EPA/SAB/78/001
  REPORT OF THE AD HOC STUDY GROUP ON



    PENTACHLOROPHENOL CONTAMINANTS
          DECEMBER 29,  1978
ENVIRONMENTAL HEALTH ADVISORY COMMITTEE



        SCIENCE ADVISORY BOARD



 U,S,  ENVIRONMENTAL PROTECTION AGENCY



       WASHINGTON,  D,C,   20460

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                              . EPA/SAB/78/001
REPORT OF THE AD HOC STUDY GROUP ON
 PENTACHLOROPHENOL CONTAMINANTS
         December 29, 1978
Environmental Health Advisory Committee
       Science Advisory Board
U.S. Environmental Protection Agency
     Washington, D.C. 20460

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                         EPA NOTICE
     This report has been written as part of the activities
of the Environmental Health Committee of the Science
Advisory Board, a public advisory group providing
extramural scientific information to the Administrator and
other officials of the Environmental Protection Agency. The
Board is structured to provide a balanced expert assessment
of the scientific matters related to problems facing the
Agency.  This report has not been reviewed for approval by
the Agency, hence its contents do not necessarily represent
the views and policies of the Environmental Protection
Agency, nor does mention of trade names or commerical
products constitute endorsement or recommendation for use.

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                       TABLE  OF CONTENTS
1.     SUMMARY AND CONCLUSIONS
  1.1    Background	  1
  1. 2    Discussion	  2
  1.3    Conclusions	  6

2.     SUMMARY OF CHEMISTRY AND ENVIRONMENTAL
       BEHAVIOR OF PENTACHLOROPHENOL AND ITS
       CONTAMINANTS
  2.1    Pentachlorophenol and its Uses	  9
  2.2    Manufacture of Pentachlorophenol
         and its Contaminants	  9
  2.3    Properties of Pentachlorophenol
         and its Contaminants	 11
  2.4    Detection and Quantification of
         PCP and its Contaminants	 11
  2. 5    Environmental Chemistry	 11

3.     TOXICOLOGY
  3.1    Toxicity of PCP in Laboratory Animals.. 17
  3.2    Toxicology of Chlorinated Dioxins
         and Dibenzofurans	 30
  3.3    Human Poisonings Involving PCP	 36
  3.4    Human Poisonings Involving Exposure
         to Chlorinated Dibenzo-p-dioxins	 40

4.     MECHANISTIC RELATIONSHIPS IN THE
       TOXICITY OF COMPOUNDS STRUCTURALLY
       RELATED TO THE CHLORINATED DIBENZO-p-
       DIOXINS	 43
       APPENDICES

5.          A - Study Group Members and their
               Affiliations	 47
6.          B - Charge to Study Group	48
7.          C - Chemistry of Pentachlorophenol
               and its Contaminants	 49
8.          D - Testimony and Comments of
               Interested Parties Concerning
               Initial Draft Report at EHAC
               Review of April 3, 1978	 99
                            111

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                       List  of  Tables


2.1   Comparison of Composition of Commercial Grade
      and  Purified Grade Pentachlorophenol	  10

2.2   Chlorodioxin Isomer Distributions in Commer-
      cial Grade PCP (Dowicide 7) and PCP-Na
      Samples 	  10

2.3   Physical Properties of Pentachlorophenol	  12

2.4   Physical Properties of Various Chlorodioxins ....  13

2.5   Solubility of Several Chlorodioxins in Various
      Solvents 	  14

3.1   Pentachlorophenol-Compositions reported for
      Some Samples used in Toxicity Testing	  18

3.2   Biological Activity Purified vs.  Technical
      Samples of PCP	  22

3.3   Toxicology Data Summary	  32

3.4   Distribution of Human Episodes Resulting from
      Exposure to Pentachlorophenol by Medical
      Attention and Circumstances	  39

7.1   Comparison of Composition of Commercial Grade
      and Purified Grade Pentachlorophenol	  52

7.2   Chlorodioxins and Chlorofurans in Dow PCP
      Products	  53

7.3   Hexa- and Octachlorodioxins in Domestic PCPs	  53

7.4   GC-MS Analyses of Monsanto PCP	  54

7.5   Chlorodioxins in a Commercial PCP and PCP-Na
      Sampl e	  55

7.6   Hexachlorodioxin Isomers  in Three Dow Products...  55

7.7   Chlorodibenzofurans in Dow PCP Products	  56

7.8   Reactions in Chlorination of Trichlorophenol	  57

7.9   Dioxin Congeners in Commercial PCP	  58
                              IV

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                     List  of  Tables  (Cont.)



7.10  Physical Properties of Pentachlorophenol (PCP)...  60

7.11  Physical Properties of Various Chlorodioxins	  62

7.12  Solubility of Several Chlorodioxins in Various
      Solvents	 63

7.13  Properties of Chlorinated Dibenzofurans	64

7.14  Melting Points of Chlorodiphenyl Ethers	65

7.15  Chlorinated Dibenzofurans, GLC Retention Times
      Relative to 2,3,7,8-Tetrachlorodibenzo-p-dioxin... 66

7.16  Chlorinated Dibenzo-p-dioxins, GLC Retention Times
      Relative to 2,3,7,8-Tetrachlorodibenzo-p-dioxin... 67

7.17  Estimated Half-Lives of Several Chlorodioxins
      in Refluxing KOH Solution	 71

7.18  Chlorinated Dibenzodioxins and Dibenzofurans
      Isomers and Sources	 75

7.19  Dibenzo-p-dioxin (D): Approximate Activity of
      Congeners in Chick Embryo Assay for Induction
      of Aryl Hydrocarbon Hydroxylate	 77

7.20  Dibenzofurans (F): Approximate Activity in Chick
      Embryo Assay for Induction of  Aryl Hydrocarbon
      Hydroxylase	  78

7.21  Estimated Vapor Density and Rate of Evaporation
      of Chlorodioxins	  79

7.22  Estimated Vapor Density and Rate of Evaporation
      of Chlorinated Dibenzofurans	  79

7.23  Major Registered Uses of PCP	  86

7.24  Some Potential Sources of Occupation Exposure to
      PCP and PCP Impurities	  87

7.25  Some Potential Sources of Incidental Exposure
      to PCP and PCP Impurities	  87

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1.   SUMMARY and CONCLUSIONS

1.1   Background

     In the fall of 1970, the U.S. Department of Agri-
culture (USDA) expressed concern about the presence of
certain chlorodioxins in some "economic poisons."  In
January 1971, the USDA held a meeting with industry
officials to discuss the problems of these chlorodioxins in
pentachlorophenol (PCP).  At that time the hexa- and
heptachlorodibenzo-p-dioxins (dioxins) were identified as
the contaminants of major concern in PCP.  Since that time
the intensity and breadth of concern about the health
implications of polychlorinated dibenzo-p-dioxins have
increased.  This concern has no doubt been stimulated by
the development and widespread publication of knowledge of
the extremely high toxicity of 2,3,7,8-tetrachlorodibenzo-
p-dioxin (TCDD). Although TCDD is or has been a contaminant
of great concern in several well publicized cases, it
should be noted that TCDD has not been identified as a
contaminant of pentachlorophenol manufactured in the United
States. Frequent references to TCDD in subsequent
discussions are because it is the only polychlorinated
dibenzo-p-dioxin that has been the object of comprehensive
toxicologic research.  Several other polychlorinated
dibenzo-p-dioxins and related polychlorinated dibenzofurans
have now, however, been identified as contaminants of
commercial samples of pentachlorophenol.  A commercial
process has been developed and patented which enables
production of pentachlorophenol with greatly reduced
concentrations of these contaminants.  This development, as
well as the scheduled reregistration procedures required
under the amended Federal Insecticide, Fungicide,
Rodenticide Act (FIFRA), stimulated the EPA to give
extensive consideration to whether or not the
polychlorinated dibenzodioxins present in PCP have
contributed to increased health hazards or environmental
degradation associated with PCP use.

     The EPA requested that the Science Advisory Board
(SAB)  consider this issue.   The request was referred to the
Environmental Health Advisory Committee of the SAB.  On
January 12, 1977, the Chairman of the Environmental Health
Advisory Committee appointed an Ad Hoc Study Group on
Pentachlorophenol Contaminants and charged it to review and
report on available information about the chemistry and
toxicology of the chlorinated dibenzodioxins and

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dibenzofurans. Additionally, to the extent possible, the
study group was asked to comment on the potential hazard to
humans which could be attributed to registered uses of PCP
and the extent to which this hazard might be mitigated
by use of a commercial process which results in lower
levels of chlorinated dibenzodioxins and related
contaminants (see Charge to Study Group—Appendix B).

     Early in its deliberations the Study Group recognized
that the breadth of the charge, as well as the relative
paucity of information on the chemistry and toxicology of
polychlorinated dibenzo-p-dioxins and dibenzofurans/
precluded an early or comprehensive response.  By
consensus, the Study Group agreed to respond to the charge
by attempting to identify the areas of information needs
required to evaluate the problem of PCP contamination with
dioxins and related compounds.  The Study Group would
supply specific information when possible and would attempt
to identify the information gaps which limit conclusions
regarding both specific regulatory questions concerning PCP
and the broad issues of total environmental contamination
by chemically and toxicologically related halogenated
dioxin-like substances.

1.2   Discussion

     Pentachlorophenol is produced and used extensively.
Production in the U.S. is estimated at approximately 50
million pounds per year; the vast majority of which is used
as a wood preservative. However, there are other uses
including use as an herbicide, a fungicide, a bacteriocide,
a slimicide and as a preservative for leather.

     Numerous contaminants have been identified and
quantified in samples of pentachlorophenol from several
major commercial producers.  The quantity and proportions
of the contaminants differ somewhat from batch-to-batch of
the technical grade product and are discussed in more
detail in Appendix C.  The contaminants include
tetrachlorophenol (5-10%), trichlorophenol (1%),
chlorinated phenoxyphenols (about 5%) and polychlorinated
dibenzo-p-dioxins and dibenzofurans ranging in
concentration from thousands of ppm in the case of
octachlorodibenzo-p-dioxin to tens to hundreds of ppm for
the hexa- and heptachlorinated dibenzo-p-dioxins and for the
octa-, hepta- and hexachlorodibenzofurans.

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     While it is technically feasible to produce
commercially purified PCP that can meet reasonable
regulatory constraints relative to chlorinated dibenzo-p-
dioxins and dibenzofurans, the production of this more
purified product entails increased production costs and,
according to some industry representatives, results in a
product that may be more difficult to handle. A patented
commercial process exists which enables the production of
PCP which contains much lower concentrations of
contaminants reducing the hepta- and octachlorodibenzo-p-
dioxins to 10 to 20 ppm and most of the other
polychlorinated dibenzo-p-dioxin and dibenzofuran
concentrations to 1 or 2 ppm.  However, the production of
the purified product results in another serious problem of
how to safely handle and dispose of the concentrated
residual waste created in the removal of the contaminants.
The matter of disposal has been a subject of serious
consideration by a previous advisory committee and by
industry representatives. (See Appendix D.)  There is no
question that the handling, transport and disposal of any
residual toxic product from the purification process must
proceed under the strictest standards. Possible disposal
methods include a suitable licensed disposal site (none is
known according to Reichhold, Appendix D) and either land
or sea incineration. Presently, the Dow Chemical Company's
Midland, Michigan petrochemical complex uses incineration
to destroy the wastes associated with PCP purification.
(See letter of Robert Johnson to Ernst Linde, Appendix D.)

     With regard to the possibility of human exposure to
PCP and/or its contaminants, it is useful to consider
certain physico-chemical properties of PCP relative to its
contaminants.  The chlorinated dibenzo-p-dioxin and
dibenzofuran contaminants are less volatile and less water-
soluble than the un-ionized form of PCP and are, therefore,
less readily transported by vaporization and air transfer
or by surface water.  Furthermore, the dioxins tend to bind
strongly to soil and wood, which further limits their
transport.  On the other hand, the contaminants are
generally more persistent than PCP, as they are only slowly
biodegradable with half-lives in soil on the order of a
year or longer.  Although there are considerable data on
the environmental persistence of TCDD, for which
photodecomposition on surfaces and microbial metabolism are
major factors in its environmental degradation, data are
very sparse on the environmental persistence and transport
of the chlorinated dibenzo-p-dioxin and dibenzofuran
contaminants of pentachlorophenol.

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     A key problem to overcome in order to make an adequate
evaluation of the relative hazard of PCP and its
contaminants is the lack of ready availability of suitably
sensitive and specific analytical methods.  Although much
progress has been made in developing appropriate analytical
capability, routine analysis has been hampered by the
unavailability of suitable analytical standards for some of
the isomers.  In fact, the availability of appropriately
specific analytical methods may be the rate limiting factor
in assessing the. hazard of dioxins and related chemicals.
Thus, when there are several isomers with widely differing
toxicities, as is the case with hexachlorodibenzo-p-
dioxins, analyses of the isomers as a group only permit
assessment of hazard based upon the most toxic isomer. This
approach may, indeed, lead to overestimates of hazard, but,
in the absence of more definitive analyses of specific
toxic chemical species, it is necessary to treat
contamination data on a toxicologically worst-case basis.

     The toxicological information necessary to make the
evaluation of relative hazard of purified versus standard
commercial PCP is also deficient.  Pentachlorophenol is a
toxic chemical in its own right.  A set of signs and
symptoms characteristic of uncouplers of oxidative
phosphorylation has been described in several cases of
accidental or suicidal poisonings.  The chlorinated
dibenzo-p-dioxins and dibenzofurans, on the other hand,
have quite a different syndrome in acute poisoning.  This
syndrome is characterized by a delayed onset and involves
widespread degenerative changes in several organs, in
particular the liver, thymus, and skin.  There are limited
data on the acute toxicity (LD^Q) of the chlorinated
dibenzo-p-dioxin and dibenzofuran contaminants of PCP, but
there are virtually no data on the chronic toxicity of the
contaminants.  Although the acute toxicity of purified PCP
is generally less than that of contaminated technical
samples, there are insufficient data to permit such a
comparison for chronic toxicity.  Studies of acute toxicity
of technical PCP suggest that some of the effects, e.g.,
liver damage, are more consistent with a dioxin effect than
with purely a PCP effect.  Induction of aryl hydrocarbon
hydroxylase (AHH) activity appears to offer a means of
comparing the relative biological activity of poly-
chlorinated dibenzo-p-dioxins and dibenzofurans and cor-
relates quite well with acute toxicity measurements. How-
ever, a problem is that this test has not been validated
for assessing relative potential for chronic injury from
the contaminants. Recent reports of the induction of

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neoplasms by TCDD (Van Miller et al., 1977; Kociba, 1977)
raises the specter that the polychlorinated dibenzo-p-
dioxin contaminants of PCP may also have this potential.
At least some of these contaminants, e.g.,
octachlorodibenzo-p-dioxin, have been started in the
National Cancer Institute's (NCI) carcinogenesis screening
program, but no data have yet been made available from NCI
on PCP itself.  (See section 3.1.4 for discussion of
purified PCP.)  A paper dealing with long term studies of
TCDD and HCDD was recently presented at the New York
Academy of Sciences Science Week (Holmes et al., 1978).

     A recent incident of illness in a herd of cows housed
in a newly constructed barn in Michigan stimulated an
investigation into possible contamination of tissue by
residues of pentachlorophenol and its dioxin contaminants.
Both PCP and some of the polychlorinated dibenzodioxins
were found in tissues of these cows (Moore, 1977, see
section 3.2.3).  This finding of low, but detectable,
levels of chlorinated dibenzo-p-dioxins in tissues of these
animals is a matter of public health concern; however, the
biological significance of this finding is not presently
known.

     There have been reports of occupational exposure to
chlorinated dibenzo-p-dioxins resulting in adverse health
effects in man.  Usually chloracne has been the predominant
sign of toxicity, although signs and symptoms of systemic
poisoning (some of which are consistent with dioxin
poisoning in laboratory animals) have also been reported in
association with these industrial exposures.  There is
insufficient information concerning the identity and dosage
of dioxins involved to allow these observations in man to
be useful in a quantitative assessment of the relative
hazard of purified PCP versus commercial products
containing dioxin contaminants.  There are no data that
permit an estimate of the relative susceptibility of humans
to systemic effects of the dioxins and related contaminants
of PCP.  The widespread (though of relatively brief
duration) exposure of humans to TCDD in Seveso, Italy
during an industrial accident in 1976 may yet provide
information that will permit some estimates of human dose-
response relationships to that dioxin.  As yet, there is no
quantitative information which permits a comparison of the
toxicity of dioxin to humans versus other animals.

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1.3   Conclusions

     1.  Toxic polychlorinated dibenzo-p-dioxin and
dibenzofuran isomers are known to be present in commercial,
technical pentachlorophenol (PCP).  The most toxic dioxin
known, TCDD, has not, however, been found in PCP.

     2.  Analytical methods and preparation of standards for
analysis of the various isomers of the hexa-, hepta-, and
pentachlorinated dioxins have been developed.  The method-
ology and equipment required, however, have limited their
widespread use.

     3.  Among the chlorinated dioxins there are marked
differences in acute toxicity of the isomers; therefore
when analysis of a PCP sample is expressed in terms of
total isomers, such as hexachlorodibenzo-p-dioxins,
evaluation of potential hazard must be based upon the
most toxic of the hexachlorinated isomers.

     4.  The polychlorinated dibenzo-p-dioxin and
dibenzofuran contaminants are more stable and persistent,
but less mobile, in the environment than PCP.

     5.  There is evidence that the dibenzo-p-dioxin and
dibenzofuran isomers can migrate from PCP-treated wood into
animal tissues and products that are consumed by man.  The
toxicological impact of this exposure cannot be quantified
with present data and information,  but, conservatively, any
exposure by this route must be considered undesirable and
attempts should be made to prevent exposure.

     6.  Numerous cases of acute human poisonings with PCP
have occurred, and some occupational exposures to PCP have
resulted in chloracne and other signs suggestive of
dibenzo-p-dioxin or dibenzofuran poisoning.   The data and
information related to these reports are inadequate to
assess the toxic hazard of PCP and its contaminants to man.

     7.  The most probable opportunity for human exposure
to toxic quantities of PCP and its contaminants is in the
PCP production and utilization industries.  Any major
changes in the application of PCP must consider the
implication to this high risk occupational group.
Environmental exposures of humans are likely to be limited
and most probably would occur from direct contact with PCP-
treated wood, from exposures through ingestion of food
contaminated by residues, or from occupational exposure
from inhalation of off-gassing vapors from improperly
treated wood.

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     8.  Certain uses of PCP, e.g., application to wood
used in human or animal housing or to wood that may come in
contact with foods or feeds, increases the probability of
exposure to man.  Restrictions on such uses might be a
first step in reducing the likelihood of injury from PCP
and its contaminants.

     9.  There are insufficient quantitative data to rank
the relative contribution of PCP to the overall
environmental contamination with dibenzo-p-dioxins and
dibenzofurans. However, because of PCP's extensive use, it
may be a major source of chlorinated dioxins in the
environment.  As regards the dibenzofurans, PCP probably
represents a lesser source. However, the similar
toxicological effects produced by the polychlorinated
dibenzo-p-dioxins, dibenzofurans, and other related
compounds (chloroazobenzenes, chloroazoxybenzenes,
chlorinated napthalenes, and polyhalogenated biphenyls)
suggest the potential for additive hazard from the many
sources of these contaminants.  Quantitative data on the
total environmental contaminants, the fractional
contribution of the major sources of these contaminants,
and the toxicological response to mixtures of contaminants
are urgently needed.

    10.  Technology is now available which could markedly
reduce the levels of dibenzo-p-dioxin and dibenzofuran
contaminants in PCP.  It would seem prudent, therefore, to
control the contaminants to the extent possible by best
manufacturing practice. This might best be accomplished by
a phasing in of improved processing.  This phasing in of
the use of the more purified product must take into account
the economic impacts as well as the possible trade-offs of
occupational hazards related to residue handling, transport
and disposal.

     Addendum;  Coincident with the final review of this
report, an" article appeared in Science (Vol. 202, p.
1166-1167, December 15, 1978) suggesting that "Dioxins"
were produced in trace quantities during the combustion of
a wide variety of materials and could be expected to have
ubiquitous distribution in the environment.  A preliminary
review of some data that formed the basis of this report
indicated that the quantities produced in most combustion
activities would contribute extremely minute quantities or
no dioxins to the environment.  However, combustion of
highly chlorinated materials in improperly fueled
incinerators resulted in sufficient quantities of
chlorinated dibenzo-p-dioxins to warrant attention and
further investigation as to a possible source of
environmental contamination.

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1.4  References

Holmes, P.A., J.H. Rust, W.R. Richter, and A.M. Shefner
     (1978).  Long term effects of TCDD and HCDD in mice
     and rats.  In:  Abstracts of N.Y. Academy of Sciences,
     Science Week (June 21-30, 1978) on The Scientific
     Basis for the Public Control of Environmental Health
     Hazards.

Kociba, R.J., Dow Chemical (1977).  Letter and attachments
     to Thomas Holloway, EPA.  September 7, 1977.

Moore, J.A. (1977).  Memorandum to Director, NIEHS (March
     21, 1977).  Subject:  Studies on Possible
     Pentachlorophenol/Dibenzodioxin Intoxication Progress
     Report #2.

Van Miller, J.P., J.J. Lalich, and J.R. Allen  (1977).
     Increased incidence of neoplasms in rats exposed to
     low levels of 2,3,7,8- TCDD.  Chemosphere 6^ (9) :
     537-544.

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2.   SUMMARY of CHEMISTRY and ENVIRONMENTAL BEHAVIOR
     of  PENTACHLOROPHENOL and ITS  CONTAMINANTS

2.1   Pentachlorophenol and  its Uses

     Pentachlorophenol (PCP) is a compound of high and
diversified biological activity.  It has been shown to be
an effective contact poison against bacteria, fungi and
higher plants and is also toxic to animals.  PCP has been
registered for a wide variety of uses, including as a wood
preservative, an herbicide,  a slimicide, a preservative for
hardboard and paper, a leather preservative, an additive
in paints, and a treatment in greenhouses.  The principal
use of PCP, however, is in wood treatment as either the
free phenol dissolved in a petroleum carrier or as the
sodium salt in a water based dip treatment.  PCP has been
used for over 40 years in wood treatment.  The current
level of production and use in the United States is
probably in excess of 50 million pounds per year.  The
manufacturing capacity is estimated to be approximately 70
million pounds per year.

2.2   Manufacture of PCP and its Contaminants

     PCP in the United States is manufactured from phenol
by a catalytic chlorination process.  During chlorination,
the temperature must be maintained above the melting point
of the products formed; this, it is felt, contributes to
the side reaction that gives rise to contaminants.
Commercial technical PCP contains other chlorinated
phenols, among them the 2,3,4,6-tetra isomer, traces of
trichlorophenol, chlorinated dibenzo-p-dioxins, chlorinated
dibenzofurans, chlorophenoxy phenols, chlorodiphenyl
ethers,  chlorohydroxydiphenyl ethers, and traces of even
more complex reaction products of phenol. Most
chlorobenzodioxins are the by-products about which there
are the greatest concerns.  Analyses of PCP have revealed
that the principal chlorodioxin and chlorodibenzofuran
contaminants are those containing six to eight chlorines.
The highly toxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
has not been identified in any sample of PCP that has been
analyzed.  The compositions of a sample of commercial PCP
and of a sample of purified PCP are given in Table 2.1.  A
representative distribution of isomers is given in Table
2.2.

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                              TABLE 2.1

            Comparison of composition of commercial grade
             and purified grade Pentachlorophenol  (PCP)

                                 Analytical Results

Component                 Commercial3         Purified
(Dowicide 7) (Dowicide EC-7)
Pentachlorophenol
Tetrachlorophenol
Trichlorophenol
Chlorinated phenoxyphenols
88.4%
4.4%
0.1%
6.2%
Octachlorodioxins 2500 ppm
Heptachlorodioxins
Hexachlorodioxins
Octachlorodibenzof urans
Heptachlorodibenzof urans
He xachlorodibenzof urans
^Sample 9522 A
Technical grade PCP reduced
125 ppm
4 ppm
80 ppm
80 ppm
30 ppm
by distillation
89.8%
10.1%
0.1%
— __
15.0 ppm
6 . 5 ppm
1.0 ppm
1.0 ppm
1.8 ppm
1.0 ppm

                              TABLE 2.2

           Chlorodioxin isomer distributions in commercial
             grade PCP  (Dowicide 7) and PCP-Na  samples.
                          (Buser, 1975;1976)

                                      ppm  chlorodioxin in
Chlorodioxin                          PCP            PCP-Na

1,2,3,6,7,9-ClgD                       1             0.5

1,2,3,6,8,9-ClgD                       3             1.6

1,2,3,6,7,8-ClgD                       5             1.2

1,2,3,7,8,9-CLgD                       0             0.1

1,2,3,4,6,7,9-C17D                    63            16.0

1,2,3,4,6,7,8-C17D                   171            22.0

l,2,3,4,6,7,8,9-ClgD                 250           110.0
                          10

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2.3   Properties of PCP and its Contaminants

     The physical properties of a compound play an
important role in how the compound behaves under different
conditions.  These properties influence the mobility of a
compound in air or water, its ability to adsorb to
surfaces, and its disappearance due to some type of
degradation.  This behavior relates to the route and rate
of exposure by which a compound might be received by man or
other organisms.  For these reasons the properties of PCP
and its principal contaminants, dioxins and dibenzofurans,
so far as possible, were evaluated in this report.  (See
Tables 2.3-2.5.)  From these tables of physical properties
it is ascertained that PCP has a higher vapor pressure, a
higher water solubility, and a lower capacity for
adsorption than the dioxins or dibenzofurans. For these
reasons PCP is likely to be far more mobile than the
dioxins or the dibenzofurans.  The dioxins and
dibenzofurans would probably show an enhanced propensity
for adsorption and hence a low availability.

2.4   Detection and Quantification of PCP and its
      Contaminants

     There are a number of methods that may be used for
analyzing PCP;  these include colorimetry, spectro-
photometry, and gas chromatography (GC).  Gas
chromatography is probably the most sensitive and widely
used method. It is routinely applied for detection and
quantification of PCP down to the parts per billion range.
Analytical methods employing gas chromatography and mass
spectrometry have been devised for the chlorodibenzodioxins
and chlorodibenzofurans. The current state of the art for
TCDD provides a reliable analysis down to the low parts per
trillion range.  Gas chromatography alone is adequate only
for the higher concentrations.

2.5   Environmental Chemistry

     PCP has been found in a number of different
environmental samples such as house dust, air, water and
urine of presumably non-exposed humans.  Frequently the
appearance of PCP in non-biological samples can be
explained by the proximity of a source of PCP, but in the
case of the urine of presumably non-exposed humans the
explanation is more elusive.  It may be that
exposure to treated wood or the use of PCP as a
preservative in certain items affords human exposure, but
another possibility that cannot be ruled out is the
generation of pentachlorophenol in chlorination of water or
perhaps even the generation of PCP by natural processes.
                          11

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                              TABLE 2.3



            Physical  Properties  of  Pentachlorophenol  (PCP)
Molecular Weight



Melting Point



Boiling Point



Density



Vapor Pressure
Solubility H20



Solubility of sodium salt,



Partition Coefficient



Molar Refraction
266.35



191°C



3lO°C (decomposes)



1.987



1.6 X I0~4mm Hg (25°)



1.2 X 10~1mm Hg (100°C)



40 mm Hg (211°C)



20 ppm at 30°C



33g/100g



1 X 105'01



53.5
                          12

-------
                                          TABLE 2.4
                        Physical Properties of Various Chlorodioxins
                                                               Estimated


Chlorodioxin
2,
2,
2,
1,
1,
1,
, 1,
1,
1,
, i'
I *'
\
i,
7,-Cl2
3,7-Cl3
3,7,8,-Cl4
2,4,7,8-015
2,3,7,8-Cl5
2,4,6,7,9-Cig
2,3,6,8,9-Clc
D
2,3,6,7,8-Cl6
2,3,7,3,9-Cl6
2,3,4,6,?,9-Cl7
2,3,4,6,7,8-017
2,3,4,6,7,8,9-Clg

Mol.
253.
287.
321.
356.
356.
390.
390.
390.
390.
425.
425.
459.

Wt.
08
53
87
42
42
86
86
86
86
31
31
75
M.P.
C
__
162
306
206
241
240
--
. 285
243
__
__
331
"P
II
Value va/
0.
0.
0.
-
-
0.

-
-
0.
0.
0.
76
86
51
-
- •
94(di

-
-
9C
90
90
Vapor
(b)
Pressure
6.0 x
3.6 x
1.7 x
—
—
6.6 x
—
—
—
3.0 x
m»m»
1.8 x
ID'6
ID'6
10"6


ID'7



ID'7

ID'7
Molar
Refraction
-_
«• ••
71.
72.

'
81.


85.

90.


4
6


1


9

7
UV Max
(CHCI) nm
302
305
310
307
303
310
--
316
317
—
—
318
  (a)  Beroza, M. and M.C. Bowman,  "p" value determined  for dioxin  between  hexane  and  acetonitrile,
      J. Assoc. Of fie. Anal. Chem.  4_8:358-370  (1965).
  (b)  Vapor pressure estimated  from data of Woolson  (Woolson e_t al. f  1973).
'•  (c)  Estimated by summing atomic  refractions.
:  (d)  "p" value determined for  mixture of hexachlorodioxin isomers.

-------
                              TABLE 2.5

    Solubility of Several Chlorodioxins in Various Solvents3


                      Solubility in rag per liter

Solvent

acetone

anisole

benzene

chloroform

methanol

toluene

o-xylene

water              0.0002


— indicates no data

(a) Firestone observed that 1,2,3,6,7,8-HxCDD is considerably
      less soluble in organic solvents than other HxCDD isomers
      The solubility of the 1,2,3,6,7,8-isomer in isooctane is
      about 20 mg/1.

^b) Dow standard 82-A, a mixture of 71% 1,2,3,6,7,8-HxCDD and
      29% 1,2,3,6,7,9-HxCDD and 1,2,3,6,8,9-HxCDD.
TCDD
90
—
470
550
10
—
__
HxCDD(b)
—
2600
1600
—
—
1800
— _
OCDD
5
1700
1000
560
—
1500
3600
                          14

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Additionally, exposure to hexachlorobenzene  (HCB) results
in excretion of significant amounts of PCP in urine. Uptake
of PCP by living organisms occurs quite readily, whether by
oral, respiratory, or dermal routes.  The material is
excreted in urine either as free phenol or as conjugated
metabolites.  The length of time for loss of the ingested
amount varies with the species and ranges up to 90 hours.

     The distribution of the dibenzo-p-dioxins and
dibenzofurans in the environment has been less widely
studied.  For the most part, in the studies that have been
conducted exposure was likely to have occurred through use
of materials containing these contaminants.  Upon direct
exposure, both the chlorinated dibenzodioxins (CDDs) and
the chlorinated dibenzofurans (CDFs) are taken up and
retained in the bodies of experimental animals.  CDDs and
CDFs do accumulate in tissues, but not as readily as some
other chlorinated organic compounds such as dieldrin, DDT
and polychlorinated biphenyls.  This would be expected on
the basis of the partition coefficients found for one or
two members of the series.  TCDD, the most toxic of the
chlorinated dioxins, has been shown to have a half-life in
rats of about 21 days.  Analyses of samples of marine
organisms for presence of TCDD were negative, but this may
have been due to the limitation of the method's sensitivity
(parts per billion range).

     PCP as a free phenol has been found to adsorb readily
on many surfaces, especially on soil.  The adsorption is
greatest when the molecule is un-ionized and least when it
is in the form of a sodium salt or at a higher pH value.
It has been found, at least in water, that even the sodium
salt is readily adsorbed by suspended particulate matter
and carried to the bottom of the water course.

     Pentachlorophenol is susceptible to photochemical
degradation, particularly in the presence of other
substances.  PCP photodegrades in water and various
solvents to yield a variety of products.

     The CDDs and CDFs are relatively less mobile than PCP.
Their vapor pressures are substantially lower and their
propensity for adsorption greater.  Degradation of CDDs and
CDFs in the environment,  particularly in soil,  is
substantially slower than for PCP.  Whereas PCP degrades in
30-50 days in moist soil, the half-life of TCDD was found
to be approximately one year.  Photodegradation of TCDD,
                          15

-------
on the other hand, was found to be very rapid in the
presence of hydrogen donors such as oils and 2,4,5-T.

     The principal dioxin contaminant of technical
pentachlorophenol is the octachlorodibenzo-p-dioxin, or
OCDD.  There is concern that this compound and the other
chlorodioxins might be generated in burning treated paper
or wood.  Studies of R.H. Stehl and L.L. Lamparski (1977)
and B. Ahling and L. Johansson (1977) indicate that low
levels of the chlorodioxins might thus be generated under
certain conditions of combustion.  The levels are
sufficiently low, however, as probably not to be a serious
source of exposure.

     Further discussion and documentation of the chemistry
for PCP and its contaminants may be found in Appendix C,
Section 7.

2.6  References

Ahling, B. and L. Johansson (1977).  Combustion experiments
     using pentachlorophenol on a pilot scale and
     full-scale.  Chemosphere 6 (7): 425.

Stehl, R.H. and L.L. Lamparski (1977).  Combustion of
     several 2,4,5-trichlorophenoxy compounds:  formation
     of 2,3,7,8-tetrachloro-dibenzo-p-dioxin.  Science 197;
     1008.
                           16

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3 .   TOXICOLOGY

3.1   Toxicity of Pentachlorophenol in Laboratory Animals

      The widespread use of pentachlorophenol  (PCP) as an
antimicrobial agent and the likelihood of commercial
products being contaminated with certain highly toxic
polychlorinated dibenzo-p-dioxins and dibenzofurans
necessitate a review of the toxicological information
currently available.  Although this review is primarily
concerned with data on PCP per se , available data on
commercial samples are included for comparative purposes.

      Results of acute toxicity studies by oral, dermal,
and injection routes, repeated oral exposures of 3-8
months, a two-year oral test with PCP containing very low
levels of contaminants, mutagenic and teratogenic studies,
and a recent study on the effects of PCP on metabolizing
enzymes are reviewed.

3.1.1   Sample Studies

      Table 3.1 lists the composition of the samples used
in the long term studies.  The PCP content varies from 85%
to 99%. There is no evidence of the presence of 2,3,7,8-
tetrachlorodibenzo-p-dioxin (TCDD) , the most toxic of the
polychlorinated dibenzo-p-dioxins.   The 1,2,3,6,7,8-
hexachlorodibenzo-p-dioxin (HxCDD)  is the major hexa isomer
(Buser, 1975;1976).  The 1, 2, 3 , 7 , 8 ,9-isomer has been
reported to produce chick edema. (Cantrell et al. , 1969).
The octachlorodibenzo-p-dioxin (OCDD) has shown little
toxicity, possibly because of its low solubility.  The
objective in recent years has been to reduce the levels of
polychlorinated dibenzo-p-dioxins and polychlorinated
dibenzofurans to a minimum in the commercial samples.

3.1.2   Acute Toxicity
      Oral;  The LD^Q for PCP in male rats has been
reported as 78 mgAg (Deichmann et al. , 1942) , 90 mgAg
(Gabrilevskaya and Laskina, 1964), 146 mg/kg (Gaines, 1969)
and 205 mg Ag t the last being Dowicide EC-7  (relatively
pure).  For the female rat, it was 135 mg/kg (Dow Chemical
Co. Summary, 1969) and 175 ing/kg  (EC-7) (Gaines, 1969).

      The LDcg for mice was reported as 130 jf 9.5 mg/kg
(Pleskova and Bencze, 1959); 100-130 mgAg for rabbits
(Deichmann et al. , 1942); for guinea pigs, 250 mgAg
(Gabrilovskaya and Laskina, 1964); and for swine 120 mgAg
                            17

-------
                                            TABLE 3.1
      PENTACIILOROPHENOL - COMPOSITIONS REPORTED FOR SOME SAMPLES USED IN TOXICITY TESTING*
                                 PURIFIED                   -  COMMERCIAL

Pentachlorophehol
Tetrachlorophenol
Trichlorophenol
Higher Chlorophenols
Caustic Insolubles  (max)
2,3,7,8-Tetrachlorodibenzo-p-
dioxins
Pentachlorodibenzo-p-dioxins
Hexachlorodibenzo-p-dioxins
Heptachlorodibenzo-p-dioxins
Octachlorodiberizo-p-dioxin
Tetrachlorodibenzofurans
Pentachlorodibenzofurans
Hexachlorodibenzofurans
Ileptachlorodibenzofurans
Octachlorodibenzofuran
*ppmunless otherwise stated
(1)   Analyses by GC-MS - Sensitivity 0.1 ppm
(2)   Analyses by GC-MS - Sensitivity 0.05 ppm
(3)   J.  A. Goldstein et al. (1977)
(4)   B.  A. Schewtz et al.  (1976)
(5)   Buser (1975)  reported 1,2,3,7,8,9 HxCDD as major isomer  (toxic),
(6)   R.  L. Johnson et al.  (1973)
Aldrich
(1) (3)
> 99%
< 0.1



< 0.1
< 0.1
< 0.1
* 0.1
S 0.1
< 0.1
< 0.1
< 0.1
< o.i
< 0.1
Dowicide EC-7
(2) (4)
90.4 ± 1.0%
10.4 + 0.2
< 0.1


< 0.05

1.0 + 0.1
6.5 + 1.0
15.0 + 3.0


3.4 + 0.4
1.8 + 0.3
< 1
Dowicide 7
(6)
85-90%
4-8 %
< 0.1
2-6%
1
None

9.27

575-2510


Detected
Detected
Detected
Monsanto
(1) (3)
84.6%
3 %



< 0.1
< 0.1
8 (5)
520
1380
< 4 •
40
90
400
260

-------
 (Harrison, 1959).  Dreisbach  (1963) has reported an estimated
dose for man to be as low as  29 mg/kg.

