&EPA
United States
Environmental Protection
Agency
Office of Water
Regulations and Standards
Criteria and Standards Division
Washington DC 20460
EPA 440/5-80-031
October 1980
C.-1
Ambient
Water Quality
Criteria for
Chlorinated Naphthalene
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AMBIENT WATER QUALITY CRITERIA FOR
CHLORINATED NAPTHALENE
Prepared By
U.S. ENVIRONMENTAL PROTECTION AGENCY
Office of Water Regulations and Standards
Criteria and Standards Division
Washington, D.C.
Office of Research and Development
Environmental Criteria and Assessment Office
Cincinnati, Ohio
Carcinogen Assessment Group
Washington, D.C.
Environmental Research Laboratories
Corvalis, Oregon
Duluth, Minnesota
Gulf Breeze, Florida
Narragansett, Rhode Island
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DISCLAIMER
This report has been reviewed by the Environmental Criteria and
Assessment Office, U.S. Environmental Protection Agency, and approved
for publication. Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
AVAILABILITY NOTICE
This document is available to the public through the National
Technical Information Service, (NTIS), Springfield, Virginia 22161.
11
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FOREWORD
Section 304 (a)(l) of the Clean Water Act of 1977 (P.L. 95-217),
requires the Administrator of the Environmental Protection Agency to
publish criteria for water quality accurately reflecting the latest
scientific knowledge on the kind and extent of all identifiable effects
on health and welfare which may be expected from the presence of
pollutants in any body of water, including ground water. Proposed water
quality criteria for the 65 toxic pollutants listed under section 307
(a)(l) of the Clean Water Act were developed and a notice of their
availability was published for public comment on March 15, 1979 (44 FR
15926), July 25, 1979 (44 FR 43660), and October 1, 1979 (44 FR 56628).
This document is a revision of those proposed criteria based upon a
consideration of comments received from other Federal Agencies, State
agencies, special interest groups, and individual scientists. The
criteria contained in this document replace any previously published EPA
criteria for the 65 pollutants. This criterion document is also
published in satisifaction of paragraph 11 of the Settlement Agreement
in Natural Resources Defense Council, et. al. vs. Train, 8 ERC 2120
(D.D.C. 1976), modified, 12 ERC 1833 (D.D.C. 1979).
The term "water quality criteria" is used in two sections of the
Clean Water Act, section 304 (a)(l) and section 303 (c)(2). The term has
a different program impact in each section. In section 304, the term
represents a non-regulatory, scientific assessment of ecological ef-
fects. The criteria presented in this publication are such scientific
assessments. Such water quality criteria associated with specific
stream uses when adopted as State water quality standards under section
303 become enforceable maximum acceptable levels of a pollutant in
ambient waters. The water quality criteria adopted in the State water
quality standards could have the same numerical limits as the criteria
developed under section 304. However, in many situations States may want
to adjust water quality criteria developed under section 304 to reflect
local environmental conditions and human exposure patterns before
incorporation into water quality standards. It is not until their
adoption as part of the State water quality standards that the criteria
become regulatory.
Guidelines to assist the States in the modification of criteria
presented in this document, in the development of water quality
standards, and in other water-related programs of this Agency, are being
developed by EPA.
STEVEN SCHATZOW
Deputy Assistant Administrator
Office of Water Regulations and Standards
111
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ACKNOWLEDGEMENTS
Aquatic Life Toxicology:
William 0. Brungs, ERL-Narrangansett
U.S. Environmental Protection Agency
David J. Hansen, ERL-Gulf Breeze
U.S. Environmental Protection Agency
Mammalian Toxicology and Human Health Effects:
Woodhall Stopford (author)
Duke University Medical Center
Steven D. Lutkenhoff (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
Jerry F. Stara (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
Larry Fishbein
National Center for Toxicological Research
Patricia Hilgard, OTS
U.S. Environmental Protection Agency
Alan B. Rubin
U.S. Environmental Protection Agency
Rolf Hartung
University of Michigan
Julian Andelman
University of Pittsburgh
Herbert Cornish
University of Michigan
Patrick Durkin
Syracuse Research Corporation
Alfred Garvin
University of Cincinnati
Jean C. Parker, ECAO-RTP
U.S. Environmental Protection Agency
Joseph Santodonato
Syracuse Research Corporation
Technical Support Services Staff: D.J. Reisman, M.A. Garlough, B.L. Zwayer,
P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper,
M.M. Denessen.
Clerical Staff: C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks,
B.J. Quesnell, T. Highland, R. Rubinstein.
IV
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TABLE OF CONTENTS
Criteria Summary
Introduction A-l
Aquatic Life Toxicology B-l
Introduction B-l
Effects B-l
Acute Toxicity B-l
Chronic Toxicity B-2
Plant Effects B-2
Residues B-2
Miscellaneous B-2
Summary B-3
Criteria B-3
References B-ll
Mammalian Toxicology and Human Health Effects C-l
Introduction C-l
Exposure C-5
Ingestion from Water and Food C-6
Inhalation C-ll
Dermal C-12
Pharmacokinetics C-12
Absorption, Distribution, and Excretion C-12
Metabolism C-16
Effects C-18
Acute, Subacute, and Chronic Toxicity C-22
Synergism and/or Antagonism C-31
Teratogenicity, Mutagenicity, and Carcinogenicity C-32
Criterion Formulation C-33
Existing Guidelines and Standards C-33
Current Levels of Exposure C-33
Special Groups at Risk C-34
Basis and Derivation of Criteria C-34
References C-38
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CRITERIA DOCUMENT
CHLORINATED NAPHTHALENES
CRITERIA
Aquatic Life
The available data for chlorinated naphthalenes indicate that
acute toxicity to freshwater aquatic life occurs at concentrations
as low as 1,600 ug/1 and would occur at lower concentrations among
species that are more sensitive than those tested. No data are
available concerning the chronic toxicity of chlorinated naph-
thalenes to sensitive freshwater aquatic life.
The available data for chlorinated naphthalenes indicate that
acute toxicity to saltwater aquatic life occurs at concentrations
as low as 7.5 ug/1 and would occur at lower concentrations among
species that are more sensitive than those tested. No data are
available concerning the chronic toxicity of chlorinated naphtha-
lenes to sensitive saltwater aquatic life.
Human Health
Using the present guidelines, a satisfactory criterion cannot
be derived at this time due to the insufficiency in the available
data for chlorinated naphthalenes.
VI
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INTRODUCTION
Chlorinated naphthalenes consist of two fused six carbon-mem-
bered aromatic rings where any or all of the eight hydrogen atoms
can be replaced with chlorine. Theoretically, 76 individual iso-
mers are possible and may exist. The commercial products are usu-
ally mixtures with various degrees of chlorination, and are pre-
sently manufactured and marketed in the United States under the
...—_ >., «„«„„.-
Mixtures of tri- and tetrachloronaphthalenes (solids) com-
prise the bulk of market use as the paper impregnant in automobile
capacitors. Less use is made of mixtures of the mono- and di-
chloronaphthalenes as oil additivies for engine cleaning, and in
fabric dyeing. In 1956, the total United States production of
chlorinated naphthalenes was approximately 3,175 metric tons
(Hardie, 1964).
Possible impurities of these products are chlorinated deriva-
tives, corresponding to the impurities in coal tar, or petroleum-
derived naphthalene feedstocks which may include biphenyls, fluor-
enes, pyrenes, anthracenes, and dibenzofurans.
The potential for environmental exposure may be significant
when these compounds are used as oil additives, in the electroplat-
ing industry, and in the fabric dyeing industry. The extent of
leaching of chlorinated naphthalenes from discarded capacitors and
old cable insulation (manufactured prior to curtailment of using
the chemical in such products) has not been determined.
