f/EPA
                                United States
                                Environmental Protection
                                Agency
                               Health Effects Research
                               Laboratory
                               Research Triangle Park NC 2771 1
                                Research and Development
                               EPA-600/S1-81-024  Apr 1981
Project Summary
                               Method  Development for the
                               Assessment  of  Possible
                               Human  Exposure  to
                               Pesticides and  Industrial
                               Chemicals

                               Thomas R. Edgerton, Robert F. Moseman, and Lynn H. Wright
                                 The determination of chlorinated
                               phenols in urine can be used as a
                               means for assessing exposure to pesti-
                               cides and industrial chemicals in the
                               human population.
                                 A method was developed for the
                               analysis of chlorinated phenols which
                               involves the derivatization of metabo-
                               lites from the urine of rats fed hexa-
                               chlorobenzene (HCB) and pentachlo-
                               rophenol (PCP). This method was then
                               applied to urine samples taken from
                               the general human population to gain
                               a  background  level.  Pentachloro-
                               phenol was detected in greater than
                               90% of the human samples analyzed.
                               The only other metabolites detected
                               were  tetrachloropyrocatechol and
                               tetrachlorohydroquinone. The urine of
                               a worker occupationally exposed to
                               PCP exhibited quantifiable amounts
                               of tetrachloropyrocatechol and tetra-
                               chlorohydroquinone along with large
                               amounts (greater than 3 ppm) of PCP.
                               Pentachlorothiophenol,  a  major
                               metabolite of HCB fed to rats, was not
                               detected in human urine.
                                The analysis of human urine for
                               underivatized  chlorinated  phenols
                               using  a direct gas chromatographic
                               method not requiring derivatization
                               detected quantifiable levels of 2,5-
                               dichloro-, 2,4,5-trichloro-,  2,3,4,6-
                               tetrachloro- and pentachlorophenol in
                               greater than  90% of the samples
                               examined. Approximately 50% of the
                               samples contained detectable levels
                               of 2,6- and 3,5-dichlorophenol  and
                               2,4,6-trichlorophenol.
                               Introduction
                                Chlorinated  phenols have been of
                               concern to the environmental scientist
                               for many years. Their toxicity to fish and
                               other aquatic life is well documented in
                               the literature The presence of chloro-
                               phenols in industrial effluents has been
                               widely demonstrated. Methodology was
                               developed to analyze for  chlorinated
                               phenols in  urine to assess possible
                               human exposure to chemicals known or
                               suspected to give these compounds as
                               metabolites.
                                The  most widely used and studied
                               chlorinated  phenol  is  pentachloro-
                               phenol (PCP). It has been used exten-
                               sively in the wood products industry as a
                               preservative and in agriculture  as a
                               fungicide. A discussion of its uses,
                               toxicity, and fate in the environment can
                               be found in the literature.  The occur-
                               rence of PCP in humans from occupa-
                               tionally exposed workers  and  the
                               general human population is also well
                               documented.

-------
Table 1 . Possible Origins
Metabolite

2, 6-dichlorophenol

2,4-dichlorophenol




2,3-dichlorophenol


2,5-dichlorophenol



3.4-dichlorophenol



3, 5-dichlorophenol


2. 3,4-trichlorophenol

2. 3, 5-trichlorophenol


2. 3, 6-trichlorophenol
2. 4,5-trichlorophenol






2. 4, 6-trichlorophenol

3, 4, 5-trichlorophenol

2, 3, 5, 6-tetrachlorophenol

2, 3, 4, 6-tetrachlorophenol


2. 3, 4,5-tetrachlorophenol



pentachlorophenol



of Various Chlorinated Phenols
Origin

Lindane

Lindane
VC-13
m-dichlorobenzene
2,4-D

Lindane
o-dichlorobenzene

Lindane
2,4, S-T
p - dichlorobenzene

Lindane
o-dichlorobenzene
Diuron

Lindane
PCP

Lindane

Lindane
PCP

Lindane
Lindane
Ronnel
Erbon
2,4,5-T
HCB
Tetrachlorvinphos

Lindane

Lindane

HCB

PCP (impurity)
Lindane

PCP
Lindane
HCB

PCP
Lindane
HCB
PCNB
Type Pesticide

Insecticide

Insecticide
Insecticide
Fumigant
Herbicide

Insecticide
Fumigant

Insecticide
Herbicide


Insecticide
Fumigant
Herbicide

Insecticide


Insecticide

Insecticide


Insecticide
Insecticide
Insecticide
Herbicide
Herbicide
Fungicide


Insecticide

Insecticide

Fungicide

Fungicide
Insecticide

Fungicide
Insecticide
Fungicide

Fungicide
Insecticide
Fungicide
Fungicide
The metabolism of PCP and other
chemicals which give rise to PCP and
other chlorinated phenols as metabo-
lites can be found in the literature. A
listing of possible sources of chlorinated
phenols is found in Table 1 . The list is by
no means complete, but does give some
insight nto possible origins of various
chlorinated phenols that might be en-
countered in exposure assessment
work.
Metabolism studies and analytical
methods development were conducted
using rats fed two chemicals, penta-
chlorophenol (PCP) and hexachloro-
benzene (HCB), which were known or
suspected to metabolize to chlorinated
phenols The method was then applied
to urine samples from the general
human population and the urine of a
worker occupationally exposed to
pentachlorophenol.
The literature contains no apparent
methodology for the determination of
lower chlorinated phenols in urine at
the low ng/g level. Because of this, a
method was developed in an attempt to
detect mono-, di-, and trichlorophenols
in urine. No metabolism studies were
performed, but the method was applied
to general human population urine
samples.


Conclusions
Pentachlorophenol, 2,5-dichloro-
phenol, 2, 4, 5-trichlorophenol and
2,3,4,6-tetrachlorophenol were found
in greater than 90% of the human urine
samples analyzed. Since all but one of
the samples was from the general
population, it is difficult to determine a
common exposure route. The urine of
workers occupationally exposed to
other chemicals which can give chlo-
rinated phenol metabolites and further
animal feeding studies need to be con-
ducted before definitive exposure
assessments can be made.
The determination of chlorinated
phenols in urine can possibly be used as
an index of exposure to numerous
chemicals.





-------
The EPA authors, Thomas R. Edgerton, Robert F. Moseman, and Lynn H.
  Wright are with the Health Effects Research Laboratory, Research Triangle
  Park, NC 27711.
Thomas R. Edgerton is the EPA Project Officer (see below).
The complete report, entitled "Method Development  for the Assessment of
  Possible Human Exposure to Pesticides and Industrial Chemicals," {Order No.
  PB 81-175 796; Cost: $6.50. subject to change/ will be available only from:
        National Technical Information Service
        5285 Port Royal Road
        Springfield,  VA 22161
        Telephone: 703-487-4650
The EPA Project Officer can be contacted at:
        Health Effects Research Laboratory
        U.S. Environmental Protection Agency
        Research Triangle Park, NC 27711
                   US GOVERNMENT PRINT!*! OFFICE 1M1-757-012/7046

-------
                                  Center for Environmental Research                                              '
United States
Env,ronmemal Protection                Information                                                           Environmental
Agency                             Cmc.nnati OH 45268                                                    Protection
                                                                                                     Agency
                                                                                                     EPA 335

Official Business
Penalty for Private Use $300
        frS   000032*
        u  s  t-'       FPUTtriTuv
        'Jin  %  ,     ''ARkflKY         "«-.ni       .-i
        ^teWlr^r
   L

-------