      These data would suggest that PCP has moderate acute
oral toxicity, but that the LDcQ value may vary with the
quality and quantity of contaminants.  Man would appear to
be more susceptible than the  rodent and the female to be
more susceptible than the male.

      Skin Absorption;  When  PCP in an organic solvent was
applied to rabbi.t skin under  occlusion for 24 hours, 200
mg/kg was lethal, but 100 mg/kg and 50 mg/kg were not (Dow,
1969).  The LD50 for rats has been reported as 96 mg/kg,
105 mg/kg, and 320 mg/kg (Demidenko, 1966; Noakes and
Sanderson, 1969; Gaines, 1969) and that for mice as 261 + 39
mg/kg (Pleskova and Bencze, 1959) .

      Subcutaneous Injection;  The LDcg for the rat was
100 mg/kg, for the rabbit 70 mgAg (5% in olive oil)
(Deichmann et al., 1942), for mice 63 +_ 3.2 mg/kg (Pleskova
and Bencze, 1959).

      Intravenous Injection;  The lowest dose of PCP
reported to kill rabbits was  22 mg/kg (Kehoe et al., 1939),
when it was instilled as a 1% aqueous sodium pentachloro-
phenate.

      Inhalation;  Exposure to 5 mg/1 dust, for one hour did
not kill male and female rats (Reichhold Chemicals, 1974).
Demidenko (1969) reported the LD5Q by inhalation to be 225
mg/kg for rats and 355 mg/kg for mice.  The exposure
concentration and the calculations to arrive at the LDcg
dose were not given in the abstract.   Workers have reported
that the dust is irritating to the mucous membrane of the
nose and throat.

      Irritancy Tests;  Rabbit eyes exposed to solid material
showed slight conjunctival and slight iritic congestion in
one of four eyes.  Exposure of rabbit skin under occlusion
caused minimal irritation on intact skin and slightly more
on abraded skin (Dow, 1969).

      Commercial samples have produced chloracne in the
rabbit ear bioassay,  whereas the purified material has not.
Positive reactions  could be produced by topical or oral
application (Johnson et al. , 1973) .

      Allergic contact dermatitis has not been a problem in
handling the chemical.
                          19

-------
      Clinical Effects;  Acute animal exposures have, in
general, caused anorexia, diarrhea, stimulation of the
central nervous system, increase in body temperature,
anuria, paralysis of the hind legs and functional
cardiovascular changes leading to death (Deichmann et al.,
1942; Gabrilevskaya and Laskina, 1964; Pleskova and Bencze,
1959; Demidenko, 1966).

3.1.3   Subchronic Feeding Studies

      Johnson et. al. (1973) compared the toxicity of
commercial PCP with improved process PCP and with a purified
PCP.  (The commercial sample contained 85-90% PCP, 9-26 ppm
of HxCDD and 575-2150 ppm OCDD and produced chlorance of
rabbit ears and chick edema in bioassays.  The improved
process PCP contained 88-93% PCP, 30 ppm OCDD and 1.0 ppm
HxCDD.  Neither the improved process PCP nor the chemically
pure PCP produced chloracne or chick edema.)  Three, 10 and 30
mg/kg per day (mixed with diet) were fed to Sprague-Dawley,
Spartan strain rats for 90 days.  The purified and the
improved process PCP caused increase in liver weight at 30
mg/kg and 10 mg/kg and increased kidney weight at 30 mg/kg.
The commercial sample caused a decrease in hematological
values, an increase in alkaline phosphatase, a decrease in
serum albumin, and an increase in liver weights at all
levels; and focal hepatocellular degeneration and necrosis at
the 30 mg/kg level.  The authors concluded that the
impurities causing toxic effects had been eliminated by the
new process.

      Knudson et al. (1974) fed PCP (Dynamit-Nobel)
containing 200 ppm OCDD, 82 ppm pre-OCDD and no detectable
TCDD to rats (SPF-Wistar) at levels of 0, 25, 50 and 200 ppm
in the diet.  Liver weight was increased in rats fed 50 and
200 ppm PCP and was accompanied by increased activity of
microsomal liver enzymes.  There were fewer calcium deposits
in the kidneys of test rats.  Twenty-five ppm was considered
the no-effect level.

      Kimbrough and Hinder (1975) fed purified PCP to one
group of ten male rats and commercial PCP to a second group
for 90 days.  A level of 1000 ppm in the diet, equivalent to
approximately 50 mg/kg per day, was chosen for the purpose of
examining liver changes by light and electron microscopy.
Enlargement of hepatocytes was observed in the livers of rats
fed pure PCP, whereas technical grade PCP caused foamy
                          20

-------
cytoplasm, vacuoles, inclusions, single hepatocellular
necrosis, slight interstitial fibrosis, and prominent brown
pigment  in macrophages and Kupffer cells. By electron
microscopy, there was an increase in the smooth endoplasmic
reticulum in the group fed technical PCP with less change
in the rats fed pure PCP.  There were many lipid vacuoles
in the former group and some in the latter. Atypical
mitochondria were observed in the livers of both groups.

    Goldstein (1977) subsequently studied the differences
between  the hepatic effects produced by commercial and
purified PCP with respect to drug metabolizing enzymes and
presence of porphyria.  Chemical analyses of the samples
used are listed in Table 3.1.  The technical grade material
contained significant amounts of PCDD's and PCDF's, whereas
the purified material contained less than 0.1 ppm of each
isomer,  the level of sensitivity of the method. Groups of
six Sherman female weanling rats were fed pure or technical
PCP at levels of 0, 20, 100 or 500 ppm mixed with Purina
Chow.  Animals were sacrificed after eight months and
hepatic enzyme activity and hepatic porphyrins were
determined.

    Technical pentachlorophenol produced hepatic porphyria
and increased hepatic aryl hydrocarbon hydroxylase
activity, glucuronyl transferase activity, liver weight,
cytochrome p-450, and microsomal heme, but not N-
demethylase activity.  The peak of the CO-difference
spectrum of cytochrome p-450 was shifted to 448 nm, and
there was a dramatic increase in the 455/430 ratios of the
ethyl isocyanide difference spectrum.   The enzyme changes
were observed at 20 ppm of technical pentachlorophenol.
Porphyria occurred at 100 and 500 ppm.  Pure
pentachlorophenol had no significant effect on aryl
hydrocarbon hydroxylase activity, liver weight, cytochrome
p-450, microsomal heme, the ethyl isocyanide difference
spectrum, or N-demethylase activity at any dose level, but
did increase glucuronyl transferase at 500 ppm.   In
contrast, both pure and technical pentachlorophenol
decreased body weight gain comparably at 500 ppm.  It was
concluded that technical pentachlorophenol produces a
number of liver changes which cannot be attributed to
pentachlorophenol itself, but which are consistent with the
effects of biologically active chlorinated dibenzo-p-
dioxins  and dibenzofurans.  See Table 3.2.
                         21

-------
                            TABLE  3.2
                       BIOLOGICAL ACTIVITY
               PURIFIED VS  TECHNICAL  SAMPLES  OF  PCP
                                                  Technical
                                      Pure          Grade
Chick edema

Chloracne

Porphyria

Increase in liver weight/body wt.

Increase in liver enzyme activity      +

Presence of pigment in liver cells    +,-

Liver histopathology                  less

Depressed body weight                  +

Embryotoxicity                         +



                     - indicates no presence

                     + indicates presence
                          22

-------
3.1.4   Two-year Feeding Study

      Schwetz et al. (1976) carried out a two-year oral
study with Dowicide EC-7, a substance which the Johnson 90-
day study had shown to act more like purified material than
commercial preparations.  Analyses of the samples used are
given in Table 3.1.

      Weanling Sprague-Dawley (Spartan-substrain) rats were
divided into five groups of 25 males and 25 females each.
They were fed a test diet of ground Purina Laboratory Chow
mixed with PCP (dissolved in anisole), the amount being
adjusted on a monthly basis to provide dose levels of 0, 1,
3, 10 or 30 mg/kg per day.  The male rats were terminated
after 22 months because of high mortality in both control
and test groups.  The female groups were terminated after
24 months.  Gross and histopathological examinations were
performed.

      Effects, which the authors attributed to ingestion of
PCP at the highest dose level of 30 mg/kg per day, were
(1) a significant decrease in body weight among female
rats; (2) a significant increase in serum glutamic pyruvic
transaminase activity in male and female rats; (3) an
increase in the specific gravity of urine among female rats
at the end of one year but not at two years; (4) an
accumulation of pigment in the liver and kidneys.  An
accumulation of pigment in the liver and kidneys was also
observed in females fed 10 mg/kg per day. There were no
other significant differences between test and control
groups with respect to clinical observations, hematological
changes, blood and urine chemistry, terminal organ weights
and pathological changes.  There was no evidence of
carcinogenic effect, tumors being similar in number and
kind in both test and control groups, nor was there a life-
shortening effect attributable to the test material.

      It was concluded, therefore, that doses of penta-
chlorophenol as high as 30 mg/kg per day fed throughout the
life span produced only mild changes which did not shorten
the life span or alter the incidence of tumors.

      The results are consistent with those found by
Goldstein (1977) when doses of approximately 25 mg/kg per
day of purified material fed for eight months caused weight
loss.  However, dark pigment in the liver reported by
Schwetz et al. (1976) was observed by Kimbrough (1972)
                           23

-------
in the livers of rats fed technical materials, but not in
those fed purified PCP at doses of 50 mg/kg.  An 18-month
feeding study with mice at 130 ppm did not elevate the
incidence of tumors (Innes, 1969).

3.1.5   Chronic Inhalation Exposures

      A Russian study has reported that chronic exposure to
3 mg/M  caused threshold changes in an unidentified
organism, but no details are given in the abstract.  Based
on this study and on observations in the workplace, maximum
allowable concentrations were determined to be 0.1 mg/M
(Demidenko, 1969).

      The American Conference of Governmental Industrial
Hygienists (ACGIH) has established a threshold limit value
(TLV) of 0.5 mg/M3 (0.046 ppm), a level below which
irritation to the nose, throat and eyes is minimal (ACGIH,
1971).

3.1.6   Mutagenic-Cytotoxic Potential

      PCP has not shown mutagenic activity in the Ames test
(Anderson et al., 1972), the host-mediated assay
(Buselmaier et al., 1973), or the sex-linked lethal test on
drosophila (Vogel and Chandler, 1974) .

3.1.7   Teratogenic and Embryotoxic Potential

      PCP did not cause deformities, but it was highly
embryolethal and embryotoxic following oral administration
to rats of 15,30, or 50 mg/kg per day on days 6-15 of
gestation.  No effects were produced at 5 mg/kg (Schwetz
and Gehring, 1973; Schwetz et al., 1974) .  Purified PCP,
with its low nonphenolic content, was slightly more toxic
than the commercial grade (Schwetz et al., 1974) .

      Oral administration of PCP to the golden Syrian
hamster at levels ranging from 1.25 to 20 mg/kg daily from
days 5 to 10 of gestation resulted in fetal deaths and/or
resorptions in three of six test groups.  PCP was found in
the blood and fat of the fetuses (Hinkle, 1973).

      Pregnant rats (Charles River-CD Strain) were given
60 mg/kg of labeled PCP on days 8 through 13 of gestation and
were sacrificed on the 20th day.  Only a small amount of PCP
crossed the placental barrier and only slight teratogenic
effects were noted (Larsen et al., 1975).
                          24

-------
3.1.8   Summary

      Laboratory studies to evaluate the toxicity of PCP as
a wood preservative or pesticide began  in the 1930 's and
have continued to the present time.  PCP is considered a
toxic compound, an economic poison, whose toxicity may vary
depending upon the quality and quantity of contaminants
which vary with different manufacturing procedures.
Samples were not adequately characterized until recently
when some insoluble contaminants were recognized to be the
highly toxic polychlorinated dibenzodioxins and furans. Due
to the difficulty of separating the isomers and in
obtaining standards for analyses, there are many gaps in
the toxicity data, creating uncertainty in any evaluation
of the potential hazard.

      An attempt must be made to differentiate between the
clinical and pathological effects of PCP, the related
phenols, and its likely contaminants, reported as (1) hexa-,
hepta- and octachlorodibenzodioxins and (2) hexa-, hepta- and
octachlorodibenzofurans .  In addition there may be
chlorophenoxyphenols and chlorinated  diphenyl ethers
(reported in European samples) whose identification,, amounts,
and toxicity have not been evaluated.
      The increasing oral LD^Q values through the years
are probably related to improved process procedures,
being reported in 1942 as 78 mg/kg and in 1969 as 205 mg/kg
for male rats.  PCP is easily absorbed through the skin,
the LD5Q for rabbits being similar to that by oral
dosing when the material was applied in a lipid solvent
under occlusion.

     In general, acute exposure of animals has led to rapid
development of high body temperature, increased respiratory
rate, moderately elevated blood pressure, hyperglycemia,
and muscle weakness, terminating in asphyxial convulsions
with cardiac arrest, which tends to occur in less than 24
hours.  Pathological examinations showed extensive damage
to the cardiovascular system.  These changes resemble those
produced by the related phenolic compound dinitro-
orthocresol (DNOC).  Barnes (1957)  concluded that both DNOC
and PCP interfere with production of high energy phosphate
compounds essential to cell respiration.   This interference
causes stimulation of the cell metabolism to the toxic
stage with accompanying fever and the other clinical signs
described above.
                           25

-------
      Most chlorinated dibenzodioxins, on the other hand,
show a very different clinical picture.  Oxidative
phosphorylation is not affected.  The effects are usually
delayed (several weeks to months) and may be accompanied by
effects on the liver, the hemopoietic system, and the
lymphatic system with thymic atrophy and lymphoid
depletion.  There is a marked increase in liver microsomal
enzyme activity and eventual histological change.  There is
a striking difference in susceptibility among species, the
guinea pig being the most susceptible and the female being
more susceptible than the male.

     Comparative chronic studies with purified and
commercial PCP have been limited.  In essence, however,
studies show a marked difference in effect on the liver.
The no-effect level for the relatively pure material in a
90 day test was 3-10 mg/kg; the no-effect level for
commercial material was not established.  A life time oral
study was done only with new process material at dose
levels of 3, 10 and 30 mg/kg.  The data showed that at
higher levels there were some functional changes which did
not result in a shortening of the life span, higher
incidence of tumors or significant pathology.

3.1.9   Conclusions

     1.  Experience has shown that dermal absorption is the
primary hazard to man from the use of PCP as a wood
preservative.

     2.  The chemical has a low vapor pressure and is a
respiratory irritant which has acted as a warning. No
complaints have been noted when the concentration does not
exceed the TLV.

     3.  In the United States there have been no reports of
chronic injury to those workers exposed for as long as 35
years while manufacturing this material.  This conclusion
is supported by Western Electric (Ochrymowych, 1978), whose
utility poles were treated with commercial grade PCP, with
no reports of injury in over two decades of service.  Deaths
and injuries have arisen from mishandling of the material
in the wood treatment process.  There has been a complaint,
however, when treated wood was used in a home interior
without further finishing, a procedure which is not
recommended.

     4.  Trace contaminants in the form of chlorinated
dioxins and chlorinated dibenzofurans are present in bio-
logically active amounts.  Due to limited knowledge of the
amounts and toxicity of the isomers present, only tentative
conclusions as to their contribution to the total toxicity
picture and the extent of the hazard to the general public
can be made.
                          26

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3.1.10   References

ACGIH (1971).  Documentation of TLV's for Substances in
     Workroom Air. Third edition.

Amer, S. M. and E.M. Ali (1969).  Cytological effects of
     pesticides.  IV.  Mitotic effects of some phenols.
     Cytologia _3_4(4): 533-40 (CA 73;24223h).

Anderson, K. J., E.G. Leighty, and M.T.Takahashi
     (1972).  Evaluation of herbicides for possible mutagenic
     properties.  >J. Agr. Food Chem. 20; 649-56.

Buselmaier, W. , G. Roehrborn, and P. Propping (1973).
     Comparative investigations on the mutagenicity of
     pesticides in mammalian test systems.  Mutat. Research
     J21(l): 25-6.

Buser, H-R  (1975).  Polychlorinated dibenzo-p-dioxins,
     separation and identification of isomers by gas
     chromatography - mass spectrometry.  J. Chromatog. 114;
     95-108.

Buser, H.-R (1976).   High resolution gas chromatography of
     polychlorinated dibenzo-p-dioxins and dibenzofurans. Anal
     Chem. _48:1553.

Cantrell, J. S., N.C. Webb, and A.J. Mabis (1969).  The
     identification and crystal structure of a hydro-
     pericardium-producing factor:  1, 2, 3, 7, 8, 9-
     hexachlorodibenzo-p-dioxin.  Acta Cryst. B25: 150-156.

Deichmann, W. B., W. Machle, K.V. Kitzmiller, and
     G.  Thomas (1942).  Acute and chronic effects of
     pentachlorophenol and sodium pentachlorophenate upon
     experimental animals.   J. Pharm. Exptl. Therap. 76; 104.

Demidenko, N. M. (1966).  Toxicological properties of
     pentachlorophenol.  Gig. Toksikol.  Pestits. Klin.
     Otravleni,  (4): 234-9.


Demidenko, N. M. , (1969).  Maximum permissible atmospheric
     concentration of pentachlorophenol.  Gig. Tr. Prof, ^abol,
     _T3  (9): 58-60.  ( CA 7 2 :47095M) .

Dow Chemical Co.  (1969) Toxicity Summary for Dowicide 7.
                          27

-------
Dreisbach, R. H. (1963).  Handbook of Poisoning;  Diagnosis
     and Treatment, p. 256.

Fed. Proc. (1943). Fed. Am. Soc. Exp. Biol. 2^:76.

Gabrilevskaya, L. N. and V.P. Laskina (1964).  Maximum
     permissible concentrations of PCP and Na-pentachloro-
     phenolate in water reservoirs.  Sanit.Okhrana Vodoemov ot
     Zagryazneniya Prom.Stochnymi Vodami,(6):251-272
     (CA 62;15304d).

Gaines, T. H. (1969).  Acute toxicity of pesticides.
     Toxicol. Appl. Pharmacol. .L4(3): 515-34.

Goldstein, J. A. (1977).  Effects of pentachlorophenol on
     hepatic drug metabolizing enzymes and porphyria related to
     contamination with chlorinated dibenzo-p-dioxins and
     dibenzofurans. (In press).

Grant, W. F. (1973).  Cytological effects of environmental
     mutagens - pesticides.  Mutat. Res. _21(4): 221-2.

Harrison, D. L.  (1959).  The toxicity of wood preservatives
     to stock, Part I:  Pentachlorophenol.  New Zealand Vet. J^.
     !_-. 89-98 (CA  55:23814e).

Hinkle,, D. K. (1973).  Fetotoxic effects of pentachloro-
     phenol  in the golden Syrian Hamster.  Tox. and
     Appl. Pharmacol. 25^(3): 455 (abstract).

innes, J. R. M. et al. (1969).  Bioassay of pesticides and
     industrial chemicals for tumorigenicity in mice:  A
     preliminary note.  J. Natl. Cane. Inst. 42; 1101-14.

Johnson, R.  L., P.J. Gehring, R.J. Kociba, and B.A. Schwetz
     (1973).  Chlorinated dibenzodioxins and pentachloro-
     phenol.  Environ. Health Perspect. 5: 171-5.

Kehoe, R. A., W. Deichmann-Gruebler, K.V.  Kitzmiller
     (1939). Toxic effects upon rabbits of pentachlorophenol
     and sodium pentachlorophenate.  J_. Indust. Hyg. & Toxicol.
     23.: 160-172.

Kimbrough, R. D. (1972).  Toxicity of chlorinated hydro-
     carbons and related compounds.  Arch. Environ. Health
     25(2):  125-31.
                           28

-------
Kimbrough, R. D. and R.E. Linder  (1975).  The effect of
     technical and 99% pure pentachlorophenol on the rat liver,
     Light microscopy and ultrastructure.  Toxicol. Appl.
     Pharmacol. 3_3: 131-132.  (Abstract).

Knudson, I., H.G. Verschuuren, E.M. Den Tonhelaar,
     R. Kroes, and P.F.W. Helleman (1974).  Short-term
     toxicity of pentachlorophenol in rats.  Toxicol. 2:
     141-152.

Larsen, R. V., G.S. Born, W.V. Kessler, S.M. Shaw,
     B.C. Von Sickle (1975).  Placental transfer and
     teratology of pentachlorophenol in rats.  Environ. Lett.
     10(2) : 121-8.

Lehman, H. J.  (1951)  Quart. Bull. Assoc. Food and Drug
     Officials 15: 122-33.

Levin, J-O,C. Rappe, and C. -A Nilsson (1976).  Use of
     chlorophenols as fungicides in sawmills.  Scand. J.
     Work Environ, and Health 2' 71-81.               ~

Noakes, D. N. and D.M.  Sanderson  (1969).   A Method for
     determining the dermal toxicity of pesticides.
     British J. of Indust. Med.  26; 59-64.

Ochrymowych, J., Western Electric  (1978).  Personal
     communication.

Pleskova, A. and K. Bencze (1959).  Toxic properties of
     pentachlorophenol.  Pracovni lekerstvi 11; 348-54.

Reichold Chemicals (1974). Report of May 28, 1974.

Schwetz, B. A. and P.J.  Gehring  (1973).  The Effect of
     tetrachlorophenol and pentachlorophenol on rat
     embryonal and fetal development.   Toxicol.  Appl.
     Pharmacol. 25_ (3):  455  (Abstract).

Schwetz, B. A., P.A. Keeler,P.J. Gehring  (1974).   The
     Effect of purified and commercial grade penta-
     chlorophenol on rat embryonal and fetal develop-
     ment.  Toxicol. Appl. Pharmacol.  28(1): 151-61.
Schwetz, B. A., J.F. Quast,C.G. Humiston,C.E. Wade,
     G.C. Jersey, R.W. Lisowe, and R.J. Kociba (1976).
     Results of a toxicological evaluation of pentachloro-
     phenol sample XD 8108.OOL administered to rats by the
     dietary route on a chronic basis.  (Dow Chemical Co.
     Report - unpublished).

Vogel,  E. and J.L.R. Chandler  (1974).  Mutagenicity
     testing of cyclamate and some pesticides in drosophila
     melanogaster.  Experientia 30(6): 621-3.
                           29

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3.2   Toxicity of Chlorinated Dioxins and Dibenzofurans

3.2.1   Toxicity of Chlorinated Dibenzo-p-dioxins

     It has been reported that hexachlorinated, heptachlor-
inated, and octachlorinated dibenzo-p-dioxins are found in
pentachlorophenol.  Of the ten hexachlorodibenzo-p-dioxin
isomers theoretically possible, only six are predicted and
have been found in pentachlorophenol (Stehl and Crummett,
1977; Vogel 1977).  Of these six, two (1,2,3,7,8,9- and
1,2,3,6,7,8-hexachlorodibenzo-p-dioxin)  would be expected
to have marked toxicity given that the 2,3,7,8, positions
are halogenated.  Previous toxicity studies have shown that
the single oral LD^Q of these two isomers in guinea pigs
ranges between 60 and 100 ug/kg (McConnell et al. , 1978).
The comparative toxicity of various dibenzodioxin isomers
does show a positive correlation between in vivo toxicity and
the ability of these isomers to induce arylhydrocarbon
hydroxylase (AHH) enzyme systems in chick embryos (Poland
and Glover, 1973).  Utilizing AHH induction data to predict
toxicity, one predicts several orders of magnitude decrease
in the toxicity of the other four hexachlorodibenzo-p-
dioxin isomers (1,2,4,6,7,9-, 1,2,4,6,8,9-, 1,2,3,6,7,9-
and 1,2,3,6,8,9-).  Specific toxicologic evaluation of the
other isomers has not been performed.

     Chronic (two year) toxicity studies of a mixture of
two hexachlorodibenzodioxins is in progress at the Illinois
Institute of Technology Research Institute through an NCI
contract.  The two isomers present in this mixture are the
1,2,3,6,7,8 and 1,2,3,7,8,9-hexachlorodibenzodioxins.  A
hexa-chlorodibenzodioxin mixture (the specific isomer
composition is unknown) has been found to induce chloracne
in the rabbit ear bioassay as indicated by the formation of
comedones (Schwetz et al., 1973).  In teratology studies,
this hexachlorodibenzodioxin mixture was found to cause
maternal toxicity in rats at a dose of 100 ug/kg/day; doses
of 10 or 100 ug/kg/day of hexachlorodibenzo-p-dioxins were
highly lethal to fetuses during late gestation.  The weight
and length of surviving fetuses were also significantly
decreased.  A significant increase in fetal abnormalities
was observed in offspring from rats that received the 100
ug/kg/day dose.  Subcutaneous edema of the fetuses was
observed at a 1 or 10 ug/kg/day dose, whereas the 0.1
ug/kg/day dose did not yield any fetal anomalies.  Schwetz
et al. (1973) also produced chick edema in birds treated
with 10 and 100 ug/kg/day of hexachlorodibenzo-p-dioxin.
                          30

-------
     There are two heptachlorinated dibenzodioxin isomers
possible, both of which have been found in pentachloro-
phenol.  Of these two, the 1,2,3,4,6,7,8- isomer would be
expected to be the more toxic.  Specific toxicity studies
on this isomer are incomplete.  In a guinea pig toxicity
study, animals survived a single oral dose of 180 ug/kg
with little or no toxicity observed (McConnell et al. ,
1978).  Further studies are currently in progress at the
National Institutes of Environmental Health Sciences
(NIEHS) in which guinea pigs are receiving doses of 200,
400, or 600
     The toxicity of octachlorodibenzo-p-dioxin is not
known.  Oral doses of 1 g/kg did not cause death in five
female rats or in four male mice that received 4 g/kg
( Schwetz et al. , 1973).  In a teratology study with
octachlorodibenzodioxin, no signs of maternal toxicity were
observed in rats that received either 100 or 500 mg/kg/day
of OCDD.  No increase in fetal absorptions or fetal
anomalies was observed at the 500 mg/kg dose.  The
incidence of subcutaneous edema was significantly
increased. In a chick edema bioassay, edema was not
observed in chicks that were maintained on a diet
containing 0.5% OCDD for 21 days (Schwetz et al. , 1973).

     Table 3.3 summarizes relative dibenzo-p-dioxin/
dibenzofuran toxicity where data are available. Comparative
toxicologic data show that the pattern of toxicity caused
by dioxin isomers is the same as that produced by TCDD
(McConnell et al. , 1978). Experiments with carbon 14-
labelled TCDD indicated that dioxins pass the placental
barrier and are secreted in milk (Moore et al. , 1976).  It
has been shown that TCDD causes immunosuppression (Vos and
Moore, 1974); increased susceptibility to bacteria (Thigpen
et al. , 1975); and fetal death or birth defects (Courtney
and Moore, 1971) .

3.2.2   Dibenzofurans

     Relatively little work has been directed toward the
specific indentif ication of dibenzofuran isomers present in
pentachlorophenol.  Preliminary work reported by Stehl and
Crummett (1977) records the presence of the 2,3,6,7- and
2,4,6,7-tetrachlorodibenzofurans and the 2,3,4,6,7-,
1,2,4,7,8- and 2, 3, 4, 7, 8-pentachlorodibenzofurans as well
as the 1, 2, 3, 6,7,8=hexachlorodibenzof uran.   Quantification
of the levels of these isomers in pentachlorophenol was not
done due to interferences with other chemicals (chlorinated
diphenyl oxides).   Of the isomers reported,  the 2,3,4,7,8
                          31

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                                                                 TABLE 3.3
                                                               TOXICOLOGY DATA SUMMARY
    (single done)
    Guinea Pig
    Mice
    Rat
    Monkey (Rhesus)
A11H Induction  In Chick Enbyro
Relative to  TCUD

Teratogenic  Doae  pg/kg
Fetotoxlc  Doae

    Hlce
    Rat
3-Generatlon Study - Rat pg/Kg


Reproduction - Primates


90-Day Study - Rat  ug/Kg


2-Year Study


Chloracne

Chick Edema Bloassay (21-day)
Increased  Disease
Susceptibility
•
DIBF.NZODIOXINS
Tetra
Ciiloro
W
2
114/283
22
<70
1
1
(mice)
1
0.5
0.01
NE 0.001
500 ppt
toxic
0.01
NE 0.001
In
Progress
Yea
lug/Kg/day
IMS/Kg
1/wk x 4 wka
• Hexnchloro-
Mlxture of
llcxa
loomers


100 .
(rat)
•?.io
• • • ** *


In
Progress
Yes
lOng/Kg/day

1,2,3,
6,7,8
70-100
1250
0.25







*v*

1,2,3,
7,8,9
60-100
>1440
0.25








•
1,2,4.
6,7,9

0.002









1*2,4,
6,8,9











1,2,3,
6,7,9

0.15








•
1,2,3,
6,8,9











lleptachloro-
1.2,3,4,
6,7,8
>180
0.15








•
1,2,3,4,
6,7,9

0.002









Octa
Chloro-
1,2,3,4,
5,6,7.8
>1, 000,000
)4, 000, 000
0.002

500 mg/K|'.





0.5Z in
Diet - Nr

D1BENZOKUKANS
Tetra
Chloro
2,3,7.8
>5<10
>6000
>1000
1000
0.7







lug/Kg/
day

Pcnts
Clilorc
2,3,4,
7.8
>3<-10
0.7









Uc.ia-
Chloro
1,2.3
6,7,3











               lo  effect
Data taken from references  In sa^pion 3.2.4

-------
and 1,2,3,6,7,8 would be of prime toxicologic interest.
Toxicity studies with the 2,3,4,7,8-pentachlorodibenzofuran
have been performed in guinea pigs ( Moore, 1977). A single
oral dose caused death in 6/6 animals that received 30 or
10 ugAg-  All animals survived a 30-day observation period
subsequent to receiving 3 or 1 ug/kg.  Toxicity was
observed at the 3 ug/kg dose while only an increase in
liver size was seen at the 1 ug/kg dose.  The pattern of
the toxic response is similar to that reported in studies
using the 2,3,7,8-tetrachlorodibenzofuran (Moore et al.,
1975).
3.2.3   Chlorinated Dibenzo-p-dioxin/Dibenzofuran Toxicity/
        Contamination Associated with Exposures to PCP

     The dibenzofurans and dibenzo-p-dioxins present in
pentachlorophenol have been responsible for animal health
problems.  The chick edema disease problem of the 1950's
and 1960's was in part traceable to pentachlorophenol
contaminants (Firestone,1973).

     Recent studies at the National Institute of
Environmental Health Sciences have identified the presence
of hexa-, hepta-, and octachlorinated dibenzo-p-dioxins in
tissues from a dairy herd in Michigan.  The results of
dioxin analyses of tissue samples taken from the herd are
summarized as follows:

         Number of   Number of Samples in which Detected
Tissue    Samples    Octadioxin  Heptadioxin Hexadioxin

Liver       15          15            15         9
Fat          77             61
Range (ppb)          0.23-47.0   0.03-12.0   0.01-1.3
A possible source of these tissue contaminants was PCP-
treated wood used in the construction of a new barn in
which the cows were housed and fed (Moore, 1977).

     Although the presence of toxic chlorinated dioxins in
tissues of food animals is a matter for serious public
health concern, there is insufficient evidence to conclude
that contaminants from PCP-treated wood were the cause of
illness in the Michigan cows.  Van Gelder (1977) concluded
that although the contaminants were more toxic than the PCP
itself, they were not present in  sufficient amounts to
cause illness.  Controlled dosing experiments, recently
completed, may help answer questions raised by the Michigan
field studies concerning the pharmacokinetics and toxicity
of PCP and its contaminats in cattle   (Moore, 1978).
Results of these experiments are  expected in late 1978.

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3.2.4   References

Courtney, K. D. and J.A. Moore (1971).  Teratology studies
     with 2,4,S-trichlorophenozyacetic acid and 2,3,4,8-
     tetrachlorodibenzo-p-dioxin.  Toxicology and Applied
     Pharmacology 20;  396-403

Firestone, D. (1973).  Etology of chick edema disease.
     Environmental Health Perspectives, Experimental Issue
     Number 5^:59-66.

McConnell, E. E., J.A. Moore, J.K. Baseman, and M.W. Harris
     (1976).  The Comparative toxicity of chlorinated
     dibenzo-p-dioxin isomers in mice and guinea pigs.
     Toxicology &^ Applied Pharmacology 37; 145, abstract
     (Manuscript in preparation).

Moore,  J. A. (1977).  Memorandum to Director, NIEHS (March
     21,1977), subject: Studies on Possible Pentachlorophenol/
     Dibenzodioxin Intoxication Progress Report #2.

Moore,  J.A. (1978). NIEHS. Personal communication. August
     1978.

Moore,  J. A., B.N. Gupta and J.G. Vox (1975).  Toxicity
     of 2,3,7,8-tetrachlorodibenzofuran - - preliminary
     results. National Conference on Polychlorinated
     Biphenyls, (November 19-21,  1975),  Chicago, Illinois,
     Conference Proceedings, EPA-560/6-75-004.

Moore,  J. A. , M.W. Harris and P.W. Albro (1976).  Tissue
     distribution of carbon 14 tetrachlorodibenzo-p-dioxin
     in pregnant and neonatal rats.  Toxicology £ Applied
     Pharmacology 37 :146, abstract  (Manuscript in
     preparation).

Poland, A. and E. Glover (1973).   Chlorinated dibenzo-p-
     dioxin:  Potent inducers of   -aminolevulinic acid
     synthetase and aryl hydrocarbon hydroxylase.   II. A
     study of the structure—activity relationship.
     Molecular Pharmacology j), 736-747.

Schwetz, B. A., J.M. Norris, G.L. Sparschu, V.K. Rowe
     P.J. Gehring, J.L. Emerson,  and C.G. Gerbig (1973).
     Toxicology of chlorinated dibenzo-p-dioxins.
     Environmental Health Perspectives, Experimental Issue
     Number 5: 87-100.
                           34

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Stehl, R. and W.Crummett (1977).  Letter to Dr. Thomas
     Bath, EPA.

Thigpen, j. E., R.E. Faith, E.E. McConnell, and J.A. Moore
     (1975).  Increased susceptibility to bacterial
     infection as a sequela of exposure to 2,3,7,8-
     tetrachlorodibenzo-p-dioxin.  Infection and Immunity
     12_ (6): 1319-1324.

Van Gelder, G. A. (1977).  Prepared statement on the
    toxicity of pentachlorophenol and chlorodioxins in
     cattle and laboratory animals and results of field
     investigations of dairy farms in Michigan.  Statement
     presented at administrative hearing, Michigan
     Department of Agriculture, Lansing, Michigan
     July 18-22, 1977) .

Vogel, S. H. (1977).  Presentation to PCP Ad_ Hoc Working
     Group (March 3, 1978).

Vos, J. G. and J.A. Moore  ( 1974).  Suppression of
     cellular immunity in rats and mice by maternal
     treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin.
     International Archives of Allergy and Applied
     Immunology 47': 777-794.
                          35

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3.3   Human Poisoning Involving PCP

      The EPA Pesticide Episode Review System Report  (PERS)
No. 60 describes poisoning espisodes involving
pentachlorophenol which occurred from 1966 to September 1,
1976.  A total of 64 alleged episodes were located, 47 of
which involved humans. Of these, 42 involved adults, four
involved children, and one did not specify the age group.
Three of the episodes involving children occurred at home
and one at a job. site. Eleven episodes involving adults
(over 17 years old)  occurred in the home and 28 at various
job sites.  Four of the human-related episodes involved
combinations of pentachlorophonel and active ingredients
other than chlorophenols and petroleum distillates.

      Twenty-nine episodes involving humans (one a child
less than 6 years old) were associated with occupational
activities.  Eight of these occurred at lumber-treating
establishments.

      Six episodes occurred during construction activities.
Four of these involved individuals who were painting or
otherwise applying the chemical to structures, and two
involved carpenters who were working with treated lumber.

      Five episodes occurred during occupationally-related
agricultural activities.  One of these involved a child who
was splashed with the chemical while watching a man apply
it to a post.  The remaining four episodes involved adults.

      Two episodes involved commercial pest control
operators engaged in application of the chemical.  In one
episode, a man sprayed PCP in the crawl space beneath a
house.  He developed symptoms of weakness, headache, double
vision, tachycardia, nausea and hyperpyrexia.  He recovered
after a short period of hospitalization.  In the other
episode, an individual working for a pest control company
accidentally splashed the chemical into his eyes.  This was
diagnosed as mild chemical conjunctivitis.

      In another job-related incident, an employee at a
greenhouse worked for several weeks around benches which
were treated with the chemical; he subsequently developed
headaches and chronic coughing.

