pro-
ject. At SRI we especially recognize and greatly appreciate the dedicated
efforts of Dr. Dale M. Coulson, Ellen L. Fernandez, and Jolene Y. Louie, in
addition to the following people:

Jennifer E. Barnett Lawrence B. Inman
Curtis W. Beeman Charles E. Lapple
Ronald W. Buckley Ilsabe C. Niemeyer
S. Sam Fratoni James H. Smith
Lois L. Gerchman Douglas S. Stivers
Mary J. Grubic Willoughby Thorn
Daniel L. Haynes El Lorraine Watson

Erick L. Hagmann

At ADL, we gratefully acknowledge the work performed by Richard H. Smith,
Dr. Philip L. Levins, Alegria B. Caragay, and Christine M. Freitas, in addition
to:

Itamar Bodek Kenneth T. Menzies
Laurence T. Damokosh Virginia A. Sherman
Martha G. Fernald Joel Weddig

Bruce E. Goodwin Ruth H. Willson
Joan B. Hastings Doris Wilson

Throughout the research effort we have appreciated very much the guidance and
support provided by the Project Officer, Dr. Laurence J. Doemeny. His efforts
have helped to make this program a very interesting and rewarding experience.
Also at NIOSH we especially recognize the continued efforts and suggestions pro-
vided by Dr. David G. Taylor and Mr. William A. Heitbrink and the method reviews
provided by:

Martin A. Abell James H. Jones
Mark F. Boeniger Bruce Lange
Michele Bolyard Howard R. Ludwig
Thomas P. Carsey Alan A. Lunsford
Mary E. Cassinelli Charles S. McCammon, Jr.
Clinton Cox James L. Oser
Harry M. Donaldson Judd C. Posner
Peter M. Eller Martha J. Seymour
Denis L. Foerst Doris V. Sweet
Robert A. Glaser Alexander W. Teass
Janet C. Haartz Samuel P. Tucker
Robert H. Hill, Jr. Allen W. Verstuyft.

R. Delon Hull
vii


so that electronic integration is possible and that a reasonable retention time
is acheived to minimize analysis time. The linear range of the detector was
established. If the instrument response was nonlinear, such as with the flame
photometric detector for sulfur, a wider range and increased number of standards
became necessary to determine the instrument response. A calibration curve was
then prepared over the range of 0.1 to 3 times the OSHA standard for the proposed
sample volume. An estimate was made of the lower detection limit. Similar
aspects for spectroscopic methods were also considered.

The effects of substances that may significantly interfere in the analysis of
the analyte were also investigated. Mixtures of the suspected interferences

and the analyte were prepared at concentrations representative of expected atmo-
spheric concentrations and analyzed. If necessary, adjustments were made in
analytical conditions to eliminate or minimize interference effects.

Analytical Recovery Tests

The sampling medium was selected by testing various media (sorbents and filters)
and desorption or extraction solvents. Samples were spiked with analyte, allowed
to equilibrate, and desorbed. The combination of sampling medium/solvent yield-
ing the most promising results was tested further, unless general methodology
was applied. For sorbents, the next step was to determine their breakthrough
volume at high humidity, as described in the next section. Once capacity was
demonstrated and the sampling flow rate and time established, more extensive
analytical recovery tests were performed.

Three sets of six samples were evaluated. For these tests, the sampling medium
was spiked to represent samples taken at 0.5, 1 and 2 times the OSHA standard
for the selected sample volume. For sorbents, stock solutions of the analyte
in an inert solvent were prepared at such concentrations that less than 10-
microliters of solvent was necessary to apply the analyte to the sorbent.

After equilibration of the material on the sorbent, the analytical recovery was
determined. Standards were prepared and analyzed at the same time as the desorbed
samples. A minimum recovery of 75% with a relative standard deviation of no more
than 7% for six samples was required before proceeding. A recovery of greater
than 90% was preferred.

Analytical recovery tests for filters were performed in a manner similar to
that for sorbents. Recoveries from filters should be quantitative (100%).

These tests were expected to show that recovery was either constant or increased
with the amount of analyte used. After these tests were completed, a graph of
recovery or desorption efficiency (amount recovered divided by the amount spiked)
as a function of the amount of spiked substance was constructed for later use

in the analyses of generated samples.

For a filter/sorbent combination sampler, recoveries from both filter and sor-
bent were evaluated. Generally, the recovery from both collectors was evaluated
by spiking with amounts of analyte representing samples collected over the
range 0.1 to 2 times the OSHA standard. Determinations over this extended
range were necessary since the vapor/particulate ratio in field samples may
differ from that in laboratory tests. Satisfactory recoveries (>90%) must be

12


SCOPE OF WORK

The protocol for validation of each sampling and analytical method consisted of
a two-part experimental study. An analytical method was first developed and
tested for the substance. The sensitivity and specificity of the method were
evaluated and the response to known interferences was determined where necessary.
After this, an appropriate sample collection medium was chosen. In the case of
particulates, a suitable filter was determined; for gases or vapors, an absorp-
tion liquid or, preferably, solid sorbent was chosen. For particulate/vapor mix-
tures, multiple stage sampling trains were developed. The sampling medium was
spiked with known amounts of the test substance at three levels corresponding

to one-half, one, and two times the OSHA environmental limit at a given air
volume. An efficient recovery procedure, such as solvent desorption/extraction,
was developed. The analytical recovery of the substance from the sampling medium
was then determined in the spiking experiments. In addition, the precision of
the analytical method was evaluated.

If the analytical method were acceptable in recovery and precision, the second
part of the validation effort was initiated. This part involved testing the
efficiency of the sampling procedure with known air concentrations of the toxic
substance prepared in a laboratory generation-dilution system. For sorbents,

the breakthrough volume was also evaluated. After the optimum sampling flow
rate and sample volume were determined, samples were collected from a laboratory
generation-dilution system. The concentration of the generated test atmosphere
was determined by an independent method of measurement. The stability of col-
lected samples was evaluated by taking the results obtained from samples that
had been analyzed immediately after collection and comparing them to samples

that had been analyzed after a storage period. Based on the results of the vali-
dation tests, an evaluation was made of the precision and accuracy of the analyt-
ical method itself and of the sampling and analytical method as a whole.

The basic criterion for successful validation was that a method should come with-
in +25% of the "true value" at the 95% confidence level. To meet this criterion,
the protocol for experimental testing and method validation was established with
a firm statistical basis. A statistical protocol provided methods of data analy-
sis that allowed the accuracy criterion to be evaluated with statistical param—
eters estimated from the laboratory test data. It also gave a means to evaluate
precision and bias, independently and in combination, to determine the accuracy
of sampling and analytical methods.

The substances studied in this program are summarized in Table 1.


where D is the average particle size of the aerosol, C is the volume concentra-
tion of solute in the solution (volume of solute per unit volume of solution),
and D_ is the average size of the mist droplets. Small pneumatic atomizers,
which are commonly used for the laboratory production of aerosols by the spray
drying technique, usually produce mists with mean diameters of 1 to 10 microns.
Consequently, for a one part per million solution (volume/volume basis), such
atomizers will produce particles in the hundredth micron size range.

The concentration of aerosols produced by the spray drying method may be varied
by varying the concentration of the solution. The relation between solution
concentration and aerosol concentration at fixed volume production rate is
roughly linear oyer a wide range of concentration. Aerosols in the concentra-
tion range of 0.001 to 10 mg/m3 may be easily produced by spray drying. The
spray drying technique has been used for most of the aerosols generated in the
validation program, including the majority of the pesticides.

Atomization--Liquid aerosols and aerosols of readily melted solids may be gen-
erated by direct atomization using, for example, a pneumatic nebulizer such as
the Collison. When a pneumatic atomizer is used, the aerosol condensation may
be varied by changing the pressure of the atomizer air supply pressure. The mass
median diameter of the aerosols produced by the small pneumatic nebulizer is
typically in the micron range. In this program, the direct atomization method
was applied to dimethylphthalate, a liquid, and dibutyl phosphate, a low melt-
ing solid.

Condensation--The condensation method requires the formation of a vapor-air mix-
ture that is supersaturated with respect to the vapor. Condensation from the
supersaturated vapor may then occur either on foreign particles present in the
gas (heterogeneous nucleation) or on small clusters of vapor molecules that are
formed at random (homogeneous nucleation).

Supersaturated vapor mixtures are usually formed by passing air or an inert gas
over a heated pool of liquid (or over a heated solid) so that the stream may pick
up vapor. The vapor-laden stream is then cooled, usually by mixing with a cooler
gas stream or by thermal conduction so that the partial pressure of the vapor
rises above the saturated vapor pressure.

The concentration of the aerosol produced by the condensation method is, of
course, determined by the partial pressure of the vapor in the supersaturated
stream. The partial pressure, and thereby the ultimate aerosol concentration,
may be varied by varying the temperature of the vapor source. Particle size

is determined by several factors: the number of nuclei present, the degree of
supersaturation achieved, and the rate of change of the degree of supersaturation.
These factors are independent. Particles ranging from about 0.01 to more than

10 microns have been prepared by this method. Although it is best known as a
method for generating monodisperse aerosols, condensation may also be used to
produce polydisperse aerosols. Dinitro-o-cresol was generated using this method.