Chlorinated naphthalenes have been detected as a contaminant
in foreign commercial polychlorinated biphenyl (PC3) formulations
A-l
-------
(Phenoclor, Clophen, and Kanechlor) along with chlorinated dibenzo-
furans, and are present in domestic PCBs (Aroclors) but at lower
levels than in foreign formulations (Vos, et al. 1970; Bowes, et
al. 1975; Roach and Pomerantz, 1974).
The synthesis of chlorinated naphthalenes generally involves
the chlorination of naphthalene by chlorine in the presence of
catalytic amounts of ferric or antimony chloride. This production
process yields mixtures of highly chlorinated naphthalenes in vary-
ing quantities by further chlorination of the lesser substituted
products. Only 1-chloronaphthalene and octachloronaphthalene are
readily isolated from the products of direct chlorination (Hardie,
1964). All of the possible two monochloro-, 10 dichloro-, and 14
trichloronaphthalenes have been isolated and identified. However,
not all of the tetra- and higher chloro-isomers have been charac-
ter ized.
Table 1 presents physical property data for all chlorinated
naphthalenes which have been isolated and identified. The physical
properties of the chlorinated naphthalenes are generally dependent
on the degree of chlorination. Melting points (MP) of the pure
compounds range from 17°C for 1-chloronaphthalene to 198°C for
1,2,3,4-tetrachloronaphthalene (Hardie, 1964). Also, as the degree
of chlorination increases, the specific gravity, boiling point
(BP), fire and flash points all increase, while the vapor pressure
and water solubility decrease (Hardie, 1964). Mixtures of the
mono- and dichloronaphthalenes are generally liquid at room temper-
ature, whereas mixtures of the more highly chlorinated naphthalenes
tend to be waxy solids (U.S. EPA, 1973).
A-2
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TABLE 1
Physical Properties of Chloronaphthalenes*
I some r
1-chloro naphthalene
2-chloronaphthalene
1,2-dichloronaphthalene
1,3-dichloronaphthalene
1,4-dichloronaphthalene
1, 5-dichloronaphthalene
1, 6-dichloronaphthalene
1, 7-dichloronaphthalene
1,8-dichloronaphthalene
2,3-dichloronaphthalene
2, 6-dichloronaphthalene
2 , 7-d ichloronaphthalene
1,2, 3- trichloro naphthalene
1,2, 4- tr ichloronaphthalene
1 , 2 , 5- tr ichloronaphthalene
1 , 2 , 6- tr ichloronaphthalene
1 , 2 , 7- tr ichloronaphthalene
1,2, 8- tr ichloronaphthalene
1 , 3 , 5- tr ichloronaphthalene
1 , 3 , 6- tr ichloronaphthalene
1 , 3 , 7- tr ichloronaphthalene
1,3 , 8- tr ichloronaphthalene
1 , 4 , 5- tr ichloronaphthalene
1,4 , 6- tr ichloronaphthalene
2 , 3 , 5- tr ichloronaphthalene
2 , 3 , 6- tr ichloronaphthalene
1,2,3 , 4- te trachloronaphthalene
1 , 3 , 5 , 8- te trachloronaphthalene
1,4 , 6, 7- te trachloronaphthalene
1,2,3,4 ,5-pentachloro naphthalene
1,2,3,4,5,6,8-
heptachloro naphthalene
1,2,3,4,5,6,7,8-
octachloro naphthalene
MP(°C) BP°C densitytemp-(°C)
ca.17 259.3 1.193820
61 265 1.265616
35 1.314748'5
61.5 291
(755 mm Hg)
67.5 287 1.299775'9
106.5
48.5
63.5 285.5 1.261199*5
88.5 1.292499'8
135 285
120
114
81
92
78
92.5
88
83
94
80.5
113
89.5
133
65
109.5
90.5
198
131
139
168.5
194
192
MP = Melting point; BP = Boiling point
A-3
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Chlorinated naphthalenes, like PCBs, exhibit a high degree of
chemical and thermal stability as indicated by their resistance to
most acids and alkalies and to dehydrochlorination (U.S. EPA,
1975).
A-4
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REFERENCES
Bowes, G.W., et al. 1975. Identification of chlorinated dibenzo-
furans in American polychlorinated biphenyls. Nature. 265: 305.
Bardie, D.W. 1964. Chlorocarbons and Chlorohydrocarbons: Chlori-
nated Naphthalenes. In; D.F. Kirk and D.E.Othmer (eds.), Encyclo-
pedia of Chemical Toxicology. 2nd ed. John Wiley and Sons, Inc.,
New York, p. 297.
Roach, J.A. and I.H. Pomerantz. 1974. The finding of chlorinated
dibenzofurans in a Japanese polychlorinated biphenyl sample. Bull.
Environ. Contam. Toxicol. 12: 338.
U.S. EPA. 1973. Preliminary environmental hazard assessment of
chlorinated naphthalenes, silicones, fluorocarbons, benzenepolycar-
boxylates, and chlorophenols. EPA Publ. No. 560/2-74-001.
Washington, D.C.
U.S. EPA. 1975. Environmental hazard assessment report: Chlori-
nated naphthalenes. EPA Publ. No. 560/8-75-001. Washington, D.C.
Vos, J.G., et al. 1970. Identification and toxicological evalua-
tion of chlorinated dibenzofurans and chlorinated naphthalenes in
two commercial polychlorinated biphenyls. Food Cosmet. Toxicol.
8: 625.
A-5
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Aquatic Life Toxicology*
INTRODUCTION
The only chlorinated naphthalenes for which data are available for
freshwater organisms are 1-chloronaphthalene and octachloronaphthalene. The
available LCgg and ECgQ values for the bluegill, Daphnia magna, and an
alga indicate similar sensitivity of these species.
Most of the data concerning the effects of chlorinated naphthalenes on
saltwater organisms are for commercial mixtures of mono- through hexachloro-
naphthalene in different proportions. Most of the remaining data are for 1-
chloronaphthalene. These results are very similar to those freshwater data
for a fish, an invertebrate, and an algal species using comparable test pro-
cedures (U.S. EPA, 1978).
EFFECTS
Acute Toxicity
A single test with Daphnia magna and 1-chloronaphthalene (U.S. EPA,
1978) provides a 48-hour ECgo of 1,600 ug/l (Table 1). The 96-hour LC50
for the bluegill and 1-chloronaphthalene is 2,270 ug/l (Table 1).
Of the saltwater invertebrate species, only the mysid shrimp has been
tested with 1-chloronaphthalene. The 96-hour LC5Q is 370 yg/1 (Table 1),
which indicates a greater sensitivity than the sheepshead minnow. The
sheepshead minnow has been exposed to 1-chloronaphthalene (U.S. EPA, 1978)
and the 96-hour LC5Q is 2,360 ug/l (Table 1). The remaining data are for
the commercial mixtures.
*The reader is referred to the Guidelines for Deriving Water Quality Cri-
teria for the Protection of Aquatic Life and Its Uses in order to better un-
derstand the following discussion and recommendation. The following tables
contain the appropriate data that were found in the literature, and at the
bottom of each table are calculations for deriving various measures of tox-
icity as described in the Guidelines.
B-l
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Chronic Toxicity
No early life stage or life-cycle tests have been conducted with fresh-
water fish or invertebrate species and any chlorinated napthalerie.
An early life stage test has been conducted with the sheepshead minnow
and 1-chloronaphthalene (U.S. EPA, 1978). The chronic value is 660 ug/1
(Table 2). This value with the 96-hour LC50 results in an acute-chronic
ratio of 3.6 for the sheepshead minnow.
Plant Effects
The freshwater alga, Selenastrum capricornutum, has been exposed to 1-
chloronaphthalene and the 96-hour EC™ values for chlorophyll a_ and cell
numbers are 1,030 and 1,000 ug/1, respectively (Table 3). The corresponding
values for chlorophyll a_ and cell numbers for the saltwater alga, Skeletone-
ma costatum, are 1,130 and 1,300 u9/l> respectively, for 1-chloronaphthalene
(Table 3).