      In one incident the affected person was working inside
a school building while pentachlorophenol and bromacil were
being applied nearby.  A quantity of the mixture was drawn
into the building through an air intake duct and blew
directly into the face of a teacher.  The only symptoms
reported were shortness of breath and weakness.
                          36

-------
      Six episode reports concerning  incidents  associated
wdth occupationally-related operations did not  specify the
type of job the affected individual was  engaged in at the
time of the accident.  Five of these were minor reactions
to the chemical; however, the remaining  episode resulted in
the death of the victim.  In this episode the individual
ingested the pesticide which was  in an unmarked bottle.
The man mistakenly thought the bottle contained  water; he
died enroute to the hospital.

      In addition to those episodes which occurred during
job-related activities, 14 others took place in the home.
Of these, 11 involved adults and three involved  children.

      Of the three episodes involving children,  one
occurred when a child spilled the chemical on himself,
resulting in a mild dermatitis; one involved a  5-year old
who took a small amount of the chemical  into his mouth
without swallowing and recovered, the only symptoms to
develop were nausea and vomiting; and one in which the
report did not specify the circumstances of the episode.

      All of the episodes affecting adults in the home were
the result of application of products containing
pentachlorophenol to the home.  Five of  these involved
reactions of persons other than the applicator  to the
chemical after it was applied.  Commonly reported in this
type of involvement was a protracted period of  illness
which increased in severity over time.   Three episodes were
reported in which individuals who applied the material were
affected.  One of these was a minor reaction; however,
those remaining were quite severe and persisted  for an
extended period.  One involved an individual who applied
the chemical to the exterior of an addition to  his home.
The man developed a severe cough persisting from at least
August through November 1974. This was allegedly in
response to an initial period of chemical application, with
more severe symptoms occurring after a second period of
application.  The man was hospitalized for an extended
period.  In the other incident the subject had  a number of
manifestations compatible with poisoning by penta-
chlorophenol or other polychlorinated phenols shortly after
exposure to the product.  These included excess
perspiration, nausea without vomiting, abdominal pain, dry
mouth, listlessness, and generalized dermatitis.  Shortly
afterwards she also developed generalized pruritus and
several peripheral nerve manifestations, particularly
numbness and pain in the left first dorsal segment,
                          37

-------
generalized paraesthesia and Herpes Zoster of the tenth
right dorsal segment.

      Two additional episodes involved individuals who were
opening cans of the chemical and were sprayed by the
material in the process.  Symptom development was not
reported in either case.  The final episode report was
submitted with no reference to circumstances of exposure or
the effects therefrom.

      Four reports did not specify the episode location.
One of these did not contain information about the circum-
stances of exposure, one involved a can which exploded in a
man's face while he was opening it, one was an attempted
suicide, and one involved a 68 year old man who accident-
ally swallowed a mouthful of 2.5 percent pentachlorophenol
and recovered after hospital treatment.

      Table 3.4 presents data showing the degree of
medical attention required in the 47 episodes of alleged
human poisoning from pentachlorophenol along with the
circumstances surrounding the episodes.

      A study (.Sato et al. , 1978) conducted in Hawaii from
1967 to 1973 examined the clinical findings in workers
exposed to PCP.  The concluding statement reads as
follows:

      "The information gathered in this study suggests that
      despite high chronic exposures to PCP, individuals in
      the wood treatment group of workers had not undergone
      any serious health effects from this exposure.  The
      only evidence of tangible health effects, part of
      which could have been caused by exposures to chem-
      icals other than PCP, were the low-grade infections
      or inflammations of the skin and subcutaneous tissue,
      of the protective membrane of the eye, and of the
      mucous membrane of the upper respiratory tract.  No
      long-time (sic) effects could be elicited in the exposed
      group."


3.3.1 References

Sato, N.M., H.W. Klemmer, L. Wong, E.L. Reichert, R.J.
      Korsak, and N.N. Rashad (1978).  Clinical findings in
      workers exposed to pentachlorophenol.  Draft report
      USEPA, Washington, D.C.
                          38

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                         TABLE 3.4
          Distribution  of  Human  Episodes  Resulting
        from Exposure to Pentachlorophenol by Medical
                Attention and Circumstances
             (PERS 1966 to September 1,  1976)*+
Medical Attention
 Circumstances
Total Number
 of Episodes
Hospitalization followed
   by death
Hospitalization followed
   by recovery
Medical attention at a
   doctor's office or
   emergency room
Effects not requiring
   medical attention
 -Ingestion                    1
 -Chronic Exposure             1
 -Unspecified                  1

-Treated wood at home          2
-Attempted suicide             1
-Ingestion                     1
-Exposed during nearby         1
      application
-Contacted chemical during     1
     application
-Spill                         1
-Reaction to treated home      1
-Unspecified                   1

-Contacted chemical during     9
     application
-Exposed to treated object     4
-Container exposed             1
-Reaction to treated home      1
-Ingestion                     1
-Exposed during nearby         1
    application
-Contacted contaminated        1
    object
-Unspecified                   8

-Opening container             2
-Reaction to treated home      2
-Contacted chemical during     2
    application
-Working with treated wood     1
-Unspecified                   2

TOTAL                        ~TT
*A cause-effect relationship has not been confirmed between the
 pesticide and reported reactions for all of these episodes.

+From the EPA Pesticide Episode Review System Report No. 60
                          39

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3.4   Human Poisonings Involving Exposure to Chlorinated
      Dibenzo-p-dioxins

      Over the last 30 years a number of cases of human
poisoning have occurred as a result of industrial exposure
to the chlorinated dibenzo-p-dioxins.  Although less well
documented, it is also possible that human poisoning has
occurred as a result of industrial and non-industrial
exposure to the chlorinated dibenzofurans.  The references
on the next two pages list reports on cases of human
poisoning from industrial exposure to the chlorinated
dibenzo-p-dioxins.  Most of these are exposures to TCDD.
Some of these reports (Baader and Bauer, 1951; Jirasek et
al., 1973; Jirasek et al., 1974; Pazderova et al., 1974)
represent dioxin poisoning in factory workers involved in
the manufacture of pentachlorophenol; these would represent
exposures to chlorinated dibenzo-p-dioxins other than TCDD.

      Chloracne was the predominant sign of toxicity
reported in these workers.  However, a number of other
symptoms have been reported.  These include emphysema,
myocardial degeneration, toxic nephritis, hypertension,
peripheral edema, anorexia, gastritis, weight loss,
bursitis, peripheral neuropathy, paraesthesia, headaches,
vertigo, coordination disturbances, fatigue, loss of
libido, easy fatigability, emotional instability,
pancreatic necrosis, polyneuritis, encephalomyelitis,
hyperpigmentation, hirsutism, eye irritation, oiliness of
the skin, hyperlipidemia and hypercholesterolemia.

     A report recently issued from a January meeting of an
NIEHS/IARC ad hoc Working Group summarizes available
epidemiological and laboratory research on chlorinated
dibenzo-p-dioxins and dibenzofurans (NIEHS/IARC, 1978).
The report includes exposure incidents and discusses
several aspects of toxicity including chloracne, hepa-
toxicity, embryotoxicity and teratogenicity.
                             40

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3.4.1   References

Baader, E.W. and H.J. Bauer  (1951).   Industrial
     intoxication due to pentachlorophenol.  Industr. Med.
     Surg. ££: 286-290.

Bauer, H. , K.H. Schultz, and U. Spiegelberg  (1961).
     Beruflich vergiftungen bei der herstellung von
     chlorphenol-verbindunge.  Arch .  f_. Gewerbepath . und
     Gewerbehyg. 18 ; 538-555.

Bleiberg, J. , M. Wallen, R. Brodkin,  and I.L. Applebaum
     (1964). Industrially acquired porphyria.  Arch. Dermatol .
     £9: 793-798.

Dugois, P. and L. Colomb (1957). Remarques sur 1'acne
     chlorique.  J. Med. Lyon 38; 899-903.
Goldman, P. J. (1973).  Schwerste akute chloracne, eine
     Massenintoxikation durch 2, 3, 6, 7-tetrachlorodibenzo-
     dioxin.  Der Hautarzt 24 ; 149-152.

Jirasek, L. , J. Kalensky, and K. Kubec  (1973). Acne chlorina
     and porphyria cutanea tarda during the manufacture of
     herbicides.  Cs Derm. 48; 306-317.

Jirasek, L. , J. Kalensky, K. Kubec, J. Pazderova, and
     E.  Lukas (1974). Acne chlorina, porphyria cutanea tarda and
     other manifestations of general intoxication during the
     manufacture of herbicides.  Cs Derm. 49; 145-157.

Kimmig, J. and K.H. Schultz (1957). Occupational acne
     (so-called chloracne) due to chlorinated aromatic cyclic
     ethers.  Dermatologica 115; 540-546.

May, G. (1973). Chloracne from the accidential production of
     tetrachlorodibenzodioxin.  Brit. J. Ind. Med. 30:
     276-283.                         ~            ~

NIEHS/IARC. (1978). Long term hazards of polychlorinated
     d ibenzodioxins and polychlorinated dibenzofurans .
     Joint NIEHS/IARC Working Group.  International
     Agency for Research on Cancer.  Lyon, France 1978.

Oliver, R. M. (1975). Toxic effects of 2,3,7,8-
     tetrachlorodibenzo 1,4 dioxin in laboratory workers.
     Brit. J. Ind. Med. 32: 49-53.
                          41

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Pazderova, J., E. Lukas, M. Nemcova, M.  Spacilova, L.
     Jirasek,  J.  Kalensky, J.  John,  A. Jirasek,  and J.
     Pickova (1974).  Chronic intoxication by chlorinated
     hydrocarbons produced during the manufacture of sodium
     2, 4, 5-trichlorophenoxyacetate. Prac.  Lek. 26: 332-
     339.

Poland, A. P., D. Smith, G. Metter,  and  P.  Fossick (1971).
     A health  survey of workers in a 2,  4-D and  2, 4, 5-T plant.
     Arch. Environ. Health 22; 316-327.

Schultz, K. H. (1957).  Untersuchungen zur atiologie der
     Chloracne.  Arch.  Klin, exp. Derm.  206;  589-596.

Schultz, K. H. (1968).  Clinical picture  and etiology of
     chloracne.  Arbeitsmed. - Socialmed. - Arbeitshyg. 3^ 25-29,

Taylor, J. S.  (1974). Chloracne - A continuing problem.
     Cutis 13: 585-591.
                         42

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4.   Mechanistic Relationships  in  the Toxicity of Compounds
     Structurally Related to the Chlorinated
     Dibenzo-p-dioxins

      The chlorinated dibenzo-p-dioxins appear as trace
contaminants in the commercial  synthesis of certain
chlorinated phenol products.  Clinical-epidemiologic
investigations of industrial and environmental accidents
involving these compounds and laboratory investigations
have established the extraordinary toxic potency of certain
chlorinated dibenzo-p-dioxins and  the potential human
health hazards they pose.  Less well appreciated is the
similar spectrum of toxic effects  produced by certain
chlorinated dibenzofurans, chlorinated azoxy- and azo-
benzenes, polychlorinated biphenyls and polybrominated
biphenyls.  We wish to draw attention to these compounds as
a group:  1) their similar toxic spectrum, 2) their
isosterism  in chemical structure,  and 3) their similar
biochemical actions.

      The prototype dibenzo-p-dioxin, 2,3,7,8-tetra-
chlorodibenzo-p-dioxin (TCDD), produces a number of well
defined toxic actions in laboratory animals and human
beings.  1) Lethality - While the  cause is unknown there is
an order of species sensitivity—guinea pigs and chickens
are very sensitive, rats and mice  much less so.  2) Chlor-
acne and Hyperkeratosis - Reported  in humans, rabbits and
hairless mice.  3) Involution of Lymphoid Tissue -
Particularly thymus"also in spleen and lymph nodes.  In
young animals this is reported to  be accompanied by
suppression of the immune response.  Thymic involution has
been seen in guinea pigs, rats and mice.  4) Terato-
genicity, Embryo Toxicity and Fetal Wastage -Has been
demonstrated in rats and mice.  5) Edematous Syndrome-Young
chickens (and occasionally in mice)"6) Liver Toxicity -
Seen in rats, rabbits and mice.  Liver necrosis is greatest
in rats and rabbits; distinct histologic damage is seen in
mice.  Little or no damage is seen in guinea pigs.  7)
Disturbance in porphyria metabolism - Induction of
aminolevulinic acid (ALA) synthetase in chicken embryos.
Porphyria in mice and chickens and presumably the causative
agent of porphyria cutanea tarda seen in factory workers.

      The administration of TCDD and certain other
chlorinated dibenzo-p-dioxins to chicken embryos,  rats and
mice induces a number of hepatic enzyme activities, the most
well studied of these being aryl hydrocarbon hydroxylases
(AHH) (Poland and Glover, 1973, 1974) and 6  -aminolevulinic
acid (ALA) synthetase (Poland and Glover, 1973).  The
capacity of halogenated dibenzo-p-dioxin isomers to induce
                          43

-------
hepatic ALA synthetase and AHII activities (in  the chicken
embryo) was found to have a well-defined, structure activity
relationship:  1) halogens in at least three and preferably
four of the lateral ring positions  (positions  2, 3, 7, and
8); 2) the order of potency for substitution was Br> Cl> F>
NO2; and 3) at least one unsubstituted ring position --
octachlorodibenzo-p-dioxin is very weak or inactive.
      This structure activity relationship for the
induction of AHH or ALA also corresponds to the structure
activity relationship for the lethality of these compounds
in experimental animals.

      Recently, a binding protein has been identified in
the cytosol fraction of mouse liver which binds TCDD
reversibly with a high affinity (Poland and Glover, 1976a).
The binding affinity of other chlorinated dibenzo-p-dioxin
and halogenated aromatic compounds for this protein
corresponds to their biologica.1 potency to induce AHH; this
and other evidence suggest that this cytosolic binding
species is the receptor for the induction of AHH activity.

      Recently it has been shown that certain chlorinated
biphenyls show symptoms of toxicity similar to the
chlorinated dibenzo-p-dioxins when administered to chickens
and to rats.  Thus, 3,4,5,3' ,4' ,5 ' -hexachlorobipnenyl
causes marked involution of the thymus, loss of
subcutaneous and visceral adipose tissues, liver necrosis
and hydropericardium when administered to chickens
(McKinney et al., 1976).  Quite similar symptoms are seen
in chickens administered either 2,3,7,8-tetrachloro-
dibenzofuran or 2, 3, 7,3-tetrachlorodibenzo-p-dioxin.  The
compound 2,3,4,3',4'-pentachlorobiphenyl has an LD^Q of
about 12 mg/kg in the rat with death occurring in about 11
days (Yamamoto et al., 1976).  A marked decrease in body
weight, disappearance of fat from adipose tJcsues and liver
necrosis were the primary symptoms of toxicity in these
animals.  These symptoms are very similar to those seen
upon administration of 2,3,7,8-tetrachlorodibanzo-p-dioxin,
2,3,7,8-tetrachlorodibenzofuran and other chlorinated
dibenzo-p^dioxins and dibenzofurans to rats.
                          44

-------
      The major symptom of toxicity in man exposed to the
halogenated dibenzo-p-dioxins is chloracne.  The outbreak
of chloracne in workers exposed to 3, 4, 3 ' ,4'-tetra-
chloroazoxybenzene and 3,4,3 .4'-tetrachloroazobenzane has
recently been reported (Poland and Glover, 1976b) .
These compounds, like 2,3,7,8-tetrachlorodibenzo-p-
dioxln and 2,3,7,8-tetrachlorodibenzofuran, are potent
inducers of arylhydrocarbon hydroxylase.  They also have a
high affinity for a receptor for 2,3,7,8-tetrachloro-
dibenzo-p-dioxin recently described in rat liver by Poland
and Glover (1976-a)'.

      Although the data is not extensive at this time,
there appears to be a strong correlation between toxic
symptoms produced by a number of halogenated  aromatic
compounds.  The prototype compounds are shown below:
2,3,7,8-tetrachloro-
d ibenzo-p-d ioxin
3,4,3',4'-tetrachloro-
 azoxybenzene
                              «-
-------
4.1   References

McKinney, J.D., K. Chae, B.N. Gupta, J.A. Moore, and
     J.A. Goldstein, (1976). Toxicology assessment of hexa-
     chlorobiphenyl isomers and 2,3,7,8-tetrachlorodibenzofuran
     in chicks.  Toxicol. Appl. Pharmacol. 36;  65-80.

Poland , A. and E. Glover (1973). Chlorinated dibenzo-p-
     dioxins: Potent inducers of  6 -aminolevulinic acid
     synthetase and aryl hydrocarbon hydroxylase.  Mol.
     Pharmacol. 9^: 736-747.

Poland, A. and E. Glover (1974). Comparison of 2,3,7,8-
     tetrachlorodibenzo-p-dioxin, a potent inducer of aryl
     hydrocarbon hydroxylase, with 3-methylcholanthrene. Mol.
     Pharmacol. 10; 349-359.

Poland, A. and E. Glover (1976a). Stereospecific, high
     affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin
     by hepatic cytosol.  J. Biol. Chem.  251; 4936-4946.

Poland, A. and E. Glover (1976b).  3 ,4,3',4'-tetra-
     chloroazoxybenzene and azobenzene: Potent inducers of aryl
     hydrocarbon hydroxylase.  Science 194(4265); 627-630.

Yamamoto, H., H. Yoshimura,  A. Fujita, and T. Yamamoto
     (1976). Metabolic and toxicological  evaluation of
     2,3,4,3',4'-pentachlorobiphenyl in rats and mice.  Chem.
     Pharm. Bull. 24: 2168-2174.
                          46

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5.   Appendix A
                   SCIENCE ADVISORY BOARD
          ENVIRONMENTAL HEALTH ADVISORY  COMMITTEE
    Ad  Hoc  Study  Group on  Pentachlorophenol  Contaminants

Chairman;

Dr. Sheldon D. Murphy, Professor of Toxicology, Department
    of Pharmacology,  University of Texas Medical School at
    Houston, P.O. Box 20708, Houston, Texas 77025

Members;

Dr. Donald G. Crosby, Professor and Toxicologist,
    Department of Environmental Toxicology, University of
    California, Davis, California 95616

Dr. David Firestone,  Division of Chemistry and Physics,
    HFF-147, Food and Drug Administration, 200 C Street,  S.W.,
    Washington, D.C.  20204

Dr. Virgil H. Freed,  Department of Agricultural Chemistry,
    Oregon State University, Corvallis,  Oregon 97331

Ms. Dorothy B. Hood,  Consultant, Toxicology, Haskell
    Laboratory for Toxicology and Industrial Medicine,
    E.I. du Pont de Nemours and Company, Wilmington,
    Delaware 19898

Dr. John Moore, National  Institute of Environmental Health
    Sciences, P.O. Box 12233, Research Triangle Park,
    North Carolina 27709

Dr. Robert A. Neal, Director, Center in Toxicology,
    Department of Biochemistry, Vanderbilt Medical School,
    Nashville, Tennessee  37323

Dr. Alan Poland,  Assistant Professor, McArdle Laboratory
    for Cancer Research,  University of Wisconsin, Madison,
    Wisconsin 53706

SAB Staff Officers;

Mr. Ernst Linde,  Scientist Administrator, Science Advisory
    Board, A-101, U.S. Environmental Protection Agency,
    Washington, D.C.  20460  Phone: (703) 557-7720

Mr. A. Robert Flaak,  Science Advisory Board, A-101, U.S.
    Environmental Protection Agency, Washington, D.C. 20460

                               47

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   APPENDIX B
         UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                          WASHINGTON. O.C.  2C460


                       .  '  January 12, 1977
                                                                   Of r«CC OF THE
                                                                   ADMINISTRATOR
SUBJECT:  Charge to ad hoc Study Group on Pentachlorophenol Contaminants

FROM:     Chairmn, Environmental Health Advisory Committee

TO:       Study Group Mieisbers        •    '  .


     A recent inquiry from EPA has been referred to the Environmental
Health Advisory Committee (EIAC).  The request (attached) asks for
opinion as to the implications regarding hazard to human health of the
observed presence of various chlorinated dibenzcaioxin iscmers iri.
pentachlorophenol (TCP).                                              .

     •The Environmental Health Advisory Committee feels that this inquiry
provides a timely opportunity to review, rather more broadly than the
original inquiry implied, the toxicology and analytical methodology
pertinent to both the chlorinated dibenzofurans and the dibenzodicxin
isoraers.

     Accordingly, we ask the study group to review and report in summary
form on the available information (with particular emphasis an recent
work) on the chemistry and toxicology of the dibenzodioxins and dibenzo-
furans.                 .             • .  .. •  .   ..   •

     To the extent possible, it would also be desirable to comment on
the potential hazard to humans which can be attributed to registered
uses of PCP and the extent that this hazard may be mitigated by use of
the commercial process which results in lower levels of the contaminants
of interest.  It would be most helpful if you can complete your work by
Jiarch 25 so that the Committee will have an opportunity to study your
report before acting to advise the Agency at its April 19 meeting'.
  •  • *
                                   •Norton N'elson

cc:  Ernst Linde

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7.    APPENDIX C

7.1   Chemistry of PCP and its Contaminants
  7.1.1   Commercial Synthesis of PCP and
          Formation of By-products	   50
  7.1.2   Composition of Commercial  PCP	   52
  7.1.3   Formation of Chlorodioxins and
          Chlorofurans During Commercial
          Synthesis of PCP	   56
  7.1.4   Chemical and Physical Properties
          of PCP,  Chlorodioxins and
          Chlorofurans	   60
  7.1.5   Reactions	   65
  7.1.6   Methods  of Analysis	   72

7.2   Environmental Contamination and Exposure
  7.2.1   Environmental Behavior of  PCP and
          its Contaminants	   76
  7.2.n   Occupational Use and Exposure	   82
  7.2.3   Environmental Transport and Exposure....   83
  7.2.4   Food and Feed	   84
  7.2.5   Biological Uptake and Concentration	   84
  7.2.6   Sources  of Exposure	   86
                             49

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7.   Appendix C

7.1   Chemistry of Pentachlorophenol and its Contaminants
    •
7.1.1   Commercial Synthesis of PCP and Formation of
        By-Products
     Chlorinated phenols, including PCP/ are excellent
bactericides and fungicides and have been widely used for
these purposes since the 1930s.  Two commerical processes
are available for the manufacture of PCP.  One process in-
volves the alkaline hydrolysis of hexachlorobenzene, and
the other process involves direct chlorination of phenol or
a mixture of chlorophenols (Doedens, 1964; Sittig, 1969).

     Pentachlorophenol is produced in the United States
solely by the chlorination of phenol (American Wood
Preservers Institute, 1977).  The overall reaction
follows:
                                    OH
            5 Cl
A1C1,  (catalyst)

    130°C
•f 5 HC
                                   Cl
The chlorination is carried out at substantially
atmospheric pressure using two reactors.   The temperature
of the phenol in the primary reactor at the start is in the
range of 65-130°C (generally 105°C) and is held in this
range until the melting point of the product reaches
95°C.  About three to four atoms of chlorine are added at
this point:
                                                   OH
                           50

-------
                          Cl.
     The temperature is progressively  increased  to  maintain
a temperature of about 10°C above  the  product  melting
poinjt, until the reaction  is completed  in  5-15 hours.   The
reaction mixture, containing about 80%  PCP is  a  liquid  so
that no solvent is required, but catalyst  concentration is
critical.  Generally, 0.0075 mol of anhydrous  aluminum
chloride is used per mol of phenol.

     The off-gas from the  primary  reactor  (largely  HC1
initially and chlorine near the end) is  sent to  a second
reactor (scrubber-reactor  system)  containing excess phenol.
The reactor is held at such a temperature  that the  chlorine
is almost completely reacted to yield  lower chlorinated
phenols, which may be separated and  purified or  returned to
the primary PCP reactor.   The residual  gas is  substantially
pure HC1.

     In the chlorination of phenol to  form PCP,  there is a
progressive increase in temperature  to  keep the  reaction
mixture fluid.  The higher temperature  not only  favors  the
primary synthetic reaction but also, to  some extent favors
formation of the various contaminants  found in PCP.

     The composition of technical  PCP from different
sources varies somewhat.   The PCP  content  is in  the range
of 85-90%.  Several percent of other chlorophenols  are  also
present, as well as a number of impurities including
chlorophenoxy chlorophenols, chlorodibenzo-p-dioxins,
chlorodioxins (1500-3000 ppm), chlorofurans (200-600 ppm)
and chlorodiphenyl ethers. The structure of these various
impurities is shown below.

The presence of hydroxydiphenyl ethers  in  tetra- and
pentachlorophenol has been discussed by  Swedish  chemists
(Jensen and Renberg, 1972; Nilsson  and  Renberg,  1974; Rappe
and Nilsson, 1972) .
                                     Chlorophenoxy cMcrophenol
                                           (predioxin)
    Cl
    Chlorophenoxy chlorophenol
        ({•sopred toxin)
chlorodipheny!  ether
             chlorodihydrcxydlphenyl ether

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7.1.2   Composition of Commercial  PCP

     Results of analysis of  a  commercial  PCP  (Dowicide  1,
Sample 9522 A), produced by  Dow Chemical  Company  in  June
1970 (Dow Chemical Co., 1971),  and a  purified  grade  of  PCP
prepared by distillation of  Dowicide-7 are  shown  in  Table
7.1. '

     The results of recent analyses of a  number of domestic
(Dow) PCP samples for chlorodioxins and chlorofurans by
Swiss workers (Buser and Bosshardt, 1976) are shown  in
Table 7.2.

     The results of analyses of hexa- and octachlorodioxin
in various domestic PCPs (Crummett, 1975) are presented in
Table 7.3.                                        .      .
                                TABLE 7.1

               Comparison of composition of commercial grade
                and purified grade Pentachlorophenol (PCP)

                                   Analytical Results

   Component              •   Commercial8         Purified"
                            (Dowicide 7)        (Dowicide  EC-7)

   Pentachlorophenol            88.4%                89.8%
   Tetrachlorophenol             4.4%                10.1%
   Trichlorophenol               0.1%                 0.1%
   Chlorinated  phenoxyphenols    6.2%                 	
   Octachlorodioxins          2500  ppm              15.0 ppm
   Heptachlorodioxins          125 ppm                6.5 ppm
   Hexachlorodioxins             4 ppm                1.0 ppm
   Octachlorodibenzofurans      80 ppm       ... 1»0 ppm
   Heptachlorodibenzofurans     80 ppm                1.8 ppm
   Hexachlorodibenzofurans      30 ppm                1.0 ppm

   ^Sample  9522 A
    Technical grade PCP reduced by distillation
                            52

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                           Table 7.2

               Chlorodioxins and Chlorofurans in Dow PCP Products
                     (Suser and Bosshardt, 1976)
PCDD^Dpm
Samel es
PCP(EC-7)
PCP(EC-7)
PCP(c)
Pcp(c)
PCP-Na^c^
PCP .
PCP
Hexa-
0.15
0.03
9.5
9.1
3.4
10.0
5.4
Hepta-
1.1
0.6
125
180
40
130
130
Oc-2-
5.5
8.0
160
280
115
210
370
Tetra-
0.45
<0.02
<0.02
0.05
<0.02
0.20
0.07
PCDF^oom
Penta-
0.03
<0.03
0.05
• 0.25
0.05
0.20
0,20
Hexa-
0.3
<0.03
15
36 '
11
13
9
Heosa-
0.5
<0.1
95
320
50
70
60
Octa-
0.2
<0.1
105
210
24
55
65
(a)  PCDD = Polychlordibenzo-p-dioxin
(b)  PCDF - Polychlorod.ibenzofuran
(c)  Dow product, supplied by Fluka, a laboratory chemical supplier.
                           Table 7.3

        Hexa-  and  Octachlorodioxins  in'.Domestic PCPs
                       (Crummett, 1975)

 Sample   Mfgr       Hexachlorodioxin3  Octachlorodioxin
   1
   2
   3
   4
   5
   6
   7
   8
   9
  10
  11
  12
  13
  14
  15
  16
  17

 (a)
         Vulcan
            II
            II
         Reichhold
            n
         Monsanto
           Dow
 lOppm
N.D.
 15
 16
 20
 17
 23
N.D.
 15
 12
 15
N.D.
N.D.
N.D.
 16
 16
 21
 1700ppm
N.D.
 2500
 3600
  700
  600
  900
N.D.
 1400
 1100
 1900
    2
    2
 N.D.
 1500
 1800
 3400
     Detection limit  0.3 ppm,  except for sample  8  which is 2
     ppm; N.D. = not  detected.
(b)  Dection limit  1  ppm,  except for sample  8.which  is 6
     ppm; N.D. = not  detected.

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     A composite lot of PCP (Lot MB-306) was recently
prepared from samples from each of the three domestic
producers of technical PCP. This sample, analyzed by
Monsanto (Vogel et al. , 1976), gave the following results
(see also Table 7.4 below, which gives results of GC-MS
analysis of a sample of Monsanto PCP):

                 Hexa-    Hepta-    Octa-

     PCDD, ppm    11       199      1170
     PCDF, ppm    19        81       137

     Since the structure-biological activity relationships
of the individual hexa- and heptachlorodioxin isomers vary
considerably (Poland et al., 1976; McConnell et al. ,
1978), it is also necessry to determine the levels of
individual isomers in PCP samples.  However, little
information is available on the levels of individual
chlorodioxin or chlorofuran isomers in PCP.  Estimates of
the relative amounts of hexa- and heptachlorodioxin isomers
in PCP (Dowicide 7) and a sodium pentachlorophenate
(PCP-Na)  sample examined by Buser (1975, 1976) are given
in Table 7.5.  The levels of individual dioxins were
estimated from chromatogram or mass fragmentogram peak
heights and the total recorded concentration of hexa- and
heptachlorodioxins.

                         Table 7.4

               GC-MS  Analyses of  Monsanto PCP
                  (Goldstein  et  al., 1977)

                   HxCDD              8 ppm
                   HCDD             520 ppm
                   OCDD            1380 ppm
                   PCDF              40 ppm
                   HCDF              90 ppm
                   HpCDF            400 ppm
                   OCDF             260 ppm


     The Dow Chemical Co.  has been engaged  in research
directed towards fractionation and identification of
contaminants present in various grades of PCP (Stehl and
Crummett, 1977).  Results of examination of three Dow
products for hexachlorodioxin isomers  are shown in Table
7.6.
                             54

-------
                            Table  7.5
       Chlorodioxins  in  a  Commercial  PCP and  PCP-Na  Sample
                       (Buser, 1975, 1976)
Chlorodioxin

1,2,3,6,7,9-ClgD
1,2,3,6,8,9-ClgD
1,2,3,6,7,8-ClgD

l'2!3f,4/6',7,9-5l7D
1,2,3,4,6,7,8-C17D
1,2,3,4,6,7,8,9-Clj
                                ppm Chlorodioxin in
                                PCP-Dowicide 7   PCP-Na
                                     1
                                     3
                                     5
                                     0
                                    63
                                   171
                                   250
                                                   0.5
                                                   1.6
                                                   1.2
                                                   0.1
                                                  16
                                                  22
                                                 110
                           Table  7.6

   Hexachlorodioxin  (HxCDD) Isomers  in  Three  Dow  Products
     as Determined  by  Gas-Liquid  Chromatography  (GLC)
                 (Stehl and Crummett, 1977)
GLC
Peak
 B


 C

 D
                      Relative Isomer'%, HxCDD Concentration
       HxCDD Isomer
       1,2,4,6,7,9-
       (or 1,2,4,6,8,9-)

       1,2,3,6,8,9-
       (or 1,2,3,6,7,9-)

       1,2,3,6,7,8-

       1,2,3,7,8,9-
Dowicide G

-)

_ \


35

43

20
2
Dowicide 7
25

50

25
Trace
Dow Std 82-A
__

29

71
— • ~*
Ratios of 25-50-25 (Dowicide 7) for the A-B-C isomers
compare with Buser's values of 10-35-55.
                          55

-------
                         Table 7.7

          Chlorodibenzofurans in Dow PCP Products

           Tetra            Penta          Hexa
          2,3,6,7-        2,3,4,6,7-     1,2,3,6,7,8-
          2,4,6,7-        1,2,4,7,8-
                          2,3,4,7,8-
     A list of Chlorodibenzofurans tentatively identified
by Dow chemists in Dowicide or EC-7 is shown in Table 7.7.
7.1.3   Formation of Chlorodioxins and Chlorofurans during
        Commercial Synthesis of PCP

     Chlorodioxins may be prepared in condensation
reactions from ortho-substituted chlorophenoxy radicals
(Kulka, 1961) or anions (Pohland and Yang, 1972). Accord-
ing to S.L. Vogel, Monsanto Industrial Chemicals Co.
(Vogel, 1977), dioxin formation occurs during commercial
synthesis of PCP via a series of reactions involving
phenoxy radicals.  Phenoxy radicals are produced from
decomposition of polychlorocyclohexadienone produced by
over-chlorination of tri-, tetra-, or pentachlorophenol.
The phenoxy radical (an electrophile) attacks electro-
negative sites (ortho or para positions)  on a polychloro-
phenol molecule to form phenoxyphenols which undergo
further reaction to form Chlorodioxins.

     The decomposition of tri-, tetra-, or pentachloro-
phenol can also be catalyzed by chlorine (the chlorine
radical is the initiator).  The tetrachlorophenol present
in commercial reaction mixtures (very little trichloro-
phenol is present) serves as a substrate for chlorine
radicals, limiting the chain reaction with PCP molecules
which accelerates PCP decomposition.  The chlorination is
normally stopped when 3-7% tetrachlorophenol remains.
Further chlorination results in increased decomposition
(Table 7.8).
                          56

-------
                  TABLE 7.8


        Reactions in Chlorination of Trichlorophenol
  OH
                     ci
                                     cl
  a

  CM
O Cl

 o
                            o
                            a

                            »
                            o
            o

                   a ci
              a
                              CJ
                              *
                              •o
                    a
                              o
  OH

Ox^a

 iQl   + CI
oY^
  a
  •
  o
                   tlx-x,,
                *  TOT   +• HCI
                  ci
                     Cl
            OH
 fc£  - ^;;^c-l6riQ
            ci
                       Ci
                        a     a      a    o
                               .C!  ,-t ^  «  ^ c.j
a
     a "*r a  CH
       a     a
                                        J^u*
                              HCI
                                          C!
           OH
  ci
                   '* * IQ
                      C/
                           a
                                   ci
                                          t- HCI
                ci
                           Cl
                           cl
  O     OH

 ^%
                                   Cl


                                   Cl
                                         CJ
                                     HCI
       Ci
                              Cl
                               a
                     a

                ci    a
                               a

                               a
                    o
                                 a
               57

-------
      Rearrangement via a spirocyclic anion (Smiles
 rearrangement)  can yield additional  isomers (Gray et  al.,
 1975).  Highly  alkaline conditions  are required  for
 efficient operation of the Smiles rearrangement  since the
 reaction  involves rapid equilibration of the anion  forms of
 a phenoxyphenol  through a spirocyclic intermediate.   This
 is illustrated  by the formation  of  1,2,3,6,7,8-  and
 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin from 2,3,4,6-tetra-
 chlorophenol.

      In the manufacture of pentachlorophenol a considerable
 amount of HC1  is present, so  the Smiles rearrangement is
 unlikely.  Dioxin congeners formed  by normal and
 spirocyclic rearrangement vs.  the levels of individual
 dioxin found  in  PCP (Vogel, 1977) are shown in Table  7.9.
 The hexachlorodioxins found agree with those predicted to
 form without  the Smiles rearrangement.
                                TABLE 7.9

                        01oxin Congeners in Commercial  FCP
   Possible Dioxin Concaners in ?C?
  No Smiles
jtearrancement

1,3,5,8  (100%)
1,2,4,7,9 (752)
1,2,3,7,9 (252)
1,2,3,6,3,9 (50%)
1,2,3,5,7,3 (252)
1,2,4,6,7,9 (25JS)
 With Smiles
Rearrangement

1,3,6,3  (252)
1,3,7,9  (755)

1,2,4,7,9 (31.252)
1,2,3,7,9 (252)
1,2,4,6,3 (43.752)

1,2,3,6,7,5 (31.252)
1,2,3,6,8,9 (18.75%)
1,2,4,6,7,9 (12.52)
1,2,4,6,8,9 (12.52)-
1,2,3,7,3,9 (13.752)
1,2,3,6,7,8 (6.252)
1.2,3,4,6,7;9 (752)   1,2,3,4,6,7,9 (752)

1,2,3,4,6,7,8 (252)   1,2,3,4,6,7,8 (252)

1.2,3,4,6,7,3,9(1002) 1,2,3,4,6,7,3,9(1002)

(a)  PCP producers composite sample.
 Relative i
Iscrcers  Found

   None
   None
  40-50

  20-40
  Trace
  20-40

  ca 60

  ca '40'

   100
PC? in ppm
          (a)
                                                               N.O.
    N,D.
                                                               ca  15
                                          ca 200
                                          ca 1000

-------
     Little information is available on the formation of
dibenzofurans during PCP production.  Formation of
dibenzofurans can be explained by the production of
polychlorodiphenyl ether intermediates (Kulka, 1961;
Plimmer, 1973; Arsenault, 1976) which can lose chlorine to
yield dibenzofuran.