Thermal decomposition--Thermal decomposition methods may be used to prepare
metal oxide fumes. An aerosol of a precursor to the metal oxide--i.e., a sub-
stance that is readily decomposed, thermally, to yield the oxide--is first gen-
erated and then is heated by passing it through a heated tube to decompose it
to the oxide. Metal formates, oxalates, and the like, which readily yield the

18


DEVELOPMENT AND VALIDATION OF METHODS
FOR SAMPLING AND ANALYSIS OF
WORKPLACE TOXIC SUBSTANCES

Ellen C. Gunderson
C. Clarine Anderson

SRI International
Menlo Park, California 94025

with contributions by
Richard H. Smith (Arthur D. Little, Inc.)
Laurence J. Doemeny (NIOSH)

Contract No. 210-76-0123

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Services
Center for Disease Control
National Institute for Occupational Safety and Health
Division of Physical Sciences and Engineering
Cincinnati, Ohio 45226

September 1980


Table A-1 (continued)

Compound OSHA standard Analytical Range
Code___No. Analyte (mg/cum) Collection medium Sample treatment * method (mg/cu m)
A S141 ‘Di tsopropylamine 20 Impinger/ 0.3 N KO Gc/FID —8.5-37.4
0.1 N H,S0,
2 HPLC 0.42-2.4
$ S214 Dinitrobenzene (all isomers) a perp/pubbler
s $166 —_Dinitro-o-cresol 0.2 a - uPLE 0.070-0.62
S $215 Dinitrotoluene ffs " - HPLC Qi)
s 824 Diphenyl. 1 Tenax GC cel, Gc/FID 0.64-2.4
S $284 Endrin 0.2 HCEF/Chromosorb ‘Toluene Gc/Ecb _0.06-0.31
102
A $361 —-2-Ethoxyethanol 740 Charcoal Methanol/methylene GC/FID 340-1460
chloride
A $105 Ethyl chloride 2600 Charcoal Carbon disulfide  GC/FID 1590-6500
A $102 _—_—-Fluorotrichloromethane 5600 Charcoal Carbon disulfide  GC/FID —-2390-10,500
S $327 Formaldehyde 3 ppm (TWA) Bubbler (Girard T) - Polar. 1.4-6.2 ppm
10 ppm (Peak) (TWA)
5 ppm (C) 4.6-19.8 ppm
(Peak)
S $173 Formic acid 9 Chromosorb 103 Water IC/ECond 4.4~21.6
Ss S17 Furfural 20 Bubbler (Girard T) - WPL 10.1-40
S $365‘ Furfuryl alcohol 200 Porapak Q Acetone Gc/FID 120-470
A $194 Hafnium 0.5 MCEF HNO3, perchloric Plasma —0. 26-105,
acid, HF emission
spectro.
S $287. Heptachlor 0.5 Chromosorb 102 Toluene GC/EC 0.23-1
A $288 ‘Hydrogen cyanide 11 MCEF/Bubbler - ISE
(0.1 N KOH)
A $57_—-Hydroquinone 2 MCEF Acetic acid HPLC 0,844.05
S $366 Iron oxide fume 10 MCEF HCL/HNO, AA 3.9-18.2
S $370 Malathion 15 Glase fiber filter Isooctane GC/FPD-P 8-35
S $85 MAP (methyl acetylene/propa- 1000 ppm Bag - Fi 4
en 1D 80-1990 ppm
S$ $199 Mercury 0.1 (C) Ag coated Chromo- Thermal desorption Flameless 0.046-0.18
sor! AA
$ $371 Methoxychlor 15 Glass fiber filter Isooctane GC/ECond 7.7-31
S $84 —- Methyl acetylene 1000 ppm Bag. - GC/FID 520-1880 ppm
S S148 Methylamine 12 Silica gel Acidify with HCl, 1C/ECond 6.24-28.1
desorb with H,0
S$ $99 Methyl chloride 100 ppm (TWA) Charcoal Methylene chloride GC/FID 59-220 ppm
200 ppm (C) (Twa)
300 ppm (Peak) 143-580 ppa
(Peak)
S $374 Methylcyclohexanol
s sor 470 Charcoal Methylene chloride GC/FID 215-920
5 Methylcyclohexanone
460 Porapak Q Acetone Gc/FID 210-850
S$ $291 Methyl formats
yl formate 250 Carbosieve B Ethyl acetate Gc/FID 108-542

A-3


Literature Search

Select Method

Evaluate Analytical Method
No
Hrs\_ Yes
>400
‘Assemble Generating Apparatus
Select Collection Medium
[ Capacity ] [[Cotlection Efficiency |
No
No Hrs\ Yes
oK >500
Yes
Recovery
N
oKy—
Yes
Analytical Set
18 Samples
No
No Hrs\ Yes
OK >500,
Yes
[ 1
Generated Set Storage Saeiy Independent
18 Samples Batam Verification
I
J No
Hrs\_ Yes
500
Validated Failure
Method Report
FIGURE 1

PROTOCOL FOR METHOD DEVELOPMENT AND VALIDATION



IMPLEMENTATION

PROTOCOL

If no specific method was designated by NIOSH for a substance, the study began
with a review of the failure report and previous experimental work performed on
the substance under NIOSH Contract No. CDC-99-74-45. If necessary, a literature
search was performed covering the following essentials:

e Physical and chemical properties.

e Sampling methods, including preservation of collected samples,
and derivatization procedures where applicable.

e Analytical methods, including specific techniques for separation,
detection, and quantification by gas or liquid chromatography,
atomic absorption, or other methods.

An experimental protocol for method development was prepared before starting
laboratory work. The general procedure, involving several interdependent experi-
ments, is illustrated in Figure 1. The protocol allowed for efficient decision-
making on a step-by-step basis. Since adverse results in any one step could
cause any previous experimentation to be rejected, it was extremely important

in any protocol to eliminate potential problems at the earliest stage possible.
A specific plan was therefore designed so that the most vulnerable point of the
proposed sampling and analytical method would be tested early in the procedure.
For example, if storage stability of collected samples or capacity of the sam-
pling media were suspected problems, then these factors were investigated in
early experiments. When a method failed to meet accuracy or precision criteria
at one stage of the validation procedure, work then reverted to an earlier stage.
How far work regressed was determined by the nature of the problem, the

point in the protocol at which the experiment failed, and the time available for
additional work. The level of effort for method development and validation was
such that no more than an average of 60 professional man-days with a maximum of
75 professional man-days were to be expended on each compound. At various deci-
sionmaking points in the protocol, meetings were held with project management to
discuss the status of work and plan for immediate testing. Consultation between
NIOSH, SRI, and ADL was also valuable in solving problems in the refinement of

a method.

ANALYTICAL METHODS

The criteria for choosing an analytical method in this program included the use
of modern instrumentation and chemical methods that were specific for the sub-
stance analyzed. The method should also lend itself to routine analysis of a

large number of samples. Where possible, the method should be economical, and


that, when possible, a combination of collection medium and solvent would be used
that yielded at least a 90% analytical recovery. Thus, an increase in recovery
caused by other compounds present in field samples would not cause an appreciable
error.

A significant accomplishment in this program included the initiation of testing
and validation criteria for high vapor pressure particulates. The need for sam-
pling particulate/vapor mixtures of single substances arose frequently. The
criteria developed for evaluating the filter/sorbent methods included the testing
of each part of the sampling device over an extended concentration range, and
analyzing in detail the results of the breakthrough test and storage stability
test. All possible concentration ratios can not feasibly be tested and it may
be more appropriate in further investigations to test a "worst case" situation.
This may be accomplished by performing breakthrough tests at elevated temperatures.
One of the problems that may occur with a sample collected on a filter/sorbent
sampling train is that a significant amount of vapor may be absorbed by the
filter. In most methods, the filter was combined with the sorbent in a glass
vial immediately after collection to prevent loss of vapor from the filter when
stored. The combined sample was then analyzed. This procedure calls for com-
plete or identical recoveries from both the filter and the sorbent. Thus,
evaluation of analytical recoveries and selection of an efficient filter/sorbent
combination is a critical step in the validation effort. The criteria for
testing should also address the manner in which analytical recoveries are
determined. Satisfactory recovery should be demonstrated separatley for each
sampling medium and possibly for the combined media. The development of a
sampling device that contains the filter and sorbent combined in either the
cassette or tube would be an improvement over the two-part sampling train.

All methods developed and validated on this program are not intended to be the
ultimate methods of sampling and analysis for toxic substances found in the
workplace. Even though the methods were rigorously tested under the validation
efforts in this program, certain modifications may be desirable to make a method
more useful. In addition, as new sampling and analytical methodology is developed,
it may be advantageous to incorporate it into existing methods or replace old
methods entirely. It should be emphasized that when a method is modified it must
be revalidated to assure precise and accurate results. A number of suggestions
are summarized below as a guide for future work in the development of new methods
and in improvement of existing methods.

Based upon results obtained from experimental work on substances for which no
method was developed, further work is needed for certain compound classes. All
the halogens and certain reactive halogenated species need to be studied in a
concentrated effort. Because of the reactivity of halogens, any collection
method for these substances should involve in situ derivatization, preferably
with a coated sorbent. The analytical method would have to be specific to dis-
tinguish between the individual halogens and other interfering substances. A
general method for the halogens would be useful, but may be an impossibility.