Residues
There are no equilibrium residue data available for chlorinated naphtha-
lenes with any freshwater or saltwater species.
Miscellaneous
A variety of acute tests of the effects of octachloronaphthalene have
been conducted with the bluegill, and Daphnia magna. (U.S. EPA, 1978). No
adverse effects were observed at concentrations as high as 500,000 to
600,000 ug/l (Table 4).
As with the freshwater species, the acute toxicity results for the
sheepshead minnow, mysid shrimp, and an alga were all greater than 500,000
ug/1 for octachloronaphthalene (Table 4). A great variety of other data is
available for various mixtures of chlorinated naphthalenes, including bio-
concentration, inhibition of algal growth, intermolt time for crabs, and
other effects (Table 4).
B-2
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Summary
Only 1-chloronaphthalene and octachloronaphthalene have been tested with
freshwater aquatic organisms. The LC5Q and EC50 values for 1-chloro-
naphthalene and the bluegill, Daphnia magna, and an alga, Selenastrum capri-
cornutum, range from 1,000 to 2,270 yg/1. Comparable results with octa-
chloronaphthalene and the same species were 500,000 ug/1.
The data base for saltwater aquatic life is comparable to that for
freshwater species except for the large number and variety of data on com-
mercial mixtures of chlorinated naphthalenes (Halowa*^ compounds). For 1-
chloronaphthalene, the LC5Q and EC5g values for the sheepshead minnow,
mysid shrimp, and an alga, Skeletonema costastum, range from 370 to 2,360
ug/1. Comparable results with octachloronaphthalene and the same species
were 500,000 yg/1. An acute-chronic ratio of 3.6 is calculated for the
sheepshead minnow with a chronic value of 660 wg/l. Lethal and sublethal
effects of the commercial mixtures occur at concentrations ranging from as
high as 1,000 wg/l to as low as 7.5 yg/1.
CRITERIA
The available data for chlorinated naphthalenes indicate that acute tox-
icity to freshwater aquatic life occurs at concentrations as low as 1,600
vg/1 and would occur at lower concentrations among species that are more
sensitive than those tested. No data are available concerning the chronic
toxicity of chlorinated naphthalenes to sensitive freshwater aquatic life.
The available data for chlorinated naphthalenes indicate that acute tox-
icity to saltwater aquatic life occurs at concentrations as low as 7.5 ug/l
and would occur at lower concentrations among species that are more sensi-
tive than those tested. No data are available concerning the chronic tox-
icity of chlorinated naphthalenes to sensitive saltwater aquatic life.
B-3
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W
Table 1
Species Method*
Cladoceran, S, U
Daphnla roagna
Bluegi II, S, U
Lepomfs macrochirus
Mysld shrimp, S, U
Mysldopsis bah la
Brown shrimp, FT, M
Penaeus aztecus
Grass shrimp, FT, M
Palaemonetes puglo
Grass shrimp (post- larva), R, M
Palaemonetes puglo
Grass shrimp (adult), R, M
Palaemonetes puglo
Grass shrimp (post-larva), R, M
Palaemonetes puglo
Grass shrimp (post-larva), R, M
Palaemonetes puglo
Grass shrimp (adult), R, M
Palaemonetes pugio
Sheepshead minnow, S, U
Cyprlnodon varlegatus
. Acute values for chlorinated naphthalenes
LC50/EC50 Species Acute
Chemical (ug/l) Value (ug/l) Reference
FRESHWATER SPECIES
1-chloro- 1,600
naphthalene
1-chloro- 2,270
naphthalene
SALTWATER SPECIES
1-chloro- 370
naphthalene
Halowax 7.5
1014**
Halowax 248
1014**
Halowax 440
1000***
Halowax 325
1000***
Halowax 74
1013****
Halowax 69
J099*****
Halowax 90
,099*»*##
1-chloro- 2,360
naphthalene
1,600 U.S. EPA, 1978
2,270 U.S. EPA, 1978
370 U.S. EPA, 1978
7.5 U.S. EPA, 1976
248 U.S. EPA, 1976
Green 4 Neff, 1977
378 Green 4 Neff, 1977
74 Green 4 Neff, 1977
Green 4 Neff, 1977
79 Green 4 Neff, 1977
2,360 U.S. EPA, 1978
* S « static, FT = flow-through, R = renewal, M = measured, U = unmeasured
** Halowax* 1014: 20? tetrachloronaphthalene, 40? pentachloronaphthalene, 40? hexachloronaphthalene
*** Halowax* JOOO: 60? monochloronaphthalene, 40? dIch loronaphthalene
**** Halowax* 1013: 10? trIchloronaphthalene, 50? tetrachloronaphthalene, 40? pentachloronaphthalene
***** Halowax* 1099: 10? dlchloronaphthalene, 40? trichloronaphthalene, 40? tetrachloronaphthalene, 10? penta-
ch loronaphthalene
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Table 2. Chronic values for chlorinated naphthalenes (U.S. EPA, 1978)
I
cn
Species
Sheepshead minnow,
Cyprlnodon varlegatus
* ELS = early life stage
Species
Sheepshead minnow,
Cyprinodon varlegatus
Method* Chemical
SALTWATER SPECIES
ELS 1-chloro-
naphthalene
Acute-Chronic Ratio
Chronic
Value
Chemical
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Table 3. Plant effects for chlorinated naphthalenes (U.S. EPA, 1978)
I
cr>
Species
Alga,
Selenastrum capr 1 cornutum
Alga,
Selenastrum capr 1 cornutum
Alga,
Skeletonema costatum
Alga,
Skeletonema costatum
Chemical
FRESHWATER SPECIES
1 -ch loro-
naphtha lene
1-ch loro-
naphthalene
SALTWATER SPECIES
1-chloro-
naphthalene
1-chloro-
naphthalene
Effect
96-hr EC50
ch lorophy 1 1 a
96- hr EC50
eel 1 numbers
96- hr EC50
ch lorophy 1 1 a
96-hr EC50
eel 1 numbers
Result
(ug/l)
1,030
1,000
1,130
1,300
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Table 4. Other data for chlorinated naphthalenes
SpecIes
Chemical
Duration
Effect
Result
(ug/l) Reference
FRESHWATER SPECIES
Alga,
Selenastrum capr Icornutum
Alga,
Selenastrum capr Icornutum
Cladoceran,
Daphnla magna
Bluegi 1 1,
Lepomis macrochirus
Alga,
Chlorococcum sp.
Alga,
Chlorococcum sp.
Alga,
Ch 1 orococcum sp .
Alga,
Chlorococcum sp.
Alga,
Chlorococcum sp.
Alga,
Dunallella tertiolecta
Alga,
Dunallella tertiolecta
Alga,
Dunallella tertiolecta
Alga,
Nitzschla sp.
Octach loro-
naphthalene
Octach loro-
naphtha lene
Octach loro-
naphtha lene
Octach 1 or o-
naphthalene
Ha lowax
1000
Ha lowax
1013
Ha lowax
1014
Ha lowax
1000
Ha lowax
1000
Ha lowax
1000
Ha lowax
1000
Ha lowax
1000
Ha lowax
1000
96 hrs
EC50 >500,000 U.S. EPA, 1978
ch lorophy 1 1 a
96 hrs EC50 >500,000 U.S. EPA, 1978
ce 1 1 numbers
48 hrs LC50 >530,000 U.S. EPA, 1978
96 hrs LC50 >600,000 U.S. EPA, 1978
SALTWATER SPECIES
24 hrs
24 hrs
24 hrs
7 days
7 days
7 days
7 days
7 days
7 days
8 ioconcentrat Ion
factor = 25-32
B Ioconcentrat ion
factor = 60-120
B ioconcentrat ion
factor = 110-140
11.7* inhibition
of growth
45.8^ inhibition
of growth
112 inhibition of
growth
18.62 inhibition
of growth
432 Inhibition
of growth
17.1? Inhibition
of growth
Walsh, et al. 1977
Walsh, et al. 1977
Walsh, et al. 1977
500 Walsh, et al. 1977
1,000 Walsh, et al. 1977
100 Walsh, et al. 1977
500 Walsh, et al. 1977
1,000 Walsh, et al. 1977
500 Walsh, et al. 1977
-------
Table 4. (Continued)
Species
Chemical
Duration
Effect
03
I
co
Alga,
Nltzschia sp.