     Cleavage of the polychlorodiphenyl ether in the
presence of HCl yields PCP and hexachlorobenzene.
OH
cirr^ci
ciJ^ci-
Cl

-JU cl
* Cl

     Various free radical reactions might also yield a
number of biphenyl compounds.
        cin*cr
n-l
                                                    n-1
                                                   OH

                                                   Cl
                                                     n
        OH
                              59

-------
Mass spectral data obtained from analysis of contaminants
in PCPs (Firestone et al. , 1972) suggested that
polychlorohydroxybiphenyls were present in these products.
7.1.4   Chemical and Physical Properties of PCP, Chloro-
        dioxins and Chlorofurans

7.1.4.1   Pentachlorophenol

     The chemical and physical properties of compounds play
an important role in their behavior, persistence in the
environment, and biological effects.  Properties of PCP are
given in Table 7.10.  PCP is volatile in steam and soluble
in most organic solvents, although of limited solubility in
CCl^ and in paraffinic petroleum oils (British Crop
Protection Council, 1971).  Also see Bevenue and Beckman
(1967) for data on solubility in various solvents.

     Differential thermal analysis of PCP (Langer et al.,
1973) revealed a solid state transition at 75°C, followed
by melting below 200°C and vaporization above 300°C.
Prolonged heating in bulk above 200°C resulted in
formation of octachlorodioxin in a tar residue.  Heating
the PCP in a sealed capillary at 250°C for ten hours
resulted in formation of about 50% polychlorophenoxyphenol
and a small amount of octachlorodioxin.  Sodium
pentachlorophenate exhibited a strongly exothermic reaction
at about 360°C; upon cooling, essentially pure octa-
chlorodioxin crystallized.

                         TABLE  7.10

       Physical  Properties of Pentachlorophenol  (PCP)
Molecular Weight

Melting point

Boiling point

Density

Vapor Pressure
Solubility H2o

Solubility of sodium salt,

Partition Coefficient

Molar Refraction
266.35

191°C

310°C (decomposes)

1.987

1.6 X 10~4mm Hg (25°)

1.2 X lO'-'-mm Hg (100°C)

40 mm Hg (211°C)

20 ppm at 30°C

33g/100g

1 X 105*01

53.5

-------
7.1.4.2   Chlorodioxins

     Properties of various chlorodioxin congeners are given
in Table 7.11.  The solubilities of 2,3,7,8-tetrachloro-
dibenzo-p-dioxin (TCDD), hexachlorodibenzo-p-dioxin (HxCDD,
a sample of mixed isomers), and octachlorodibenzo-p-dioxin
(OCDD) in several solvents (Stehl and Crummett, 1977) are
shown in Table 7.12.

      The visible absorption  spectra and electron  spin
resonance spectra and g factors of a number of chlorodioxin
cation radicals have been reported (Pohland et al., 1973) .
The crystal structures of  several chlorodioxins have been
determined by x-ray diffraction studies.  The compounds
studied included 1,2,3,1,8,9-hexachlorodibenzo-p-dioxin
(Cantrell et al., 1969), and 2,7-dichloro-2,3,7,8,-
tetrachloro- and octachlorodibenzo-p-dioxins (Boer et al.,
1973).  The x-ray diffraction data indicate that the
C-C1 distances shorten with increasing chlorine
substitution on the rings.  This effect could result from a
reduction in effective electronegativity difference between
Cl and C as more electron density is drawn from the
aromatic ring, which should, in turn, result in increased
covalency of the C-C1 bonds and give shorter distances
(Boer et al., 1973).

     Infrared spectra and characteristic frequencies of a
number of chlorodioxins as well as 2,8-dichloro- and
octachlorofuran have been reported by Chen (1973) .

7.1.4.3   Chlorofurans

     Little information is available to date on the
physical and chemical properties of chlorofurans.   It is
presumed that in the immediate future  increased emphasis
will be placed on identification of specific chlorofuran
isomers occurring in commerical PCP and synthesis  of these
compounds for chemical and toxicological study.  Some
properties of several chlorofurans (Gray et al., 1976;
Page, 1976) are given in Table 7.13.

7.1.4.4   Chlorodiphenyl Ethers and Chlorophenoxy Phenols

       Data on the physical and chemical properties of
Chlorophenoxy phenols are limited.  Lundstrom and  Hutzinger
(1976) prepared several Chlorodiphenyl ethers and  also
cited a number of these compounds prepared by other workers
via various routes.  The melting points of some of the
Chlorodiphenyl ethers are given in Table 7.14.
                           61

-------
                                         TABLE  7.11
                       Physical Properties of Various  Chlorodioxins
                                                               Estimated
Chlorodioxin
2,
2,
•i ,
1,
1,
I/
1,
1,
1,
1,
1,
1,
7,
3,
3,
*• r
2,
2,
2,
2,
2,
2,
2,
2,
-ci2
7-C1
7,
4,
3,
4,
3,
3,
3,
3,
3,
3,
8,
7,
7,
6,
6,
6,
1,
4,
4,
4,
3


:14


8-Cl5
8-C1,.
7,
3,
7,
8,
6,
6,
6,
9-C1
9-C1
8-C1
9-C1
6
6
6
6
7,9-Cl?
7,8-Cl7
7,8,
9-Cl8
Mol.
253.
287.
321.
356.
356.
390.
390.
390.
390.
425.
425.
459.
Wt.
08
53
87
42
42
86
86
86
86
31
31
75
M.P. "P" . « Vapor (b)
C Value13' Pressure
0.76 6.0 x 10~6
162 :. 0.86 3.6 x 10~6
306 0.51 1.7 x 10~&
206
241
240 0.94(d) 6.6 x 10~7
__ —
285
243 —
0.90 3.0 x 10~7
0.90
331 0.90 1.8 x 10~7
Molar UV Max
Refraction i'CHCI) rr\
302
305
71.4 310
72.6 307
308
310
81.1
315
317
85.9
--
90 :i 318
(a)   Beroza,  M.  and M.C. Bov/man, "p" value determined  for  dioxin  between hexane and acetonitrile,
     J.  Assoc.  Offic. Anal. Chem. 4_8:358-370  (.1965).
(b)   Vapor pressure estimated from data of Woolson  (Woolson  e_t  al.,  1973) .
(c)   Estimated by summing atomic refractions.
(d)   1:^* value determined 'for mixture of hexachl^odioxin  isomers.

-------
                              TABLE 7.12

    Solubility of Several Chlorodioxins in Various Solvents3


                  	Solubility in mg per liter

Solvent

acetone

anisole

benzene

chloroform

methanol

toluene

o-xylene

water              0.0002


— indicates no data

(a) Firestone observed that 1,2,3,6,7,8-HxCDD is considerably
      less soluble in organic solvents than other HxCDD isomers
      The solubility of the 1,2,3,6,7,8-isomer in isooctane is
      about 20 mg/1.

(b) Dow standard 82-A, a mixture of 71% 1,2,3,6,1,8-HxCDD and
      29% 1,2,3,6,1,9-HxCDD and 1,2,3,6,8,9-HxCDD.
TCDD
90
—
470
550
10
—
_ _
HxCDD(b)
—
2600
1600
—
—
1800
_ _
OCDD
5
1700
1000
560
—
1500
3600
                           63

-------
Octacliloro
                                               TABLE 7.13

                                      Properties  of Chlorinated Dibenzofurans
Molecular
Weight
Dichloro 209.1
2,4
3,7
2,0
Trichloro 243.5
2,4,6
2,3,8
2,4,7
2,4,8
Tetrachloro 278.1
1,4,6,8
2,4,6,8
2,3,6,8
2,4,6,7
1,2,7,8
2,3,7,0
2,3,6,7
3,4,6,7
Pentachloro 312.6
1,3,4,7,8
1,2,4,7,8
1,2,3,6,7
2,3,4,7,8
Heptachloro 381.6
Melting Vapor Pressure*3'
Point °C (Estimated) 25°C


/ \
185* /
116-117^}
189-191* '



/ i\
198-200r
202-203iaj

227-228l/d)



234-235^



-6
7.3 x 10 °
7.0 x 10"^
6.8 x 10"°
4.0 x 10"f
3.7 x 10~°



2.5 x 10~£
2.5 x 10"?
2.2 x 10~°
2.1 x 107
2.0 x 10~7
2.0 x 10~£
1.9.x l(f£
1.8 x 10"°
-fi
1.3 x 10 *
1.3 x 10"7
1.1 x 10~£
1.1 x 10

416.1
4.4 x 10
3.6 x 10
3.0 x 10
1.9 x 10
                                                     -7
                                                     -7
                                                                  Molar
                                                                Refraction
                                                                   60.2
                                                                   65.0
                                                         (b)
                                          •UV max
                                         (CllCla) nm
                                                                   69.8
                                                                   74.6
                                                                   84.2
89.0
(a) From data supplied by Dr.  David Firestone—private communication.
(b) Calculated from Table of Atomic Refraction.                      ,
(c) II.  Gtlman, ^t al.. ±.  Am.  Cliein.  Soc., ^6:2473,  1934.
(d) A.P.  Gray, et af., J.  Or_a.  Chein.,  41(147^8,  1976.
                                                                                     256,302,313
                                                                                   257,294,310,323
                                                                                     259,309,316
                                                                                   263,272,297,320
                                                                                     256,266,297

-------
                         Table 7.14

          Melting Points of Chlorodiphenyl Ethers

    Diphenyl ether                        M.P.°C
2,4,4'-
2,2',4,4'-
2,3',4,4'-
3,3',4,4'-
2,3,4,5,6-
2,2' ,4,4*5-
2, 3', 4', 5'-
2,2',4,4',5
2, 3', 4,4', 6-
2, 2', 3, 4, 5,6,6'-
Deca-
51-52
70
oil
oil
132-133
oil
65-67
oil
36
147-148
224-225
7.1.4.5   Gas Liquid Chromatography (GLC) Behavior of
          Chlorodioxin and Chlorophenol Congeners

     The GLC behavior of various chlorodioxins and
chlorofurans on nonpolar (OV-101) and Polar (Silar 10-C)
columns is recorded in Tables 7.15 and 7.16.  Retention
times depend on the number and location of chlorine atoms
in the ring system.  Order of elution and retention times
of chlorodioxins on glass capillary columns is reported by
Buser (1975, 1976).

7.1.5   Reactions

7.1.5.1   Pentachlorophenol

     PCP is relatively stable and will not decompose when
heated up to its boiling point; however, it is rapidly and
extensively degraded by ultraviolet irradiation in the
laboratory and by sunlight (when PCP is in solution) and is
decomposed by strong oxidizing agents (Bevenue and Beckman,
1967).

     Similar to any phenol, the phenolic hydroxyl of PCP
takes part in nucleophilic reactions, e.g., it forms esters
with organic and inorganic acid and ethers with alkylating
agents such as methyl iodide or diazomethane.  Electron
withdrawal by the ring-chlorines causes PCP to be unusually
acidic (pK,5,26), roughly comparable to propionic acid
(pK»4.9), and causes it to be a relatively weak nucleo-
phile while stabilizing its salts (sodium pentachloro-
phenate is a stable item of commerce).  While the high
degree of chlorination makes the aromatic ring sufficiently
electropositive to form stable charge-transfer complexes
with electron donors, the ring chlorines are as resistant
to nucleophilic displacement under normal conditions as are
those of the chlorinated aromatic hydrocarbons.
                           65

-------
                             •TABLE 7.15

                       Chlorinated Oibertzofurans
                    GLC Retention Times  Relative to
              2,3,7,3-Tetrachlorodibenzo-p-dioxin (TCDD)
Conqener
2,4,-Clj,
3, 7-01 ^

2,4,6-CU
2,3,8-CH
2,4,7-01^
2,4,8-013
1 .i, 6, 8-01.
2; 4, 5,3-01,
2,3,6,8-Cn
2,4,6,7-01,
1,2,7,8-Ci:
2,3,7,3-017.
2',3,5,7-Cn
3,4,5,7-CIJ
1,3,4,7,8-01,
1,2,4,7,3-01^
1,2,3,6,7-Ci:
2,3,4,7,8-01^
C17
/-•] /
Clj
C18
(1) RRT = retention
(2) Data of O.W. Ph
OV-101(2^
0.24
0.25 ,
0.26
0.44
0.47
—
—
0.70
0.70
0.80
0.82
0.89
0.39
0.93
0.95
1.35
1.35
1.52
1.63
....
—
—
8.3
time relative to TCDD.
illipson, FOA; 2 m x 0.2 cm
Silar lOC^'
0.38
0.40
0.47
0.73
0.83
0.64
0.64
._
--
._.
1.26
1.04
' 1.5Q
1 .56
1.78
1.27
1.27
1.66
—
3.95
4.78
5.87
8.75

i.d. column packed with
     3%  OV-101;  column  temperature,  200°C.
(3)   Data  of O.W.  Phillipscn,  FDA;  2 m  x  0.4  cm  i.d.
     3/c  Silsr IOC;  column  temperafure,  200°C.
column packed with
                             66

-------
               TABLE 7.16

      Chlorinated Dibenzo-p-dioxiris,
      GLC Retention Tiines Relative,  to
2,3,7,8-Tetrachlorcdibenzc-p-dioxin  (TCOO)
o\ c\\
.Conoener OV-101U' Silar 10CU'
2,7,-Cl2D — . 0.30
T,2,4-CUD • .0.49 0.52
2,3,7-Cl^D 0.55 0.54
1,3,6,3-C1,D 0.76 0.62
1,3,7,3-C1,D 0,38 0.78
2,3,7,3-CltO 1.00 1.00
1,2,3,4-ClJO 0.97- 1.01.
1 ,2,3,8-Cl-JD 0.99' . 1.04
1,2,4,7,3-Cl^O 1.57 1.56
1 ,2,3,4, 7-CT:D 1.70 1..76.
l,2,3,7,3-Cl50 1.80 1.82 -
1,2,4,6,739-C1,0 2.48 2.62
1,2,3,6,7,9-C1°0 2.73 2.92
1,2,3,4,7,3-CnO 3.05 3. 11
1,2,3,6,7,3-CHD 3.10 3.23
1,2,3,7,8,9-CUO 3.24 3.56
0
1,2,3,4,6,7,9-C17D 4.75 5.41
1,2,3,4,6,7,8-CUO 5.32 6.20.
CUD 9.1 10.3
o
(1) RRT = retention time relative to 2,3,7,8-Cl^O,
(2) Data of D. Firestone, FDA; glass coil, 2m x'0,4
2% OY-101 on 30-100 mesh Chromosorb WHP; column
(3) Data of 0. Firestone; glass coil, 2m x 0.4 cm i
Silar ICC on 80-100 mesh Chromosorb WHP; column
(4) EC Response = nanograms to give 1/2 full scale
at 16 x attenuation. Hewlett-Packard Model 571
(d.)
EC Response v '
(Silar IOC Column)
0.90
.0.38
0.40
0.32
0.41
0.40
0.25
—
0..41
0.41
0.33
0.23
0..36
0.40
0.37
0.42
0.60
0.70
0.84

cm i.d. , packed with
temperature 210°C.
.d. , packed with 1 .2%
temperature 200°C.
deflection (127 mm)
3A gas chroma tograph.
                 67

-------
     Chlorination  of  PCP  (or  overchlorination  of  phenol
during PCP manufacture) can give rise to a series of
interconvertible nonaromatic cyclic ketones including
hexachloro-2,5-cyclohexadien-l-one, hexachloro-3-
cyclohexen-1-one, heptachloro-3-cyclohexen-l-one, and
octachloro-3-cyclohexen-l-one.   Reduction of these
compounds under mild conditions or treatment with base
provides chlorophenols; for example, PCP is formed from
heptachloro-3-cyclohexen-l-one by boiling with aqueous
acetone or from hexachloro-2,5-cyclohexadien-l-one by
reduction with aqueous sulfur dioxide or potassium iodine.
Heat (as in a gas.chromatograph) also generates phenols
(Svec and Kubelka, 1975).

     Pentachlorophenol, being a weak acid, reacts with
strong bases to give the corresponding water-soluble salts
at a pH of 5.0; the solubility of the sodium salt is about
79 ppm; at pH 8.0, the solubility is greater than 4000 ppm.
PCP is readily converted to the ether derivative, which is
useful for analysis by gas chromatography.  PCP is a
powerful uncoupler of oxidative phosphorylation in various
tissues and apparently reacts with bovine serum albumin
(anion-anion reaction) to form a stable complex from which
the PCP can be liberated with strong base.  PCP forms
colored electron acceptor complexes as do other phenol
derivatives (Hutzinger, 1969);  these complexes are useful
for chromogenic detection and mass spectrometric
identification.

     Treatment of PCP with powerful oxidizing agents
produces pentachlorophenoxyl  radicals which combine
reversibly to form "dimers."   For example, in the presence
of fuming nitric acid or nitronium fluoroborate,  PCP
provides 2,3,4,5,6-pentachloro-4-pentachlorophenoxy-2,5-
cyclohexa-dienone (Chang, 1962).  The radicals or their
dimers can be oxidized further to 2,3,5,6-
tetrachlorobenzoquinone (chloranil).  Chemical oxidation of
PCP under anhydrous conditions was found to result in
production of the radical dimer 2,3,4,5,6-pentachloro-2-
pentachlorphenoxy-3,5-cyclo-hexadienone (Denivelle and
Fort, 1954).

     Pyrolysis of alkali metal salts of PCP (300°C)
results in condensation of two molecules to form OCDD,
1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (Sandermann et
al., 1957).  The reaction proceeds through an intermediate
phenoxyphenol, now called a "predioxin," which is readily
detectable in technical PCP.   Nonvolatile, polymeric
phenylene ethers are formed concurrently by reaction of the
chlorophenol at positions other than ortho.  Small amounts
of initiators such as chlorine or hexachloro-2,5-cyclo-
hexadien-1-one allow OCDD formation to take place at
comparatively low temperatures (200°C) in high yield from
PCP rather than its salts (Kulka, 1961); and pyrolysis of
the chlorinated cyclohexenes themselves smoothly provides
OCDD  (73% yield from hexachloro-2,5-cyclohexadien-l-one at
270 - 280°C), probably through a pentachlorophenoxy-
pentachlorocyclohexadiene such as 2,3,4,5,6-4-pentachloro-
phenoxy-2,5-cyclohexad ienone.

-------
      Results  of  combusting  wood  and paper  treated  with  PCP
or  PCP-Na  indicate  that octachlorodioxin was  not formed
during  combustion with PCP.   However,  ppm  levels of
octachlorodioxin are  formed during  combustion of paper
treated  with  PCP-Na (Stehl  and Lamparski,  1977; Ahling  and
Johansson,  1977).

      The absorption of light  energy rather than heat  allows
PCP to  undergo a number of  reactions under very mild
.conditions; maximum light absorption lies  in  the ultra-
violet  region (245.  and 318  nm) .   In either water or organic
solvents,  PCP undergoes photochemical  reduction to isomeric
tri- and tetrachlorophenols (Crosby and Hamadmad,  1971).
Nucleophiles, such  as bromide  ion,  can displace chloride
from the PCP  ring (Crosby and Wong, 1976),  and in  water the
predominant reaction  is replacement of an  ortho-,  meta-, or
para-chlorine by hydroxyl to provide tetrachlorocatechol,
tetrachlororesorcinol, and  tetrachlorohydroquinone,
respectively. The pentachlorophenoxide anion  can also
displace chloride in  sufficiently concentrated solution
with eventual cyclization to OCDD in water  at ambient
temperatures  (Crosby  and Wong, 1976).

      Photoreactions of PCP  in organic  solvents result
primarily  in  reductive dechlorination  (Zabik  et al., 1976).
The  sodium  salt of  PCP in aqueous solutions yields a
variety  of  colored  products when  irradiated with sunlight
including phenoxybenzoquinones, chloranilic acid (2,5-
dichloro-3,6-dihydroxybenzoquinone), and 2,4,5,6-tetra-
chlororesorcinol (Munakata and Kuwahara, 1969). Plimmer et
al.  (1973)  showed that alkaline aqueous solutions  of PCP,
irradiated  with light in the 300-350 nm region, yielded
octachlorodibenzo-p-dioxin.  Although  a free  radical
mechanism was proposed to account for  the observed products
of  unsensitized photolysis of PCP-Na (Munakata and
Kuwahara, 1969), Crosby and Wong  (1976) demonstrated that
octachlorodibenzo-p-dioxin  is generated photochemically
from PCP in dilute  aqueous sodium hydroxide by a cycli-
zation  process analogous to its generation  from PCP by  heat
(Sandermann et al., 1957).  This mechanism  involves
photonucleophilic displacement of chloride  ions from PCP by
pentachlorophenoxide  ion.
                                            CJ
                          69

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7.1.5.2   Chlorinated Dibenzodioxins

     OCDD and related cyclic ethers appear to be rather
stable chemically/ perhaps due to their planar and
electropositive rings.  For example, OCDD distills
(sublimes) unchanged at 350°C and can be recovered
quantitatively from hot sulfuric acid (Sandermann et al. ,
1957).  However, these polychlorinated ethers share with
PCP the facile photochemical reduction upon ultraviolet
irradiation.  For example, in the presence of an organic
solvent as hydrogen donor, 2,3,7,8-tetrachlorodibenzo-p-
dioxin is rapidly dechlorinated via tri- and dichloro-
dioxins (Crosby et al., 1971); di-and octachloro-dibenzo-
furans are dechlorinated more slowly, and the rate of OCDD
photoreduction is still slower although transient hepta-
and hexachlorodioxins are detectable.
     These compounds are relatively stable and only slowly
biodegradable.  When dissolved in concentrated sulfuric
acid or trifluoromethanesulfonic acid with oxidizing
agents such as f^C^ or KNO-j or with ultraviolet
irradiation, blue to blue-green colored species are
obtained, due to formation of cation radicals (Pohland et
al., 1973; Yang and Pohland, 1973).
                  CF,SO,H —-
                   J  J  C"~
     TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)  is quite
stable to 700°C (50% decomposition at this  temperature
after 21 second exposure),  whereas decomposition is com-
plete at 800°C after 21 second exposure  (Stehl  et al. ,
1973) .
     TCDD is stable in refluxing aqueous alkali solution
(50 ml of 32% aqueous KOH solution plus 20 ml ethanol)
whereas other higher chlorinated dioxins decompose at
varying rates (first-order reaction), presumably due to
hydrolysis (nucleophilic displacement of halogen by
hydroxyl groups) (Firestone, 1977).  Estimated half-lives
(t 1/2) of several dioxin congeners in refluxing KOH
solution are shown in Table 7.17.
                           70

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                         Table 7.17
              Estimated Half-Lives (t 1/2) of
   Several Chlorodioxins in Refluxing KOH Solution ^a'

Congener                                      t 1/2

1,2,3,5,7,8- and 1,2,3,7,8,9-HxCDD              7 hrs
1,2,4,6,7,9- and 1,2,3,4,7,8-HxCDD              2 hrs
1,2,3,4,6,7,8- HCDD                            23 min
1,2,3,4,6,7,9-HCDD                             16 min
1,2,3,4,6,7,8,9-OCDD                          4.5 min

(a) 10-40 ng chlorodioxin refluxed gently with 50 ml of 32%
    aqueous KOH solution and 20 ml ethnol.
     Crosby et al. (1971, 1973) found that TCDD is
rapidly photodecomposed (by reductive dechlorination) in
alcohols whereas octachlorodioxin is much more stable.  In
either sunlight or simulated sunlight, 2,7-dichloro-,2,
3,7-trichloro- and 2,3,7,8-tetrachlorodibenzo-p-dioxins (5
mg/1 in methanol) were entirely decomposed in a few hours.

     Kim et al. (1975) irradiated various chlorodioxin
congeners in isooctane as well as in methanol. The
photolysis rates of the Chlorodioxins in methanol solvent
were similar to those reported by Crosby et al. (1973).

     While photochemical dechlorination is by far the most
rapid known reaction of these compounds, three conditions
are required: the dioxin or dibenzofuran must be accom-
panied by an organic, hydrogen-donating solvent (such as a
pesticide or formulating agent), UV light in the wavelength
region of 290-320 nm must be present, and the light must
penetrate the solvent (Crosby and Wong, 1977). The rate of
photoreduction is inversely proportional to the degree of
chlorination, and, therefore, dechlorinated products do not
accumulate.  Unlike PCP and 2,8-dichlorodibenzofuran, pure
OCDD and TCDD do not appear to be photolyzed in water at
appreciable rates due, perhaps, to their very low
solubility.

     It has been reported that a hydrogen-donating solvent
is not required for photolysis to occur.  There are
indications that a cellulose substrate will permit
photolysis.*
     *See Testimony of Robert D.  Arsenault,  Koppers
Company, Inc., April 3, 1978, in "Testimony of Interested
Parties," section 8.2.3 of this report.


                           71

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     It seems probable that the observed hexa- and hepta-
chlorodioxins are formed thermally from o-phenoxyphenols
(predioxins), detectable in technical PCP and originating
in the small proportions of tri- and tetrachlorophenol
present (Jensen and Renburg, 1973).  (In environmental
samples, these dioxins can arise by similar ring closure by
photoreduction.)  Other phenoxyphenols ("isopredioxins")
are also detectable and may account for the observed
dibenzofurans; dibenzofurans can also be formed photochemi-
cally by rearrangement and subsequent dehydration of £-
phenoxyphenols (Crosby et at., 1973).  The original  ~
pyrolytic conversion of a PCP salt to OCDD was accompanied
by a large proportion of hexachlorobenzene (Sandermann et
al. , 1957),  suggested to arise from decomposition of
decachlorodiphenyl (Kulka, 1961), but this reaction has not
been confirmed.

7.1.6  Methods of Analysis

7.1.6.1   Pentachlorophenol

     The review of PCP by Bevenue and Beckman (1967)
discusses a variety of colorimetric and chromatographic
methods of analysis, including gas chromatography.
Colorimetric methods suffer from lack of sensitivity and
from spectral interferences.  Gas chromatographic methods
usually involve preparation of the methyl ether derivative
with diazomethane.  Argauer (1968) prepared the
chloroacetate for detection of chlorophenols including PCP
by electron-capture gas chromatography (EC-GLC).  Rudling
(1970) described a method for determining PCP in tissues
and water by acetylation of extracted PCP and analysis by
EC-GLC. The identity of PCP in sample extracts was con-
firmed by combined gas chromatography-mass spectrometry
(GC-MS). Farrington and Munday (1976) described the pre-
paration of chlorophenyl 2,4-dinitrophenyl ether for EC-GLC
determination of trace amounts of PCP and other
chlorophenols.

     Barthel et al. (1969) described a method for deter-
mination of PCP in blood, urine, tissue and on clothing in
which the extracted, underivatized PCP was injected on a
GLC column containing 3% diethylene glycol succinate (DECS)
plus 2% syrupy phosphoric acid.

     Fountaine et al. (1975) reported a procedure for
determining PCP in water by ultraviolet ratio spectro-
photometry.  Fritz and Willis (1973) described the
chromatographic separation of PCP and other phenols using
an acrylic resin, and Renberg (1974) reported an ion
exchange technique for determination of PCP in fish and
water.
                           72

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     Yip (1971) reported a modified method for PCP and
chlorophenoxy acid herbicides in total diet samples
involving extraction of the sample with acetonitrile or
chloroform, methylation, Florisil chroma tography to sep-
arate PCP from the other herbicides, and EC-GLC. analysis .
Modifications, based on Yip's method, are currently used by
FDA for total diet analyses.  However, the method suffers
from low and .erratic recoveries, particularly for high-fat
samples at the limits of detection (ca 0.01-0.02 ppm).   In
some instances diethyl ether or diethyl ether-petroleum
ether (1:1) have been used as extracting solvents in an
effort to improve recoveries of PCP.

7.1.6.2   Chlorodioxins , Chlorofurans and Other
          Contaminants in PCP

     PCP contains a number of hexa-, hepta- and octachloro-
dioxins as well as other contaminants (Firestone et al. ,
1972; Woolson et al., 1972; Buser, 1975).  Until recently,
EC-GLC had been used mainly for chlorodioxin analysis.  But
because of the presence of other components, mass
spectrometry has come into use for specific detection and
confirmation of chlorodioxins as well as chlorof urans.

     Villanueva et al . (1975) compared four methods
(Firestone et al. , 1972; Jensen and Renberg, 1973; Crummet
and Stehl, 1973; Rappe and Nilsson, 1972) for analyzing for
chlorodioxins in PCP.  The Crummett and Jensen method,
which involved extraction of non-acidic material in PCP
with etherhexane (1:1), gave the best recoveries, although
the Crummett method, employing ion exchange to remove the
acidic components, was simpler than the Jensen method.

     Crummett and Stehl (1973) employed GC-MS for
determination of hexa- and octachlorodioxin in PCP.  Buser
(1975) developed a specific method for analysis of
chlorodioxins and chlorofurans in PCP and other chloro-
phenols.  Phenolic compounds were extracted with alkali and
the neutral material chromatographed on a basic alumina
micro-column to eliminate polychiorinated benzenes and poly
chlorodiphenyl ethers.  The fraction containing
chlorodioxins and chlorofurans was then subjected to mass
f ragmentographic (GC-MS) analysis at selected m/e values.
It is important to remove orjbho-phe no xy phenol isomers from
the extract since they can undergo ring closure by
elimination of HC1 upon injection in the gas chromatograph,
resulting in formation of a chlorodioxin (Jensen and
Renberg, 1973) .
                           73 '

-------
Recoveries were determined with hexachlorodioxin; the
values ranged from 85% at the 0.2 ug level  (0.05 ppm) to
over 95% at the 10 ug level  (2.5 ppm).

     Buser and Bosshardt  (1976) employed the GC-MS
procedure to examine a number of commercial PCP and PCP-Na
samples.  Chlorodioxins and chlorofurans were detected by
mass fragmentography and  their presence confirmed by
complete mass spectral analysis.  Hexachlorodioxins were
recovered from PCP and PCP-Na samples with 80-95%
efficiency (0.1-30 ppm), and octachlorodioxins with 95%
efficiency (10-30. ppm).

     Buser (1976)  prepared glass capillary columns with 0V-
101, OV-17 and Silar IOC stationary phases for high
resolution gas chromatography of chlorodioxins and
chlorofurans.   The best  separations of hexachlorodioxin
isomers were obtained with the OV-17 glass capillary column.
Sample introduction was  effected by a isothermal splitless
injection technique, using n-tetradecane as the solvent for
column temperatures in the range of 205-225°C. The use of
high resolution glass capillary columns permits the
detection and  quantization of individual isomers.

     Pfeiffer (1976) investigated the use of liquid
chromatography for determination of chlorodioxins in PCP.
The technique was found  to be useful for paid examination of
non-phenolic impurities  in PCP.   Samples could be analyzed
in four hours with detection limits of 0.2 ppm for hexa-
chlorodioxin and 0.1 ppm for octachlorodioxin.

     Vogel et al.  (1976) evaluated three methods for ana-
lyzing for chlorodioxins in PCP.  In method (A)  (Blaser et
al., 1976) phenolics are removed by ion-exchange chrom-
atography, and hexa- and octachlorodioxin are determined by
GC-MS.  In method (B), proposed by J.P Mieure and 0. Hicks,
Monsanto Industrial Chemical Co.,  phenolics are removed by
chromatography on slightly deactivated basic alumina, and
chlorobenzenes, chlorobiphenyls and chlorodiphenyl ethers
are removed by activated  (super 1) basic alumina. Quant-
ization of chlorodioxins and chlorofurans is accomplished by
GC-MS.  In method (C), also proposed by Mieure and Hicks,
chlorodioxins and chlorofurans are isolated by chromato-
graphy on activated basic alumina and examined by GC-MS (or
GLC). Good agreement was obtained  between the three methods.
Method (B) was considered the most sensitive when MS
detection was used; methods (A)  and (C), however, required
less time for analysis.
                           74

-------
     Hass (1977) reported a procedure for analysis of
chlorodioxins in beef liver and fat samples involving solvent
extraction, 112804 cleanup, chromatography on basic
alumina and mass spectral analysis using either electron
impact (El) mass spectrometry or negative chemical ionization
(NCI) mass spectrometry (Hunt et al., 1975) in the selected
ion monitoring mode.  Limits of detection of hexa-, hepta-,
and octachlorodioxin in liver (17-25 g sample) were 0.2-0.5
ng/g (El) and 0.005-0.1 ng/g (NCI); in fat (3-5 g sample) the
respective detection limits were approximately 2 ng/g (El)
and 0.01 ng/g (NCI) .

     Firestone (1976) reported detection of 0.1 to 28 ppb of
total chlorodioxins (hexa-, hepta-, and octachlorodioxin) in
commercial gelatin.  Samples after extraction and cleanup on
alumina and Florisil columns were examined by EC-GLC.  The
presence of hexa-, hepta-, and octachlorodioxin and penta-,
hexa-, and heptachlorofuran in one of the samples (imported
from Mexico) was confirmed by GLC-MS.  Photodechlorination was
used to confirm the presence of octachlorodioxin in some of
the samples.

     The possible number of positional isomers of
chlorodioxins and chlorofurans are shown in Table 7.18.
Aryl hydrocarbon hydroxylase activity (AHH) for dibenzo-p-
dioxins and dibenzofurans are shown in Tables 7.19 and
7.20 respectively.
                           TABLE 7.18

          Chlorinated Dibenzodioxins and Dibenzofurans
                       Isomers  and  Sources

             Possible  Number of  Positional  Isomers


                                     No. of Isomers
Cl Substitution                      Dioxin   Furan
Mono-                                  2         4
Di-                                   10        16
Tri-                                  14        28
Tetra-                                22        38
Penta-                                14        28
Hexa-                                 10        16
Hepta-                                 2         4
Octa-                                  1         l
                                      75       135
                            75

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7.2   Environmental Contamination and Exposure

7.2.1   Environmental Behavior of PGP and its Contaminants

7.2.1.1   Atmospheric Behavior

     Most compounds have a measurable vapor pressure at
ambient temperatures.  It is this characteristic of the
chemical that gives an indication of the propensity for the
substance to escape into the air.  Vapor pressure alone is not
the determining factor in the rate of escape or volatilization
since other factors such as absorption, heat flux, air
movement, i.e., the thickness of diffusion layer, and a number
of other factors are of equal importance (Hartley, 1969; Haque
and Freed, 1974; Plimmer, 1973).  It is the rate of escape or
volatilization that is of interest in considering aerial
contamination and transport rather than vapor pressure, per
se.  The rate of volatilization may be determined experi-
mentally, but, where constraints make this impractical the
rate of volatilization may be calculated using the vapor
pressure data by the following equation:
                   Q = 6 P
This equation gives an estimate of the rate of volatilization
in terms of g/cm2/sec when the material is vaporizing from
its own surface.  However, when adsorbed on a solid surface or
within a matrix, the rate of volatilization is reduced by a
factor of 10-100 by adsorption forces.  Where dealing with
compounds such as pentachlorophenol and its contaminants, a
conservative factor would be about 20 fold.  In view of the
apparent strength of adsorption of these materials, this
factor is more likely to overestimate rate of volatilization
than underestimate.

     Turning to the consideration of pentachlorophenol, we
observe that it has a vapor pressure of 1.6 x 10" _mm Hg at
25°C and this would yield a vapor density of 2.3 x 10~9
g/cm  when evaporating from its own surface.  Following
adsorption pn a solid surface, the calculated rate of evapora-
tion would be 1.7 x 10~10 g/cm2/
•/sec.
                            76

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                            TABLE 7.19

                        Oibenzo-p-dioxins (0):
        Approximate Activity of.Congeners in Chick Embryo Assay
           for Induction of Aryl  Hydrocarbon Hydroxylate(l)

                                     t~\            Approx. Activity,
      Comoound                 Source^ '         •  Relative to TCDD  *
1,2,3,4,7-ClJD^
1 ,2,3,7,8-ClHD
1,2,3,6,7,8-01 "0
1,2,3,7,3,9-ClgO

1,2,3,4,6,7,9-CU
1,2,3,4,5,7,3-01^

1-01 0                            A                     Inactive
2-C1 D                            A
1 ,3-01 0                          B                    .
1,6-ClJD                          B   .
1 ,9-Ci;o                          B                        "
2,3-Ci;D                         B,D
2,7-Ci;0                         Af,E   '
2,8-01 £0      .                    A

1,2,3-01 .,0                        B                 ...
1,2,4-CnD                        A
2,3,7-Clp      '                A,B,C                   0.001

1,2.,3,4-ClJD                     A,B                    Inactive
1,2,6,7-Clp                      B                     0.002
1 ,3,6,8-Cl,0                      A                     Inactive
1,3,7,8-ClJD                      B                     0.1
2,3,7,8-CljD (TCDO)           A.B.C.D.E                 1,0
                                  A         ..           O.T
                                  C                     0.3
1,2,4,7,8-Cl^O                    C

1,2,4,6,7,9-01,0                 A,C                    0.002
1,2,4,6,8,9-CL?0                  B
1,2,3,5,7,9-CnO                  C                     0.15
1,2,3,4,7,3-0120                A,0,0             '      0.3
              °                   C                     0.25
                                  C                     0.25
                 0                C                     0.002
                 0                C                     0.15
1,2,3',4,6,7,8,9-CLD             A,E                    0.002
                  o

2,3-Cl?(UL-U0)0^                 8                     Inactive
2,3,7,3-a4(l,6-JH)0              B                     1.0

(1) Activity data provided by A.  Poland; see also  Environmental. Health .
    Perspectives (1973) 5:245-251; J. Org.  Chem.  (1974), 931-937;  and
    J. Siol. Chem. (19767 251_:4936-4945."
(2) (A) A.£. Pohland (See J.  .Ag.  Food Chem.  (1972) -20:1093-1099);  (b)
    A.S. Kende (See paper ORGN 130, manuscript in  preparation,  167th
    Nat. Mtg. ACS, L.A., Cal., April 4,  1974); (C) A,  Gray (See Tetra-
    hedron Letters (1975) No. 33: 2373-2975  and j. Org.  Chem.  (1975)  4_1_
    2435-2427; (0) J.O. McKinney; and (E) Cow Chemical  Co.  ,
(3) 2,3,7,3-TCOO is assigned  a relative  activity of  1.0.
(4) Contains 5% of 1,2,3,4,7,8-ClgO impurity.