It would definitely be a challenging future objective. Validated methods are
also needed for reactive substances such as methyl and ethyl mercaptan, the iso-
cyanates, and some amines. These substances also usually require derivatization
to stabilize the collected sample before analysis.

37


Sc

Add Gas
or—dq
Aerosol

AP Gauge

°

N
2
IS)
°
iS}

0-10

cm H,0 K <
Main Line
JS —> Vent
Y Flow 0.5S 1S 2s we '
ul ent
Orifice Ne Z | <5 as
(Extra) To ah -
FID FID FID 1g 2S FID
Switching Val
T, 7273 3. 3 vos . ive
Vac 0.55 § Breakthroug!
ry Gauge
163)
Pyrometer
Ooo ©
Collection ee wy,
Manifold FID
Ad afin + \! '!

1 To +

Vacuum

Pump

Syringe Drive

Variac

FIGURE 4 ADL VAPOR GENERATION/DILUTION/SAMPLING SYSTEM

Y = Critical Flow Orifice (CFO)


Table A-1 (continued)

Compound OSHA standard Analytical Range
Code No. Analyte (ng/cum) Collection medium Sample treatment * method __(mg/cu m)
A S43. Methyl methacrylate 410 XAD-2 cs, Gc/FID 193-725
A $319 Nitric acid 5 Impinger (water) - ISE 2.6-10.8
A $321 Nitric oxide 25 ppm Draeger oxidizer, TEA Color. 11.1-48 ppm
TEA coated Molecular
Steve
A 87 p-Nitroaniline 6 MCEF Isopropanol HPLC 3.9-12.9
A $219“ Nitroethane 310 XAD-2 Ethyl acetate GC/FID 147-600
A $320 Nitrogen dioxide 5 ppm TEA coated Molecviar TEA Color. 3-1-11.5 ppm
Sieve
A $220“ Nitromethane 250 Chromosorb 106 Ethyl acetate GC/AFID 123-500
A $294 Paraquat 0.5 PIFE filter Water HPLC 0.256-1.03
A 8297 Pentachlorophenol 0.5 MCEF Ethylene glycol ‘HPLC 0.265-1.130
A $296 Phosdrin 0.1 Chromosorb 102 Toluene GC/FPD-P 0.027-0.145
A $332. Phosphine 0.4 HgCN coated silica Acidic permanganate Color.  0.195-0.877
gel
A S257 Phosphorus pentachloride 1 PVC filter/bubbler Sodium molybdate/ Color. 0.55-2.0
(water) hydrazine sulfate
complexation
A $334 Phosphorus yellow O.1 Tenax GC Xylene GC/FPD-P 0.056-0.244
A $228 Pieric acid 0.1 MCEF 70% aq. methanol ‘HPLC 0.036-0.189
A $298 Pyrethrum 5 Glass fiber filter Acetonitrile HPLC 1.41-8.5
A S181 Quinone 0.4 XAD-2 Ethanol/hexane HPLC 0.17-0.75
A $299‘ Ronnel. 10 MCEF/Chromosorb ‘Toluene GC/FPD-P  2.82-17.1
102
A $300‘ Rotenone 5 PIFE filter Acetonitrile HPLC 1,16-11.1
A $182 Silver, metal and sol. compds. 0.01 MCEF HNO, Plasma 0.0036-0.0181
emission spectro.
S $301 Sodium fluoroacetate 0.05 MCEF Water IC/ECond _0-020-0.137
A $381‘ Sodium hydroxide 2 PIFE filter HCL NaOH back- 0. 76-3.9
titration
A 8243 Stdbine 0.5 HgCl, coated Cone. HCL Color. 0.119-1.008
siliéa gel Rhodamine B
A $302 Strychnine 0.15 Glass fiber filter HPLC mobile HPLC 0.073-0.34
phase
S $308 Sulfur dioxide 13 Bubbler (H,0,) Add isopropyl Barium per- 6 .6-26.8
alcohol, adjust chlorate
pH w/perchloric titration
acid
S $244 Sulfur hexafluoride 1000 ppm Bag, - Gc/Tcp ‘500-2010 ppm
S 8245 Sulfuryl fluoride S ppm Bag - GC/FPD-S 2.54 ~
10.29 ppa


measured volumes of air thus achieves serial dilutions to 1 times and 0.5 times
the OSHA standard level.

The dilution ratios from chamber to chamber can also be varied by simply
changing the amount of dilution air that is added. This is particularly advan-
tageous in generating aerosols, where wall deposition of particles in the
rationing system can be offset by changing the rate of addition of dilution air.

The cylindrical section at the base of each sampling chamber contains the fit-
tings necessary to collect samples, using any of a variety of sampling media--
solid sorbent tubes, filters, liquid scrubbers, or a combination of these. Sis
to twelve samples each at three concentration levels can be collected simultan-
eously. A metal bellows vacuum pump is used for sampling from each chamber.
Separate critical flow orifices are used for each sample. Air taken from the
chamber during sampling is returned via the sampling pump exhaust line to the
chamber outlet line, thus preserving the proper air flows during the time of sam—
pling. The sampling rate therefore does not affect the concentration of material
in any of the chambers. All three chambers can be monitored with a hydrocarbon
analyzer and a gas chromatograph fitted with a gas sampling loop.

The entire system is maintained at 1-inch water vacuum to prevent toxic materials
from escaping into the laboratory. All exhaust air streams (from the vacuum
exhaust system and excess from the primary dilution chamber) are fed into a com-
bustion chamber where all toxic materials present are burned before entering

the atmosphere.

Arthur D. Little, Inc. Gas and Vapor System-—

The vapor generation/dilution system used for the validation studies of vapors
and gases, is shown schematically in Figure 4. The system basically consists
of a main line air stream to which are added predetermined amounts of various
liquids, gases or aerosols to generate the desired vapor concentrations. From
the main line, three dilution arms branch off in which the desired multiples 0.5,
1, and 2 times the OSHA standard concentration level are established. Six sam-
pling devices are connected in parallel to the 0.5S dilution lines and six to
the 2S dilution line; twelve sampling devices are connected to the 1S dilution
line. All these devices are connected via critical flow orifices (CFOs) to

the corresponding vacuum lines.

Air flow rates through the system are established by means of CFOs and flow
restrictors. The primary air system derived from the house air compressor is
maintained at 20 psig. The appropriate orifice diameters are chosen to main-
tain an air flow of approximately 0.1 cu m/min in the main line and an addition
of 0.05 cu m/min to each of the dilution lines. The main line is maintained at
8 cm H70 pressure by a needle valve. Appropriate flow restirctor diameters are
chosen for the 0.5S, 1S, and 2S dilution lines so as to give the desired final
concentrations of vapor in air.

The system was designed to generate either 4 times or 2 times the OSHA standard
concentration in the main line. When a 4 times level is generated, 0.05 cu m/min
of dilution air is added to each dilution line. Orifices are selected so that
the 0.5S, 1S, and 2S lines have flows equal to approximately 0.007, 0.017, and
0.050 cu m/min respectively of the main line concentration added to the dilution
air, thus giving the desired final concentrations. When a main line concentration

24


INTRODUCTION

The Occupational Safety and Health Act of 1970 (Public Law 91-596) requires
monitoring and the maintaining of records to determine if and when employees are
exposed to toxic hazards in the workplace. Exposure standards have been estab-—
lished for certain substances by the Occupational Safety and Health Administra-
tion (OSHA). The National Institute for Occupational Safety and Health (NIOSH)
is responsible under the Act for providing reliable sampling and analytical pro-
cedures in order that the work environment can be monitored to determine
compliance.

For many years the level of employee exposure to toxic substances has been deter-
mined by collecting an air sample within the breathing zone of the worker. Be-
cause most of the air standards are 8-hour time-weighted averages (TWA) and be-
cause workers move about, personal, portable sampling and collection systems have
been required. Since some air standards are ceiling and/or peak values, they
require additional samples collected over short time intervals (15 minutes) to
determine if an exposure might occur at or above the maximum allowable levels.

To ensure the established standards, valid sampling and analytical methods must
be available. In 1974, as part of a joint effort by NIOSH and OSHA to complete
the existing Standards (29CRF 1910.1000), NIOSH entered into a contract to vali-
date sampling and analytical methods for 386 compounds (NIOSH Contract No. CDC-
99-47-45). This total effort, known as the Standards Completion Program, was
completed in September 1976. In the method validation part of the total effort,
methods were not validated for 170 substances because of nonavailability of
methods, contractual constraints, statistical requirements, or other reasons.

For some substances, methods may never be developed; for others, storage, recov-
ery, precision or accuracy requirements make it unlikely that validation would
be achieved. Therefore, 130 compounds were selected for additional work. The
experimental protocol and methodology described herein formed the basis for the
development and validation of sampling and analytical methods for these 130
substances.