Alga,
Nltzschia sp.
Alga,
Nltzschia sp.
Alga,
Skeletonema costatum
Alga,
Skeletonema costatum
Alga,
Tha lassioslra pseudonana
Alga,
Thalassiosira pseudonana
Alga,
Thalassiosira pseudonana
Horseshoe crab,
Limulus polyphemus
Horseshoe crab,
Limulus polyphemus
Horseshoe crab,
Limulus polyphemus
Halowax
1000
Halowax
1013
Halowax
1013
Octach loro-
naphthalene
Octach loro-
naphthalene
Ha lowax
1000
Ha lowax
1000
Halowax
1013
Halowax
1099
Halowax
1099
Ha lowax
1099
7 days
7 days
7 days
96 hrs
96 hrs
7 days
7 days
7 days
27 days
42.3? inhibition
of growth
13.2* Inhibition
of growth
16.6JC inhibition
of growth
Ch lorophy 1 1 a
EC50 ~
Cel 1 numbers
EC50
21.3* inhibition
of growth
48.4? inhibition
of growth
7.1* Inhibition
of growth
Time required for
50? mortal ity
(LT50) of T,
stage larvae
Average length of
time of intermolt
between ~$j ar>d T,
stages reduced by
3.4 days
Average length of
time of intermolt
between T^ and T^
stages reduced by
14.8 days
Result
(ug/l) Reference
1,000 Walsh, et al. 1977
500 Walsh, et al. 1977
1,000 Walsh, et al. 1977
>500,000 U.S. EPA, 1978
>500,000 U.S. EPA, 1978
500 Walsh, et al. 1977
1,000 Walsh, et al. 1977
1,000 Walsh, et al. 1977
80 Neff & Glam, 1977
40 Neff & Glam, 1977
20 Neff 4 Glam, 1977
-------
Table 4. (Continued)
Chemical
Duration
CO
I
vo
Horseshoe crab,
Limulus polyphemus
Horseshoe crab,
Limulus polyphemus
Horseshoe crab,
Limulus polyphemus
Brown shrimp,
Penaeus aztecus
Grass shrimp.
Pa 1 aemonetes pugio
Grass shrimp.
Pal aemonetes pugio
Grass shrimp.
Pal aemonetes pugio
Mysid shrimp,
Mysldopsis bah la
Mud crab,
Rh Ithropanopeus harrlsi
Mud crab,
Rh Ithropanopeus harrlsi
Mud crab,
Rh Ithropanopeus harrlsi
Ha 1 owax
1099
Ha lowax
1099
Ha lowax
1099
Ha lowax
1014
Ha lowax
1000
Ha lowax
1013
Ha lowax
1099
Octach loro-
naphthalene
Ha lowax
1000
Ha lowax
1099
Ha lowax
1000
4 days
15 days
12 days
5 days
96 hrs
13 days
27 days
Effect
Average length of
time of Inter mo It
between T* and T4
stages reduced by
16.8 days
Average length of
time of intermolt
between I, and T4
stages reduced by
18.4 days
Increased rates of
respiration of Tj
and ?2 stages
B ioconcentrat Ion
factor =2,300
B ioconcentrat Ion
factor = 63
B Ioconcentrat Ion
factor = 187
B ioconcentrat Ion
factor = 257
LC50
Slightly lowered
Result
(ug/l)
20
80
20
and
40
-
-
_
_
>500.000
300
Reference
Neff & 61 am, 1977
Neff & Glam, 1977
Neff & Glam, 1977
U.S. EPA, 1976
Green & Neff, 1977
Green & Neff, 1977
Green & Neff, 1977
U.S. EPA, 1978
Neff, et al. 1977
survival of larvae
to megalopa
15Jf survival of
larvae to megalopa
Length of Intermolt
time from 4th zoeal
molt to megalopa
stage extended to
2.9 days
100 Neff, et a I. 1977
300 Neff, et al. 1977
-------
Table 4. (Continued)
Species
Chemical
Duration
Effect
Mud crab,
Rhithropanopeus harrisi
Mud crab,
Rhithropanopeus harrisi
Mud crab,
Rh 1 thropanopeus harrisi
Mud crab,
Rhithropanopeus harrisi
CO
1 Sheepshead minnow,
M Cyprlnodon varlegatus
o — "
Sheepshead minnow,
Cyprlnodon varlegatus
Striped mullet (juvenile),
Mugl 1 cephalus
Ha low ax
1099
Halowax
1099
Ha lowax
1000
Ha lowax
1099
Halowax
ION
Octach loro-
naphthalene
Ha 1 owax
1014
Length of Intermolt
time from 4th zoeal
molt to megalopa
stage extended to
4.9 days
- Supernumerary zoeae
(a fifth zoeal
stage)
Deformed mega lopa
(eyes talks and
appendages
ma 1 formed )
Deformed mega lopa
(eyes talks and
appendages
malformed)
96 hrs LC50
96 hrs LC50
96 hrs LC50
Result
343 U.S. EPA, 1976
>560,000 U.S. EPA, 1976
>263 U.S. EPA, 1976
-------
REFERENCES
Green, F.A., Jr. and J.M. Neff. 1977. Toxicity, accumulation, and release
(ft
of three polychlorinated naphthalenes (Halowaxw 1000, 1013, and 1099) in
postlarval and adult grass shrimp, Palaemonetes pugio. Bull. Environ. Con-
tarn. Toxicol. 14: 399.
Neff, J.M. and C.S. Giam. 1977. Effects of Arocloi*® 1016 and Halowa;®
1099 on Juvenile Horseshoe Crabs, Limulus polyphemus. ln_: F.J. Vernberg, et
al. (eds.), Physiological Responses of Marine Biota to Pollutants. Academic
Press, New York. p. 21.
Neff, J.M., et al. 1977. Effects of Polychlorinated Biphenyls, Polychlori-
nated Naphthalenes and Phthalate Esters on Larval Development of the Mud
Crab, Rhithropanopeus harrisii. In; C.S. Giam (ed.), Pollutant effects on
marine organisms. Lexington Books, D.C. Heath and Co., Lexington,
Massachusetts.
U.S. EPA. 1976. Semi-annual report, Environ. Res. Lab., Gulf Breeze,
Florida. April-September, 1976. U.S. Environ. Prot. Agency.
U.S. EPA. 1978. In-depth studies on health and environmental impacts of
selected water pollutants. Contract No. 68-01-4646. U.S. Environ. Prot.
Agency, Washington, D.C.
Walsh, G.E., et al. 1977. Effects and uptake of chlorinated naphthalenes
in marine unicellular algae. Bull. Environ. Contam. Toxicol. 18: 297.
B-ll
-------
Mammalian Toxicology and Human Health Effects
INTRODUCTION
Chlorinated naphthalenes consist of two fused six carbon-mem-
bered aromatic rings where any or all of the eight hydrogen atoms
can be replaced with chlorine. Theoretically, 76 individual iso-
mers are possible and may exist. The commercial products are usu-
ally mixtures with various degrees of chlorination, and are pre-
sently manufactured and marketed in the United States under the
trade name, Halowaxes™
Mixtures of tri- and tetrachloronaphthalenes (solids) com-
prise the bulk of market use as the paper impregnant in automobile
capacitors. Less use is made of mixtures of the mono- and di-
chloronaphthalenes as oil additivies for engine cleaning, and in
fabric dyeing. In 1956, the total United States production of
chlorinated naphthalenes was approximately 3,175 metric tons
(Hardie, 1964).