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                                TABLE 7.20
                             Dibenzofurans  (F) :
Approximate Activity in Chick- Embryo Assay  for Induction  of Aryl Hydrocarbon
Hydroxylase.1
Compound
2,4-Cl2F
2,8-Cl F

3'7'ci2F
2,3,4-Cl F
2,3,6-Cl>
2,3,7-Cl^F
2,3,8-Cl^F
2,3,9-Cl F
2,4,6-Clp-  .
2,4,8-CljT

1,4,6,8-C1 F
1,2,7,8-C1*F
1,3,6,7-C1>
i,3,7,8-ci>
2,3,6,7-Cl>
2,3,6,8-Cl F
2,3,7,8-ClTF
2,4,6,7-Cl F
2,4,6,8-Clp1
3.4,6,7-Cl*F

1,2.3,6,7-Cl F
1,2,3,7,8-Cl F
1,2,4,7,8-Cl^F
1,3,4,7,8-Cl^F
2,3,4,6,7-Clp
2,3,4,7,8-Cl^F
2,3,4,6,7,8-Cl F
2,3,4,7,8,9-ClgF

1,2,3,4,6,7,8-C17F

1,2,3,4,6,7,8,9-ClgF
                              Source
                                 D
                               A,B .:
                                 B

                                 B
                                 B
                                B,C
                                B,C
                                 C
                                 C
                                 B

                                 F
                                 C
                                 B
                                 B
                                 B
                                B,C
                                B,C
                                 B
                                B,C
                                 B

                                 B
                                 B
                                 C
                                C,D
                                 B
                                 B

                                B,E
                                 B

                                 B

                                A,B
Approx. Activity Relative to TCDD'
           Inactive
           0.001
           0.001

           0.001
           0.001
           Inactive
           0.02
           0.01
           0.005
           0.7
           0.01
           Inactive
           0.01
           0.2
           0.2

           0.005
           0.1
           0.7
           0.2
           0.3
           0.2
           0.002
     Activity data provided by A.
251, 4936-4946.
                                  Poland; see also J. Biol. Chem.  (1976)
     (A) A. E. Pohland:  (B) A. S. Kende (See paper ORGN 130. manuscript  in
preparation.  167th National Meeting, American Chemical Society, L. A. .  Cal. ,
April 4. 1974): (C) A. P. Gray (See J. Org. Chem. (1976) "41, 2428-2434);  (D)
I. H. Pomerantz; and  (E) J. D. McKinney (in preparation);  (F) S.W. Page  (See
paper ORGN 63, manuscript in preparation.   172 nd National Meeting, ACS,
San Francisco, Cal, Aug. 30-Sept 3, 1976.)

      2,3,7,8-TCDD is assigned a relative activity of 1.0.
                               78

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     Table 7.21 presents the estimated vapor density and
rate of evaporation of chlorodioxins.  The low vapor pressure
of the chlorodioxins coupled with the strong adsorption to
surfaces, as indicated by the high molar refraction and the
data of Kearney et al. (1972, 1973), lend credibility to the
values.
                          Table 7.21

              Estimated  Vapor Density3 and Rate
              of Evaporation*3  (Q) of Chlorodioxins
Compound

2,7-di
2,3,7,8-tetra
penta
hexa
hepta
octa
                                     •5           ^
                  Vapor Density  (g/cm  )   Q (g/cm /sec)
8.2 x
2.9 x
1.7 x 10~
1.4 x 10"jf
6.9 x ID"*2
4.5 x 10"12
                                          6.1 x
                                          2.0 x 10
                                          1.1 x 10
                                          8.4 x 10
                                          4.0 x ID
                                          2.5 x 10
                                                  ~12
                                                  ~13
(a) Above own surface, (b) from adsorbing surface.
     According to Table 7.21, the rate of volatilization of
the chlorodioxins is very low.  This low rate of evaporation
compared to pentachlorophenol could very rapidly explain the
findings of Levin et al. (1976).

     Table 7.22 presents similar data for the chlorinated
dibenzofurans.  The data here indicate a slightly greater
vapor density and evaporative loss for the chloro-
dibenzofurans.  This would be expected of compounds of
slightly lower molecular weight, higher vapor pressure, and
lower molar refraction.
                          TABLE 7.22
            Estimated Vapor Density3 and Rate of
                    *3
Compound
          Evaporation*3 (Q)  of  Chlorinated  Dibenzofurans

                 Vapor Density (g.cm3)     Q (g/cm2/sec)
2,4-di
2,4,6-tri
2,3,7,8-tetra
1,4,6,8-tetra
2,3,4,7,8-pen
1,3,4,7,8-pen
          penta
          penta
  8.2 x 10
  5.2 x 10
  3.0 x 10
  3.7 x lO
  1.9 x lO
  2.2 x 10
  4.3 x 10
                                             6.8
                                             4.0 x 10'12
                                             2.1 x 10~^2
                                             2.7 x 10~J-2
                                                     '
                                             1.3 x
                                             1.5 x
                                             2.5 x
                                                   10~
(a) Above own surface, (b) from adsorbing surface.
                            79

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     Although PCP has a relatively high vapor pressure (1.6 x
10"4 torr at 25°C and 3.1 x 10~3 torr at 50°C, the
temperature of a sunlit surface), there is evidence that it
may be slow to volatilize.  However, its volatilization from
wood into an enclosed airspace is measurable, and the
atmosphere in a wood-treatment plant has been shown to contain
as much as 1.7 ug/m3 of PCP (Wyllie et al., 1975).  PCP has
been detected in rainfall (Bevenue et al., 1972), but the
possibility remains that of this may have been due to its
presence on airborne particles rather than as atmospheric
vapor.  Laboratory experiments indicate that PCP vapor is
stable to sunlight.

     No evidence exists concerning the presence of dioxins or
dibenzofurans in air.  The solubility and vapor pressure of
TCDD and OCDD are roughly similar to those of DDT, and DDT is
known to volatilize readily from soil and rapidly from water.
Neutral PCP impurities might logically be expected to behave
similarly, but their vapor should be stable to light.

7.2.1.2   Behavior in Soil

     Three processes are of significance in soil.  These are
adsorption, leaching and breakdown (Hamaker, 1975; Haque and
Freed, 1974).  Adsorption occurs predominantly on the organic
matter (Hartley, 1969) and clay of soil, though the coarser
mineral particles also adsorb.  Laboratory measurements that
have been shown to correlate well with adsorption include
molar refraction, latent heat of solution, and partition
coefficient.  Based on this, one would expect that penta-
chlorophenol and its various contaminants would all be
relatively strongly adsorbed by soil.

     A number of studies have been performed on the soil
behavior of pentachlorophenol.  PCP is adsorbed to a moderate
degree under acidic conditions (as neutral molecules) but
moves quite readily in ionized form (under neutral or alkaline
conditions) (Kuwatsuka, 1972).  Adsorption is greatest in a
soil in the pH range of 4.6-5.1, with very little adsorption
above pH 6.8 (Choi and Amoine, 1974).  Microbial degradation
is relatively rapid, especially in wet soil where a variety of
tetra-, tri-, and dichlorophenols are formed; meta-chlorines
are the most stable (Ide et al., 1972).  In aerated soil,
oxidation and methylation to pentachloroaonisole and 2,3,5,6-
tetrachlorol,4-dimethoxybenzene represent major routes of
degradation. Similarly, Kearney et al. (1973) and others
indicate a strong adsorption of 2,3,7,8-tetrachloro-
dibenzodioxin and octachlorodioxin (Arsenault, 1976).

     Neither pentachlorophenol (Bevenue and Beckmen, 1967;
Arsenault, 1976; Kearney et al., 1973) nor the dioxins have
been found to leach readily in soil, largely because of the
strong adsorption.
                            80

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     The breakdown of pentachlorophenol and chlorodioxins in
soil have been incompletely studied.  In the case of penta-
chlorophenol, it is known that the breakdown is fairly rapid
(5 to 8 weeks in a moist soil at rates up to 20 Ibs/acre).
Kearney et al. (1972, 1973) report a half-life of approxi-
mately one year for 2,3,7,8-tetrachlorodibenzo-p-dioxin in
soil; the number of species of microorganisms attacking the
chemical appears limited (Matsumura and Benezet, 1973).

     The fate of PCP and its impurities in or on treated wood
is not known, but practical experiments indicate that PCP
remains fungicidally effective for years (Arsenault, 1976).
PCP conceivably could generate OCDD in sunlight, but the usual
presence of hydrocarbon solvents would tend to promote
eventual dioxin photolysis on the wood surface.  The burning
of PCP-treated wood or sawdust generates OCDD which sub-
sequently volatilizes, but the proportion is small in com-
parison to that already present in the wood (Crosby et al.,
1973; Stehl et al., 1973; Jensen and Renberg, 1973).   (There
is a report, presently discounted, that TCDD forms similarly
from organic matter containing trichlorophenol derivatives
(Buu-Hoi et al., 1971), but attempts to repeat the observation
have failed.)

7.2.1.3   Behavior in Aquatic Systems

7.2.1.3.1   Physical Behavior

     The transport and persistence of PCP and sodium PCP in
aquatic systems has been extensively studied, particularly
where these chemicals had been used as a molluscicide  (Strufe,
1968).  Here it has been found that the material is rapidly
adsorbed on suspended particulates.  Where there is a heavy
load of sediment in the water, the concentration of PCP or
sodium PCP is rapidly reduced in the aqueous phase and the
material settles to the bottom with these particles.  PCP,
both as a free phenol and as a sodium salt, has been found to
undergo quite rapid degradation in water, both from sunlight
and anaerobic processes in the bottom mud.

     Little information is available on behavior and fate of
the chlorodioxins and the chlorodibenzofurans in aquatic
systems, but it would seem correct to infer that with their
greater propensity for adsorption they would even more rapidly
and tightly bind to sediment than PCP.  Since the biological
activity of pentachlorophenol has been shown to be markedly
reduced by the adsorption (Strufe, 1968), it would be presumed
that the same would hold true for the dioxins and dibenzo-
furans.

7.2.1.3.2   Breakdown in Aquatic Systems

     In dilute aqueous solutions exposed to sunlight, PCP or
its salts undergo the replacement of ring chlorines by
hydroxyl groups described above.  The resulting tetrachloro-
hydroquinone and tetrachlorocatechol are readily oxidized by
air to quinones which in turn are dechlorinated.  If the
original PCP solution is sufficiently concentrated (as in the

                            81

-------
case of a rice-paddy), the tetrachlorodiphenols can react with
the quinones to give a variety of nontoxic minor products.
However, under most circumstances, the quinone solution  is
rapidly degraded to dichloromaleic acid which itself is
converted to small fragments within a few days (Wong, 1977).

     Considering the similarity between the vapor pressures
and solubilities of TCDD or OCDD and DDT, one might expect
more rapid volatilization of dioxins from water than from
soil.  As mentioned, dioxins in water appear stable to light
due, perhaps, to their insolubility.  In view of their high
degree of adsorption to particulate matter, the amount in
solution would be expected to be low (Matsumura and Benezet,
1973; Isensee and Jones, 1975).

7.2.2   Occupational Use and Exposure

     Pentachlorophenol, both as a free phenol and as a sodium
salt, has been used as a wood preservative, an herbicide, a
fungicide, and a molluscicide.  Use as a wood preservative in
recent years has consumed many times more pentachlorophenol than
all of the other uses. In fact, the use of pentachlorophenol or
sodium pentachlorophenate as an herbicide or a fungicide has
markedly declined in recent years as other chemicals have
replaced them.

     In the United States pentachlorophenol, in an appropriate
solvent, has been the principal form used in wood preservation.
There are limited uses of the sodium pentachlorophenate for
prevention of the development of "blue mold."  However,  in some
countries, e.g., Indonesia, sodium pentachlorophenate is the
principal form in which this preservative is used.

     There are two principal methods by which pentachlorophenol
may be applied for wood preservation (Arsenault, 1976),
pressure treatment or direct application of a solution of penta-
chlorophenol by painting, dipping or spraying.  For the most
part the last three methods are employed by the individual while
the pressure treatment is used by commercial treatment plants.
Another commercial treatment is the thermal process (hot and
cold bath/submersion) which is used to introduce PCP into wood
(Ochrymowych, 1978).

     In the pressure treatment with pentachlorohenol, the
phenol, in appropriate solvent, is applied to the pole or lumber
in a pressure retort at somewhat elevated temperatures.  The
pressure treatment may be preceeded by a vacuum to increase
penetration, and it may be followed by a flash vacuum to reduce
surface deposits. Occupational exposure of humans, in this case,
may occur during preparation of the treatment solution or when
the retort is opened following treatment and the system is still
hot. Relatively lower levels of exposure would be expected in
handling the treated wood.  The greatest exposure comes to the
worker in the immediate area of the treatment operation, whether
by dip, spray, or pressure treatment.  In most of these
instances unless there is direct contact with the treatment
mixture or treated materials, the principal route of exposure
appears to be respiratory.  This is in contrast to the
experience in Indonesia where the worker handles the freshly
dipped lumber or in herbicide treatment where there may be
direct dermal exposure.

                             82

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7.2.3   Environmental Transport and Exposure

      Pentachlorophenol has been found in a number of
different environmental samples (Kutz et al. , 1976), e.g.,
house dust, air, water, and in the urine (Bevenue et al. ,
1972) of presumably non-exposed humans.  This would appear
to indicate a rather high environmental mobility for penta-
chlorophenol.  However, it must be remembered that
pentachlorophenol may be generated in chlorination of water
and that there is a residual background found upon analyses
of soil that gives analytical results similar to PCP.
However, based on the properties of pentachlorophenol,
namely that of vapor pressure and rate, of volatilization,
measurable quantities would be expected to escape into the
air either from the chemical's own surface or from poorly
adsorbing surfaces to which it had been applied.  But based
on pentachlorophenol's propensity for adsorption, one would
expect that a substantial amount of this vaporized material
would be found adsorbed to particulates in air.  Another
route of transport to air would be the erosion of
contaminated dust particles.

      On the other hand, the chlorodioxins and chlorodi-
benzofurans that occur in pentachlorophenol, having much
lower rates of volatilization, would not be expected to be
found as frequently in air samples.  Again, because of the
propensity for adsorption and the low water solubility
(about 3 ppt for OCDD; Arsenault, 1976) one would not
expect to find a great deal of these materials in water. As
indicated earlier, the relative vapor pressures and rate of
evaporation of pentachlorophenol, chlorodioxins and
dibenzofurans would perhaps account for the findings of the
Swedish workers (Levin et al., 1976).  Here it appeared
that the ratio of chlorodioxins and chlorodibenzofurans to
pentachlorophenol in wood increased appreciably over the
ratio found in the original treatment solution.  It seems
that a reasonable explanation would be the probable greater
loss of pentachlorophenol through vaporization from the
sawdust in contrast to the other two types of chemicals.

      Though pentachlorophenol and its contaminants are
probably transported by air and water (probably in the
adsorbed state), their biological activity is probably much
reduced by adsorption, thus attenuating the effect of
exposure.  It has been found, for example, that penta-
chlorophenol adsorbed on sediment found in water had low
activity so far as control of snails is concerned (Strufe,
1968).  It is likely that the adsorptions of the chloro-
dioxins and chlorodibenzofurans also result in a reduction
of their biological availability.
                          83

-------
      Breakdown is another factor in reducing the concen-
tration and biological effects on these chemicals in
transport.

7.2.4   Food and Feed

      PCP is a powerful herbicide, and its intentional use
around food crops would be expected to be negligible.
However, PCP is used as a desiccant on seed alfalfa and seed
clover, and sodium PCP is used in dilute aqueous solution
as a postharvest fungicidal dip.  These are considered as
non-food uses, and no tolerance has been established,
although feeding treated forage or threshings to livestock
is not permitted in the United States.

      Measurement of total diet residues (FDA Market Basket
Survey) has shown occasional PCP contamination (for example,
nine of 30 composite samples showed 0.01-0.02 ppm of PCP in
1972-3; two dairy products, one legume vegetable, and six of
sugar) (Johnson and Manske, 1976). OCDD and HCDD have not
been reported in food, although Firestone (1976) reported the
presence of dioxins in commercial and "edible" packages of
gelatin.  The presence of dioxins (chick edema factors) in
food grade oleic acid and oleic acid derivatives, e.g.,
glyceryl monooleate and a food emulsifier,  prompted FDA to
issue a food additive regulation in 1960 (Firestone, 1973).
Chlorinated anisoles, originating in henhouse litter, have
been detected in chicken meat (0.02-0.08 ppm) and have caused
a musty taste (Curtis et al., 1972).  PCP was reported to
occur at low ppb levels in fish caught in open water not
expected to contain appreciable levels of PCP (Zitko et al. ,
1974).

7.2.5   Biological Uptake and Concentration

      Higher plants do not absorb appreciable amounts of PCP
or TCDD from soil (Miller and Aboul-Ela, 1969; Isensee and
Jones, 1971), and administration of these compounds directly
to leaves resulted in retention rather than translocation.
Algae, however, rapidly absorbed and concentrated TCDD about
10,000 fold from water (Isensee and Jones,  1975), although
they metabolized rather than concentrated PCP (Lu and
Metcalf, 1975) .

      Rodents excreted PCP partly unchanged,  partly as
glucosonide conjugate, and partly as tetrachlorohydro-
quinone and its conjugates (Jakobson and Yllner, 1971;
Ahlborg et al., 1974).  Tetrachlorohydroquinone  also was
detected in the urine of human workers occupationally
                          84

-------
exposed to PCP (Ahlborg et al. , 1974).  However, the rhesus
monkey excreted PCP more slowly, and apparently only as
free PCP, with a half-life of about 40 hours in the male
and 90 hours in the female (Braun and Sauerhoff, 1976).
There appear to be no data on organ accumulation of PCP
during chronic exposure, but recovery of PCP and its
conjugates from urine and feces certainly is not quanti-
tative; for example, about 11% of a 10 mg/kg dose of PCP
was still retained by the monkey after 360 hours (1% in
liver, 7% in intestines, and 3% in other organs) (Braun and
Sauerhoff, 1976).

      Animals in a model aquatic ecosystem concentrated PCP
as much as 300-fold during 48 hours of continuous exposure
(Lu and Metcalf, 1975), although up to 74% of the applied
dose was metabolized in that period.  Fish accumulated the
most PCP after 120 hours of exposure to 0.1 ppm of PCP.
Fish had concentrated it 1000-fold, primarily in the gall-
bladder; return to clean water caused an initially rapid
clearance, mostly in conjugated form. Eventually up to 30%
of the original PCP body burden was retained (Kobayashi and
Akitake, 1975).

      Surprisingly, no data were available on the biocon-
centration of dioxins or dibenzofurans in higher animals
during chronic exposure.  After a single oral dose of
50 ug/kg, the rat cleared TCDD with a half-life of 17 +_ 6
days (Piper et al., 1973).  Retention was primarily in the
liver and secondarily in the fat; the liver still contained
47% of the initial dose after three days and 11% after 21
days. Body burden of TCDD was only determined to 21 days,
at which time it still represented 40% of initial dose;
there is no indication of what terminal residue eventually
might exist, if any.  No metabolism of dioxins was evident.

      Bioconcentration of TCDD in aquatic model ecosystems
was reported by Matsumura and Benezet (1973) and Isensee
and Jones (1975).  Bioconcentration was proportional to the
amount of TCDD in the water; the bioconcentration factor of
approximately 10  in the species included and was rather
independent of the aqueous concentration.  Attempts to
detect TCDD and other dioxins in samples from terminal
predators in the environment (gull eggs, eagle fat, and
sea-lion blubber) were unsuccessful, although the
analytical sensitivity was limited to the ppb range
(Woolson et al., 1973; Bowes et al., 1973).
                          85

-------
     While the potential exists for limited bioconcentration of
PGP from food and the environment, its rather effective
metabolism by higher and lower animals suggests that the
effect may not be pronounced.  On the other hand, TCDD shows
a bioconcentration potential (104) roughly similar to
that of the more inert chlorinated hydrocarbons (10 ).

7.2.6   Sources of Exposure

          Table 7.23 lists major registered uses of PCP.
From these, it is possible to determine a variety of
potential sources of occupational exposure (Table 7.24), but
in only a few instances (primarily in wood treatment
industries) has the exposure of workers been analyzed
(Klemmer, 1972; Ahlborg et al., 1974; and Wyllie et al.,
1975, are typical).

     The widespread use of PCP in these applications
likewise provides increasing opportunities for incidental
exposure of the public to PCP and its impurities in the
home, business, and outdoor environment.   Table 7.25 lists
a few of the more obvious possibilities.   Such instances as
the detection of ppb levels of PCP in rainfall over a
remote island (Bevenue et al., 1972), in freshwater and
marine fish caught in areas remote from direct PCP dis-
charge .(Zitko et al., 1974), and in the urine of random
samples of human populations not exposed  occupationally
suggests a continual low-level background of environmental
PCP which requires further investigation.


                        Table  7.23

                Major  Registered Uses  of  PCP

Herbicide and desiccant for forage seed crops
Insecticide for beehives,  seed flats, greenhouse use.
Microbiostat for commercial and industrial water cooling
Postharvest wash for fruit
Microbiocide for burlap, canvas, cotton,  rope, and twine
Microbiocide for leather
Microbiocide and insecticide for wood treatment
Preservative for oil- and water-based paint
Slime control for pulp and paper
Microbiocide for petroleum drilling mud and flood water
Fumigant for shipping-van  interiors
Preservative for hardboard and particle board
Herbicide for non-food vegetation control
                          86

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                         Table 7.24

       Some Potential Sources of Occupational Exposure
                 to PCP and PCP Impurities

Manufacture and shipping of industrial chlorophenols
Sawmills
Wood-treatment plants
Carpentry and other lumber and wood working
Termite control
Agricultural pesticide application
Greenhouses
Industrial cooling towers and evaporative condensers
Treatment and handling of burlap, canvas, rope, leather
Paper manufacture
Petroleum drilling
Paint manufacture and use
Telephone and electrical line work
                         Table  7.25

       Some Potential Sources of Incidental Exposure
                 to PCP and PCP Impurities

Smoke from sawmills and burning scrap lumber
Sawdust (fuel, floor covering,  particle board, etc.)
Vapor from treated lumber and plywood
Home treatment of lumber for termite control
Burlap, canvas, and rope
Leather products
Paper products
Contact with paint and painted surfaces
Uses of utility and structural  poles and railroad ties
Ornamental wood-chips
Dairy products, sugar products, and fish
                          87

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Argauer, R.J. (1968).  Rapid procedure for  the chloro-
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     & Sons,  New York, pp. 336.

Dow Chemical Company (1971). Private communication.

Dow Chemical Company (1973). Private communication.
                          90

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Farrington, D.S. and J.W. Munday (1976). Determination
     of trace amounts of chlorophenols by gas-liquid
     chromatography.  Analyst 101;639.

Firestone, D. (1977). Report on oils and fats. £. Assoc.
     Offic. Anal. Chem. 60;354.

Firestone, D. (1973). Ethology of chick edema disease.
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Firestone, D. (1976). Determination of polychlorodibenzo-
     p-dioxins and polychlorodibenzofurans in commercial
     gelatins by gas-liquid chromatography. J. Agric.
     Food Chem.  25^:1274.                    ~~

Firestone, D., et al. (1972). Determination of polychloro-
     dibenzo-p-dioxins and related compounds in commercial
     chlorophenols. J. Assoc. Offie. Anal. Chem. 55;85.

Firestone, D., M. Clower, A.P. Borsetti, R.H. Teske, and
     P.E. Long (1978). Polychlorodibenzo-p-dioxin and PCP
     residues in milk and blood of cows fed commercial
     PCP. Submitted to J. Agric. Food Chem.

Fountaine, J.E., P.B. Willis (1973). Chromatographic
     separation  of phenols using an acrylic resin. J.
     Chromatog.  79;107.

Fountaine, J.E., P.B. Joshipura, and P.N. Keliher (1975).
     Determination of pentachlorophenol by ultraviolet
     ratio spectrophotometry. Anal. Chem. 47 ;157.

Fritz, J.S. and  R.B. Willis (1973). Chromatographic
     separation  of phenols using an acrylic resin.
     J.  Chromatog. 79:107.

Gab, S., e_t al.  (1975).  Photomineralization of certain
     aromatic xenobiotica. Chemosphere 4;251.

Goldstein, J.A., M. Friesen, R.E.  Linder, P.  Hickman,
     J. R. Hass,  and H. Bergman (1977).  Effects of PCP on
     hepatic drug-metabolizing enzymes and porphyria
     related to  contamination with chlorinated dibenzo-
     p-dioxins and dibenzofurans.  Biochem. Pharmacol. 26:
     1549.

Gray, A.P., S.P. Cepa, and J.S. Cantrell (1975). Inter-
     vention of  the Smiles rearrangement in synthesis
     of dibenzo-p-dioxins 1,2,3,6,7,8- and 1,2,3,7,8,
     9-hexachlorodibenzo-p-dioxin (HCDD).  Tetrahedron
     Letters 33:2873.
                          91

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Gray, A.P., V.M. Dipinto, and I.J. Solomon (1976).
     Synthesis of specific polychlorinated dibenzo-
     furans. J. Org. Chem. 41:2428.

Hamaker, J.W.  (1975). In:  Environmental Dynamics of
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Haque, R., and V.H. Freed (1974). Residue Reviews 52;89.

Hartley, F.S.  (1969). In: Adv. Chem. Series 86:115.

Hass, J.R. (1977). Private communication.

Helling, C.S., e_t al. (1973). J. Env. Qual. _2:171.

Hunt, D.F.,  T.M. Harvey, and J.W. Russell  (1975). Oxygen
     as a reagent gas for the analysis of 2,3,7,8-tetra-
     chlorodibenzo-p-dioxin by negative ion chemical
     ionization mass spectrometry. J_. Chem. Soc. Chem.
     Comm. 151.

Hutzinger, e_t _al. (1973). Photochemical degradation of
     di- and octachlorodibenzofuran. Environ. Health
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Ide, A., et al. (1972).  Decomposition of pentachloro-
     phenoT in a paddy soil. Agric. Biol. Chem.  36;1937.

Isensee, A.R., and G.E.  Jones (1975). Distribution of
     2,3,7,8-tetrachlorodibenzo-p-dixon (TCDD) in aquatic
     model ecosystem. Environ Sci. Technol. j):669.

Isensee, A.R., and G.E.  Jones (1971). Absorption and
     translocation of root and foliage applied 2,4-
     dichlorophenol, 2,7-dichlorodibenzo-p-dioxin, and
     2,3,7,8-tetrachlorodibenzo-p-dioxin. J Agr. Food
     Chem. ,1£:1210.

Jakobson, I., and Yllner (1971). Metabolism of 14C-
     pentachlorophenol in the mouse. Acta Pharm. Toxicol.
     _29:513.

Jensen, S. and L. Renberg (1972). Contaminants in penta-
     chlorophenol:  chlorinated dioxins and predioxins
     (chlorinated hydroxy-diphenylethers), Ambio 1:62.

Jensen, S. and L. Renberg (1973). Chlorinated dimers
     present  in several technical chlorophenols  used
     as fungicides. Environ. Health Perspect. _5:37.

Kearney,  P.C., e_t al. (1973). In: Chlorodioxins—Origin
     and Fate  (E.H. Blair, ed.). ACS Series 120.
                          92

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Kearney, P.C., et. _al. (1973). Environ. Health Perspect.
     _5:273.

Kearney, P.C. e± a±. (1972). Environ. Sci. Technol. 6^:1017.

Kende, A.S., et al^  (1974). Regiospecific synthesis and
     NMR spectroscopy of toxic polyhalodibenzo-p-dioxins
     and dibenzofurans.  Paper presented, 167th Ann.
     Mtg. Am. Chem.  Soc. March 31, 1974 (Abstract ORGN
     130) .

Kim, P., et al. (1975). Photochemical dechlorination
     of chlorTnated  dibenzo-p-dioxins. Paper presented,
     1st Chemical Congress of North America, November 30-
     December 5, 1975, Mexico City.

Kobayashi, K. and H. Akitake (1975).  Studies on the
     metabolism of chlorophenols in fish-I. Absorption
     and excretion of PCP by goldfish.  Bull. Jap. Soc.
     Sci. Fish.  41(1);87-92.

Kulka, M. (1961).  Octahalogenodibenzo-p-dioxins. Can.
     J. Chem. 3_2:1973.

Kutz, F. et al. (1976).  In: Air Pollution by Pesticides
     and Agricultural Processes (R. Lee, ed.) . Chapter 4,
     CRC Press.

Kuwatsuka, S. (1972).  Degradation of several herbicides
     in soils under different conditions.  In: Environmental
     Toxicology of Pesticides (F. Matsumara, G.M. Boush,
     and T. Misato, eds.). Academic Press, New York, p. 385,

Langer, H.G. , e_t al. (1973).  Thermal chemistry in
     chlorinated phenols, In: Chlorodioxins—Origin and
     Fate. ACS Series 120, Washington, D.C. p. 26.

Leo, £t al.  (1971).  Chemical Reviews 71:525.

Levin, J. ejt al. (1976) .  Scan.  J_._ Work Env. Health 2:11.

Lu, P.-Y and R.L.  Metcalf (1975).  Environmental fate and
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     in a model aquatic ecosystem.  Environ. Health
     Perspect. 10;269.

Melnikov (1971). Residue Reviews 36.

Matsumura, F. and H.J. Benezet (1973).  Studies on the
     bioaccumulation and microbial degradation of 2,3,
     7,8-tetrachlorodibenzo-p-dioxin. Environ. Health
     Perspect. 5:253.
                          93

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McConnell, E.E., J.A. Moore, J. Baseman and M. Harris
     (1978).  The comparative toxicity of chlorinated
     dibenzo-p-dioxins isomers in mice and guinea
     pigs. Toxicol. Ajppl. Pharmacol.  In press.

Miller, C.S. and M.M. Aboul-Ela (1969).  Fate of penta-
     chlorophenol in cotton. £. agr . Food Chem. 17;1244.

Munakata, K. and M. Kuwahara (1969).  Photochemical
     degradation products of PCP.  Residue Reviews, 25;13-23,

Nilsson, C.-A. and L. Renberg (1974) .  Further studies on
     impurities in chlorophenols.  J Chromatogr. 89 ;325.

Ochrymowych, J. , Western Electric (1978).  Personal
     commun i ca t i on .

Page, S.W. (1976). Synthesis of chlorinated dibenzofurans,
     Paper presented at the 172nd Am. Chem. Soc.  Mtg.
     San Francisco, California, August 30- September
     3, 1976 (Abstract ORGN 63).

Pfeiffer, C.D. (1976).  Determination of chlorinated di-
     benzo-p-dioxins in pentachlorophenol by liquid chroma-
     tography. J^ Chroma tog. Sci.  14; 386.

Pierce, R.H. (1978).  Fate and impact of PCP in a fresh-
     water ecosystem.  U.S. EPA,  600/3-78-063, pp 1-62.

Piper,  W.N. , J.Q. Rose, and P.J.  Gehring (1973).   Excre-
     tion and tissue distribution of 2, 3, 7,8-tetrachloro-
     dibenzo-p-dioxin in the rat.  Env.  Health Perspect.
     _5:241.

Plimmer, J.R., ejt al . (1973).  Photochemistry of  dibenzo-
     p-dioxins. In: Chlorodioxins: Origin and Fate.  ASC
     Services 120, pp. 44-54.

Plimmer, J. R. , and U.I. Klingebiel  (1971).  Riboflavin
     photosensitized oxidation of 2,4-dichlorophenol :
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     Science 174 ;407.

Plimmer, J.R. (1973). Technical pentachlorophenol: origin
     and analysis of base-insoluble contaminants. Environ.
     Health Perspect. J5:41.

Pohland, A.E. and G.C. Yang (1972).   J. Agric. Food Chem.
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     and confirmative techniques for dibenzo-p-dioxins
     based upon their cation radicals. Environ. Health
     Perspect. 5:9.
                          94

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Poland, A. and E. Glover  (1976).  Stereospecif ic high
     affinity binding of  2, 3, 7,8-tetrachlorodibenzo-
     p-dioxins by hepatic cytosol. J. Biol. Chem.
Rappe, C., and C. A. Nilsson (1972).  An artifact in the
     gas chromatographic determination of impurities
     in pentachlorophenol. J. Chromatogr . 67;247.

Renberg, L. (1974) .  Ion exchange technique for the
     determination of chlorinated phenols and phenoxy
     acids in organic tissue.  Soil ^ Water Anal. Chem.
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Rudling, L. (1970). Determination of pentachlorophenol in
     organic tissues and water. Water Research ^:533.

Sandermann, W., H. Stockmann, and R. Casten (1957).
     Pyrolysis of pentachlorophenol. Chem. Ber . 90;
     690.

Sittig, M. (1969). Organic Chemical Process Encyclopedia.
     2nd edition.  Noyes Development Corp., Park Ridge,
     New Jersey, pp. 506.

Stehl, R.H., £t a_l. (1973). The stability of pentachloro-
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Stehl, R.H., and W.B. Crummett (1977).  Letter of 2/15/77
     to T.D. Bath.

Stehl, R.H., and L.L. Lamparski (1977).  Combustion  of
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     Science 197:1008.

Strufe, R. (1968).  Residue Reviews 24:79.

Sundstrom, G. , and 0. Hutzinger (1976).  The synthesis of
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Svec, P. and V. Kubelka  (1975). Anomalous behavior of
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Villanueva, E.G., £t al. (1975). A comparison of analytical
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                          95

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Vogel, S.H., et al. (1976). Determination of chlorinated
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Vogel, S.H. (1977).  Communication of 3/7/77 to T. Atkeson
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Woolson, E.A., et al. (1973).  Dioxin residues in Lakeland
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     112.

Woolson, E.A., R.F. Thomas, and P.D.J. Ensor (1972)
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Wong, A.S. (1977). The environmental degradation of penta-
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Wyllie, J.A., et al. (1975).  Exposure and contamination
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Yang, G.C., and A.E., Pohland (1973).  Cation radicals of
     chlorinated dibenzo-p-dioxins.  In: Chlorodioxins—
     Origin and Fate. ACS Series 120, pp. 33.

Zabik, M.J., R.A. Leavitt, and G.C.C. Su (1976).  Photo-
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Zitko, V., O. Hutzinger, and P.M.K. Choi (1974).  Deter-
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                          96

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8.   APPENDIX D

8.1   Agenda of April 3-4, 1978 Meeting of
      EHAC	 100

8.2   Testimony of Interested Parties

  8.2.1   Mr. Dennis Lindsay (AWPI)	 103
  8.2.2   Mr. Dennis Lindsay (VMI)	 107
  8.2.3   Mr. Robert Arsenault (Koppers)	 109
  8.2.4   Dr. Gary A. van Gelder	 129
  8.2.5   Mr. Fred Shelton (Reichhold)	 140
  8.2.6   Dr. Robert L. Johnson (Dow)..	 153

8.3   Comments of Interested Parties

  8.3.1   Mr. Paul. E. des Rosiers  (EPA)...		 158
  8.3.2   Dr. Gary A. van Gelder	 161
  8.3.3   Dr. Robert L. Johnson (Dow)	 165
                        97

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8.1   Agenda  of  Environmental  Health  Advisory Committee
                 Meeting of April  3-4,  1978.

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                                                               FINAL
                    U.S. ENVIRONMENTAL PROTECTION AGENCY
                           SCIENCE ADVISORY BOARD
                   ENVIRONMENTAL HEALTH ADVISORY COMMITTEE

                         Conference Room A (Room 1112)
                          Crystal  Mall Building No.  2
                             Arlington, Virginia

                               April  3-4, 1973

                                   AGENDA


 Monday, April  3, 1973

 9:00 a.m.    1.   Introductions and Opening Remarks             Dr.  Whittenberger

              2.   Draft Report of Study Group on Pentachlorophenol
                  Contaminants TDraft dated March 1978)

                  - Introductory Remarks                       Dr.  Murphy

 9:30 a.m.    3.   Statements by Members of the Public

                  - Mr. Dennis Lindsay, Chairman, PCP Committee
                    American Wood  Preservers Institute

                  - Mr. Robert Arsenault, Director,  New  Product Development
                    Koppers Company

                  - Mr. Dennis Lindsay, Technical  Services
                    Vulcan Materials  Company

                  - Dr. Gary A. van Gelder, Veterinary Toxicologist,
                    College of Veterinary Medicine
                    University of  Missouri, Columbia, Missouri

                  - Mr. Fred Shelton, Vice President, Science and Technology
                    Reichhold Chemicals

                  - Dr. Robert L.  Johnson, Senior Research Analyst
                    Dow Chemical Company

11:00 a.m.                      ***BREAK***
                                      100

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April  3. 1978

11:15  a.m.    4.
                 ENVIRONMENTAL HEALTH  ADVISORY COMMITTEE

                             April  3-4,  1978

                                 AGENDA
                               (Continued)
Comments and Discussion
by Members of Committee and Study Group
                                                                 Dr.  Whittenberger
                                       ***
12:30 p.m.                      ***LUNCH

 1:30 p.m.    5.   Comments  and  Discussion  (Cont'd) and
                 Development of Committee  Recommendations

 3:00 p.m.    6.   Informational  Items

                 -  Publication  of
                   "Noise  - A  Health  Problem"

                 -  Status  of Benzene  Assessment Reports

 3:30 p.m.    7.   Concluding Remarks
                                                Dr.  Whittenberger
                                                Mr.  Marrazzo

                                                Dr.  Saz

                                                Dr.  Whittenberflgr
                              ***RECESS***
 Agenda Notes:

 Dr. James L.  Whittenberger,  Professor  of  Physiology, James  Stevens  Simmons
     Professor of Public  Health,  School of Public Health, Harvard  University,
     Boston, Massachusetts

 Dr. Sheldon D. Murphy,  Professor of Toxicology, Department  of  Pharmacology,
     University of Texas  Medical  School at Houston, Houston, Texas

 Mr. Rudy Marrazzo, Science Advisor, Office of Noise Abatement  and Control ,
     U.S. Environmental  Protection Agency, Washington, D. C.