Substances for which NIOSH had planned to prepare criteria documents were given
highest priority and work was scheduled early in the contract. Other substances
were scheduled to coordinate with the completion of NIOSH in-house and contract
work.


where parallel samples were collected on different filters. For particulate/
vapor mixtures, when the proposed method used a filter and sorbent, a different
type of filter followed by a bubbler was used to sample from the same atmosphere.
The alternative method was also thoroughly tested, using a reasonable number of
samples. Because this technique relied heavily on good collection efficiency,
all the sampled material was accounted for. It was assumed that there was no
discrimination of particle sizes collected resulting from different inlet veloc-
ities of the two samplers.

Storage Stability of Generated Samples

To determine if collected samples can be stored for 1 week before analysis, 12
samples were collected simultaneously from a test atmosphere at the OSHA stan-
dard level. Six samples were analyzed immediately after collection and the
remaining six were stored on the laboratory bench for 7 days. The average con-
centration determined from the six samples analyzed immediately was compared to
the average concentration determined from the six samples analyzed after 7 days
storage.

At times the storage stability of the collected sample was a critical factor in
the method. If poor stability was suspected, tests were conducted early in
experimental studies to determine corrective measures.

Method Validation

For a sampling and analytical method to be validated, certain requirements based
on statistical criteria must be met. The criterion for a valid method was based
on whether the overall sampling and analytical result could come within 25% of
the "true" yalue at the 95% statistical confidence level for any individual
sample. A detailed discussion of the statistical protocol for this program and
the definition of terms are in Appendix B. To meet this requirement, an unbiased
method must have a coefficient of variation (CV) of less than 0.128. Taking into
account random errors of estimation, the total CV from laboratory validation data
(with 15 degrees of freedom) should not exceed 0.105. This includes a maximum
allowable imprecision of 5% due to the use of a personal sampling pump. A biased
method must meet more stringent requirements. A summary of the criteria that were
used to evaluate the test method is listed below:

e Analytical recoveries Three sets of six samples were spiked at 0.5
1, and 2 times the OSHA standard for the recom-
mended sample volume, Recovery must be at
least 75% (preferably >90Z).

@ Capacity At least six determinations were made at twice
the OSHA standard at greater than 80% relative
humidity (for sorbents). The recommended sam-
pling volume must be less than two-thirds the
breakthrough volume.

e@ Storage stability 12 samples were collected from test atmospheres
at the OSHA standard; 6 samples were analyzed
immediately, 6 after 7 days storage. Means of
concentrations found for each set must agree
within 10%.

15




REPORTING
ROUTINE PROJECT COMMUNICATIONS

The progress in methods development and validation efforts was reported to the
NIOSH project officer (PO) on a weekly basis via telephone calls from SRI and ADL.
Weekly telephone communications were also made between SRI and ADL. These com—
munications provided a very useful and timely exchange of information. Written
progress reports were submitted to the PO monthly.

Quarterly meetings were held by the project steering committee to discuss pro-
gress, problems, and plans for future work. The committee was composed of pro-
ject management staff from NIOSH, SRI, and ADL. These meetings were held at
locations alternating between the offices of NIOSH, SRI, and ADL, in addition
to laboratories (Los Alamos Scientific Laboratory and OSHA) where information
could be gained that would benefit the project effort. Meetings were also held
in conjunction with technical society meetings.

METHOD REPORTS

Upon successful completion of validation studies for a particular substance,
the following three draft reports were prepared in a specified format and sub-
mitted to NIOSH for review:

e Sampling and Analytical Method (SAM)--This report describes
the method of collection of the sample and subsequent analysis.
Data regarding the useful range, interferences, precision, and
accuracy of the method are summarized.

e Sampling Data Sheet (SDS)--This is a guide for the person col-
lecting samples in the field. Detailed instructions are given
for sample collection and shipment of samples to the testing
laboratory.

e Backup Data Report (BUD)--This document describes the procedures
used to validate the method and includes supporting experimental
data, a description of the test atmosphere generation system
and the method used to determine atmospheric concentration, a
discussion of any problems with the method, and an evaluation
of the precision and accuracy.

The methods validated in this program are classified by NIOSH as Class B methods
with "accepted" status. A summary of the validated methods appears in Appendix A,
Table A-1.

If a valid method did not result from the validation effort, a failure report
was submitted, which discussed the experimental approach, reasons for failure,

32


and recommendations for further work. The philosophy of this report was to pro-
vide a thorough background in the chemistry of the particular substance with
regard to sampling and analytical methodology which could be a useful guide or
starting point for future work. A list of these reports is in Appendix Ay
Table A-2.

On occasion, a method was not validated because a single criterion was not met--
for example, storage stability of samples was questionable at room temperature,
accuracy was not thoroughly evaluated, or further testing of a newly developed
sorbent was recommended. In this case, if the method had the potential for pro-
viding precise and accurate results with the aid of correction factors or spe-
cial sample treatment, the method was submitted as a Class E method with "proposed"
status. A SAM, SDS, and BUD were prepared as above for a validated method. In
addition, a failure report cover page discussed the reasons why the method was

not validated, its limitations, and what testing was needed to upgrade the method.
A summary of these methods also appears in Appendix A, Table A-1.

DELIVERY AND REVIEW OF DRAFT REPORTS

Several months before the report was received at NIOSH, a technical reviewer was
assigned from the Inorganic Methods Development Section or the Organic Methods
Development Section of the Measurements Research Branch. In addition to the
contract project officer (PO) and the alternate project officer (APO), the
reviewer was available to provide technical guidance to SRI or ADL during experi-
mental studies on a particular substance.

In addition to the PO, draft copies of each substance report were submitted for
review to:

Chief of the Industrial Hygiene Section
Industry Wide Studies Branch

Division of Surveilance

Hazard Evaluation and Field Studies

and to:

Director of the OSHA Laboratory
Salt Lake City, Utah.

The PO coordinated the review of the substance reports. Two to three weeks after
receipt of the reports, the PO and APO met to review the reports and written com-
ments provided by the technical reyiewer, the Industrial Hygiene Section, and
OSHA. The review covered topics such as determining if the criteria for a vali-
dated method were satisfied, safety of the method, contractual requirements, and
technical issues, In those cases where the draft report was for a validated
method, the report was usually returned with a few minor comments. Sometimes it
was necessary to recommend additional work. In rare cases, the data did not
support a validated method. However, if the method was sufficiently encouraging,
the PO and APO would recommend that a failure report, combined with a Class E
method, be written. Otherwise, a failure report was recommended.

33


how small were the CV, and cv, for other sampling errors and analysis errors,
respectively).

DEFINITIONS AND SYMBOLS

Mean arithmetic average (x), defined as the sum of the observations
defined by the number of observations (n).

Standard deviation
the positive square root of the variance which is defined as the
sum of squares of the deviations of the observations from their
mean (x) divided by one less than the number of observations (n - 1).

n
D(x, - Sy"
standard deviation = Bes
n-1
cv coefficient of variation or relative standard deviation, defined

as the standard deviation divided by the mean.

standard deviation

cv
mean
cv, coefficient of variation (estimated value) for the six analytical
samples at 0.5, 1, and 2 times the OSHA standard level.
cv, coefficient of variation (estimated value) for the six generated
samples at 0.5, 1, and 2 times the OSHA standard level.
w pooled coefficient of variation, in this program, the value derived

from the coefficients of variation (of a given type e.g., CV, or CV»)
obtained from the analysis of six or fewer samples at each of the
three test levels - 0.5, 1, and 2 times the OSHA standard level.

The mathematical equation is expressed as:

cv =
where:
fy = degrees of freedom, equal to number of observations (n,)
minum one, at the ith jevel. :
cv, = coefficient of variation (CV or CV2) of the observations
at the ith concentration level.
z
£ = 1
i=1 2
ek = index for the three concentration levels,

B-4


times the standard, and samples are collected simultaneously at the three con-
centrations. A schematic of the generation system and associated components is
presented in Figure 2. A photograph of the system is in Figure 3.

The generation system is large enough to be used for polydispersed aerosols as
well as for gases and vapors. The primary dilution chamber is 48 inches by

4 inches and may handle air flows up to 400 L/min. The large volume dilution
chamber is important for several reasons, Even at high air flow rates, the
velocity of particles is low to allow complete solvent evaporation in the genera-
tion of aerosols. The air velocity is also low enough to avoid impaction on the
walls while great enough to prevent particle diffusion to the walls. For these
same reasons, the sample rationing system is only 1 inch in diameter and handles
a flow of only 52 L/min. Gravitational settling is avoided by maintaining a
sufficient air velocity.

The sampling cones for the three chambers are 6-inch I.D. at the base (point of
sample collection) and narrow to l-inch I.D. at the point of attachment to the
sample rationing system. A constant total air flow of 26 L/min through each
cone causes a gradual reduction in aerosol velocity toward the point of sample
collection. The air velocity at the collection point is 2.4 cm/sec.

All portions of the generation system that come in contact with the test atmo-
sphere are constructed of stainless steel or Teflon to avoid contamination.
Sections of the generation system at which dilution air is added are constructed
such that the incoming air forms a "high-velocity sheath" around the air/analyte
mixture that is to be diluted. This sheath serves two functions. The dilution
air sheath becomes increasingly less coherent and stable as it moves downstream
of its point of entrance and hence is turbulently mixed with air/analyte test
atmosphere. At the point of entrance of the dilution air stream, a Venturi
effect accelerates the air/analyte mixture to a high velocity. The dilution
air sheath also prevents interaction of the accelerated air/analyte stream with
the walls of the chamber, thus eliminating a large source of aerosol loss by
impaction.