Possible impurities of these products are chlorinated deriva-
tives, corresponding to the impurities in coal tar, or petroleum-
derived naphthalene feedstocks which may include biphenyls, fluo-
renes, pyrenes, anthracenes, and dibenzofurans.
The potential for environmental exposure may be significant
when these compounds are used as oil additives, in the electroplat-
ing industry, and in the fabric dyeing industry. The extent of
leaching of chlorinated naphthalenes from discarded capacitors and
old cable insulation (manufactured prior to curtailment of using
the chemical in such products) has not been determined.
C-l
-------
Chlorinated naphthalenes have been detected as a contaminant
in foreign commercial polychlorinated biphenyl (PCB) formulations
(Phenoclor, Clophen, and Kanechlor) along with chlorinated dibenzo-
furans, and are present in domestic PCBs (Aroclors) but at lower
levels than in foreign formulations (Vos, et al. 1970; Bowes, et
al. 1975; Roach and Pomerantz, 1974).
The synthesis of chlorinated naphthalenes generally involves
the chlorination of naphthalene by chlorine in the presence of
catalytic amounts of ferric or antimony chloride. This production
process yields mixtures of highly chlorinated naphthalenes in vary-
ing quantities by further chlorination of the lesser substituted
products. Only 1-chloronaphthalene and octachloronaphthalene are
readily isolated from the products of direct chlorination (Hardie,
1964). All of the possible two monochloro-, 10 dichloro-, and 14
trichloronaphthalenes have been isolated and identified. However,
not all of the tetra- and higher chloro-isomers have been charac-
ter ized.
Table 1 presents physical property data for all chlorinated
naphthalenes which have been isolated and identified. The physical
properties of the chlorinated naphthalenes are generally dependent
on the degree of chlorination. Melting points (MP) of the pure
compounds range from 17°C for 1-chloronaphthalene to 198°C for
1,2,3,4-tetrachloronaphthalene (Hardie, 1964). Also, as the degree
of chlorination increases, the specific gravity, boiling point
(BP), fire and flash points all increase, while the vapor pressure
and water solubility decrease (Hardie, 1964). Mixtures of
the mono- and dichloronaphthalenes are generally liquid at room
C-2
-------
TABLE 1
Physical Properties of Chloronaphthalenes*
Isomer MP(°C) BP°C densi tytemp< ( C)
1-chloronaphthalene
2-chloronaphthalene
1,2 -dichloro naphthalene
1, 3-dichloronaphthalene
1,4-d ichloronaphthalene
1, 5-dichloronaphthalene
1 , 6-dichloronaphthalene
1,7-d ichloro naphthalene
1,8-d ichloro naphthalene
2, 3 -dichloro naphthalene
2 , 6-d ichloronaphthalene
2, 7-dichloronaphthalene
1, 2, 3 -tr ichloronaphthalene
1,2 , 4- tr ichloronaphthalene
1 , 2 , 5- tr ichloronaphthalene
1 , 2 , 6- tr ichloronaphthalene
1,2 , 7- tr ichloronaphthalene
1 , 2 , 8- tr ichloronaphthalene
1,3,5-tr ichloronaphthalene
1,3 ,6- tr ichloronaphthalene
1,3 ,7-tr ichloronaphthalene
1,3 , 8- tr ichloronaphthalene
1,4 ,5-tr ichloronaphthalene
1,4 ,6- tr ichloronaphthalene
2 , 3 , 5- tr ichloronaphthalene
2,3 ,6-tr ichloronaphthalene
1,2,3 , 4 -tetrachloro naphthalene
1,3,5 ,8- tetrachloro naphthalene
1,4,6 ,7- tetrachloro naphthalene
1,2,3,4, 5-pentachloronaphthalene
1,2,3,4,5,6,8-
heptachloronaphthalene
1,2,3,4,5,6,7,8-
octachloro naphthalene
*Source: Hardie, 1964
MP = Melting point; BP = Boiling
ca.17 259.3 1.193820
61 265 1.265616
35 1.314748'5
61.5 291
(755 mm Hg)
67.5 287 1.299775*9
106.5
48.5
QQ 5
63.5 285.5 1.2611y*
88.5 1.292499'8
135 285
120
114
81
92
78
92.5
88
83
94
80.5
113
89.5
133
65
109.5
90.5
198
131
139
168.5
194
192
point
C-3
-------
temperature, whereas mixtures of the more highly chlorinated naph-
thalenes tend to be waxy solids (U.S. EPA, 1973).
Chlorinated naphthalenes, like PCBs, exhibit a high degree of
chemical and thermal stability as indicated by their resistance to
most acids and alkalies and to dehydrochlorination (U.S. EPA,
1975).
Polychlorinated naphthalenes have been used in various indus-
trial processes since the turn of the century. Peak use of these
compounds occurred during World War I in Germany, where they were
used in place of rubber, and in the United States during World War
II, where they were used to a large extent in heat-resistant elec-
trical insulation. Since then many uses of polychlorinated naph-
thalenes have been replaced by a growing variety of plastics. In
1956 production and utilization of polychlorinated naphthalenes in
the United States had decreased to approximately 3,200 metric tons
per year. By 1972 production had decreased further to approximate-
ly 2,300 metric tons per year. At the present time, Halochem, Inc.
in Boonton, N.J. is the only known manufacturer of polychlorinated
naphthalenes in the United States. Amounts of chlorinated naphtha-
lenes processed in 1978 were less than 22 metric tons for mono-
chloronaphthalene, less than 45 metric tons total for di-, tri-,
and tetrachloronaphthalene, less than 1 metric ton for pentachloro-
naphthalene, and virtually zero for the more highly chlorinated
naphthalenes (Cuozzo, 1978). Projected production for 1979 totaled
less than 270 metric tons, with 20 percent of this total expected
to be monochloronaphthalene, less than 5 percent pentcichloronaph-
thalene, and none of the more highly chlorinated naiphthalenes.
C-4
-------
Although several foreign companies manufacture polychlorinated
naphthalenes, there are no known imports of these compounds. Be-
cause of their chemical and thermal stability, dielectric proper-
ties, and low viscosity in a liquid state, polychlorinated naphtha-
lenes are still used as engine oil additives, cutting oil addi-
tives, capacitor dielectrics, and electroplating stopoff com-
pounds. They are also used to some extent in the production of
fabric dyes. In the past, polychlorinated naphthalenes have been
used as pesticides, waterproofing and flame retardant compounds,
and cable-covering materials (Minagawa, 1976).
During World Wars I and II, the industrial use of polychlori-
nated naphthalenes was implicated in many cases of chloracne and,
to a lesser extent, liver disease. The purpose of this report is to
summarize available information on the occurrence, pharmacokinetic
properties, and health effects of polychlorinated naphthalenes
(PCNs) in an effort to set a criterion for acceptable levels of
polychlorinated naphthalenes in water.
EXPOSURE
Polychlorinated naphthalenes do not occur naturally in the
environment. Potential environmental accumulation can occur around
points of manufacture of polychlorinated naphthalenes or products
containing them, near sites of disposal of polychlorinated naph-
thalene-containing wastes, and, since polychlorinated biphenyls
(PCBs) are to some extent contaminated by polychlorinated naphtha-
lenes (Vos, et al. 1970; Bowes, et al. 1975), near sites of heavy
polychlorinated biphenyl contamination.
C-5
-------
Currently available industrially-produced polychlorinated
naphthalenes occur as mixtures of various isomers as noted in
Table 2 (Brinkman and Reymer, 1976). These mixtures are marketed
by Koppers, Inc. under the trade name Halowax. ®
Ingestion from Water and Food
To date, polychlorinated naphthalenes have not been identified
in either drinking water or market basket foods. Polychlorinated
naphthalenes have been found in waters or sediments adjacent to
point sources or areas of heavy polychlorinated biphenyl contamina-
tion (Table 3).
Polychlorinated naphthalene-contaminated sediments occur less
frequently than polychlorinated biphenyl-contaminated sediments.