 Dr. Arthur K.  Saz, Criteria  Development and Special Studies Division,
     Office of Research  and Development, U.S. Environmental  Protection
     Agency, Washington,  D. C.
                                   101

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8.2  Testimony of Interested Parties
                102'

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 8.2.1            SAB Meeting - April 3, 1978



             Statement as AWPI Committee Chairman







     My name is Dennis Lindsay.  I am employed by Vulcan



Materials Company, a pentachlorophenol producer.  The remarks



I wish to make now are on the behalf of the American Wood



Preservers' Institute, also known as AWPI.   Approximately three



years ago the wood preserving industry organized an Environmental



Programs Task Group within the AWPI, a pre-existing trade associa-



tion.  The purpose and goal of the task group was and still is



to make possible the survival of the wood preserving industry



during this time of extensive governmental regulation.  We monitor



the governmental regulatory agencies and comment when appropriate



upon proposed regulation.  We frequently offer our assistance



in helping the agencies understand what it is they are attempting



to regulate.  Our task group chairman appoints subcommitties and



assigns to them various responsibilities.



     I am Chairman of EPTG subcommittee #6, on pentachlorophenol



which was formed about two years ago with the primary purpose



being to defend penta during the anticipated RPAR process and



eventually get it reregistered under FIFRA.



     Our subcommittee appeared before your study group on penta



contaminants at a meeting they held 13 months ago today.  We



made comments and supplied information which I trust was somewhat



useful to them.  Your study group has worked diligently as



evidenced by their draft report.  It is by far the most

-------
 comprehensive document to date and does an excellent job of

 explaining the many facets of this complex problem.

      Our subcommittee has also been very active during these

 past 13 months, both as a group and as individual companies.

 I wish to point out some of our activities and inform you of

 certain facts.
                                                       /

      First of all I wish to call to your attention the fact

 that we, as penta producers, are one less in number than we

 were a year ago.  In the fall of 1970, when the U.S. Department

 of Agriculture first expressed concern about the presence of

 chloro-dioxins in some "economic poisons", that now missing

 producer was the greatest among us.  Their production and sales.
 j-f ptnJ'Q'
Exceeded that of any other producer.

      Thirteen months ago, I reported to your study committee

 that we had been negotiating with the Pacific Bio-Medical Research

 Center at the University of Hawaii concerning the retrieval and

 statistical analysis of data generated in a long term project

 known as the Community Studies on Pesticides.  This study deals
          QC.t Kjgg-/*''** * (
 with chronic/sexposure to technical penta.  We did fund that project,

 We had hoped for an earlier report; however, it is due within

 the next two or three months.  We will make it available to

 your study group and would hope that they at least consider the

 report before writing their final draft and recommendations.

      This committee has also made possible the generation of

 other data relevant to the charge of your study group.  Most of

 the work done during the past year by Dr. Gary Van Gelder,

 University of Missouri, concerning Michigan dairy herds was funded
                                 104

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by this committee.  It was largely Dr. Van Gelder's work which



led the hearing officer, Dr. Gilbert H. Wise, D.V.M. to conclude:



     "The evidence, while not removing all possibility of



     hazard, does not support a finding of any measurable



     magnitude of risk or likelihood of harm to the human



     food chain from exposure of food animals to CDD in



     technical penta."  (Page 16 of hearing officer's report).



     I have attached a copy of Dr. Wise's full report and findings



for your information.  The underlining and notations are my own.



     Next, I would like to call your attention to the current



draft report.  Under in, Section 2, "Toxicology of Chlorinated



Dioxins and Dibenzofurans"; page 5, the last sentence states,



     "Controlled dosing experiments, recently initiated,



     may help answer questions raised by the Michigan field



     studies concerning the pharmacokinetics and toxicity



     of PCP and its contaminants in cattle."



     It is hoped that that report, when completed, would also



be considered by your study group prior to their reaching a



conclusion and recommendation.



     In addition, we are aware of a study by Dr, Firestone in



which he fed technical penta to lactating cows.  Any information



relevant to this problem should be considered prior to a final



report by this committee.



     Our committee is currently considering the funding of a



180-day calf feeding study using varying doses of different kinds



of pentachlorophenol which would be done by Dr. Van Gelder.
                                105

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We are presently waiting upon the results of the Firestone



and Moore studies to help us decide what questions remain



unanswered.



     At the request of AWPI, the American Wood Preservers'



Association, AWPA, the standards writing organization for our



industry, has appointed a special committee to establish



standards for treating wood intended for use in housing food



producing animals.  My point is to show you that we are attempting



to act responsibly in dealing with these problems.
3/28/78

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                SAB Meeting - April 3,  1978



               Statement as VMC Representative







     Gentlemen, I am changing hats now.   The remarks I will



make from here on are as a representative of Vulcan Materials



Company.



     I would first like to direct your  attention to the draft



report, I, page 4.  The last sentence of the top paragraph reads



as follows:



     "Of course, the production of this  more purified



     product entails increased production costs, and some



     representatives of industry felt this would result



     in a product which may be more difficult to handle."



     That statement is not strong enough.  I am convinced that



this would result in a product which is  more difficult to handle.



I know of three separate cases where it  was attempted to use



Dowicide EC-7 in conventional bulk handling systems.  All were



considered failures in the eyes of the  customer, and one resulted



in considerable damage to the equipment.



     Dow has apparently acknowledged this fact, since they



recently announced that they will now produce penta only in the



block form.  That action has caused a large number of smaller



consumers of penta who have been Dow customers to come to the



other producers for a source.  They (the smaller consumers)



cannot afford to purchase the block dissolving equipment.



Vulcan introduced bulk handling of penta ten years ago, and



we believe it to be unequaled in convenience, flexibility and
                               107

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reducing exposure to plant personnel.  Blocks may be a



useful manner of handling penta, but blocks or bulk handling



simply will not serve the purpose of everyone in the industry.



     Thirteen months ago our greatest concern with penta was



that of its contaminants.  Today we hear concern expressed over



fetotoxicity, teratogenicity and even mutagenicity.   In the



face of these concerns, it is difficult for a producer to justify



the capital expenditure in purification facilities for a product



with an environmentally doubtful future.  One producer has ceased



production; and while environmental considerations were not the



underlying reasons, you can be sure that the uncertain future



for this product helped tip the scale in their decision-making



process.



     I would like to propose what I believe is a common sense



solution to this problem.  It is not a new idea.  Others have



proposed it before, but in my opinion, it has merit.



     After studying the draft report of your study group, I



conclude that sufficient scientific evidence upon which to base



a decision is lacking.  Further, since technical penta has been



used for 40 years with only minor and controllable incidents,



I believe that this study group should direct their attention



to outlining the testing which would enable them to make a



decision.  Such testing might be accomplished on a cooperative



basis by the chemical producers.  In this way the wood treaters



would be spared the cost of different handling equipment until



such time as it was necessary, if at all.
3/30/78                        >:-..



                              108

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                               Forest Products Division. Koppers Company, Inc.
                               Pittsburgh, PA 15219, Telephone 412-S3UOTOO 227-2460
8.2.3
Robert 0. Arsenault
Manager
Product Development
Architectural and
Construction Materials
 Dear Mr.  Linde:
                              April 13, 1978
                               Mr.  Ernst Linde
                               Scientist Administrator
                               Science Advisory Board,  A-101
                               Environmental Protection Agency
                               Washington,  D. C.    20460
        Attached  is the written statement of essentially what I said at thai
 SAB Meeting.
                              Sincerely yours,



                              Robert D.  Arsenault
 RDA/mz

 enclosures
                                109

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              Testimony to the EPA Science Advisory Board
     Environmental Health Advisory Committee on Pentachlorophenol
                              April 3, 1978
My name is Robert D. Arsenault.  I am Manager of Product Development,
Forest Products Group, Koppers Company, Inc. I was formerly associated
with Monsanto Company, Paper &  Wood Chemicals Group,  as  Market
Manager for pentachlorophenol and as such I had considerable working
knowledge of pentachlorophenol chemistry and use in wood  preservation.
Koppers Company uses considerable quantities of PCP in its wood treating
facilities and  in formulating blended products for millwork, sapstain control
and other uses.  In addition,  Koppers sells PCP as a broker,  formerly for
Monsanto and now for Reichhold and Vulcan.

I appreciate the opportunity to speak to the Environmental Health Advisory
Committee today.  I will restrict my comments to the draft report of the
Study Group on PCP Contaminants.  I will first make some general com-
ments followed by specific comments.

On the whole I feel that the study group has done an excellent job  in reviewing
the current knowledge on PCP contaminants.  Their conclusions concerning
the potential hazards are especially noteworthy, but these conclusions  are
inconsistent with the  bottom line conclusion.

For example,  on page 1-5 the statement reads, "there is really very little
data on the environmental persistence and transport of the dioxin and dibenzo-
furan contaminents of pentachlorophenol".  On page  1-6 the paper reads,
"The toxicological information necessary to make the evaluation of relative
hazard of purified versus  standard commercial PCP  is also deficient.
Pentachlorophenol itself is a  toxic chemical in its own right.." On page  1-7
the paper reads, "This finding of low, but detectable, levels of chlorinated
dioxins  in tissues of these animals is a matter of public health concern,
however, the  biological significance of this finding  is not presently known. "
And,  "There is insufficient information concerning the identity and dosage
of dioxins  involved to allow these observations in man to be useful in a
quantitative assessment of the relative hazard of purified PCP versus com-
mercial  products containing dioxin contaminants.  There are no data that
permit an  estimate of the  relative  susceptibility of  humans  to systemic
effects of the  dioxins and related contaminants of PCP. "  "As yet, there is
no quantitative information which permits a comparison of the toxicity  of
dioxin to humans versus other animals. "
                                   110

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                                   -2-
All these statements  reinforce our consistent opinion that there are no
known significant hazards  related to the current levels of impurities in
PCP, and there are no data to set any target level judged to be "safe".
Yet, these conclusions were the result of a  review of all known data on
hazardse  No such  review  was made of the costs associated with  gaining
these unstated  "benefits" from removing the impurities; yet,  the state-
ment is made on page 1-4, "Of course, the production of this  more
purified  product entails increased production costs and  some  represen-
tatives of industry  felt this would result in a product which  may be more
difficult  to handle".  A thorough study of the "costs" would  have  shown
that not only are they huge, but the  costs would include  an increase in
exposure to PCP due to the product  being more dusty.  Also,  the costs
would include disposal problems with dioxin still bottoms and difficulty
in using  the purer grade in some industry solvents such as  Koppers
Cellon process.

Despite all the above mentioned  lack of information, the Study Group wrote
conclusion 10 which simply states that since technology is available to clean
up PCP, "it would  seem prudent" to do so.  This statement seems to  us to
be unjustified,  though it is politically expedient.

On pages II-7 and V-3-35 acknowledgement  is  made that some of the PCP
in the environment may come from  generation of PCP by chlorinaticn of
water or creation by  natural processes,,  However, the  implication is  that
PCP  in the environment, found  in urine of non-exposed  humans,  and in
tissue comes from exposure to treated wood in the environment.

One of the problems that has arisen is that pentachlorophenol in the environ-
ment seems to be ubiquitous.  It is  found in  samples taken from the environ-
ment, from animals, and  from  humans.  For example,  the March 1st issue
of Pesticide &  Toxic  Chemicals News reports that the "Environmental
Protection Agency's national human monitoring program has found in the
400 samples of human urine analyzed that nearly 85% of the samples show
'quantifiable amounts of pentachlorophenol', a constituent of many wood
preservatives and a contact herbicide".  Also,  the June 30, 1976 issue  of
Pesticide Chemical News  contained  an article that stated, "hexachloroben-
zene  residues have been found in 75% of mother's milk samples and 95% of
human adipose tissue samples collected in the U.S. by the EPA".  Attached
is a copy of the entire text of this article.  It also states that  HCB contami-
nation of meat is increasing and breast fed infants, in a worst case situation,
could be exposed to HCB levels approaching those demonstrating adverse
effects in laboratory animals.
                                    Ill

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                                  -3-
Tying these two findings together in order to show that PCP and HCB are
interrelated one would only have to prove that pentachlorophenol is a metab-
olite of hexachlorobenzene, or vice-versa.  Since pentachlorophenol is used
in small quantities as a wood preservative compared to hexachlorobenzene
production in the chemical industry,  one would have to agree that pentachloro-
phenol could be a metabolite of hexachlorobenzene in humans, if shown in
laboratory animals.  In fact,  it was shown in monkeys that hexachlorobenzene
metabolized to pentachlorophenol.  I am attaching a copy of a  paper by Yang,
et al entitled,  "Chromatographic Methods for the Analysis of Hexachloroben-
zene and Possible Metabolites in Monkey Fecal Samples".

Another paper  by Engst, et al,  "The Metabolism of Hexachlorobenzene in
Rats",  confirmed earlier findings by Mahendale in 1975 that pentachloro-
phenol was a metabolite of hexachlorobenzene in animals.  I am also
attaching a copy of a paper by Rourke,  et al entitled,  "Identification of
Hexachlorobenzene as a Contaminant in Laboratory Plastic Wash Bottles",
which references three papers by Yang,  et al on the metabolism of hexa-
chlorobenzene  in Rhesus monkeys.  I have given you a copy of the paper by
Renner entitled,  "2, 4, 5-trichlorophenol, A New Urinary Metabolite of
Hexachlorobenzene".

Now how does the hexachlorobenzene get in the environment?  To answer
that question I  am enclosing a copy of a paper written for the Hazardous
Waste Management Division of EPA entitled, "Sources, Characteristics,
and Treatment and Disposal of Industrial Waste Containing Hexachloro-
benzene".  According to the paper there are  23,665 tons per year of
hexachlorobenzene containing waste materials from chlorinated solvent
production alone plus 2,650 tons of hexachlorobenzene from chlorinated
solvents which were presumably removed from the chlorinated solvents
before the sale of the solvents.  It is also known that many of the chlori-
nated solvents  used for dry cleaning contained traces  of hexachlorobenzene
and this could be another reason why humans are exposed to hexachloro-
benzene everywhere.

Another paper  which was sent to us from the Office of Toxic Substances
entitled, "Hexachlorobenzene, A Man Made Pollutant", is attached for
your information.

It is apparent also that this  is not a one-way  proposition.  Fentachloro-
phenol could conceivably degrade to hexachlorobenzene under  certain
conditions,,  Dr.  Donald Crosby in his paper to the EPA Science Advisory
Board,  "Reactions and  Environmental Fate of Pentachlorophenol and its
                                 112

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                                 -4-
Impurities", stated, "the original pyrolytic conversion of a PCP salt to
OCDD was accompanied by a large portion of hexachlorobenzene, sug-
gested to arise from decomposition of decachlorodiphenyl, but this has
not been confirmed".  Hexachlorobenzene also appears to be a byproduct
of UV light degradation of pentachlorophenol on the surface of wood.  It
is my impression that hexachlorobenzene contamination of the environ-
ment is caused from the hexachlorobenzene impurities in chlorinated
chemicals as well as the over 26 million tons per year of HCB containing
waste which are dumped.

Also attached are two  articles which appeared in J. Environ. Sci. Health
in 1976, both covering another source of penta in the environment.  The
use of lindane as an insecticide on  lettuce and endives resulted in the
lindane to convert to trichlorophenol, tetrachlorophenol, pentachlorophenol,
and conjugates of tetra and pentachlorophenols. Non-polar compounds
including hexachlorobenzene were also formed.  In the top soil was also
some penta.  While the article calls these breakdown products metabolites
from the crop, I think it more likely that they are UV light breakdown
products.

The other article covers the metabolism of lindane in rats.  Pentachloro-
phenol is shown to  be  one of the metabolites.  Other metabolites include
2, 3, 4, 6-tetrachlorophenol, 2, 3, 5S 6-tetrachlorophenol, and 2, 4,6-tri-
chlorophenol.  Minor  metabolites were gamma  E, 3, 4, 5, 6-pentachloro-
cyclohexene and  its metabolite, tetrachlorocyclohexanol.

This work also shows  other chemicals which have penta as a  metabolite.
They are pentachlorobenzene and 2, 3, 4, 5, 6-pentachlorocyclohexene-(2)-
ol-(l) and gamma 2,3,4,5,6  pentachlorocyclohexene.

It is beginning to look  like there are many ways for penta to end up in
the food chain, both as metabolites and as breakdown products of other
commonly used pesticides, including hexachlorobenzene  and lindane.

We at Koppers feel so strongly about this issue of pentachlorophenol
being a universal contaminant "caused by use in wood preservation" that
I asked R.  S.  Detrick  of Koppers to present a paper which appeared in
the Forest Products Journal in 1977.  Attached is a copy of the paper.
It refers to many of the items which I have already discussed, but in
summary it shows  that pentachlorophenol in the ppb level can be caused
from other factors  than pentachlorophenol exposure.

There is another area of concern which I feel must be dealt  with in the
Report.  Photolysis of PCP can create OCDD and hexachlorobenzene in
                                113

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                                  -5-
the environment.  Since both of these contaminants are already present
in technical PCP, we question why take them out if they are only going to
form again from sunlight.  However, they also rapidly break down in the
same sunlight.

The paper on  page II-8 states that PCP photodegrades in water and various
solvents. This is covered again briefly on pages V-3-17,  V-3-19, V-3-20,
V-3-22, and V-3-32.  However, on page V-3-22 the Report states that
organic, hydrogen-donating solvent must  be  present for photolysis of
dioxins or dibenzofuran to occur.  This is not true.  We have demonstrated
repeatedly that photolysis and rapid  degradation occurs when dioxins are
present on cellulose  substrate without solvent.  We have extensive infor-
mation to EPA with a letter to Mr. Edwin Johnson dated June 1,  1977 on
the degradation of PCP and OCDD by sunlight and artificial UV light.  None
of these data are referenced in this report.

I am attaching a copy of that June  1st letter and also a copy of a letter
written to Dr.  Donald Islib as part of the  Michigan Hearing Record.  These
documents show that  both technical PCP and EC-7 PCP  reach the same
maximum of OCDD level in micrograms per unit surface area after one
day irradiation by UV light.  This  maximum was then depleted as the OCDD
photodegraded and there  is no difference in the rate of buildup or the  rate
of breakdown  between commercial PCP and EC-7 PCP.  The OCDD con-
centration on the surface reached  3060 ppm on the basis of initial PCP
concentration regardless whether the initial  PCP started with commercial
PCP (1600 ppm OCDD) or EC-7 PCP (60 ppm OCDD).

Hexachlorobenzene also is a degradation byproduct of photolysis  of PCP.
However, HCB is also  a contaminant of PCP. In fact, we  found a sample
of EC-7  PCP  contained approximately four times the HCB  level (170 ppm)
as Monsanto's PCP (45 ppm).  In wipe tests  of wood utility poles exposed
to sunlight for less than one week, poles treated with EC-7 PCP in oil had
approximately ten times the level of HCB  on  the surface of the poles as
expected based on the amount of PCP present.  When compared to poles
treated with commercial  PCP in oil after  three years exposure in Ohio
(different oil), the EC-7 treated  poles had about four times the level of
HCB on the  surface as the commercial PCP treated poles.  While these
levels are not judged to be an environmental  hazard (levels of 0.001 to
0.02 ug/in.^ HCB), they  do indicate that there is no benefit from the
environmental standpoint of reducing the contaminants in PCP.

We are continuing our work on photolysis  of  PCP,  OCDD,  and HCB using
wood as  a substrate.  As more information is generated, we are finding
that UV light degradation eliminates  these products from the environment.
                                  114

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                                  -6-
Therefore, although the grade of PCP makes no difference in quantitative
amount of impurities formed,  in reality the impurities are not a hazard,
whether in the PCP initially or formed from UV light.
                                 115

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                            June 1, 1977
                            Mr.- Edwin L,. Johnson
                            Deputy Assintant Administrator
                               for Pesticide Programs
                            Environmental Protection Agency
                            Washington, D. C.    Z0460
 Dear Mr. Johnson:

 In the past we have submitted information to you on the environmental
 fate of peatachlorophcnol (PCP) Including information on  degradation of
 PCP in soil and the degradation of octachlorodibenzo-p-dioxin (OCDD)
 in soil.   This  was a  part  of the  package which was  submitted by  Ron
 Drear to the Science Advisory Board Ad Hoc Panel studying the  dioxin
 question.

 We understand that the Science  Advisory Board  will shortly be completing
 their report and recommendations.  One part of the Draft copy of the
 report, written by Dr. Crosby, referred to pcntachlorophcnoxide-ion
 undergoing cycllr.ation to OCDD in water, and also photodegradation of
 OCDD by ultraviolet (UV) light in  the presence of a hydrogen donor such
 as alcohol.  Dr. Cronby wrote that, "the rate of photo-reduction is
 inversely proportional to the degree of chlorination",  indicating  that the
 lower chlorinated dioxina degrade faster than the higher chlorinated
 dioxins.  lie further wrote that, "PCP could conceivably  generate OCDD
.in sunlight,  but the usual presence of hydrocarbon solvents would tend
 to promote eventual dioxin photolysis on the wood surface".

 A« pA rt of our continuing program of environmental and health studies
 with wood pr eservat Ives, we have been  in vest igating the photochemistry
 of pentachloroplu nol And the contained  dioxins.  Thus  far, this work
 Rupportn  the fltatrmenlfl  made by  Dr. Cronby, and thr reHults emphasize
 that dioxind that may be  generated from PCP irradiation  on  the surface
 of the wood are themsrlves degraded.  A hydrogen donor  solvent, however,
 is not n.ecessary.  Ccllulosic  material  can  act as the hydrogen donor.
                                116

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                           Mr. FMwln L. Johnson
                           Page 2
                           June 1, 1977
From an environmental point of view the surface of the treated wood la
Important because  It constitutes an avenue of exposure to man and the
environment.   In order to simulate the surface of the wood without having
interactions such as bleeding, variability, and analytical difficulty, we
have done most of our work with filter paper Impregnated with a solution
of PCP or OCDD.

We have conducted several experiments exposing technical PCP,  purified
PCP, Dowicide EC-7 PCP, and OCDD on filter paper and technical PCP
and Dowicide  EC-7 PCP on wood,  with and without oil present, in artifi-
cial UV light and In sunlight.   Our experiments are continuing, but we
have preliminary results that we feel are meaningful even though we have
not yet completed  these studies.

Working with  filter paper, our  studios show that when PCP Is  exposed to
UV light, photodegradatlon occurs and OCDD Is one of the products formed.
Continued exposure to UV light degrades the  OCDD.  These chemical
reactions occur whether the PCP being  exposed to  UV light is  of the  EC-7
grade or the technical grade.  What surprised us In our studies,  however,
wao that regardless of the original  OCDD content of the  PCP,  the ultimate
level to which the  OCDD builds up  Is about the same.

The EC-7 sample  we used contained 13  ppm of OCDD.  The commercial
PCP sample contained 1,466  ppm of OCDD.  When 15 mg of EC-7 grade
PCP was irradiated for two days,  the dioxin  level on the filter paper  rose
from the initial 0.2 ug to 58 ug of OCDD.   When 15 mg of commercial PCP
was irradiated, the dioxin level rose from the Initial 22 ug to 64 ug. .  The
EC-7 grade PC P generated 58 ug  in the same time that commercial PCP
generated 42 ug, and both grades  of PCP developed approximately the
same level of OCDD.  Once a critical level of OCDD was reached, the
OCDD photodegradcd to lower levels.

After seven days only 3% of the original PCP remained and the OCDD
level had dropped  about 33% from the peak value.   After ten days  the
OCDD level had dropped to about 50% of the peak value.

In our te«ts,-a large part  of the PCP wan  lost due to  volatilization rather
than photolysis.  Working without UV light, but keeping  all other  condi-
tions constant,  f'2% of a 7. 5 mg sample volatilized In three dnys'  exposure.
Similar studies hnvc n.ot been conducted an yet on  OCDD.  However,  Inas-
much as OCDD has a vapor pressure less than 1/800 that of PCP, It Is

                                    117

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                            Mr. I'd win L. Joltnncm
                            r.ip.e 3
                            June 1.  1977
aflaumcd that nlgnificant Ions by volatlt Izat lou does not occur.   V.'e would  .
expect hiphcr chlorinated dloxlns to degrade on the surface by UV light
rather than vaporize into the environment.

Our work with  PCP treated v/ood polos han not reached the point today
that we can prove conclusively that dtoxins are formed from the PCP
on the surface  of wood that in  exposed to sunlight.  V/e believe, however,
that such IB the case.  The work docs  Indicate that there is a breakdown
of dioxlns that  are originally present or which may be formed  oa the aur-
face of the wood.

Wipe  teats conducted on three commercial PCP/Cellon treated poles
which were in  place for three  years in California, show lower PCP and
OCDD concentratlone  on the ounny south  side of the pole than on the north
shaded side.  The  PCP content on the south side  of these poles averaged
0.34 ug/sq. in. and on the north side averaged 2. 08 ug/sq.  in. The
corresponding  OCDD levels  were 0.010 ug/sq. in.  on  the south side and
0.024 ug/oq. in. on the north  side.  The lower OCDD  content on the south
side of the pole, as compared to the north side reflects the effect of UV
light on OCDD. V/e interpret  the higher  ratio of  OCDD to PCP on the
south side of the pole  as compared  to the north side of the pole to reflect
both the  effect  of UV light on the degradation of PCP aud vaporization of
PCP..

We have found  somewhat the same relationship when PCP/oil treated
polos were tested.  Thene also had been  In service three years. On the
south aide of thene poles the PCP level wan 0.7 ug/nq. in. and on the
north side the  PCP level \vas 3.1 ug/sq.  in^  The OCDD levels  respec-
tively were 0. 01 3 and 0. 032 ug/sq. in.  These data substantiate that
even though dioxtns m ight form from  PCP In wood exposed to the sun,
they also arc eventually destroyed by the sun.

"\Ve have indications that these fjame phenomena occur  on poles treated
with EC-7/oil  solution.  The wood inside thene poles was extracted and
analyzed to confirm that (he polen were.  In fact,  treated with FC-7.
The PCP contained the average of 22. 5 ppm of CCDD.   The. wood con-
tained an average of 1 . 1 ?"/'• TCP.  However,  on the surface of the  poles,
wipe testa showed from 0.001  to 0. 008 ug/oq. in. of OCDD on  poles
which were two week.i to two months old.  V>'c have found substantially
the same levela of OCDD (.001 to .008 ug/oq. In.) on the surface of
                               118

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                            Mr. J'-lwln JL. Jolinnon
                            r.->«r -t
                            June 1,  1977
Ccllon polca treated with the technical pradr of PC P after 15 weeks'
c-xponurc to the oun In Pennsylvania.  Whether thcoc numbers reflect
rcaulta from bleeding,  PCP loaa or sunlight generation is unconfirmed.
 •
We feel that thcor  rcaulta nupport the conclualona drawn from the
laboratory testa thnt (1) FC-7 grade  PCP on a cellulone aubatratc
exposed to UV  lipht photodegrades to OCDD, reaching the same OCDD
concentration level an technical  grade PCP exposed under the same
conditlona,  and (2) after  reaching some critical level,  the OCDD con-
centration dccreaacs due to photodcgra.datl.on..                       -...__

It  Is Important to note that we have not found any tctrachlorodibenzo- p-
dioxin formed, due to photolysis of PCP or OCDD,  cither in the
laboratory or field studies.   Much of the work  reported here are the
preliminary results In a  continuing study,

We will keep you informed aa new Information  \a generated.  We will
appreciate the  opportunity to visit with you to discuss the results of
our work In more detail.
                           Sincerely youra,
                           Robert D. Araenault
RDA/mz

bcc:  H.  1". S|>;>(•/.
      I),  lj, I);ivir
      D.  G. n.-illn
                                119

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                             July 20, 1977
                             Mr. Donald R. Islib
                             Chief Deputy .Director
                             Michigan Dept. of Agriculture
                             Louis Cass Bldg.
                             P. 0. Box 30017
                             Lansing, Michigan 48909
                             Subject:  Effect of UV Light on
                                       Pentachlorophenol (PCP)
Dear Mr. Islib:

At the Public Hearing on Proposed Regulation No. 637 on May 26, 1977, our
Mr. R.. D. Arsenault mentioned that studies by Koppers Company had shown
that pentachlorophenol deposited on cellulosic.filter paper and exposed
to UV light was decomposed and one of the products of decomposition was
octachlorodibenzodioxin (OCDD) which in turn was also decomposed by the.
UV light.  At the continuation of the hearing on July 12, the validity of
the Koppers data was questioned on the basis that the artificial Tight
used by Koppers was substantially different from sunlight.  The purpose
of this letter is to provide you with additional information and comments
on these subjects.

Even though pentachlorophenol is toxic in its own right, much of the
discussion of risks before the hearing board has focused on the chloro-
dibenzodioxins that are impurities in commercial grades of pentachloro-
phenol.  Octachlorodibenzodioxin (OCDD) is the most prevalent chloro-
dibenzodioxin in commercial grades of pentachlorophenol and i^s analysis
is subject to fewer uncertainties.  Therefore, much of the following
discussion will focus on octachlorodibenzodioxin (OCDD).  Tetrachlorodi-
benzodioxin (TCDD) was not detected as a degradation product of either
OCDD or pentachlorophenol.  Hexa- and heptachlorodibenzodioxins were
detected, but not quantified.

Octa- and tetrachlorodibenzodioxins (OCDD and TCDD) deposited on filter
paper, are readily degraded by UV light from both sunlight and artificial
light sources.  Experimental data are summarized in the attached tables
I and II.  These tables include long and short wavelength intensities of
the artificial light source and Pittsburgh sunlight and are shown to be
similar.  The calculated velocity constants, assuming first order reactions,
are shown in Table  III.  The experimental procedure by which these data were
obtained is also attached.
                                     120

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                                    Mr. Donald R.  Islib
                                    July 20,  1977
                                    2.
 Pentachlorophenol  (PCP)  (both  commercial grade and Dow EC-7 grade) deposited
 on  filter  paper  is  readily  degraded by UV  light.  Experiments were confined
 to  artificial  light,  because this  light source was considered to be a
 reasonable facsimile  of  sunlight,  it  is uniform from hour to hour while
 sunlight  is  not,  and  the degradation  of pentachlorophenol by sunlight  had
 already been demonstrated by other investigators.

 The attached paper  entitled "Weathering and  Stabilization of Polyolefins"  by
 J.  A.  Melchore (I&EC  Product Research & Development, Vol.1, No. 4 pp 232-235
 (1962) describes  the  artificial  light source used in our work.  The wave-
 lengths of light  in sunlight and the  artificial light are shown in Figure  1.
 Both sources emit light  at  wavelengths below 350 my which is the wavelength
 below which  pentachlorophenol  (PCP) absorbes UV light.  Pentachlorophenol
 (PCP)  absorbes UV light  strongly at wavelengths below about 310 my.
 Presumably,  these are the v/avelengths that provide the energy for the
 observed degradation  of  PCP.

 Experimental data for the UV degradation of  pentachlorophenol (PCP)
 obtained  in  recent  weeks are summarized in Table IV and V, for commercial
 grade and  EC-7 grade  PCP, respectively.  Starting at 7500 yg PCP, about
 the same concentration on the  filter  paper that would be used for the
 treatment  of wood,  more  than 90% of the PCP  had degraded in seven days.
 In  both cases, OCDD was  produced as a degradation product at a peak value
 of  23 yg OCDD  regardless of the  initial concentration of OCDD in the PCP.
 The same data  are shown  in  Tables  VI  and VII, in which the OCDD on the UV
 exposed paper  is  expressed  in  parts per million (ppm) of the initial
 quantity of  PCP  that  v/as applied to the paper.  On this basis, the OCDD
 concentration  reached 3060  ppm in  both cases.

 In  assessing the  risks of exposure of either humans or animals to treated
 wood,  chemicals  on  the surface of  the wood should be the principal concern,
 not the chemicals embedded  in  the  internal structure of the wood.  From
 this point of  view, the  foregoing  experiments on filter paper strongly
 suggest that exposure of either  humans or  animals to either commercial
 grade or EC-7  grade of Pentachlorophenol would not be significantly
 different.

                                    Yours  truly,

                                      9
                                    f\
       .^'.
P.. S. Detrick, Manager
Environmental  Health and Safety Section
 RSD:mjt

 Attachments

bcc:  !r.  15.  fc.
      Hr.  D.  1..  Dr;'/1f!S
                                      121

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            EFFECT OF UV LIGHT ON PtLNTACIILORQPHENQL (PCP)
                   AND SELECTED CHLOKODIBEKZODIOXlffiS
 1.  Experimental  Procedure

 Standards of OCDD and  1,2,3,4-TCDD were obtained from Analabs, and the
 2,3,7,8-TCDD from D. Firestone of the FDA.  All dioxins were used without
 further purification.  All stock solutions were prepared in reagent
 grade benzene, and stored in aluminum foil covered bottles in the dark.
 All work concerning the TCDD was done on the 1,2,3,4-TCDD isomer unless
 noted.

 Dioxins to be irradiated by UV were applied in benzene solutions via a
 2 cc pipet onto a 2-inch by 5-inch strip of Whatman No. 42 ashless filter
 paper.  The weight of  a strip of filter paper was 0.72 gram, and the
 concentrations of the  OCDD were calculated to be in the same ratio as
 they exist on a typical penta-treated pole.

 The UV degradation rates of OCDD and TCDD in various sample systems
 were determined in both sunlight and artifically produced UV light.  The
 description and operation of the artificial UV exposure system is
 discussed by Melchore.3  The UV radiation was measured at the surface
 of the samples by an Ultra-Violet Products UV Meter at both short and
 long wavelengths.  The average intensities for the unit were 1.02 milli-
 watts/cm  for the short wavelength (254 nm peak), and 0.63 mwatts/cm
 for the long wavelength (365 nm peak) detector.

 The dioxins were recovered from the filter paper by cutting the paper into
 small strips and placing them in a small bottle along with a 25 cc
 aliquot of benzene.  The samples were shaken on a wrist action shaker
 for 30 minutes, and the benzene solution was analyzed by a gas chromato-
 graphlc technique.

 Gas chromatographic analyses (GC) were carried out on a Hewlett-Packard
 Instrument (Model 5701A) using a 3.'  x 1/4" glass column packed with 10%
 OV-101 on 60/80-mesh Chrom Q, a si lane-treated diatomaceous earth support.
 Programmed temperature gas chromatography was used for the analysis of
 allsamples containing OCDD.   Samples containing only TCDD were analyzed
 isothermally at 250°C.   The temperature program consisted of holding
 at 250°C for 8 minutes, raising the temperature to 2CQOC at S^C/min.
 and holding at that temperature for an additional 8 minutes.   Under
 these conditions the TCDD eluted at 4.4 minutes and the OCDD at 17.0
minutes.   A Ni63 electron capture detector was used because of its
 sensitivity to halogenated compounds.   The carriar gis  was a 90/10
mixture of argon/methane,  and its flow rate was 40 cc per minute.   Samples
were analyzed quantitatively for either TCDD or OCOD by using band area
measurements (the height x width at half-height method) and abso1ut2
standards.
3.  "Weathering and Stabilization of Polyolefins," Melchore,  J.A.,
    I&EC Product Research and Development. Vol.  1_ No.  4, pp 232-235,
    December, 1962,

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2.  Clean-up Procedures

    a.  Monsanto Method No. 70-20

This method provided by Monsanto is designed to remove from the sample
phenolic compounds which might interfere with the analysis of the
various chlorodioxins.  In this method, the sample, which has been
dissolved in benzene, is extracted three times with 20-cc portions of
5% Na"OH, and backwashed twice with 20-cc portions of distilled water
containing about 0.2 gram NaCl.  The benzene solution is then passed
through clean cotton in the tip of the separatory funnel.  This benzene
solution is either analyzed directly or further purified by the alumina
column described below.

    b.  Alumina "Mini" Columns
The "mini" columns were prepared from 5 mm I.D.  glass tubing which was
drawn to a fine tip.  A small plug of glass wool was inserted, and the
column filled with Alcoa F-20 alumina heated for 16 hours at 400°C.  The
height of the alumina was approximately 200 mm.   A 5-cc aliquot of the
sample solution was placed on the column.  Since some of the sample
solution was absorbed on the column, additional  benzene was added until
exactly 5 cc was eluted from the column.  This was done by placing the tip
of the column into a 5-cc volumetric flask and  filling it to the mark as
the benzene solution eluted from the column.