The system being used to generate the initial concentrations of vapor, gas, or
particulate is interfaced with the dilution apparatus at the primary dilution
chamber. The output of the generator is diluted with the appropriate amount of
air to obtain a concentration 2 times the OSHA standard. Of the total amount of
material generated at twice the level, a flow of 52 L/min enters the rationing
system. Under control of a vacuum exhaust orifice, material at 2 times the level
enters the first sampling chamber at a rate of 26 L/min. Downstream of the en-
trance to the first sampling chamber, dilution air is added (via a critical
orifice) at a rate of 26 L/min. Thus, the flow of material at 2 times the level
that did not enter the first sampling chamber (26 L/min) is diluted with air at
a flow rate of 26 L/min to a final concentration of 1 times the OSHA standard
level. Analyte at the 1 times level then enters the second sampling chamber at
a rate of 26 L/min. The remaining flow, 26 L/min is diluted again with air at
26 L/min to achieve 0.5 times the OSHA standard level. The analyte/air mixture
at the 0.5 times level is drawn into the third sampling chamber at 26 L/min.

The remaining material in the rationing system not drawn into the sampling cham-
bers is removed at a rate of 26 L/min by the fourth critical orifice in the
vacuum exhaust system. This removal of test atmosphere volumes and addition of

21


cv, = pooled coefficient of variation of 18 generated samples
Va; = coefficient of variation of six generated samples at the
ith jevel
ma
fy = degrees of freedom associated with (CV,,)° and equal to
number of observations at the it levef minus one.
3
£ = Uf,
i=1)>

To pass Bartlett's test at the 1% significance level, chi-squared must be less
than or equal to 9.21 (chi-squared has two degrees of freedom).


Delivery and Review of Draft Reports .....

Distribution of Methods ..........
Conclusions and Recommendations .
Appendix A ..
Appendix B ........2-

iv



Table A-1 Validated Methods

‘ompot tandard Analytical Range
Code bar a Analyte oSiag/ee a). Collection medium Sample treatment * method _(mg/cu a
S $345 Acetaldehyde 360 Bubbler (Girard T) - HPLC 170-670
S S169 Acetic acid 25 Charcoal Formic acid GC/FID —-12.5-50
S $342 Alkyl mercury compounds 0.01 (TWA) Carbosieve B Thermal desorption Flame-  .004-.017 (TWA)
0.04 (c) less AA .02-.08 (C)
A 8346 Allyl glycidyl ether 45 Tenax GC Diethyl ether GC/FID 19-87
S S158 2-Aminopyridine 2 Tenax GC Thermal desorption GC/FID _0.91-3.60
S S347 Ammonia 35 H,S0, treated 0.1 N H,S0, ISE 17-68
#
sflida gel
A $348 Ammonium sulfamate 15 MCEF Water I¢/ECond 6.4-27.3
S $163 Anisidine (ortho & para isomers) 0.5 XAD-2 Methanol HPLC 0.25-1.16
A 82 Antimony & compounds 0.5 MCEF HCL AA 0.258-1.08
S S276 ANTU 0.3 PIFE filter Methanol HPLC 0.128-0.76
S $253 Benzoyl peroxide 5 MCEF Diethyl ether HPLC 3.12-19.10
A $138 n-Butylamine 15 (C) —-HyS0, treated 50% aq. methanol © GC/FID.—«8.1-35.5
silica gel
S $350 n-Butyl mercaptan 35 Chromosorb 104 ‘Acetone GC/FPD-S  16.8-74
A $313 Cadmium fume 0.1 (TWA) -MCEF #0, /HCL AA 0.04-0.275 (TWA)
0.3 (C) 0.122-0.57 (c)
‘A $249 Carbon dioxide 5000 ppm Bag - Gc/TeD 2270-10, 099,
A $340 Carbon monoxide 50 ppm Bag - Electro-  24.7-115.4
chemical Ppa
A $278 Chlordane 0.5 MCEF/Chromosorb Toluene Gc/EcD _-0.156-1.17
S S11 _—_Chloroacetaldehyde 3 ©) Silica gel 50% aq. methanol GC/ECD —-1.8-6.4
s $120 Chlorodiphenyl, 42% Cl 1 Glass fiber filter/ Isooctane GC/ECond = 0.51-2.7
Bubbler (isooctane)
A S211 _—_1-Chloro-1-nitropropane 100 Chromosorb 108 Ethyl acetate GC/FID 51-206
S $112 Chloroprene 90 Charcoal Carbon disulfide  GC/FID 44-174
A $203. Cobalt metal fume & dust 0.1 MCEF Aqua regia AA 0.031-0.22 (£)
0.040-0.26 (d)
S $354 Copper fume 0.1 MCEF HNO, AA 0.05-0.37
S $356 Crag herbicide a5 MCEF Water/methylene Color. 5-27
blue complex
S$ S279 -2,4-D 10 Glass fiber filter Methanol HPLC -20.3
S $280 Demeton 0.1 MCEF/XAD-2 Toluene GC/FPD-P 0.06-0.33
S$ $111__Dichlorodifluoromethane 4950 Charcoal Methylene chloride GC/FID  2940-10,500
A $109 Dichloromonof luoromethane 4200 Charcoal Carbon disulfide © GC/FID 1730-7600
S S108 —_—Dichlorotetrafluoroethane 7000 Charcoal Methylene chloride GC/FID  3500-14,100
S $140 _Diethylaminoethanol 50 Silica gel Acidify with HCL, GC/FID 25-113

desorb w/MeOH-H,0

basify w/Na0u-MéoH


There is a definite need for improvement in methods that require cumbersome sam-
pling equipment such as gas sampling bags, bubblers, or impingers containing
liquid absorbing solutions. Passive or active sorbents should be developed and
tested to replace liquid absorbing reagents. A reliable integrated gas sampler
should be developed to replace the present bag sampling technique. The methods
should be changed or upgraded with the arrival of new innovative sampling method-
ology. For example, many methods based upon sorbent tube collection may be
adapted to the passive monitor or badge concept of sampling. In the latter
case, the sorbent is contained in a badge that is attached to the worker near
the breathing zone. The sample is collected by diffusion through a membrane to
the sorbent, thus eliminating the personal sampling pump. Of course, this con-
cept must be thoroughly investigated and results demonstrated to be equivalent
to those obtained from conventional personal sampling methods.

The source of storage stability problems or poor recoveries from some sorbents
could not be easily explained in some cases. These occurrences reflect the
need for further study of the composition of the sorbents, the effectiveness of
cleaning procedures, and the chemical effect of impurities.

An effort was made in this program to develop methods that could be applied to
classes of compounds, rather than single substances. Further work in this area
would result in more practical and useful methods. This would also include
developing methods that are suitable for a particular industry. For example,

if workers were being exposed to a number of solvents in a single industry, the
sampling and analytical method should be capable of determining all the solvents.

A very important resource in determining the usefulness of a newly developed
method is feedback from users. This information is often not voiced or received
so that others may benefit from it. In the course of upgrading present methods
or developing new methods, input from users would be very valuable. The NIOSH
Manual of Analytical Methods would be an appropriate place to list the pertinent
NIOSH office, address, phone number, and contacts, where the industrial hygienst
or chemist can obtain information or give suggestions. A number of self-addressed
postcards attached to the manual may encourage more feedback.

The information contained in this report is the culmination of 3-1/2 years of
intensive work. The basic goal of this effort was to develop and validate methods
which ultimately benefit workers exposed to toxic substances. Although time and
funds have limited the exploration of many aspects of sampling and analysis, the
objectives of this study have been met. But much work remains to be performed

in the development and continual updating of methods, development of new instru-
mentation, extending the limits of detection, and investigation of all aspects

of worker protection.

38


fiber, and recently, polytetrafluoroethylene (PTFE). Any high-efficiency fil-

ter usually functions well for collection purposes; therefore, selection was
usually based on the final analytical requirements. However, in this program,
poor recoveries were observed for some substances (such as thiram) when glass
fiber filters were used, and the filter medium was found to be at fault. The

PTFE filters, being inert, were very useful for collecting reactive substances.

In the analytical method for sodium fluoroacetate by ion chromatography, surfac-
tants used as wetting agents on some filters were found to significantly interfere.

MCE filters were generally used when the sample was extracted, digested, or
otherwise treated to create a solution for final analysis. PTFE filters were
not the first choice because of their expense, but they were useful for reactive
substances and in cases where the analytical procedure required a solvent that
was not compatible with other filter media. For example, when HPLC was the pre-
ferred analytical technique, the choice of sampling device, especially the fil-
ter, was dependent upon the solvents used in HPLC analysis. The material was
usually extracted from the filters in the same organic solvent that was used as
the HPLC eluent. MCE filters dissolve in solvents such as methanol and acetoni-
trile, which are commonly used HPLC eluents. PTFE filters, being very inert,
were widely used here.

Generally, any of these filters satisfied the requirements for collection of
most of the particulates to be analyzed. However, certain analytes and their
associated analytical methods gave better results with alternative filters.

The filter cassette was also tested as part of the total sampling device. Some
substances were partially collected on the cassette and the substance had to be
rinsed from the cassette with solvent to avoid losses.