Law and Goerlitz (1974) found polychlorinated naphthalenes in only
1 of 39 sediment samples from streams emptying into San Francisco
Bay. In contrast, 97 percent of the samples contained measurable
levels of polychlorinated biphenyls.
Polychlorinated naphthalenes do appear to be magnified in the
aquatic ecosystem. As noted in Table 3, Crump-Wiesner, et al.
(1973) found that concentrations of polychlorinated naphthalenes in
sediments were 220- to 877-fold greater than in the water overlying
these sediments. Erickson, et al. (1978) found a polychlorinated
naphthalene level in contaminated sediments near a capacitor fac-
tory that was only sixfold greater than the level in the overlying
water. Algae definitely accumulate polychlorinated naphthalenes.
Walsh, et al. (1977) have found polychlorinated naphthalene levels
in algae that were 24- to 140-fold higher than in the surrounding
water. The degree of biomagnification was greater for the more
C-6
-------
o
I
TABLE 2
Approximate Compositions (WT.%) of Halowaxes (PCNs)*
Types
Halowax
Number Mono- Di- Tri-
of Polychlor inated Naphthalene
Tetra- Penta- Hexa- Hepta- Octa-
1031 95 5
1000 60 40
1001
1099
1013
1014
1051
10 40
10 40
10
40
40
50
20
10
10
40
40 40
10 90
*Source: Brinkman and Reymer, 1976
-------
TABLE 3
Water and Sediment Polychlorinated Naphthalene Levels
Industry Type
Airplane engine
overhaul
Airplane engine
overhaul
None identified
Reprocessing oil
Polychlorinated Naph-
of Sample
Sediment
Water
Sediment
Sediment
Water
Level
(jug/kg or jjg/1)
1250-5000
5-7
55
trace
n.df-1.4
Reference
Crurnp-Wiesner ,
et al. 1973
Crurnp-Wiesner,
et al. 1973
Law and Goerlitz,
1974
Minagawa, 1976
Erickson, et al.
thalene manufacturer
Capacitor manufac- Water
turer A
Capacitor manufac- Water
turer B
Capacitor manufac- Sediment
turer B
Capacitor dumps (2) Water
n.df
n.dr-0. 6
1.8-2.6
n.df
1978
Erickson, et al.
1978
Erickson, et al.
1978
Erickson, et al.
1978
Erickson, et al.
1978
n.d. means not detectable with a
for water and 0.5 ug/kg for soil
sensitivity threshold of 0.2 ug/1
and sediment.
C-8
-------
highly chlorinated polychlorinated naphthalene mixtures. Biomag-
nification of polychlorinated naphthalenes also occurs in shrimp.
Grass shrimp concentrate various mixtures of polychlorinated naph-
thalenes by a factor ranging from 63 to 257 compared to the sur-
rounding water (Green and Neff, 1977). As with algae, there is
also greater biomagnification in grass shrimp with the more highly
chlorinated naphthalenes.
A bioconcentration factor (BCF) relates the concentration of a
chemical in aquatic animals to the concentration in the water in
which they live. The steady-state BCFs for a lipid-soluble com-
pound in the tissues of various aquatic animals seem to proportion-
al to the percent lipid in the tissue. Thus, the per capita inges-
tion of a lipid-soluble chemical can be estimated from the per
capita consumption of fish and shellfish, the weighted average per-
cent lipids of consumed fish and shellfish, and a steady-state BCF
for the chemical.
Data from a recent survey on fish and shellfish consumption in
the United States were analyzed by SRI International (U.S. EPA,
1980). These data were used to estimate that the per capita con-
sumption of freshwater and estuarine fish and shellfish in the
United States is 6.5 g/day (Stephan, 1980). In addition, these
data were used with data on the fat content of the edible portion of
the same species to estimate that that the weighted average percent
lipids for consumed freshwater and estuarine fish and shellfish is
3.0 percent.
No measured steady-state bioconcentration factor is avail-
able for any of the following compounds, but the equation
C-9
-------
"Log BCP - (0.85 Log P) - 0.70" can be used (Veith, et al. 1979)
to estimate the steady-state BCF for aquatic organisms that contain
about 7.6 percent lipids (Veith, 1980) from the octanol/water par-
tition coefficient (P). Calculated log P values for monochloro-
naphthalenes and octachloronaphthalenes were obtained using the
method described in Hansch and Leo (1979). The other values were
obtained by linear interpolation between these two values. The
adjustment factor of 3.0/7.6 = 0.395 is used to adjust the esti-
mated BCF from the 7.6 percent lipids on which the equation is
based to the 3.0 percent lipids that is the weighted average for
consumed fish and shellfish in order to obtain the weighted average
bioconcentration factor for the edible portion of all freshwater
and estuarine aquatic organisms consumed by Americans.
Chemical
Monochloronaphthalenes
Dichloro naphthalenes
Trichloronaphthalenes
Tetrachloronaphthalenes
Pentachloro naphthalenes
Hex achloro naphthalenes
Heptachloronaphthalenes
Octachloronaphthalenes
Calc.
Log P
4.01
4.72
5.43
6.14
6.85
7.56
8.27
8.98
Estimated Weighted
steady state BCF Average BCF
511
2,050
3,230
33,000
133,000
532,000
2,140,000
8,570,000
202
810
3,250
13,000
52,500
210,000
845,000
3,385,000
Erickson, et al. (1978) noted a higher level of polychlori-
nated naphthalenes in a dead fish (39 pg/kg) than in the surround-
ing water (0.2 ug/1).
C-10
-------
Erickson, et al. (1978) also noted a higher relative biomagni-
fication of the least chlorinated naphthalene by the fruit of apple
trees grown on contaminated soil. The soil was found to have a
polychlorinated naphthalene level of 190 jug/kg, of which 1.6 jug/kg
was monochloronaphthalenes. While the apples grown on this soil
had only 90 jug/kg of polychlorinated naphthalenes, the level of
monochloronaphthalenes was 62 jug/kg.
Inhalation
The two major effects of chlorinated naphthalenes in man are
chloracne arising primarily by the direct contact route, but also
shown in animals to result from ingestion, and liver damage arising
primarily as a result of inhalation in the industrial setting.
Drinker, et al. (1937) first reported the potential problem of
systemic effects arising from inhalation citing 3 fatalities among
individuals exposed to chlorinated naphthalenes. Acute "yellow
atrophy of the liver" was the cause of death in each instance.
Mayers and Smith (1942) recorded toxic hepatitis in a worker ex-
posed to 3,000 pg/m of trichloronaphthalene (tetrachloro-
naphthalene probably present). Strauss (1944) presented an addi-
tional fatal case and reviewed the literature of reported expo-
sures, including 6 fatal cases. One severe but non-fatal case was
reported where air concentrations of Halowax ® 1014 was reported to
be 3.4 mg/m .
Elkins (1959) noted air concentrations of 1,000 to 2,000 jug/m
of a penta- and hexachloronaphthalene mixture in a factory where
two fatal cases of toxic hepatitis occurred. Erickson, et
al. (1978) found ambient air concentrations of polychlorinated
C-ll
-------
naphthalenes ranging from 0.25 to 2.90 pg/m3 near a polychlorinated
naphthalene production plant. Concentrations of trichloronaph-
thalene were as high as 0.95 pg/m3, while hexachloronaphthalene
concentrations never exceeded 0.007 pg/m3. Near one capacitor fac-
tory, ambient air concentrations of polychlorinated naphthalenes
ranged from non-detectable to 0.005 pg/m3, while at a second fac-
tory they ranged from 0.0098 to 0.033 pg/m3.
Dermal
The likelihood of significant dermal absorption of polychlori-
nated naphthalenes from a water source appears negligible. Water
solubility is low thus skin exposure levels would be minimal.
Link, et al. (1958) found no evidence of systemic disease after
spraying pigs with 6,710 to 8,250 mg/kg of hexachloronaphthalene
over a period of 28 days, while a total dose of 198 mg/kg of hexa-
chloronaphthalene given orally over a period of nine deiys was uni-
formly fatal.