3.  Recovery of OCDD and TCDD from Filter Paper  Strips

Standard solutions of OCDD and TCDD, were applied to the filter paper
strips and recovered as previously described.  The recovery was determined
for various periods of time.  These included:   (a) immediately after the
benzene had evaporated, (b) after 18 hours in  the dark, and (c) after
67 hours in the dark..  The results show that the recovery of OCDD was
at least 95% with or without oil; the recovery of TCDD averaged 92%
with or without oil.

4.  Recovery of OCDD from Alumina "Mini" Columns

Since the alumina "mini" columns were used to clean up the wood extracts,
the recovery of the OCDD was determined to insure that no OCDD was being
adsorbed by the columns.  A 5-cc aliquot of an OCDD standard,  treated
as previously described, gave 100% recovery.

5.  Degradation Rates of OCDD and TCDD by Artificial UV Light

Standards of OCDD, 1,2,3,4-TCDD, and 2,3,7,8-TCDD were applied to filter
paper strips and exposed to artificial I'V light  for varying periods of
time.  The data which is shown in Table I can be summarized as follows:
a) the degradation of TCDD is faster than OCDD,  b) the degradation of
OCDD is faster in systems containing oil (P-9 or Nujol) than in systems
not contain'inq oil, c) the degradation of OCDD is faster in systems containing
Nujol than systems containing P-9 oil, and d) the degradation  of 2,3,7,8-TCDD
is faster than that of 1,2,3,4-TCDD.  The UV degradation of both OCDD
and TCDD on cellulose appears to occur at a faster rate than in solution.1

1.  "Photo Decomposition of Chlorinated Dibenzo-p-Dioxins," Plimmer,  J. R.,
    and Woolson, E. A., Science. August 1971.
                                    123

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                                                                        J.
6.  Degradation- Rat^-s _o_f p^D_d'id_ H,hJ by_.S

Standards of OCDD, with an without oil, and TCDD were applied to filter
paper strips and exposed to sunlight for varying periods of time.  The
8-hour and 16-hour exposure tests were run over a period of 2 to 3 days,
and were stored in a darl< cupboard overniyht.  The UV intensity during
exposure was measured quite frequently because of the extreme variation that
was observed.  The intensity data was intc-grated over the exposure time
to measure total exposure.  The degradation data which can be seen in Table IV
showed the same trends observed for the samples exposed to artificial UV
light, except that the rates in sunlight were slower than those observed in
the artificial light.  The first order velocity constants were calculated
for all samples to further substantiate the observations noted above and
can be seen in Table III.
                                     124

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                             Table 1
          Degradation nf OCDD and TCDD by Artificial UV Light
Dloxin
OCDD
TCDD
None
TCDD
    I/
OCDD
None



Nujol

P-9
Exposure
.. (hrs.)

   1
   2
   4
   6
  16
  67

   1
   2
   4
   6
  16

   4
   8
  16

   6
  16
  67
                             Exposure  Intensity
                               (mwntts/cm'")
                      Long Wavelength   Short Wavelength
 0.63
 1.26
 2.52
 3.78
10.1
42.1

 0.63
 1.26
 2.52
 3.78
10.1

 2.52
 5.04
10.1

 3.78.
10. L
42.1
 1.02
 2.04
 4.08
 6.12
16.3
68.3

 1.02.
 2.04
 4.08
 6.12
16.3

 4.08
 8.16
16.3

 6.12
16.3
68.3
Remaining

  94
  88
  85
  77
  60
  33

  86
  81
  69
  58
  20

  38
  28
   6

  ' 2
 < O.f
   8
    I/  This TCDD is the -2,3,7,8 isomer.
                                125

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                              Tahle It
           Degradation p_f. Of: DP  ami  1C DP b v _ fei tu r a_i_Sj i uj. i£h_
Dioxin Oil
•
OCDD None


OCDD P-9


OCDD Nujol

TCDD None


Exposure
(hrs.)
5.5
a
16
5
8.8
16
5
3.8
16
5.5
8.8
16
Exposure Intensity
(mwatts/cm~)
Long Wavelength Short Wavelength
2.26
3.86
6.88
2.26
3.86
fr.88
2.26
3.86
6.88
2.26
3.86
6.88
4.19
6.78
12.1
4.19
6.78
12.1
4.1.9
6.78
12.1
4.19
6.78
12.1
7, Remaining
89
91
83
47
47
34
48
42
18
82
77
57
                              Table III

               Velocity Constants  for  the  Decomposition
                           of OCDD and  TCDD
Dioxin

OCDD
2 ,3,7,8-TCDD

OCDD
1,2,3,4 -TCDD
2,3,7,8-TCDD

OCDD
OCDD
OCDD
1,2,3,4-TCDD
UV Source
Oil
Velocity Constant, Hrs.
                                                                    -i
Artificial
Art if icial
Art if ic ial.
Art if icial
Artificial
Sunlight
Sun light
Sunlight
Sunlight
-
-
Mont?
Nor. 2
None
N<;n2
P-9
Nujol
None
.002--'
. 140*
.039
.100
-215
.012
.081
.108
.035
"•''These reaction velocity constants vere calcul.it-'d  by  the  Mathematics Group
 from data presented in the papor "Photo Decomposition of  Chlorinated
 Dibenzo-p-Dtoxins t" PI i rimer, J. R. and W.»olson,  K. A.,  which  appeared in the
 August 1971 issue oL' Sc ience.  Rate studies were done in  methanol solutions.
                                                    r-

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                        Tahlu IV I
                  Effect of UV Light on
           Commercial  Pentachlorophenol  (PCP)
                   on  Filter Paper
                   (7.5 mg PCP)
Exposure                  OCDD                PCP
Time                      Found             Remaining
Days                       ug                  ug
 0                         12                  7500
 1                         23                  2540
 2                         23                  1800
 3                         19                  1350
 7                         15                   450
14                          7.8                 150
                         Table V
                  Effect of UV Light on"
              EC-7 Pentachlorophenol (PCP)
                    on Filter Paper
                      (7.5 mg PCP)
Exposure                   OCDD                  PCP
Time                       Found               Remaining
Days                        yg                    yg
 0                         0.45                  7500
 1                        23                     2100
 2                        23   .                  1420
 3                        21                     1350
 7                        18                      6<30
14                         8.5                    180
                              127

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                Table VI
         Effect of UV Light on
   Commercial.Pentachlorophenol (PCP)
            on Filter Paper
      OCDD Relative to Initial PCP
Exposure                        OCDO as
Time                         ppm of starting
Days                             PCP	
 0                               1600
 1                               3060
 2                               3060
 3                  .             2530
 7                               2000
14                               1040

               Table VII
        Effect of UV Light on
       EC-7 Pentachlorophenol (PCP)
           on Filter Paper
     OCDD Relative to Initial PCP
Exposure                        OCDD as
Time                          ppm of starting
Days                             PCP	

 0                                60
 1                              3060
 2                              3060
 3                              2800
 7                              2400
14                              1130
                     128

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     8.2.4
March 24, 1978
TO:       Environmental Health Advisory Committee
          Science Advisory Board
          U.S. EPA
         ' Washington, D.C.  20460

FROM:     6. A. Van Gelder
          Veterinary lexicologist
          College of Veterinary Medicine
          University of Missouri
          Columbia, Missouri  65201
          Telephone  314-882-7011
                                             i
RE:       Draft Report on Pentachlorophenol


Introduction:

     During the past year I have served as a consultant to FDA, the
American Wood Preserver's Institute, Reichhold Chemical Company and
Vulcan Materials Company in matters relating to pentachlorophenol
and animal health.  My reports have been made a matter of public
record.

     THIS STATEMENT WAS PREPARED AT MY OWN INITIATIVE AND EXPENSE.
IT REPRESENTS MY PERSONAL OPINIONS IN THIS MATTER AND NOT NECESSARILY
THOSE OF ANY OTHER INDIVIDUAL OR ORGANIZATION.

     In the interest of your and my time this statement will  be brief.
In summarizing complex issues there is a risk of being imcomplete or
misunderstood.  If any of the committee have questions please feel free
to call or write.  A copy of a letter I wrote earlier is attached as an
appendix.  This discusses in more detail some of the animal health
aspects.

Background:

1)   I have visited most of the farms, including those in Michigan,
     in which pentachlorophenol related health problems were alleged.
2)   I have conducted limited studies with pentachlorophenol  and related
     concentrated contaminants.
3)   I have reviewed the available chronic rodent studies with penta-
     chlorophenol including inhouse reports submitted as part of the
     Michigan hearings.
4)   I set  through and heard all testimony at all the Michigan Penta-
     chlorophenol Hearings except for the one day Dow Hearing on the proposed
     rule.
5)   I reviewed all material available under freedom of information
     in.  the files of the Michigan Department of Agriculture related
     to  the alleged pentachlorophenol related herd health problems.


                                    129

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Page 2


6)   I have studied in detail the medical and diagnostic records related
     to the herds in question.

Opinions and Conclusions:

1)   The statement on page III-2-4 which in part states ". . .  dioxins in
     tissues from a dairy herd in Michigan in which there were undiagnosed
     health problems of chronic duration.", is not an accurate statement of
     the facts in this case.  Serious communication and decision making
     process related problems existed within the diverse group of people
     handling this herd.  In fact, a number of diagnoses were made.  The
     problem was one of poor communication.  To the best of my knowledge
     not a single person involved in that case had all of the information
     in front of him.  Investigator A was not aware of what investigator B
     had found previously.  The regulatory people acted without a
     careful review and understanding of the .situations on the several
     farms.  Politics played a larger role than sttence.  The problems
     existing on the Lemunyon farm based on information in the Michigan
     Department of Agriculture files included:

     a)   fatty cow syndrome related to feeding of high energy ration
          in excess of milk production.
     b)   a random culturing of cows showed a 50% incidence of infectious
          mastitis, including bacteria that are more resistent to usual
          treatment.
     c)   infectious diseases in the calves of a type that are associated
          with severe early calf losses.
     d)   a serious ventilation problem in the barn.
     e)   at times a lack of adequate bedding that contributed to the
          mastitis problem.

     A complete serious study of the multiple herd health findings in
the Lemunyon herd does not support the statement of "undiagnosed health
problems."  Some of the problems went unmanaged, others received
partial attention.

     The second part of the statement that needs amplification is ".  . .
problems of chronic duration."  The problems were persistent in that
mastitis, calf losses and cow losses continued over a two year period.
However, this does not mean that individual cows were sick for extended
periods.  In fact, a careful review of the history shows that cows
became ill during the 21 day post-calving period, loss body condition and
in many cases died.  This is generally recognized as part of the fatty
cow syndrome.

     Continuing calf losses due to infectious diarrhea and respiratory
diseases in calves maintained in a totally unventilated, unheated calf
room are not unexpected.

      It is my opinion that the allegation of undiagnosed health problems
should be deleted from the draft report.  There is no need to perpetuate
this unfounded statement any further than has already been done.
                                     130

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Page 3
     The problems in the Lemunyon herd do not provide acceptable
scientific data on which decisions related to potential adverse health
effects of pentachlorophenol can be based.  In my opinion, the Lemunyon
herd represents a pentachlorophenol and dioxin chemical residue problem
and not a toxicologic problem.

2)   As an example of the decision making process occurring at the time,
it is pointed out that one of the herds included in the pentachlorophenol
related quarantine had blood penta levels reported as 2 parts per billion.
This is consistent with the fact they were not being housed in a penta
treated facility.

3)   Two toxicologists have estimated the daily penta exposure in the
Lemunyon cattle.  One estimate was 0.12 mg/kg and my estimate was 0.3 mg/kg.
Both levels are less than the no significant effect levels in long term
rodent feeding studies with technical or purified pentachlorophenol.
                                             t
     No one has shown by experimental studies or by calculations that
there is any reason to believe that the levels of exposure occurring in the
cattle could account for death or even illness.

4)   In my opinion, the principle source of dioxin exposure for the Lemunyon
cattle was the sludge residue on the 2x6's used to construct the sides
of the feedbunk.  I have been in numerous penta treated pole barns and
wood eating is something you just do not see with cattle.  It did not
occur even in the herd that was not being fed an adequate diet.

     The sludge was present as dry residue on the wood that could be
scrapped off with a knife.  The residue was' pretty much gone from both
sides of the feedbunk by February 1977.

5)   The data in the table at the bottom of page III-2-4 means next to
nothing to a toxicologist.  What the toxicologist wants to know is:

     a)   what were the levels?
     b)   what were the "recoveries for-the method and,
     c)   what was the repeatability?

     If the levels of HxCDD were 10-60 ppt then it should be so stated.
Few readers of this report are likely to have access to the actual data
unless it is included.

6)   Page III-2-5 refers to my work on this problem.  The pertinent
findings were:

     a)   injections of extracts of the surface residue did not affect
          the health of mice at doses estimated to be equivalent to the
          cattle consumming all of the material in 1-2 days.
     b)   Extracts of the residue did not cause skin lesions when
          injected subcutaneously in albino rabbits.
     c)   Guinea pigs fed finely ground wood obtained from the Lemunyon
          barn were unaffected during the 64 day exposure to wood,
          solvent, penta and whatever else was in the wood.  Exposure
          was at a level comparable to the cattle eating the barn in
          180 days.             -  -                                 '


                                     131

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Page 4


7)   I am incompleteaV quoted on page III-2-5 where the statement
"... Van Gelder concluded . . . that the PCP contaminants in the treated
wood were less toxic than PCP itself."  Certainly, HxCDD is more toxic
than penta.  But when one is exposed to technical penta, for each gram
of material there is much more penta present than HxCDD.  My position
has been and continues- to'be that if one eat3 technical pentachlorophenol
the level of penta exposure will kill you several times over before the
HxCDD exposure gets to a significant level.

8)   Regulations and standards are needed relative to where treated wood
should and should not be used and also specifications should be
developed on the type of treatment and surface characteristics that are
acceptable for various end uses.

9)   -I am unconvinced that low non-phenolic pentachlorophenol solves any
significant actual real world, problems.  I follow the arguement on a
theoretical basis; but on a realistic basis the hazard to people and
animals  is greater for pentachlorophenol than> for the contaminants when
considered from the viewpoint of relative exposures.

TO)  One must keep in mind that reported laboratory studies with technical
pentachlorophenol do shed light on the relative toxicity of the contaminants,
Statements like "minimal focal hepatocellular degeneration" in rats
fed 30 mg/kg technical pentachlorophenol for 90 days is hardly alarming.

11)  Considerations of chloroacne In industrial workers is a mixed bag.
Most of  these people are also exposed to other chemicals, some including
TCDD.  A process of producing low non-phenolic penta from technical
penta does not eliminate the industrial exposure.  Workers are still
needed to operate, clean and maintain the technical penta manufacturing
equipment.  In addition, individuals involved in the distillation of
technical penta to produce the Tow non-phenolic product are also
potentially exposed.  Arguements based on industrial considerations must
include  full consideration of the entire process.

12)  The overall hazard of accumulating concentrated penta related
contaminants in barrels, tanks or flasks for later off-line incineration
or other form of disposal needs to be weighed against the low magnitude
of problems generated by technical pentachlorophenol manufacture and
usage over the past 40 years.  One judgement error in handling.^ barrel of
contaminants could have great environmental and/or health" impact.
                                    132

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UNIVERSITY OF MISSOURI-COLUMBIA
           December 13, 1977
                                                               College of Veterinary Medicine
                                                                 Veterinary Anatomy-^-Physiok
                                                                              Veterinary Sen
                                                                          Columbia. Missouri 65201
                                                                          Telephone (314) 882-7011
           Dr. B. A. Schwetz    .
           Research Manager
           Toxicology Research Laboratory
           Health S*Environmental Research
           1803 Building
           Dow Chemical U.S.A.
           Midland, Michigan  48640                   '

           Dear Bern:

           Thank you for your letter of December 3.  I certainly agree that
           cousnuni cations are needed in this entire matter.  Unfortunately,
           your letter catches me at a rather busy time.  Consequently I will not
           be able to generate a detailed assessment of tha Michigan PCP-D1oxin
           situation with cross references to testimony and laboratory reports.
           A complete description of my appraisal and analyses of the Michirjan
           dairy herd health situation would require a minimum of 50 pages.

           1)   Statistical Analysis:

           As I stated in our October 13 meeting, I quite agree that Dunnett 1s
           an appropriate test for comparing treatment means against a coimon control
           group.   (Dunnett, J. Am. Stat. Assoc.  50:  1096-1121, 1955).  My
           point is that Dunnett should also be used on the data from the first
           study.  See Steel and Torrie (1960)  pages 101-112 for a discussion
           of the various multiple comparison tests and their relative sensitivity.
           I disagree that the Dunnetts t would have detected more differences
           than a blanket application of student t tests.  If you make 78 comparisons
           at the 5% level, 4 of than by chance alone will appear significant.
           Dunnetts is a more conservative test.  Dunnetts will discover more 'Veal"
           differences in your data, that is differences due to treatment as
           compared to differences due to treatment and chance.

           My concern 1s not that you would declare EC-7 similar to 95/5 on the
           basis of your analyses, but rather that by using the multiple "t" tests
           on the Dow-7, 95/5 data you would ba led Into declaring differences
           which may be due to chance.  Whether or not you or your management
           makes those decisions 1s your business.  I hardly think decisions costing
           minions of dollars based on less than appropriate available statistical
           procedures 1s an academic matter.  I do not know 1f the results would
           change if you used Dunnett on the original data.  You will have to run
           the  analysis to find out.  Check me to see 1f I am wrong, but 1f you use
           the  multiple t test on the EC-7, 83 day data, I believe you .would find
                                            133; -

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Van Gelder
Page 2
December 13, 1977

that 1 mg/kg has a statistically significant effect on absolute liver
weight.  In other words, multiple t finds differences that Dunnetts
more conservative test which takes Into consideration the number of
treatment levels keeps the investigator from declaring significantly
different.

My other points regarding the 83 and 2 year studies not addressed
in your summary are included here.  There ara 2 biological changes occurring
in the Dow-7 groups that do not fit the overall response pattern.  The
first is the depression in RBC (and coupled PCV, Hb) at 30 no/kg.
This effect at the high dose (1/4 - 1/5 the acute LD^Q) has been found
by others and not found by others.  Since it is a relatively small change
and occurs at such a high dose it can be described as interesting but
not very exciting.                          ,

The other effect was the change in albumin levels with Dow-7.  My question
was why you did not follow that up in the EC-7 studies?  Since the
EC-7 studies, do not include this measure one cannot say much about it.

The other responses fit a common pattern although there are differences
in dose-response.  But my point is that before one can completely
compare the results one v/ould like to see the data analyzed with a
uniformly applied method.

2)   Communication:

It is my opinion that had MDA personnel been communicating with each
other and with tha MSU faculty a lot of the present situation v/ould have
been avoided.  For example, it was very clear from my first visit to
Michigan in February, 1977, that the MDA-MSU people were not comtnunicatinn
in a 2-way manner.  One person would say the problem was XYZ and another
would later say 1t was ABC.  Consequently, my first report recommended
"I think all those involved should reconsider the evidence upon which
they are making various decisions.  Hy concern is that we not chase
after something v/hich may turn out to be present but only as a
secondary or tertiary factor and not related to the cause of the
problem.  Those parties involved are encouraged to go back and review
the information upon v/hich they are making decisions to ensure that each
decision is being made on cold, hard facts and not on isolated comments
or observations."  My report also pointed out "there also seems to be a
number of different ideas amoung the people who have been Involved In
the problems associated with this farm (Lemunyon).  I am not sure who
is responsible ta try and pull all these people together with all the
information that each one has and present some kind of debate or discussion
as to what the problem(s) really is(are).  Further"as a start it would
seem appropriate for someone to obtain or prepare a detailed history as
to when the death losses occurred, how long the cows were in the barn
before dying, when.did deaths occur relative to calving and what
diagnostic services were actually conducted on each of the animals that
died."
                                 134

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Van Gelder
Page 3
December 13, 1977


3)   Regarding the Herd Health Problems in Michigan:

You need to decide whether you are going to be in  or  out on this  matter.
In the past, Dow has maintained the posture of "non-involvement".  If
now you want to get involved then please do your homework.   Read  all  the
transcripts, study the laboratory reports, go to the  farms, look  at
the cattle, look at the management, get a herd history,  look at the
entire picture.

Furthermore, separate out the conditions on the various  farms,  each one
was different in one aspect or another.  I did not intend to leave
the impression that the only problem on the Lemunyon  farm was Fat Cow
disease.  He had other problems as well.  Certainly all  of these
disease problems can interact.  The diagnosis of fatty cow was  not mine,
it was made by Dr. Coy in a Tetter to Lemunyon on  August 24, 1976,
and by Phase III team in a report on October 27, 1976, and by Dr. Davis
in a visit to the farm in Hay 1975> at which time  he  necropsied a cow
that had just died.  The other piece of information to consider is the
herd history.  The problem as defined by MDA occurred during the  early
post parturo period which is all part of the fatty  cow syndrome.  Your
summary table on body weight changes is confused because you did  not
separate acute from chronic effects in ths fatty cow  syndrome.   Reread
the paper by Morrow, p. 1626 - "1,'hen recovery from the fat cci.v  syndrome
does occur there is frequently a delay in.the onset of post partum
estrus and conception due to retained fetal membranes and metritis,
and a marked loss in weight in severely affected cows".

By way of explanation one needs to sort some things out  in this complex
situation.  First, one rarely finds only one problem  present in a herd
health situation with dairy cattle.  One often finds  a number of
problems including mastitis, metritis, some foot/joint problems
especially with cattle on concrete 24 hours/day and compounded  by deficient
bedding, some calf problems and some nutritional problems.   If I  left
the impression that the only problem v/as fatty cow than  I was too brief
in my consnents since my findings in this matter from  the very beginning
have Identified a number of problems.

One must also sort out the clinical workups and necropsies done on
animals submitted live versus those done on animals dying on the  farm.
The diagnosis of fatty cow was based on animals necropsied at the
farm.  The clinical workup reported by Dr. Ellis et^al_was on chronically
ill, live cows submitted to the University

I also seriously question the purported observation of "general
debilitation" in the Michigan dairy cattle.   I observed the cattle
on the Lemunyon farm as well as four other involved farms.  Even  in
Lemunyon's case one could not say there was a general debilitation.  The
herd I saw in February was in average condition.  There  were some thin  •
                                135

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Van Gelder
Page 4
December 13, 1977


cows as well as some very fat cows.  They were bright, alert, active.
The alleged chloracne simply was not present.  The few skin lesions I
observed on the dorsal neck were typical of skin rubbing lesions seen
1n cattle that have an opportunity to rub the top board on the manger.
In the casa of Leinunyon, this was a 2x6 with tongue down.  The tongue
was worn smooth.  To conclude that chloracna was present without
substanting histopathology is unwarranted In my opinion.  Consequently,
since I have personally observed the cattle, looking specifically for
significant skin lesions and not finding them I must conclude that they
did not exist.  I do not know who actually made such a diagnosis.  The
discussions I attended alluded to open abscesses or bleeding skin ulcers
on the legs. ,Again, I did not see these when I examined the cattle.

What I did see were some hemotomas on the legs which often result from
cattle getting banged around against free stalls and other corners
or protrusions.  On occasion these become infected, abscess and ulcerate.
You might be interested in noting that some Michigan farmers were
blaming the hemotomas on PBBVs as they stood and talked to you while
leaning on a sharp ended pipe jutting out in the main alley way*

The herd in the worst shape was the Dale Mice herd in which he- had
been quarantined for unsanitary conditions because of a deep accumulation
of manure and several dead cows being found in the barn by the milk
Inspector.  Hardly a usual situation.  He v/as quite frankly, by his own
admission, not providing adequate caro for tha cows.  Consequently,
he lost his inilk market, then ran out of feed, was broke and
could not buy feed, and his cattle, as per the Michigan Veterinary
Diagnostic Laboratory report of February 28, 1977, suffered from
malnutrition secondary to poor quality faed; suppurative mastitis.
I saw the Hies herd in March, they "were uniformly thin, but alert and
active.  They were receiving a minimal amount of hay as their total diet.
Anyone wanting more information on the management and operation of this
farm can obtain access to other reports in MDA files under the Michigan
sunshine law.  I have read them and as a result concur with the opinion
of Dr. Davis, MDA that the problems on the Mice farm were caused by factors
other than PCP or dioxins.  If cattle are being fed a grossly inadequate diet
one does net need to look under rocks to determine the cause for loss
of body flesh.

The diagnoses of mastitis and calf viruses were made by MDA or MSU
veterinarians.  The remarkable conclusion Is that the mastitis was
claimed to be caused by bacteria which were allegedly cleared up by
antibiotics but cell counts persisted.  This conclusion was reached
1n the light of  1)  there is nothing concrete in the. record that any cows
were cultered after treatment to see if in fact the infection v/as
eliminated.  This in the light of a 50% infection rate that included not
only strep, but also staph.  A background staph problem is more difficult
to eliminate than the strep and furthermore, a background staph problem
may become n-ore-severe when the strep infection is cleared up.
                                 136

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Van Gelder
Page 5                           :
December 13» 1977


A great deal was being made about immune suppression based on this
mastitis situation.  One must seriously question such an  implication
based on the above workup.  The other factors  not accounted for in  the
workup as testified to included lack of evidence that milking equipment
was, in fact, checked to make sure it was in proper working condition,
the stage of lactation was not considered in the evaluation of cell counts
and other stress factors such as bedding were  either Ignored or not
considered.

Other information on the Lemunyon herd was obtained which showed that cow
death losses were occurring primarily in tha period of 21 days post partum.
This fits the fatty cow syndrome.  This coupled with the  feeding pattern
and radical changes in diet, to advice given Mr. Lemunyon to feed dry
cows separately from lactatinn cows plus the HQA diagnosis of fatty cow
syndrome cannot be Ignored.

If one reads the paper of Morrow one finds that narked loss of weight
1s seen in severely affected cattle.  What one needs to differentiate is
pre-partum condition from post partum condition.  Consequently, the
initial recommendation to MDA was to get a good herd history.  This
was never done by MDA to the best of tr.y knowledge.  Others have
done more in this area.

A similar restraint 1s warranted in the interpretation of clinical
pathology data.  Are tha samples from acutely  ill  cows?  Chronic cows?
Cows with systemic Infections?  These are important factors because
fatty cow syndrome is not a simple pathologic  condition.

Regarding your conanent about white blood cell  counts the  following  is
offered.  Cows have WBC counts ranging from 7-10,000 with aged dairy
cows having counts as low as 5,000.  Cattle normally have (approximate)
25-3G£ neutrophils, 60-652 lymphocytes, 5% monocytes and  2-5" eosinophils.

If you look at the blood picture for the 13 Lemunyon cows obtained  by HSU
in March, 1977 you will find two cows with elevated WBC counts both of
which have greatly increased neutrophil counts' which indicates an
active infectious process.  The remaining cows have WBC counts
within published normal ranges.  Furthermore,  if one looks closely  at
the chlorodioxln immune suppression data one gets a picture of immune
suppression coupled with a decrease in absolute lymphocyte counts.   If
you carefully analyze the Lemunyon blood data  you will find that absolute
lymphocyte counts are within normal ranges with the exception of the
two cows with a left shift Indicating an active Infection.

The above comments hold for the blood picture  on the other farms as I
remember them.  It has been some time since I  carefully studied those.
Consequently, I do not know what data your summary table  is referring to
when  it makes the suirsnary statement of "WBC count markedly increased".
                                13-7-

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Van Gelder
Page 6
December 13, 1977

Dr. Coy mentioned an eoslnophelia in six cows.  I would guess you were
as surprised as I was when he did not follow that up with a diagnostic
check for Internal parasites.  You may recall the response from Dr.  Wise
the hearing officer.         ,

As an aside we also found a marked eosinophelta in the Mice cattle we
necropsled.  The intestinal parasitic lesions fit the usual pattern.
I would suggest a bottom line along this avenue.  Both Dow toxicologists
and myself have estimated the PCP dose for Lemunyon's cov/s to be 0.12-0.3
mg/kg per day.  Your group analyzed the lumber and as I interpret the
results the dioxin levels found indicate a typical technical  PCP. Based
on all your studies on PCP and on all the literature do you really
think there is any perceptible risk to the health of a cow with 10 ppt
HxCDD or 1.4 ppb HxCDD in liver in light of the published work on
larger TCDD liver residues in rats at levels claimed to be no effect?
I appreciate the fact one can alv;ays say "We do not know because we
have not tested it", but as a toxicologist one often uses his total  data
base in making interpretations subject to experimental verification.

I feel much more confident about accepting the t1DA diagnosis of fatty
cow, mastitis and viral infections and questioning the totally unsubstantiated
diagnosis of ch'Ioracne than I would be by accepting the chloracne diagnoses
and rejecting the other diagnoses mace by MDA.  At least I know MDA
veterinarians have seen the other conditions on numerous occasions.
I doubt if they ever saw chloracne or ever heard of it before.  Add  staph
to your list of causes of infectious mastitis.  It is an important
consideration in view of the way the situation was handled.

Also, differentiate between the acute phase of fatty cow and the chronic
sequalea.  Cows may take one entire lactation to recover.  If appropriate
management changes are not made then the syndrome can be more severe
in the second and third lactations.

Dr. Davis's primary reservation with the fatty cow diagnosis as the  primary
factor was  because he had not seen such large death losses previously.  Yet
has published on such a high mortality.  More recent studies out of
Tennessee support the finding of high morbidity and high mortality with
this disease.

I am a little bit confused by your reference to the gross and histopath data
on the various PCP studies as being the primary concern.  In the production
grade study of November 1971, on page 10 of the report it is stated
"Gross examination at necropsy revealed no compound related changes.
Minimal focal hepatocellular degeneration and necrosis were observed upon
microscopic examination of Hvers from rats maintained on diets containing
the top dosage level of sample 9822A; these changes were not observed
1n rats maintained on a diet containing 95/5 which provided a similar dosage
of PCP."   In view of the apparent minimal nature of the changes at a
dally dose equivalent to 1/4 - 1/5 the acuts LD5Q one can also come  to the
conclusion that there is not much of a hazard associated with low level
(fractions of mg's) exposure to technical PCP.

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Van Gelder
Page 7
December 13, 1977


I quite agree with the findings  of Dr.  Wise that sensible use  restrictions
and use guidelines will  do more  to reduce the hazard associated with  POP.
Alone that line has Dow come up  with  a  recommendation on the use of EC-7
to treat feed bunks?

I quite agree with your statement "also because the dioxin content of PCP
could be reduced, we have consistently  recommended that the nonphenolic
content of PCP be reduced, etc.".   If I was a corporate manager and had
just invested a million dollars  in a  thermal oxidizer(incinerator) and
saw an opportunity to get dual use by cleaning up 2,4,5-T and  PCP
at the same time, I would do it  also.  It is a neat marketing  manuver.
Unfortunately, the toxicologic picture  is less clear because of the
difference in opinion on the actual hazard associated with technical
penta.  Is Dow aware of any problems  encountered in livestock  related
to the non-phenolic content in Dowicide-7?  Or did that product have  a
clean use record for 30 years except  for the obvious occasional misuse?

Sincerely yours,
Gary A. Van Gelder, D.V.M., Ph.D.
Professor and Chairman

GAVGrnc

cc:  Dennis Lindsay
                                 139

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   8.2.5
REICHHOLD  CHEMICALS,  INC.
Creative. Oic/TTU&fcr
                 ru
                                            RCI BUILDING, WHITE PLAINS, N. Y. 10603
                            April 18, 1978
                                                               Address Reply To
                                                           REICHHOLD CHEMICALS. INC.
                                                                P.O. Box 1482
                                                            Tacoma. Washington 98401
                                                             Telephone 206-572-5500
                                                              Teletype 910-449-2355
Dr. Sheldon D. Murphy
Professor of Toxicology
Department of Pharmacology
University of Texas Medical School at  Houston
P.O. Box 20708	
Houston, Texas 77025

Dear Dr. Murphy:

                       SCIENCE ADVISORY BOARD
            ENVIRONMENTAL HEALTH ADVISORY COMMITTEE
           Ad Hoc Study Group on Pentachlorophenol Contaminants
                Draft Report — Public Hearing April 3, 1978


The  purpose  of  this communication is to  amplify. Reichhold's testimony pre-
sented to the Committee April 3, 1978.

On page k of our testimony. I made reference to the Committee's draft report,
page 1-10, paragraph 10, where it  is concluded that technology is now available
which could  markedly  reduce the  levels of chlorodioxin and  dibenzofuran
contaminants in pentachlorophenoi (PCP).  I pointed out  that consideration must
be given to the  question of trade-off  of occupational hazards.  It is assumed
that the process referred to in the draft report  is the facility designed to
produce low-dioxin content  pentachlorophenoi at  Dow Chemicals' Midland,
Michigan complex. It has been known for some time, to those skilled in the art,
that the dibenzo-p-dioxin and  dibenzofuran contaminants can be separated from
pentachlorophenoi  and  tetrachlorophenol  by  various methods.   The problem
arises in how to safely handle and safely dispose of the concentrated residual
waste streams  created by  removing these contaminants.   We  have been
informed by Dow that  they destroy these  contaminants by diluting  them with
large quantities of other liquid wastes and  then incinerating thiii large quantity
of highly contaminated material.

Reichhold has considered a number of possible ways of handling and disposing of
the waste streams, which would result from  removing and concentrating these
contaminants, and have discarded each because of potentially insurmountable
problems.  Some of the disposal methods which we have considered include:

1.   Collecting  and shipping to a suitable disposal site.  No disposal  site is
     known which is licensed  to accept these wastes.  In addition, permits to
     transport these hazardous wastes would have to be obtained from various
     governmental agencies.  Also, transportation requirements would have to
     be set out.
                                   140

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Dr. SheJdon D. Murphy
April 18, 1978
Page 2
2.   Incineration.   It has  been suggested  in  the report that technology  to
     dispose of  these waste streams  exists  -- presumably this  means by
     incineration.  Construction of a suitable incinerator designed to handle
     this highly  toxic chlorinated material, as  the principal material to be
     incinerated, is a very  expensive and difficult proposition.  Experts advise
     us that these highly chlorinated refractory materials require temperatures
     in the order of 1200°C  to  assure complete conversion  to HC1, CCu and
     H-O.  Because  of the presence of  HC1 and other corrosive by-prodUcts,
     the materials of construction are critical and expensive.  Operating costs
     to achieve and hold the necessary temperatures are high.

     To the best of our knowledge, there is no licensed incinerator in operation
     that  will  accept these  materials for incineration.  Therefore, we  must
     conclude  that the technology is not available to satisfactorily dispose of
     these waste streams with the confidence that the chlorinated materials
     will be completely destroyed. We are aware of work performed by various
     departments of government which have addressed this problem.  Reichhold
     strongly suggests that before the assumption is made that technology is
     available  to safely  dispose of the  hazardous waste streams created by
     removing  and concentrating the contaminants in PCP, that the Technology
     Assessment Pollution Control Advisory  Committee of the Science Advi-
     sory Board be  requested to review this  entire question.  The secretary of
     this Committee is Lloyd  Taylor.

We have applied substantial resources to the investigation of the chlorination of
phenol without the  formation of chlorodioxins  and have, as  a  result of this
study,  substantially  reduced the chlorodioxin and dibenzofuran content.   This
reduction yields a technical grade PCP with a total dioxin content in the range
of 1200 ppm.

The ideal solution would be to produce pentachlorophenol without co-producing
any toxic contaminants.   The technology to  do this is not known.  We believe
that the years of  experience with  technical  grade  pentachlorophenoi has
indicated that  it is far  better to widely  distribute  a less  than  no effect
concentration of the contaminants than to have them separated and exist in one
highly  concentrated stream at several  widely dispersed manufacturing sites.
These  highly concentrated  streams  would be subject to  possible catastrophic
error  in handling which  would  result in a  major hazard  to the immediate
surroundings.  The  handling and disposing of these highly toxic waste materials
is subject  to all  of the hazards of  transportation — broken  pipelines, leaking
drums, derailed rail cars, etc.

If they are ultimately conveyed safely to an incinerator, then  the safe operation
of  the incinerator  is of  paramount  importance.   The  incinerator  must be
constantly monitored or the  contaminants will  merely be made airborne and
dispersed over  a substantial area in more than toxic effect concentrations.  An
improperly  operated incinerator could  contaminate large areas of land and
create an  incident  of the  magnitude comparable to that which occurred  at
                                      141

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Dr. Sheldon D. Murphy
April 18, 1978
Page 3
Seveso, Italy.   We  feel that the  question  of  safe disposal  of  the highly
contaminated waste streams created by removing the impurities from technical
grade PCP must be thoroughly addressed by experts before industry is forced to
create a dangerous waste for which there is currently no acceptable means of
disposal.

We would appreciate your communicating this addendum of our testimony to the
Committee members for consideration.