Sorbents

The procedure most commonly used for sampling vapors, especially organic vapors,
is a glass tube containing two sections of activated charcoal. This tube con-
tains a 100-mg front section for sample collection and a 50-mg backup section

for indication, by subsequent analysis, of breakthrough of the front section.

Both petroleum-based and coconut-based charcoal have been used in these tubes,
along with some other types. For some cases where charcoal was inadequate, silica
gel was used as, for example, in sampling amines.

In this program, many of the organic vapors studied were not amenable to col-
lection on charcoal for reasons such as reactivity with the charcoal, irrevers-
ible adsorption, or incomplete desorption. Silica gel has also been used exten-
sively in the past; however, for most substances, it has severely reduced col-
lection efficiency under humid conditions. The use of porous polymers as sor-
bents has been studied considerably in the validation tests. Methods have been
developed in these studies using the following sorbents:

Charcoal (petroleum- or coconut-based)
Silica gel

Tenax-GC

XAD-2

Chromosorbs 102, 103, 104, 106, 108
Porapak Q

Carbosieve B.


cv, coefficient of variation of total procedure which consists of the
composite variations in sampling and analysis, desorption efficiency,
and pump error.

— _ = 2 2, —.2
Cv, = ¥ Gi, + Ose)” + Gi)
or:
= _ —.2 —, 2 = 2
WV, = ¥@q, - (CV,) “ + 1.1667 (CV,)” + (0.05)
or
CV. Cy 2 ae 2 1m "
WV, = (CV,)” + 0.1667 CV,” + (0.05)" (see "Note" page B-5)

Grubb's test for rejction of an observation is applied in order to determine if
one of the observations should be rejected as being an outlier. The following
equation was used for the test:

By = 22 or (2)

where:

x = observation being tested (most distant from the mean)
xX = mean of n observations

s = standard deviation based on n - 1 degress of freedom

' '
For any six observations, a value can be rejected if B, 21.944. The B, limit
is based on a 1% significance level (i.e., a By' value calculated from Ene data
can be expected to exceed 1.944 only 1% of the time if the observation is a
legitimate one conforming to the underlying theory).

Bartlett's test for homogeneity of CVs is applied in order to test the feasi-
bility of "pooling the coefficients of variation" for any set of 18 generated
samples (i.e., 6 at each of the 0.5, 1, and 2 times OSHA standard level). The
following equation for chi-squared, with two degrees of freedom, was used:

= © = fl
f In (CV,)° - De, In (CV,,
2) jar i ah

chi-squared =

B-6


may also depend on sample loading. For example, in a short sample time, vapor
may be efficiently collected on a filter, but longer term sampling may reveal
saturation of the filter with vapor and eventual passage of the vapor into a
backup bubbler or sorbent tube.

For substances that exist as both a vapor and a particulate, both a filter and
sorbent tube or backup bubbler or impinger were used. Desorption efficiencies
were performed for each part of the sampling train and, possibly, for the sam-
pling devices combined. The vapor/particulate ratio was determined at a mini-
mum of one level.

Other Sampling Methods

At present the most acceptable procedure for sampling some stable gaseous mate-
rials is collection in bags. These gases are usually too volatile to be collec-
ted efficiently with a sorbent tube. Methods were developed and validated for
carbon monoxide, carbon dioxide, sulfur hexafluoride, sulfuryl fluoride, methyl
acetylene, and methyl acetylene/propadiene mixture using this technique.

GENERAL METHODS

A concerted effort was made to develop methods that could be applied to several
substances within the same compound class. This approach was reasonably success-
ful for pesticides, aldehydes, and organolead compounds. The outcome was satis-—
factory for substances with similar properties; however, special treatment was
necessary for single compounds within a class that were unusually more reactive
or volatile.

Pesticides

The development of a universal filter/sorbent sampling train for pesticides was
an objective of high priority in this program. Where possible, a 37-mm MCE fil-
ter followed by a sorbent tube containing 20/40 mesh Chromosorb 102 was used.
The filter and sorbent were combined and the pesticide was desorbed with toluene.
The resulting solution was analyzed by GC with an appropriate detector. This
method was validated for endrin, chlordane, and ronnel. Methods were also vali-
dated for phosdrin, TEPP, and heptachlor using a Chromosorb 102 sorbent tube
only. Chromosorb 102 was not a satisfactory sorbent for some substances. A
method was validated for demeton using an MCE filter/XAD-2 sampling train with
the same analytical methodology described above,

When HPLC was the preferred analytical method for a pesticide, the choice of
sampling device and sample treatment procedure was affected by the HPLC eluent.
PTFE or glass fiber filters were used in methods were solvents such as methanol
and acetonitrile were the appropriate extraction solvents or when the MCE filter
was not satisfactory. Validated methods include ANTU, 2,4-D, paraquat, pyre-
thrum, rotenone, 2,4,5-T, thiram, and warfarin.

Aldehydes
The aldehydes studied in this program include acetaldehyde, chloroacetaldehyde,
formaldehyde, furfural, crotonaldehyde, and acrolein. Because of the insta—

bility of the aldehydes, they are best collected by derivatizing in the field

10


CONTENTS

Disclaimer ...
Abstract
Acknowledgments
Introduction ...
Scope of Work
Implementation .
Protocol ..
Analytical Methods .
Sampling Methods .

Filters ...
Sorbents .....
Impinger/Bubbler

Particulate/Vapor Sampling Methods
Other Sampling Methods
General Methods
Pesticides
Aldehydes ...
Organoleads .
Other .....
Laboratory Tests ......
Calibration Curve
Analytical Recovery Tests .
Determination of Breakthrough Volume or
Collection Efficiency .
Breakthrough Volume . .
Collection Efficiency ......
Generation and Collection of Samples .
Independent Method of Determining Test Air

Concentration ....... eee e cece cece ec csoes
Storage Stability of Generated Samples ..
Method Validation ...... .

Generation of Test Atmospheres
General
Methodology ......

Aerosols ......

Gases and Vapors .

Main Dilution/Sampling System .

SRI International . wae eee

Arthur D. Little, Inc. Gas and Vapor System ..

Arthur D. Little, Inc. Aerosol System ...... 606

REPOCLANg eel eile eisielayeraiel er sees
Routine Project Communications
Method Reports ....... oe

plete

be
Be

COCOYN RR ENH fd


Air Supply--Air from the house compressed air system is treated by successive
passage through a cotton filter, a silica gel bed, and a high efficiency glass
fiber filter, and a membrane filter. These collections remove, respectively,
oil and water droplets, water vapor, and fine particles.

The treated air then passes to two parallel air supply manifolds, each of which
is equipped with valves for controlled air flow to various parts of the genera-
tion/dilution system. One of the manifolds supplies air to the dilution system.
The second supplies air to the aerosol generator, either directly or through
calibrated rotameters as may be required by the particular generator being used.
Pressure in each manifold is maintained at a fixed level by Moore Nullmatic
Pressure regulators and is measured with bourdon gauges (6-inch Ashcroft test
gauges).

31


oxides and which do not produce objectionable side products, are commonly used
precursors. In this program, fumes of iron oxide, vanadium oxide, and copper
oxide were generated using this method.

Dust dispersion--Aerosols of mineral particles and a few other materials may be
prepared by dust dispersal techniques. A number of dust dispersal devices have
been constructed. A commonly used one is the Wright Dust Feeder. In this device
the dust is compressed into a cylindrical compact, which is placed in an electri-
cally driven mechanism that rotates it and drives it against a fixed knife blade
at a fixed rate. Material is scraped off the compact by the blade, entrained

in an air stream, and blown against a metal plate to break up particle aggregates.

For the dust dispersal method to be used, it must be possible to obtain the
material of intent as a finely divided powder. In addition, for the Wright Dust
Feeder to be used, it must be possible to prepare a dispersable compact of the
powder. Soft materials that compress into a solid compact in which the indivi-
dual particles are merged obviously cannot be dispersed by this method.

The concentration of the dust produced by the Wright mechanism is varied by vary-
ing the rate of advance of the dust compact. Particle size, in principle, at
least, is the same as the size of the particles in the initial powder; however,
in practice complete breaking up of aggregates may not occur. This method was
used to generate dusts of warfarin, zinc oxide, rotenone, and tantalum.

Gases and Vapors--
Test atmospheres of gases and vapors are generally prepared dynamically by the
following methods:

Dilution

Syringe injection
Vaporization
Permeation
Chemical reaction.

Dilution--For gases, the simplest method of introduction into the system is
dilution. A cylinder of the compressed gas is fitted with a metering apparatus
(regulator and/or critical flow orifice) and the effluent stream injected

directly into the dilution system. The flow rate of the analyte can be cali-
brated and the concentration of each test atmosphere can be calculated with the
known dilution air flows. Most nonreactive gases were generated by this technique.

Syringe Injection--Injection of a volatile liquid at a known rate into an air
stream of known flow rate is a convenient method for producing vapor mixtures
of known composition. Syringe drives may be used to inject liquids or gases at
constant rates as low as a few microliters per minute. This method may be used
to prepare mixtures of nonreactive compounds, with concentrations of parts per
million to the fractional percentage level. Since the rate of delivery of the
syringe drive may be accurately determined by weighing the amount of liquid
delivery over a known period of time and from measuring the dilution air flow
rate, very good accuracy may be obtained by this method. The syringe injection
technique has been used for many vapors in this program.