However, Sikes, et al (1952) applied 250 mg (weekly) of used
crankcase oil containing polychlorinated naphthalenes to the verte-
bral column of a Jersey cow with a 4-month-old calf. Both cow and
calf developed hyperkeratosis and systemic toxicity suggesting skin
absorption and secretion in milk. No restraint of either cow or
calf was attempted, thus it is not possible to completely rule out
oral ingestion by licking of the material from the skin.
PHARMACOKINETICS
Absorption, Distribution, and Excretion
There is currently no information on the pharmacokinetic mech-
anisms of absorption, distribution, and excretion of polychlori-
nated naphthalenes in man. Chu, et al. (1977a) noted that in rats
C-12
-------
fed 14C-l,2-dichloronaphthalene, the half-life of this compound in
the blood after the first day was 24 hours. Blood samples were
collected every hour for 8 hours, then at 24 and 48 hours. Total
radiactivity was highest in the one hour sample indicating rapid
absorption from the gastrointestinal tract. Tissue distribution in
rats at 24 hours, 48 hours, and 7 days is shown in Table 4. At 24 and
48 hours, the highest levels of radioactivity (DPM/mg), in descend-
ing order, were found in intestine, kidney, bladder, liver, lung
and adipose tissue. Thus adipose tissue showed no great tendency
to accumulate 1,2-dichloronaphthalene although traces were still
present in adipose tissue, in contrast to other soft tissues, after
one week. Twenty-six percent of the total dose was excreted in the
urine in 24 hours, 33 percent by 48 hours, and a total of 35 percent
at 7 days. Nineteen percent of the total dose was excreted in the
feces in 24 hours, 31 percent in 48 hours, and 42 percent by day 7.
Thus urinary and fecal excretion accounted for 77 percent of the
original dose by day 7. Twenty-three percent of the dose remains
unaccounted for, since tissue levels were essentially zero at 7
days. Serial sample collection of bile from a series of bile-duct
cannulated rats demonstrated that 62 percent of the total dose was
excreted via the bile within 24 hours. In intact animals only 42
percent of the dose was excreted via the feces over a 7-day period,
thus considerable reabsorption of the compound or its metabolites
from the gut must occur. This indicates a rather active entero-
hepatic circulation of these compounds with much of the reabsorbed
material being eventually excreted in the urine. Thin layer
choomatography in this study showed the labeled fecal compound to
C-13
-------
TABLE 4
Tissue Distribution9 of radioactivity (DPM) in rats after a
14
single oral dose of C-l,2-dichloronaphthalene,
20 uCi/kg (400 mg/kg) in corn oil*
o
t
Adipose
Lung
Liver
Bladder
Kidney
Intestine
Skin
Gl-content
Fecal excretion
Ur ine
24 hours
DPM/mg
8.1
14.1
21.3
30.6
39.6
87.0
4.7
1124.0
post dose
%
0.10
0.04
0.70
0.01
0.18
0.45
0.07
18.30
18.90
26.40
48 hours
DPM/mg
11.7
14.3
34.3
42.4
46.5
251.0
5.7
1963.0
post dose
%
0.15
0.03
0.07
0.01
0.15
3.60
0.08
17.90
30.80
32.60
7 days post dose
DPM/mg %
3.26 0.04
-
-
-
-
-
0.73 0.01
7.60 0.04
42.00
35.20
*Source: Chu, et al. 1977a
aThe average value of four or more animals. The S.D. are within 40% of the means.
DPM/mg = radioactivity per mg of dried tissue
% = percent of total administered dose
-------
be unchanged dichloronaphthalene. No unchanged compound of free
chloronaphthol was found in the urine. The urinary metabolite was
identified as the glucuronide of a dihydrodiol.
Ruzo, et al. (1976) studied the tissue uptake and distribution
of 1- and 2-chloronaphthalene in pigs. The chloronaphthalenes were
injected into the carotid artery and blood samples were collected
over a 6-hour period at which time the pigs were sacrificed. The
blood concentrations of 1- and 2-chloronaphthalenes were 5 to 6
ug/g at 10 minutes and essentially zero 4 to 5 hours after the
injection. 4-Chloronaphthol, a metabolite of 1-chloronaphthalene,
was first detectable in the blood at 160 minutes and was at its
highest level at 300 minutes when the parent compound was not
detectable. Similarly 3-chloro-2-naphthol, a metabolite of 2-chloro-
naphthalene, was first detectable in blood 200 minutes after injec-
tion of the compound, and was at its highest level at 300 minutes
when the animals were sacrificed. Tissue distribution studies
indicated that kidney and brain contained the highest levels of the
injected 1- or 2-chloronaphthalene at the time of sacrifice. Meta-
bolite levels were highest in liver, kidney, urine, and bile.
These two studies utilized chloronaphthalenes of low levels of
chlorination. Both found little evidence of accumulation in fat,
rather rapid metabolism, and considerable biliary excretion.
No comparable studies are available with more highly chlor-
inated samples which may be more slowly metabolized and more lipo-
philic, thus enhancing fat storage capabilities.
In seagulls with environmental exposures to chlorinated naph-
thalenes, analyses of fat, liver, and plumage resulted in the
C-15
-------
detection of polychlorinated naphthalenes only in liver samples,
the highest value being 62,500 jug/kg calculated as octachloronaph-
thalene (Vannucchi, et al. 1978).
Metabolism
In mammals there appears to be appreciable metabolism of poly-
chlorinated naphthalenes containing four chlorine atoms or less.
Cornish and Block (1958) investigated the excretion of polychlori-
nated naphthalenes in rabbits. They found that 79 percent of 1-
chloronaphthalene, 93 percent of dichloronaphthalene, and 45 per-
cent of tetrachloronaphthalene were excreted in the urine as meta-
bolites of the parent compounds. There was no measurable urinary
excretion (either as metabolites or the unchanged compound) of
penta-, hepta-, or octachloronaphthalene. The authors suggested
that high degrees of chlorination may prevent the formation of
dihydrodiol intermediates.
There have been detailed studies of the urinary metabolites of
several polychlorinated naphthalenes as noted in Table 5. Metabo-
lism may involve direct hydroxylation or hydroxylation and dehalo-
genation.
Because of the difficulty of synthesis and purification of
specific isomers of the more highly chlorinated naphthalenes, most
of the metabolic studies have been carried out with mono- and di-
substituted compounds (Table 5). Ruzo, et al. (1976) found
2,4-dichloro-l-naphthol is a metabolite of 1,4-dichloronaphthalene
which is consistent with an arene oxide intermediate accompanied by
a susequent 1,2-C1 shift. In this study no dehalogenated metabo-
lites were found. Chu, et al. (1977b) reported on the metabolism
C-16
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TABLE 5
Polychlorinated Naphthalene Metabolites Found in Urine
Parent
Metabolite
Animal Reference
1-chloro-
naphthalene
2-chloro-
naphthalene
1,2-dichloro-
naphthalene
1,4-dichloro-
naphthalene
2,6-dichloro-
naphthalene
2,7-dichloro-
naphthalene
1,2-dichloro-
naphthalene
1,2,3,4-tetra-
chloronaphthalene
1,2,3,4,5,6-hexa-
chloronaphthalene
4-chloro-l-naphthol
3-chloro-2-naphthol
3,4,-dichloro-l-
naphthol
2,4,-dichloro-l-
naphthol
6-chloro-2-naphthol
2,6-dichloronaphthol
(free and conjugated)
7-chloro-2-naphthol
(free and conjugated)
5,6-dichloro-l,2-dihy
droxy-1,2-dihydronaph-
thalene (glucuronide)
5,6,7,8-tetrachloro-l-
and -2-naphthols
none
frog
pig
pig
pig
pig
frog
rat
rat
- rat
pig
pig
Sundstrom,
et al. 1975
Ruzo, et al.