Again, thank you for  the opportunity  to appear before your Committee.  We
deeply appreciate the many hours of concentrated effort  that  the members
applied in  bringing the facts to light regarding pentachiorophenol.
                                   Very truly yours,

                                   REICHHOLD CHEMICALS, INC.
                                   F. J. Shelton
                                   Vice President
                                   Science 
-------
                TESTIMONY ON PENTACHLOROPHENOL TO THE
             SCIENCE ADVISORY BOARD ENVIRONMENTAL HEALTH
                            ADVISORY COMMITTEE

                                 April 3, 1978
           My name  is  Frederic  J.  Shelton.   I  am  Vice  President, Science  
-------
to assess the safety of  commercial  grade PCP.   As a  result of the work  which



Reichhold has conducted, the company is  not  aware of any studies or reports  which



support  the  premise that  commercial grade PCP containing trace  quantities of



contaminants,  including  chlorodibenzo-p-dioxins  (CDD's)  and chlorodibenzofurans



(CDF's),, present  any significant hazard to man and the environment when properly



used.  The  results of these studies and investigations have  been presented to the



Federal EPA as well as to various state regulatory bodies.



            Reichhold  conducts physical  examinations  on each  of  its production



employees on an annual  basis, and more often if the man requests. No unusual physical



conditions have ever been reported for these men. Reichhold field personnel have had



more than twenty years of contact with its PCP users and are unaware of any human



or animal health problems attributable to properly used  PCP.  PCP finds commercal



use in the wood treating and preservation industries because of its toxic properties.  It



must be handled and treated with respect because of its innate toxicity.  The handling



and treatment afforded PCP and PCP containing  products, because of  the toxicity of



PCP  itself,  is sufficient to  protect  the users,  and others who  come into contact with



PCP treated wood, from any hazards due to the chlorodioxins contained in the product.



            In the early 1950's, PCP was used  and recommended for a broad spectrum



of pesticide uses.  In most of these uses, PCP was applied from a solution prepared by



dissolving the PCP in a petroleum  distillate.  If a water solution was required,  the



alkali salt of PCP was prepared by reacting the PCP with  aqueous sodium or potassium



hydroxide.  Early uses of  PCP included all phases of wood preservation and protection,



both  against microorganisms and insect attack. The preservation of water based paints



and adhesives, and the preservations of textiles and cordage, as well as  weed control,



were also significant uses of PCP.  In addition,  PCP was used in red mite control in
                                   1.4%-

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poultry houses. Reichhold felt that many of these historical uses of PCP presented the


possibility of excess user exposure to the irritationai and toxicological properties of


PCP itself.  Although Reichhold has had a large number of registrations covering a


wide variety of PCP uses, it currently maintains a registration for the use of PCP for


manufacturing  purposes (wood  preservation)  only.     Reichhold's  PCP is  sold  to


commercial wood treaters and is used in the industrial treatment of wood by a variety
                 $i

of processes.  We believe that commercial grade PCP, as manufactured by Reichhold


and others, does not pose undue hazard to man, livestock and  the environment, when


properly used.


           We  would like to now comment  specifically on  several portions  of the


draft report of  the Ad Hoc  Study Group on  pentachlorophenoi  contaminants,  dated


March 1978.  On page 1-8, under Item 3, Conclusions, paragraph 1, Reichhold confirms


that it  has  not detected any  TCDD  (2,3,7,8-tetrachlorodibenzo-para-dioxin)  in any


samples of PCP which  it has analyzed.  On page 1-9, paragraph 5, the conclusion  is


drawn that exposure to man and animals  to CCD's  migrating from PCP treated wood


should be prevented.  Reichhold supports this conclusion and  suggests that consider-


ation be given to promulgating appropriate rules and regulations to prevent contact of


human foodstuffs or animal  feeds directly with PCP treated  wood.  In  addition, we


think it would be desirable to restrict the use of  uncoated PCP treated wood from


certain portions of decorative fencing, porches and other recreational structures where


direct human contact could be anticipated.


            Reichhold agrees with the conclusion drawn in  paragraph 7 that the most


probable opportunity for excess human exposure to PCP is  in the PCP  production and


utilization industries.  Reichhold would like to emphasize the point that any proposed


significant changes  in manufacturing or application of PCP must consider the effect

-------
that these changes would have on the workers involved.



            A number  of  alternative methods for producing various grades of PCP



have been  proposed.   Some  of  these processes present  the possibility of increased



worker exposure  to PCP and/or PCP contaminants because of  the characteristics of



the final PCP produced.   Reichhold has  examined its  process  for  the production of



PCP, as  well as  the  handling characteristics  of its  finished product, and feels that



presently it cannot suggest a reasonable alternate to its PCP product.  Reichhoid urges



that before any action is  taken, that all aspects of the production and utilization of



any new  PCP product be thoroughly examined.  We feel that particular emphasis should



be placed upon the physical characteristics of the final PCP product, as well as  the.



creation  and disposal of any waste or by-products caused by its production.



            On page I-1Q,  paragraph 9, Reichhoid certainly agrees that certain uses of.



PCP be  objectively  examined  and that regulation  be considered  to  reduce those



applications of PCP treated wood which may come in contact with humans or animals,



or food products.  However, as we have repeatedly stated, we believe that there is an



absolute  need for PCP treated wood  for use  in and  around  farm buildings  and



structures  where degradation by microbial attack from  soib and other materials  is



critical.



            Paragraph  10, on the same page, states that certain technology has been



disclosed which is designed to reduce the levels of CDD's and CDF's in PCP through



distillation of technical PCP.  However,  we do not totally agree with the statement,



"It would seem prudent	to control the contaminants to the extent possible by best



manufacturing practice."  We would  like to emphasize that consideration must be given



to the question of trade-off of  occupational hazards.  Reichhoid feels that there are



significant  occupational hazards associated with  the  use and  handling of the PCP
                                  146

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products which it has seen on the market which are claimed to have reduced levels of



CDD's and CDF's.  Reichhold, furthermore, is very concerned about the concentration



of CDD's and CDF's in waste streams generated by the distillation process used for the



cleanup of the  technical PC P.  The economic impact evaluation would have to take



into  consideration  the  distillation process and  cleanup of  PCP as well  as  the



incineration of  the waste stream generated.  It would also have to take into account



the automation of the process which  would  then minimize  exposure to  the waste



stream. The commercial process used by Reichhold to produce PCP does not produce a



concentrated waste  stream  containing CDD's  and  CDF's.    We  urge the Science



Advisory Board Environmental  Health Advisory Committee to very seriously consider



this possible route of exposure to concentrated CDD's  and CDF's streams produced in a



PCP distillation process when considering possible hazard trade-offs.



            Continuing, on page II-3, a  chart is given  exemplifying the composition of



a  purified grade of  PCP,  labeled Dowcide  EC-7.   It  is noted  that only  certain



chlorinated CDD's are listed, namely the octachloro,  the  heptachloro and hexachloro



dibenzo-para-dioxins.  However, on referring to Section  V-3, page 52, Appendix No. 4,



it is indicated that the possible  number of CDD's are listed as being 75 in number.  The



hexa, hepta and octa CDD's would account for approximately 13 of the possible 75.



This would appear to leave 61  additional  CDD's  which  could  be  present since it  has



been  established that no  2,3,7,8-tetrachlorodibenzo-para-dioxin has  been detected in



any domestic grade of PCP commercially available today.  Since the purpose of this Ad



Hoc Study Group is to examine and report on all of the CDD contaminants in PCP, we



feel that  comment is needed relative to the presence or absence of one or  more of



these other  possible CDD's. We feel that the study should be  thorough and complete



before any regulatory action is  taken. It would be extremely disruptive  to the industry
                                   147

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if considerable sums of money and technical development were expended to reduce


certain  CDD's only to learn at some later date that certain remaining CDD's were


present  at levels which were then determined to be environmentally undesirable.  It is


Reichhoid's  position that prior to  any regulatory action mandating  a reduction in

chlorodioxins, that consideration should be given to all of the chlorodioxins which

might be present.
             *,'.

            On page III-l,  the report  states that octochlorodibenzo-para-dioxin, or

OCDD,  has  shown  little toxicity.   Reichhold  would  like to  point out that  the

commercial  technical grade  of PCP  which it manufactures, as  well as material

manufactured by other companies, contains as  the major CDD contaminant, OCDD.

Typically, the amount of OCDD present is  on the order of five to seven times greater

than the amount of hepta and hexa CDD's.


            On page III-3, one reference was cited which detailed an experiment pro-

ducing chloracne in rabbit ears.  This test  indicated that commercial samples of PCP

have produced chloracne in  the rabbit ear bioassay tests wherein purified PCP did not

produce chloracne.   Reichhold conducted  similar tests  at  IBR-US Laboratories, in


Miamisville,  Ohio.  The results of these tests indicated that no significant  differences

could be discerned  in the  results  obtained using either commercial, analytical or


purified commercial  grades of PCP.   The results obtained  from one material were

comparable to results obtained with another. This information was submitted to the

Science Advisory  Board Ad Hoc Group,.and the results of this  tests have not been

included in this report.

            On page III-9, paragraph  4, reference  is made to work done by Kimbrough


in  1972.    Reichhold has  reviewed  all  referenced articles  authored  by  Renate

Kimbrough, dated  1972 and  has not seen any report implicating technical grade PCP in
                                148

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causing teratogenic effects in women. We suggest that this reference be verified.

            On page III-12, Conclusion 4, Reichhold agrees that all commercial grades,

technical and purified, of PGP contain quantifiable amounts of CDD's; however, we are

not convinced, nor are we aware of any studies which conclusively demonstrate that
                                                                &af^t-4^^ze A*<
the concentrations of CDD's present in technical PCP are sufficient to*.bo-biologically
 
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allegedly  connected with  PCP exposure, has resulted  in a  number of papers being



published  which define and describe the herd  health problems in these  Michigan dairy



herds. As a result of this work, it  was concluded that these dairy herd problems were



not related to exposure to PCP or  CDD contaminants.  All of these data and reports



have  been previously  submitted to the  National  Institute of  Environmental Health



Sciences,  Environmental  Protection  Agency,  as well as  to  the  Food  and  Drug



Administration, and to the Ad Hoc Study Group on pentachlorophenol contaminants.



                 In addition,  the  Michigan Department of Agriculture conducted a



hearing on the application of Reichhold for reinstatement of its state PCP registration



which was summarily suspended  during the dairy herd incident.  Dr. Gilbert  H. Wise,



DVM, the  hearing officer appointed by the Department concluded, after the week-long



hearing, that the cancelled registrations should  be reinstated.  Dr. Wise, in an 18-page



decision, found in part as follows:



                 "No  evidence was developed showing that wood preser-



            vative formulations containing penta have presented demon-



            strable  risk  to  the food  chain  through exposure  of food



            animals to CDD  (chlorodioxins) in penta.             .  .



                 "The  evidence, while not removing  all possibility of



            hazard,  does  not  support a  finding of   any  measurable



            magnitude  of  risk or liklihood of harm to  the human food



            chain from exposure of food animals to CDD in technical



            penta."



            On page IV-5, a  hypothesis has been put forth which  suggests that chlorin-



ated  dioxoins,  chlorinated dibenzofurans,  polychlorinated  biphenyls, polybrominated



biphenyls, and  chlorinated azoxy benzenes should be considered as  a  class from the
                                150

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toxicological standpoint.  Reichhold disagrees with this premise because it has been

repeatly demonstrated that specific members of a class of compounds may have vastly

different biological activities.  One needs only  to review the work done in the drug

industry to realize that it is dependent upon these variations in activity, relative to

structure, to produce drugs  which minimize pain and  suffering. We think it would be

extremely risky and unsupportable to  regulate various  individual  readily identifiable
                 •f
chemical compounds as a class rather than as individuals.  .

            There are numerous reports that PCP has been found in many parts of the

environment, including in man and animals.  It has generally been assumed that this

PCP  has  been  coming  from the  wide-spread  commercial  use of PCP as a  wood

preservative or pesticide. It should be noted that it has been reported that PCP may
                            /'«
be formed as  a. metabolite from  animals and microorganisms.  Furthermore, it is re-

ported that PCP may be formed in the environment from  other  chemicals such as

hexachlorobenzene and LINDANE and from the chlorination of drinking water.

            The source  of  CDD's  in the environment  is not exclusively from  PCP.

Other chemicals such as hexachlorophene and polychlorinated biphenyls also contribute

CDD's.   Other  widely used  pesticides such  as  2,4,5-T are recognized as containing

CDD's.

            PCP has a  number  of registered uses for  which there are  reasonable

alternatives.  Reichhold  would urge consideration of these registered uses of PCP  and

that an effort be made to determine where proven alternative materials are available.

Perhaps this concern over a wide-spread use of  PCP can be  more easily regulated by

restricting the  registered uses of PCP to  those for  which there is no  reasonable

alternative, such as for wood preservation.

            On the whole, Reichhold applauds the work which has gone  into the pre-
                                    151

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paration of this draft report.  We feel that  much effort has been made  to factually



evaluate and report  on  the data and literature which is available; however, we would



appreciate consideration of the points which we have raised today.



            Again, thank you for this opportunity to appear here today.
                                    152

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8.2.6 Testimony of Dr.  Robert L. Johnson


  •The Dow Chemical Company's position with respect  to  the  non-
  phenolic impurities in PCP has been and continues  to be:

  1.  that pentachlorophenol containing such impurities  above
      certain levels manifests enhanced toxicological  responses
      as demonstrated by laboratory test animal experiments.

  2.  that these non-phenolic impurities should be minimized by
      the manufacture and use of a PCP containing the  least
      amount of these impurities technically possible.

  3.  that it would not be possible to assess adequately the hazard
      of the many individual non-phenolic impurities in  PCP.
      Therefore, it was logical and prudent to reduce  these impuri-
      ties to the lowest possible level for commercial PCP and,
      thereby minimize the risk to the producer, the users, and
      the environment.

  4.  that readily identified adaptable technology is  available
      to separate the non-phenolic impurities from PCP and that.
      disposal of such impurities can be dealt with at the pro-
      ducing site where acknowledged risk can be minimized.

  5,  that a pentachlorophenol can be manufactured in  commercial
      quantities that mimics chemically purs PCP in both acute
      and subchronic toxicological studies.  With the  urging of
      the EPA and at reasonable expense to Dow, such a commercial
      facility has been constructed and is being operated.

  The ad hoc committee draft report represents a significant and
  worthwhile effort to compile all the available information per-
  tinent to the presence of non-phenolic impurities in technical
  PCP.  The report is thorough in pointing out that:
                               153

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1.   Suitable analytical methods for the specific dioxin and
   ' furan isomers present in technical PCP are lacking.

2.   There are very little data on the environmental persistence
    and transport of the dioxin and furan contaminants of PC?.

3.   The comparative chronic toxicological information on purified
    versus standard commercial PCP is limited. (Sub-chronic
    studies have revealed toxicological differences between
    these two grades of PCP, especially in the liver.)

4.   There are virtually no data on the chronic toxicity of the
    non-phenolic contaminants of PCP.

5.   The biological significance of the finding of low, but
    detectable, levels of chlorinated dioxins. in tissues of
    farm animals is not presently known.

6,   There is insufficient information on occupational exposure
    of man to these PCP contaminants by manufacturers or users
    to allow quantitative assessment of the relative hazard of
                                              «.
    purified PCP versus commercial products containing dioxin
    contaminants.

These information deficiencies are used in the draft report to
explain why an ultimatum to the wood treating industry to manu-
facture and use only purified grades of pentachlorophenol cannot
be issued.
                             154

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On the other hand,  the  draft report,  without exception,  describes
the. constant concern  associated with the presence  of  the non-
phenolic impurities in  PCP.   For example:

1.  The toxicity of the polychlorinated dibenzodioxins  and
    dibenzofurans is  recognized.

2.  The recent reports  of  induction of neoplasms by TCDD raise
    the specter that  the polychlorinated dibenzodioxin  contami-
    nants in PCP may  also  have this potential.

3.  The finding of  low  but detectable levels of chlorinated
    dioxins in tissues  of  farm animals is a matter of public
    health concern.

4.  Reports of occupational  exposure to chlorinated dibenzo-
    dioxins, which  resulted  in adverse health effects in man,
    were mentioned.

All these references  and comments clearly indicate the  relevenc^
of conclusion, No.  10,  which reads in part,
     "Tec/mo£og«/ -ci now ava-c£a6£e u)ki.c.h. dou.id ma.A.ke.d£y
     reduce tkt £ivzt&  o
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The PGP producers were initially urged by federal regulatory
agencies to reduce the non-phenolic impurities content in 1971,
and again advised to proceed in that direction in 1973.  It is
now 1978; specific timing as to when all commercial PCP should
be of a purified grade, or the specific reasons as to why a
purified PCP grade is no longer necessary, is urgently needed.
The original charge to the ad hoc committee was to comment, to
the extent possible, on the potential hazard to humans which
can be attributed to registered uses of PCP and the extent that
this hazard may be mitigated by the use of the commercial pro-
cess which results in lower levels of the contaminants of
interest..  We urge that this charge be completely satisfied as
soon as possible in a less ambiguous manner and without
encumbrances of" economic constraints which have created ambiguity
in the present conclusions.
                             156

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8.3  COMMENTS OF INTERESTED PARTIES
                157

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8.3.1

 SUBJECT:  Comments on EPA Science Advisory Board Environmental Health
           Advisory Committee Meeting:  Pentachlorophenol Contaminants
           (April 3, 1978)

 TO      :  Ernst Linde, Executive Secretary, Science Advisory Board  (RD-673)

 FROM   :  Paul E. des Rosiergf'Senior Staff Engineer, Industrial and
           Extractive Division  (RD-681)
           I believe it is important  that  the Science Advisory Board  (SAB)
      be made aware of certain facts  in order that all aspects of  the
      pentachlorophenol (PCP) contaminants issue are addressed correctly.

           As you know, I was present during the session held on
      Monday, April 3, 1978, during which  time current producers of PCP,
      namely, Dow Chemical Company, Reichhold Chemicals, and Vulcan
      Materials Company presented  their respective statements to the
      SAB Environmental Health Advisory Committee.  I am considered an
      Agency expert on the treatment  and control of organochlorine
      chemicals, have in-depth experience with military defoliants
      dating back to 1967, and as  a result, am thoroughly  familiar with
      disposal/detoxification methods for Herbicide Orange and its teratogenic
      artifact, tetrachlorodibenzo-p-dioxin (TCDD).

           In this respect, I was  a member of the EPA Herbicide Orange
      Disposition Advisory Panel to the U. S. Air Force/Defense Supply
      Agency, provided technical consultation to the State of Missouri
      Department of Health concerning the Verona, MO TCDD  episode, and was
      interviewed by the British Broadcasting Corporation  regarding the
      Seveso Icmesa plant TCDD incident in Italy.

           In retrospect, I was particularly impressed at  the meeting by
      the perception of Dr. Van Gelder, a veterinarian, who in his
      testimony, alluded to the fact  that disposal of concentrated
      quantities of PCP contaminants  might prove to be more of a problem
      than maintaining the status  quo.

           At this time, I wish to delineate some pertinent historical
      facts relating to significant dioxin-type incidents:.

          (1)  2.3 million gallons  (24 million Ibs) of Herbicide Orange
      with approximately 2 rag/kg TCDD (about 49 Ibs) could not be  disposed
      of by incineration either in Illinois (Monsanto's Sauget facility)
      or in Texas (Rollins contract facility), or by land  assimilation

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in Utah or In Oregon.

   (2)  Chemical detoxification of Herbicide Orange was proposed to
the U. S. Air Force by the Velsicol Chemical Corporation, which entailed
deesterification via alkaline hydrolysis/solvent extraction/UV-photo-
chemical decomposition/reformulation; however,  Velsicol withdrew its
proposal.  Agent Chemical Incorporated was selected by the Air Force
to demonstrate at pilot scale, an activated coconut charcoal method
for "stoichiometric" selective removal of TCDD from Herbicide Orange;
however, disposal of spent charcoal cartridges containing high concen-
trations of_ TCDD presented a significantly greater environmental risk,
and the project was officially curtailed.

   (3)  The M/T Vulcanus incinerator ship was employed to combust
Herbicide Orange at sea some 200 miles southwest of Johnston Island
in the South Pacific.  Incineration of the defoliant was accomplished
at 1250-1450°C with a dwell/retention time of 1.3 second, at a cost
exceeding $3 million.   Subsequent to the successful incineration,
the M/T Vulcanus has been unable to obtain recertification because
of contamination of the ship's storage tanks/deck with miniscule
amounts of TCDD (ppt).

   (4)  There also exists today in Verona, MO,  approximately 4600
gallons of highly contaminated (300-350 ppm TCDD) chlorinated still
bottoms from previous hexachlorophene manufacture.  Systex Agribusiness,
the present owners of the industrial site, and the State of Missouri
have been unable to secure an environmentally acceptable method for
the ultimate disposition of the waste residue.

   (5)  Presently, for every 5000 Ibs/hr of PCP manufactured,
approximately 10 percent or 500 Ibs/hr of still bottom residues
are produced, which may contain, at varying concentrations:  octa-,
hepta-, hexa- chlorodibenzodioxins and chlorodibenzofurans, tetra-
chlorophenol, trichlorophenol, chlorophenoxyphenols, hydroxydiphenyl
ethers, hexachlorobenzene, chlorinated biphenyls, chlorinated polymers,
etc.  This residue production would be equivalent to roughly a 2000
tons/year quantity requiring disposal.


  Specifications for the first at-sea incineration of Shell Chemical
  Company organochlorine waste residues by the M/T Vulcanus were based
  on Mississippi State University Prof. B. J. Stojanovic's muffle
  furnace data obtained with analytical grade TCDD.v%He found TCDD
  completely combusted between 980-1000°C.
     From the foregoing, it becomes obvious that public awareness and
anxiety play important roles as to how, when, where, and by which
method a "dioxin" contaminated material/waste, is to be treated.
                                 159

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Should the SAB Environmental Health Advisory Committee recommend that
technical grade PCP be purified to reduce contaminant levels to less
than 0.1 percent, then EPA is faced with a predicament - the question
of trade-off of occupational hazards.

     There is no doubt that it is technically feasible, although at a
higher cost, to produce commercially purified grade PCP that can meet
reasonable regulatory constraints relative to chlorinated dioxins and
dibenzofurans.  Furthermore, I have doubt concerning Dow's contention
that it possesses incineration capability to "destroy" the waste
residues therefrom.  Nevertheless, the Dow case is unique - the Midland,
MI facility represents probably the largest integrated petrochemical
complex in the U. S. and large volumes of waste residues are admixed
with relatively small volumes of PCP wastes, the latter essentially
losing its identity through volumetric dilution before incineration
commences.>

     Such is not the case with Reichhold and Vulcan, however.  Special
incinerators would have to be designed, parts ordered, constructed,
and subsequently evaluated prior to application for an operating
permit.  Such a permit request would undoubtedly require a public
hearing because "dioxins" are present in the wastes.  Based on my
experience,  I can assure you.that the resulting permit requirements
will be severely restrictive (e.g., exhaustive monitoring, operational
constraints, etc.) and quite possibly could eliminate land-based
incineration as a technology option.  (Since both Reichhold and
Vulcan would solicit strong guarantees from EPA that, once equipment
was on order, they would indeed be allowed to proceed with full-scale
construction and be able to operate the incineration units without
undue harassment from environmental groups.  Naturally, EPA would be
in no position, legally or otherwise, to honor such requests.)

     In my opinion, there are but four alternatives available for
consideration by the SAB regarding this matter:
   (1)  At-sea incineration aboard a vessel similar to the M/T
        Vulcanus.
   (2)  Privately owned/contractor operated incineration facility
        (e.g., Marquardt's high efficiency SUE incineration unit.)
   (3)  In-process change/process modification (i.e., catalyst
        substitution) to minimize dioxin/dibenzofuran byproduct
        production - to include analysis of feedstock (phenol)
        quality.
   (4)  Encouragement of accelerated R&D into incorporation of PCP
        waste residues as feedstocks to cement kilns.

All options could be explored should the SAB desire.
                                160

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               8.3.2
UNIVERSITY OF MISSOURI-COLUMBIA
        April  24,  1978
College of Veterinary Medicir


 Veterinary Anatomy—P|^»lo

          Columbia. Missouri 65*
          Telephone (314) 382-7C
        Mr.  Ernst  Linde
        Executive  Secretary
        Environmental Health Advisory Committee
        Science Advisory Board A-101
        Washington, D.C.  20460

        Dear Mr. Linde:

        Enclosed are 20 copies of a report containing my additional comments
        on the draft report on pentachlorophenol contaminants.

        Please distribute these to the proper persons.

        Sincerely  yours,


             '.£/£.
        Gary A. Van Gelder, D.V.M., Ph.D.
        Veterinary lexicologist

        GAVGrnc
                                        161

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                                             April  15, 1978
                                             Part II (part I dated
                                               3/24/78)
TO:       Mr. Ernst Linde

FROM:     Dr. Gary Van Gelder

RE:       Comments on Draft Report on Pentachlorophenol


The following additional comments are made relative to the draft report.

1)   The charge to the committee was to assess the hazard to humans due
     to contaminants in pentachlorophenol.  Other than industrial
     chloracne resulting in all probability from exposures to mixtures
     of various 'chemicals the document fails to document any significant
     human health hazard that has resulted from 40 years of use and
     exposure.  This statement is made with the acknowledged exception
     of reported instances of gross negligence or intentional ingestion
     resulting in illness and death.

     The report fails to clearly elucidate the point that the present
     methods of producing low non-phenolic content PCP will still
     possess the presently alleged chloracne hazard since the starting
     reactions are similar for both processes.  The report implies
     that obtaining concentrates of the contaminants is less hazardous
     than working with very diluted concentrations.  The above implication
     is made in the report without any evidence that there was any
     attempt to assess the risk involved.  Additionally, comments made
     at the hearing clearly demonstrated the lack of unanimous agreement.
     among waste disposal specialists on the reliability of incineration.
     Critical issues are:

     a)   frequency of stack monitoring
     b)   levels of detection
     c)   location of stack relative to wind direction and population
     d)   presence of fail/safe devices
                                                               t
     Without such information and risk assessment data, how can a
     responsible decision be made to move from technology A to technology
     B, especially when technology A has not been shown to be associated
     with any significant, isolatable problem?  Risk assessment involves
     more than simply saying since process B exists we should use it.

2)   Page 1-7 of the report refers to dioxins being found in milk from
     Michigan cattle but no data are presented.  The report later refers
     to dioxins in liver and fat.  This point needs clarification.

3)   Page 111-14, Table II - The data are summarized in such a way as to
     ignore dose.  An important part of risk assessment is consideration of
     dose and evaluation of dose-response patterns.
                                162

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     In one sense the draft report begins to pull  together the available
     information.  The next steps are evaluation and interpretation.
     In my opinion, the last steps remain as uncompleted tasks for the
     committee.

4)   Page II1-9  - states "technical  grade PCP has been implicated in
     causing teratogenic effects in women - Kimbrough, 1972."  The
     report by Kimbrough does not make this statement.  Stillbirths with
     PCB's are reported.

5)   Page II1-9 - The Larsen study cited is inadequate to address the
     question of placenta! transfer.   Based on information presented
     it is likely that placenta/fetal PCP levels are comparable to
     maternal blood levels.

6)   Statistical methods used to evaluate the various 90-720 day studies
     are not consistent.  See my letter to Dr. Schwetz of Dow Chemical
     which was attached to my comments dated March 24.

7)   While I appreciate the comments  of several  members of the committee
     that their concern is not animal health, I  need to point out that
     there are people in the public sector who,  based on their understanding
     of comments made by members of this committee believe that low level
     exposures to technical PCP kills cows.  I am satisfied with the
     progress being made to resolve that-misconception.

8)   The remaining issue is one of safety/hazard evaluation.  It is
     amazing that an EPA sponsored committee was not provided or did not
     review the results of studies sponsored by  EPA to evaluate the human
     health effects of PCP.  Why this body of information has been ignored
     is unexplainable.

     One cannot prove safety for any product or  process, what one does
     is evaluate toxicity and assess  risk (hazard).  Consequently,
     studies done where technical PCP was fed to animals provide information
     on the toxicity of the PCP related contaminants.

     Furthermore, evaluation of worker related health problems or the
     lack of problems are also important items to consider in risk assessment.

9)   My principle concern in this entire matter  has been based on a
     broad view of the entire situation.  First, PCP is an economic
     poison.  Fortunately, it's toxicologic characteristics are such that
     it does not present a large hazard.  But PCP residues have been
     found in food products of animal origin. To the extent -that those
     residues can be reduced or eliminated without causing a major
     economic effect is a worthwhile goal.  Additionally, PCP constitutes
     only 5% of what is put into wood to preserve it.  The toxicity and
     residue characteristics of the other 95% of the material has not
     been determined.  What is found as residues are generally those things
     that excite an electron capture detector.

     These considerations plus my own observations of over use and
     unnecessary use of PCP treated wood in places that facilitate
     animal exposure leads me to a broad based recommendation that addresses


       •    .......           163"    ,                                   .

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     the entire problem.   Namely,  the need to develop  sensible  use
     restrictions to reduce animal  exposure.   The  casual  rubbing
     against a post or occasional  lick of a post is  of no concern to
     me.  The issue is one of feed bunks, bunker silos and use  of
     treated wood in above grade,  dry locations.  The  concern expressed
     in item 10 below is  also a part of my decision  information base.

10)  I have reason to believe that .the level  of dioxin formation on the
     surface of treated wood exposed to light is higher than that felt/to
     occur as expressed in the committee discussion.   It is of  sufficient
     concern that Dow has conducted and has expressed  their intent to
     conduct additional studies in this regard.
                                164

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                DOW  CHEMICAL  U.S.A.
May 9, 1978                                        P.  o.  BOX
                                                 2040  DOW CENTER
                                             MIDLAND, MICHIGAN 48640


Mr. Ernst Linde
Executive Secretary
Environmental Health Advisory Committee
Science Advisory Board
U. S. Environmental Protection Agency
Washington, D. C.  20460


Dear Mr. Linde:

Attached is the requested description of the general procedures
utilized by Dow Chemical U.S.A. to contain and destroy the  con-
taminants resulting from the production of DOWICIDE* EC-7
Antimicrobial grade of pentachlorophenol.  We believe  this  is
the kind of additional information that was needed by  the
Environmental Health Advisory Committee Study Group  on Penta-
chlorophenol Contaminants to assure itself that these  impurities
can be feasibly handled.

As Dow has repeatedly stated, we contend that disposal of the
toxic impurities inherent to commercial pentachlorophenol
should be dealt with at the producing site where acknowledged
risk, would be minimized.  The fact that we produce and market
a grade of pentachlorophenol with significantly reduced non-
phenolic impurity content supports this position.

We have included 10 copies of the requested information.  If
additional copies are required for distribution, for example,
to members of the Environmental Health Advisory Committee,
please do not hesitate to let us know.

Very truly yours,
Robert L. Johpson
Designed Pro&ucts Department
Technical Service & Development
517/636-1524

mbh

attach.

*Trademark of The Dow Chemical Company
             AN OPERATING UNIT OF THE DOW CHEMICAL COMPANY

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           DISPOSAL OF PENTACHLOROPHENOL IMPURITIES
                     Dow Chemical U.S.A.
The product known as DOWICIDE* EC-7 Antimicrobial grade of.
pentachlorophenol (PCP) differs in chemical assay from the
older form of PCP.  Numerous publications describe the com-
mercial process utilized in the U.S. to make PCP.  As noted
in these publications, the process reaction mixture is main-
tained as a liquid  (approximately 10°C above the product
melting point); no  solvent is used or required.  The commer-
cial process utilises final chlorination and the necessary
temperatures to produce a product with a pentachlorophenol.     ~  —
content in the range of about 85-90% .  These production con-
ditions also result in the formation of the various contaminants:
found in PCP.

The finished reaction mixture/ in the Dow process, is distilled.
to yield a grade of PCP which meets the imposed specifications
for DOWICIDE EC-7.  A copy of the DOWICIDE EC-7 technical.
bulletin, which describes the composition, is attached.

The still bottoms resulting from this additional PCP processing
contain the non-phenolic contaminants identified as chlorinated
dibenzo-p-dioxins and chlorinated dibenzofurans..  Other materials
included in the still bottom residue, or tars, are the chloro-
phenoxyphenols, chlorodiphenyl ethers, and even a percentage of
higher phenols such as pentachlorophenol itself.

These tars are handled, stored and transported to the Dow
tar burner in closed systems.  Eye protection, rubber gloves
and protective clothing are routinely used by all personnel
*Trademark of The Dow Chemical Company

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                              -2-
involved in these operations.  A rigorous industrial hygiene
and health monitoring program is and has been in effect for
these personnel.  Anytime that work on contaminated equipment
is needed/ extreme protective measures are taken including
full rubber suits and self-contained breathing apparatus.

Normal operating conditions in the tar burner are maintained
to achieve a minimum 1.8-second residence time at temperatures
of 900-1000°C.  The temperature is continuously monitored with
appropriate warning alarms and shut-off devices.  Combustion
gases go through a three-stage scrubbing system before discharge
to. the atmosphere.  The scrubber water is treated in the waste
water treatment plant before recycle and/or discharge to the  ..
Tittabawassee River.
5/9/78
                         167

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                                                  technical data
                    DOWICIDE, EC-7 ANTIMICROBIAL
GENERAL            	'
DOWICIDE  EC-7.Antimicrobial is Daw's designation  for pentachlorp-
phenol, purified grade.   This., antimicrobial is designed to comple-
ment DOWICIDE 7 Antimicrobial in  all industrial uses that require
the control of bacteria and fungi,  particularly in the area of
wood preservation.   "          -  . "        ':  . =•  •

PHYSICAL  PROPERTIES.                          '
(These are laboratory or literature-data typical  of the product   ~
and are not to' be considered as,  or. confused with,  specifications".)!

STRUCTURE           "    ':
Formula ...... -....-. . .  .  .,...;.. .-, . .  ..  .. .  .  . .
Molecular Weight.   ........  ..  ... .. . ....  .  .  .. .. 266.
Flash  Point, °F ...................  ..... Non
Fire Point, °F  .............. ...... . .. None-
Specific Gravity,  25/25°C ........ ....... .1.9
Solubility, approx.  g/100 g solvent  at 25 °C
   Acetone  . . ...... .  ..... .........  52
   Methanol ...................  .... 175
   Ethanol (F30)   ...............  ..... 125
   Isopropanol  ..........  .  . . . .......  80
   Diacetone Alcohol  .  . ................ 145
   DOWANOL TPM Glycol Ether .........  ...... 115
   Ethylene Glycol  ......  .............  12
   Methylene Chloride .....  .  ......  ......   7
   o-Xylene ....  ......  7  ......  ......  18
   Turpentine ........ .........  .  ,..; ....   7
           NOTICE: This information is presented in good faith, but no warranty, express or implied, is given
           nor is freedom from any patent owned by The Dow Chemical Company or by others to be inferred.
                  THE DOW CHEMICAL COMPANY
           DESIGNED PRODUCTS DEPARTMENT • MIDLAND. MICHIGAN 48640

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DOWICIDE EC-7 ANTIMICROBIAL
Page 2


PRODUCT DESCRIPTION
DOWICIDE EC-7 Antimicrobial has. the following composition:

     Active ingredients 	 100%
        Pentachlorophenol	  88%
        2,3,4f6-Tetrachlorophenol 	  12%

     Chlorinated Dioxins
        Octachlorodibenzo-p-dioxin  	 30 ppm, max.
        Hexachlorodibenzo-p-dioxins 	  1 ppm, max.

     Description	 Off-white te
                                                    light yellow
                                                    prills.
EPA Reg. No. 464-431


PACKAGES
Prilled and pelleted forms of DOWICIDE EC-7 Antimicrobial are
sold in multiwall paper bags having a net weight of 50 pounds,
in fiber drums having a net weight of 300 pounds/ in wire-bound
boxes having a net weight of 2500 pounds and in bulk to be
transported in tank trucks and rail cars.  The block form is
sold in units, having a net weight of 2000 pounds.

(Typical Laboratory Data)
                                                 % DOWICIDE EC-7
              Test Organism                      for Inhibition

Trichoderma. viride, ATCC#8678                    0.0025-0.005
Trichoderma sp., Madison P-42                    0.001-0.0025
Ceratocystls pilifera, ATCC215457                0.0005-0.001
PolyporusTullpirerae, ATCC211245                <0.0001
Rhi2opus"gtolonifer/ ATCC#6227a                  '0.0001-0.00025
Lenzxtes trabea, Madison 617                     0.0001-0.00025
Ceratocystis ips, ATCC#12860                     0.001-0.0025
Chaetomxum qloEosum, ATCC#6205                   0.0001-0.00025
Aspergillus nigefT"ATCC#6275                     0.001-0.0025

Bacillus cereus var. mycoides, ATCCf11778        0.0005-0.001
Bacillus subtilis, ATCCS8473                     0.005-0.01
Escherichia coli, ATCCS11229                     0.025-0.05
Pseudomonas aeruginosa, ATCC#15442               0.1-0.25
Enterobacter aerogenes, ATCCf13048               0.05-0.1
Streptomyces griseus, ATCC^10137                 O.OOOS-OJOOl
FlavobactirTum arborescens, ATCCS4358            0.00025-0.0005

Formulators may be required to develop their own efficacy data
well as use and precautionary labeling based on the represented
properties and intended uses of their finished formulations, anc
in accordance with all pertinent laws and regulations.

                         —169

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