19


DISCLAIMER

The contents of this report are reproduced herein
as received from the contractor.

The opinions, findings and conclusions expressed
herein are not necessarily those of the National
Institute for Occupational Safety and Health, nor
does mention of company names or products consti-
tute endorsement by the National Institute for
Occupational Safety and Health.

NIOSH Project Officer: Laurence J. Doemeny
Alternate Project Officer: David G. Taylor

Project Director: Dale M. Coulson
SRI International Task Leaders:
Ellen C. Gunderson
C. Clarine Anderson
Arthur D. Little, Inc. Task Leaders:
Philip L. Levins

Richard H. Smith
Alegria B. Caragay

DHHS (NIOSH) Publication No. 80-133

di


Table A-1 (concluded)
Compound OSHA standard Analytical Range
Code No. Analyte Kag/eu'm) Collection medium Sample treatment * method __(ng/cu m)
s $303 _2,4,5-T 10 Glass fiber filter Methanol HPLC 4.9-21.4
A $201 ‘Tantalum 5 MCEF HNO, perchloric 2.5-10.0
acid and HF
spectro.
A $383. -‘Tetraethyl lead 0.075 XAD-2 Pentane Gc/PID _0.045-0.20
A $384 ‘Tetramethyl lead 0.07 XAD-2 Pentane cc/PID _-0.040-0.18
Ss $256 Thiram 5 PIFE filter Acetonitrile HPLC 3.0-12.2
A $391 Vanadium, V,0, dust 0.5 MCEF Naow AA/HGA —0.24-0.90
A $388 «Vanadium fume 0.1 (Cc) -MCEF NaoH flameless 0.060-0.29
AA/HGA
A $316 Zinc oxide fume 5 Pvc filter - X-ray 2.4-9.9
diffraction
Proposed (Class £) Methods
‘A P&CAM 304 o-Chrorobenzylidene
(S154) malononitrile (OCBM) 0.4 PIPE filter/ 20% methylene HPLC 0.147-0.82
Tenax GC chloride in hexane
S$ P&CAM 291 alpha-Chloroacetophenone 0.3 Tenax GC Thermal desorption GC/FID  0.18-0.62
(89)
S  P&CAM 285 Crotonaldehyde 6 Bubbler - Polar. 2.9-23.4
(s177) (hydroxylamine)
S  P&CAM 294 Cyclopentadiene 200 Chromosorb 104 Ethyl acetate cc/FID 76-380
$83) coated with
maleic anhydride
A P&CAM 297 Dibutyl phosphate 5 PIFE filter Acetonitrile, Gc/FPD-P 2.3-10.0
(8390) trimethylsilyl
reagent
A P&CAM 295 Dichlorvos (DDVP) 1 XAD-2 Toluene GC/FPD-P 0.38-1.71
(8282)
S  P&CAM 302 Maleic anhydride il Bubbler (H,0) = HPLC 0.50-2.14
(8180)
‘A P&CAM 315 TEPP 0.05 Chromosorb 102 Toluene GC/FPD-P 0.025-0.124
(8305)
A P6&CAM 313 Warfarin 0.1 PIFE filter Methanol HPLC 0.054-0.24
(8307)
Codes for Analytical Methods
AA = Atomic absorption spectrometry Gc/FPD-s = "/flame photometric detector-
sulfur mode
AA/HGA = "/high-temperature graphite analyzer
cc/PID = "/photoionization detector
Color = Colorimetric spectroscopy
cc/tcp = "/thermal conductivity detector
GC/AFID = Gas chromatography/alkali flame
donization detector HPLC = High-performance liquid chromatography
Gc/ecD = "“/electron capture detector Ic/ECond = Ion chromatography/electrolytic
conductivity detector
Gc/ECond = "/electrolytic conductivity detector
ISE = TIon-specific electrode
Gc/FID = "/flame ionization detector
Polar. = Polarography
Gc/FPD-P = "/flame photometric detector-

phosphorous mode

otherwise noted, samples are desorbed/extracted in the solvent indicated.

A-5


These branches are designated as A, B, and C. The dilution and sampling branches
A and C are identical and each is equipped with a sampling manifold with six sam-
ple ports. The dilution and sampling branch B, on the other hand, is equipped
with a sampling manifold with fourteen sample ports. Figure 6 and 7 show these
dilution and sampling branches in more detail.

Aerosol dilution ratios in the system are fixed by critical flow orifices.
Usually an aerosol with a concentration twice the OSHA standard is prepared in
the main line, and this aerosol sampled without dilution in one dilution/sampling
section and diluted twofold and fourfold in the other two sections. Other dilu-
tion modes may be accommodated simply by changing the critical orifices.

Aerosol dilution occurs in the Teflon venturi-shaped inserts shown in Figures

6 and 7. Dilution air is injected radially into the venturi throat. The quan-
tity of dilution air introduced is fixed by a critical orifice which is con-
nected to one of the constant pressure air manifolds, as described in the section
on air supply below.

Isokinetic sampling probes, six for branches A and C, and fourteen for branch
B, are located approximatey 30 centimeters downstream of each diluter. The
probes convey aerosol to sample collectors (filter cassettes) mounted radially
around the outside of the sampling section. There is a luer fitting on each
sample port to mate with the filter cassette. Sample flow rate is fixed at
1.5 L/min by critical orifices (sapphire orifices supplied by Richard H. Bird
and Co., Waltham, MA) mounted on the sample manifold (Figure 5).

As is indicated in Figure 5, a critical orifice is located downstream from the
sample probes in each dilution/sampling branch. This orifice is protected from
contamination by a Filterite high efficiency filter. For the dilution/sampling
branches A and C, there are seven outwardly flowing streams in each branch--one
stream is that which flows through the orifice mentioned above (flow rate Qp)
and the other six are the sample streams (total flow rate Qg) for the dilution/
sampling branch B, the flowing streams consist of one which flows through a criti-
cal orifice downstream from the sample probes (flow rate Q;) and fourteen from
the sample streams (total flow rate Qg). There are two inflowing streams—-the
dilution air stream (flow rate QQ) and the aerosol stream entering from the main
line (flow rate Q,). The dilution ratio, R, in each branch is given by the
correlation:

ao he
%q + %
or, since Qp + Qs = %M + W (with the assumption of uniform pressure and tempera-
ture in the system).
Qn * Bs = %

Qp s Qs

The flow rates Qp, Qg, and Qp are controlled by the action of critical orifices;
consequently the dilution ratios are fixed solely to flow through the critical
orifices.

27


Techniques in sample collection and handling to be noted include:

e Active sorbent methods--acid coated silica gel for
ammonia and some amines, maleic anhydride coated Chromo-
sorb 104 for cyclopentadiene, silver-coated Chromosorb P
for mercury, triethanolamine-coated molecular sieve for
nitrogen dioxide, mercuric cyanide-coated silica gel for
phosphine, and mercuric chloride-coated silica gel for
stibine.

e Girard T reagent for collection of aldehydes.
e Solid sorbents used extensively, 49 methods developed

e Thermal desorption apparatus designed and fabricated in
methods for 2-aminopyridine and a-chloroacetophenone.

Some discussion is in order regarding the usage of the methods by other labora-
tories, how it relates to certain aspects of the experimental protocol used in
this study, and possible deficiencies that may arise in special situations. It
should be emphasized that this does not pertain to a majority of the methods,
but rather points out some areas of which users should be aware.

First, this study has been entirely a laboratory validation effort and the effects
of potential interfering materials that one may encounter under field conditions
have not been thoroughly studied. Within the scope of the project, known inter-
ferences were evaluated, but they could not be tested in detail. Obvious samples
of situations that may be encountered are, for instance, deactivation of sorbents
by co-pollutants or reaction of the analyte with other materials on the col-
lection medium. Considerable modification of GC conditions may be required for
the analysis of field samples, especially when determination is attempted for a
very toxic substance in the presence of relatively high concentrations of several
other compounds.

The methods were tested over an atmospheric concentration range of approximately
0.5 to 2 times the present OSHA environmental limit. To extend the range lower
or higher, one must proceed carefully and perform tests accordingly. Reduced
analytical recoveries, limited detection capabilities of analytical instru-
mentation, and poor precision are major obstacles to be considered when trying
to extend the range lower. Analytical recoveries of less than 90% should not

be considered acceptable for most substances, since complications could result
in determination of the actual field sample concentration. Breakthrough capa-
city of a sorbent is a major factor when extending the upper limits of the range.

The methods used for determining desorption efficiency (DE) or analytical method
recovery (AMR) have often been criticized as inappropriate, since the application
of an analyte in solution does not simulate collection from air. In those cases
where an accurate independent determination of the test airborne concentration
was made during the validation study, the use of an incorrect DE or AMR would
have resulted in poor agreement of the "taken" and "found" concentrations, and

a remedy sought. When this comparison was not possible, an inappropriate recovery
may have occurred. Since users of the method must generally rely on the DE or
AMR determined by their own spiking experiments, we decided in early studies

36


(a4

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=r ne aese eatunaron | | Saru'neareD nner Sinaron our prcoriey eR
cowtmoc VaLvE cenenaton TH CONST inter oatenaton wate CVCLONE FEEDER recon vata CYCLONE va
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VAPOR GENERATION EQUIPMENT HOUSE COMPRESSED AIR ‘SUPPLY
Oncamermoncane AEROSOL

GENERATION EQUIPMENT

FIGURE 2. SRI GENERATION/DILUTION/SAMPLING SYSTEM



easily applied by experienced technicians with technical school or some college
experience. When such methods were not available, more sophisticated methods
were investigated.

Analytical methods were chosen on the basis of selectivity and sensitivity. The
method chosen influenced the choice of the sampling system and the solvents used
in the analysis. Solvents and sampling media were selected for compatibility
with the specific detector or analytical system rather than vice versa. In gen-
eral, this policy allowed lower levels of detection. In selecting analytical
methods, the effects of known interferences were also considered. For example,
in gas chromatography, columns were chosen to optimize resolution from these
interferences.

The majority of analytical methods developed in the validation studies utilized
gas chromatography (GC) and high-performance liquid chromatography (HPLC). Gas
chromatographic analysis was the predominent analytical method of choice for
volatile organic compounds. Since many of the substances investigated were vola-
tile organic compounds, GC coupled with selective detectors provided very sensi-
tive and selective analytical methods. Detectors used in this program included
thermal conductivity, flame ionization, electron capture, electrolytic conduc-
tivity, flame photometric, alkali flame ionization, and photoionization. Com-
monly used GC packings were used. Glass GC columns were necessary for many sub-
stances. In most cases, samples of the analyte in a solvent were injected into
the GC by syringe, either by hand or automatic injector. A gas sampling loop was
used to inject samples collected in bags. A specially designed apparatus was
fabricated to introduce samples into the GC from a sorbent tube by thermal
desorption. .

HPLC with UV absorption detection was frequently used in this program. This
method was suitable for less volatile organic substances that were thermally
unstable, had high UV absorptivity, or were particularly suited to liquid chro-
matography. Separation modes used included absorption (normal phase), partition
in normal and reverse phases, ion exchange, and paired-ion chromatography.

Ion chromatography (IC) coupled with conductimetric detection provided an
efficient and sensitivie method of analyzing specific organic or inorganic ionic
species. IC methods were developed and validated for formic acid, sodium
fluoroacetate, ammonium sulfamate, and methylamine.

Atomic absorption (AA) spectroscopy was the method of choice for most metals and
metallic compounds. Several different excitation sources were used in addition
to standard flame techniques, including the electrodeless discharge lamp and
graphite furnace. A de plasma emission spectrometer was used in the analysis of
hafnium, tantalum and silver. For these compounds, the concentration levels of
interest were too low for conventional AA analysis to be of sufficient precision
and accuracy.

Colorimetric methods were developed only when reproducibility and selectivity
of the method represented an improvement over other methods. This was the case
for stibine and phosphorous pentachloride. In the case of phosphine, a stable
derivative was formed that was particularly suited to colorimetry.


Table A-2 Failure Reports

Analyte

OSHA Standard

Code Compound No.
s s21
s $157
A $277
rN $230
A $231
s $322
A $212
A $207
s $127
A $34
A $136
s S145
s $362
s $363
s $325
s $364
s $239
A $252
s $373
A $221
A si71
s S27.
A $159
A s14
s $270
A $304
A $184
s $346
s $226

Acrolein
Acrylamide

Azinphos, methyl

Boron trifluoride
Bromine

Chlorine
Chloropicrin

Dibrom

1,3-Dichloro-5, 5- dimethylhydantoin
Dimethylphthalate
Ethanolamine
Ethylenediamine

Ethyl mercaptan

Ferbam

Fluorides in dust
Fluorine

Iodine

Methyl isocyanate

Methyl mercaptan
1-Nitropropane

Oxalic acid
Perchloromethyl mercaptan
p-Phenylenediamine

Pival

Sulfur monochloride

TEDP

Tin, organic compounds
2,4-Toluenediisocyanate

Trinitrotoluene

(mg/cu m)
0.25
0.3

0.1

3 (Ceiling)


estimate is not precise enough to keep its upper confidence limit below the

target value. Such decision errors, referred to as "type-1 errors," will occur
randomly but with a controlled frequency of less than 5% of cases. The 5% prob-
ability of type-l error is by definition the complement of the confidence level.

As an example, consider the Wr which is a pooled value determined from three
groups of six samples. The CV would have to be less than 0.105 in order for us
to be 95% confident that the true CVp <0.128 (i.e., in order for us to be 95%
confident that future errors by the same method would not exceed +25% more than
5% of the time). The critical value of CVy is 0.105 at the a = 0.05 type-1
error level. Thus, for an unbiased method, the largest laboratory-determined
CVp should not exceed 0.105.

To be reasonably sure that a test method meets the NIOSH accuracy standard, we
have adopted the following decision rule: if the estimate (CVy) is below 0.105,
the 95% upper confidence limit on CVy would be below 12.8% and the method would
be found satisfactory. This decision rule is based on assumptions that errors
are normally distributed and the method is unbiased. Figure B-l provides adjust-
ments to the critical values of CV; when a method is biased. The dotted curve
gives critical values of CV7 as a function of bias for a statistical signifi-
cance test performed at the 5% type-l error level (i.e., 95% confidence level).

It is important to note that the critical values of CVp for Figure B-1 were com-—
puted under the assumption that the bias is a known quantity. This was necessary
because the protocol contains no standard statistical experimental design for
determination of bias by means of an independent method. However, the bias was
estimated as the difference between the mean of the test results and the true
value (determined from the independent method) divided by the true value. In cases
where confidence limits can be calculated for the bias, the critical CV7 should
be read from the dotted curve at a position corresponding to the 95% upper confi-
dence limit for the bias. This is a conservative procedure, but better critical
values could only be determined if the standard error of the bias were known.

The caluclated points through which the curves of Figure B-l were drawn using a
French curve are given below:

Bias Target cv, Critical vy
Ce) —@)__- —
0 12.8 TOR
2o8} 1275 103)
5.0 11.8 9.8
10.0 9.1 7.9
15.0 6.1 5.8
16.8 5.0 5.0
20.0 3.0 (Unattainable)
25.0 10) (Unattainable)

Since CVp, the coefficient of variation of pump error, is assumed to be 5%, any
method with a bias above 16.8% could not meet the accuracy standard (no matter

B-2


The Tenax-GC, XAD, Chromosorb, and Porapak materials are porous polymers that
have surface areas ranging from about 35 to 800 m/g. Tenax-GC is a polyphenyl
ether, while most of the Chromosorbs, XADs, and Porapaks are cross-linked poly-
styrenes. Carbosieve is a high purity synthetic carbon. Sorbent tubes based on
these types of media represented the most attractive means of collecting vapors
and gases. The sorbent tube is least obtrusive to wear, stores well, and ships
reliably. The handling procedures for such tubes are simple and efficient.

In choosing a sorbent for a particular compound, we tried to standardize upon

one type of sorbent. However, it was found in early work that significant dif-
ferences in analyte recovery, capacity, and storage stability can be obtained

with different sorbents. Batch-to-batch variation in the same sorbent was also
observed. To overcome this, cleanup procedures were established to reduce the
effects of residual solvents, unreacted monomers, or other impurities in the
porous polymer. The mesh size of the sorbent was a factor in determining the
physical dimensions of the sorbent tube. Lower mesh sizes, in the range of 20/50,
were desirable since they produced less resistance to air flow. Most personal
sampling pumps do not have sufficient capacity to draw more than 1 inch of mercury.

All the sorbents described above are intended to trap analytes by a process of
physical adsorption. An alternative set of sampling procedures involves "active"
chemisorption, in which the analytes are not only removed from the gas stream
being sampled but altered in structure. The advantages of the active type of
method are that sorption is frequently more efficient and more specific for the
analyte of interest. In addition, the analyte may be converted into a more
stable species during the sampling procedure.

Active sorbents developed included Chromosorb 104 coated with maleic anhydride
to collect cyclopentadiene, and mercuric cyanide-treated silica gel for collec-
tion of phosphine. A triethanolamine-coated molecular sieve was used to collect
nitrogen dioxide.

Impinger/Bubbler

Midget bubblers and impingers, filled with either solvent or reactant solutions,
were used in this program; however, because of their inconvenience in industrial
hygiene applications, these samplers were used only when solid sorbents were
ruled out. Since the solutions must be shipped from the field to the labora-
tory, the choice of solvent was limited to those having a flashpoint at or above
60°C (140°F).

Particulate/Vapor Sampling Methods

The simultaneous collection of vapor and particulate is a difficult problem in
personal sampling. The use of a filter/bubbler combination is awkward, and
selection of the bubbler solvent is often limited by shipping regulations. Al-
though some vapors may be collected on filters, this was not found to be quanti-
tative in this program. The problem of storage of a volatile substance on a
filter must also be considered.

As discussed earlier, in many instances, it is necessary to generate test atmo-

spheres to determine the physical state of a compound and the collection effi-
ciency of a filter and/or sorbent. The estimation of the vapor/particulate ratio

9