1976
Ruzo, et al.
1976
Ruzo, et al.
1976
Ruzo, et al.
1976
Sundstrom,
et al. 1975
Chu, et al.
1977b
Chu, et al.
1977b
Chu, et al.
1977b
Ruzo, et al.
1976
Ruzo, et al.
1976
C-17
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of a series of dichloronaphthalene isomers. Ring hydroxylation
and/or hydroxylation-dechlorination was reported in several in-
stances (Table 5), thus also establishing a metabolic dehalogena-
tion pathway for these compounds.
Ruzo, et al. (1976) also studied the metabolism of
1,2,3,4-tetrachloro- and 1,2,3,4,5,6-hexachloronaphthalene in
pigs. The tetrachloronaphthalene was hydroxylated on the adjacent
ring while no metabolites of the hexachloronaphthalene were found.
These findings are consistent with the early report of Cornish and
Block (1958) who found considerable metabolism of mono-, di- and
tetrachloronaphthalenes in the rabbit, primarily as the gluronide.
They, also, were unable to detect metabolism of the more highly
chlorinated naphthalene.
Ruzo, et al. (1976) also investigated the 1,2 shift during the
metabolism of l-chloro-4-(2H) naphthalene. Eighteen percent of the
deuterium was retained in the metabolite after hydroxylation at the
4-position to yield 4-chloronaphthol. Thus the deuterium must have
shifted to another position on the metabolite (Figure 1). The
formation of an arene oxide intermediate is one mechanism which
could account for this finding.
EFFECTS
In man the first disease that was recognized as being associ-
ated with exposure to polychlorinated naphthalenes was halowax acne
(a form of chloracne), also known as "cable itch" or "cable rash."
Occurrence of this disease was associated with the manufacture or
use of polychlorinated naphthalene-treated electrical cables.
During World War II chloracne was commonly found among shipyard
C-18
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Cl
Cl
FIGURE 1
Conversion of 1,4-dichloronaphthalene to 2,4-dichloro-
1-naphthol Via a Proposed Arene Oxide Intermediate
Source: Brinkman and Reymer, 1976; Ruzo, et al. 1976
C-19
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electricians. Individuals who stripped the polychlorinated naph-
thalene-treated covering from cables would often contaminate their
clothes with dust or flakes from the covering. If they wore their
dirty work clothes home, their wives or children could get a milder
form of chloracne (Schwartz, 1943). Chloracne has resulted from
both skin contact and inhalation of polychlorinated naphthalene
fumes. Polychlorinated naphthalenes dissolve readily and concen-
trate in the sebum material found in hair follicles (Jones, 1941).
Initial symptoms are loss of the sebaceous glands emptying into the
follicle, derangement of keratin formation, and plugging of the
follicle with resultant comedo. If exposure stops at this point,
the sebaceous glands can empty into the follicle with resultant
comedo; the sebaceous glands can regenerate and the rash can clear
after several months. Continued exposure injures the follicle
walls, causing an inflammatory reaction and formation of a pustule.
Later, the walls deteriorate and rupture with loss of follicular
material to the surrounding tissues. This results in the formation
of a cyst or sterile abcess.
Not all polychlorinated naphthalenes are acneigenic. Shelley
and Kligman (1957) applied various polychlorinated naphthalenes to
human subjects. They found chloracne only after treating their
subjects with a suspension containing a mixture of penta- and hexa-
chlorinated naphthalenes. Similarly, Hambrick (1957) noted chlor-
acne only after treating his subjects with a 3 percent solution of
hexachloronaphthalene or a mixture of penta- and hexachlorinated
naphthalenes. In addition, these were the only two mixtures that
produced hyperkeratosis when applied to the ears of rabbits.
C-20
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Epidemiologic studies confirm these clinical and experimental
impressions. Crow (1970) noted a continuing incidence of chloracne
in a capacitor plant that utilized both tri-/tetrachlorinated and
penta-/hexachlorinated naphthalene mixtures. As soon as the use of
the latter mixture was stopped, chloracne ceased to be found at
this factory. Kleinfeld, et al. (1972) noted that an electric coil
manufacturing plant had no problems with chloracne while using a
mono- and dichloronaphthalene mixture. When a tetra-/pentachlori-
nated naphthalene mixture was unwittingly substituted for the orig-
inal mixture, 56 of the 59 potentially exposed workers developed
chloracne within a short time. They also complained of puritis,
eye irritation, headaches, fatigue, vertigo, nausea, loss of appe-
tite, and weight loss. Liver function studies in five of the af-
fected individuals were normal. Kimbrough and Chamblee (1972)
provided a general review of the toxic response of industrial popu-
lations exposed to chlorinated naphthalenes as paraphrased below.
Individuals with high-level exposures to the fumes of poly-
chlorinated naphthalenes can develop acute or subacute liver dis-
ease with or without an associated chloracne. With a rapidly pro-
gressive course there are jaundice, abdominal pain, edema, ascites,
and decrease in liver size. At autopsy the liver is small and
necrotic with evidence of fatty metamorphosis, a condition called
acute yellow atrophy. With less exposure the course can be long
enough for the development of a postnecrotic-type of cirrhosis or
liver scarring. At the time of death, common findings include evi-
dence of damage to the heart, pancreas, gall bladder, lungs, adre-
nal glands, and kidney tubules in addition to severe liver damage
C-21
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(Greenburg, et al. 1939; Strauss, 1944). With even less exposure,
there may be few or no clinical findings and only mild-to-moderate
laboratory evidence of liver dysfunction that resolves with time
(Cotter, 1944).
Acute, Subacute, and Chronic Toxicity
Almost invariably, clinical evidence of damage from polychlor-
inated naphthalene exposure has occurred only after repeated expo-
sures. Consequently, there have been few tests of acute toxicity.
Cornish and Block (1958), in investigating metabolites of poly-
chlorinated naphthalenes, gave groups of three rabbits single oral
doses of various compounds at a level of 500 mg/kg and followed
their course for 7 days. No mortality or illness occurred in the
rabbits given mono-, di-, or tetrachloronaphthalenes. One of the
three rabbits given pentachloronaphthalene died. All of the rab-
bits given a solution of hepta- or octachloronaphthalene died.
During 1930-1940 a number of herds of cattle were afflicted
with hyperkeratosis of cattle. This unusual disease is also known
as "X-disease" of cattle. Severely afflicted animals developed
coarse, wrinkled skin, a chronic cough and shortness of breath,
weight loss with associated inflammation of the upper portion of
the gastrointestinal tract, pancreatitis and pancreatic scarring,
kidney damage, gall bladder disease, severe liver damage, hair
loss, and reversible suppression of spermatogenesis (Vlahos, et al.
1955). In addition cattle were found to be more susceptible to a
viral infection, proliferative stomatitis, which caused warty
growths of the mucosal lining of the nose, mouth, and intestinal
tract .. (Olson, 1969). This disease was eventually traced to the
C-22
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ingestion (either by licking farm equipment or by eating contam-
inated food pellets) of oil or grease containing polychlorinated
naphthalenes. The investigation of the origins of this illness
stimulated studies on the subacute and chronic toxicity of orally
ingested polychlorinated naphthalenes. Although many studies were
performed using several species, including rats (Bennett, et al.
1938), sheep (Brock, et al. 1957), pigs (Link, et al. 1958), and
hamsters (Schoettle, et al. 1955) (Table 6), the most comprehensive
studies involved cattle and calves (Bell, 1953; Sikes and Bridges,
1952; Sikes, et al. 1952; Vlahos, et al. 1955) (Table 7).
The early studies by Bennett, et al. (1938) were undertaken
because of reports of fatal jaundice in several workers exposed to
chlorinated naphthalenes. The various chlorinated naphthalenes
were mixed in the diet and fed to rats housed 10 per cage. The
animals fed trichloronaphthalene survived but developed slight
liver damage (swelling of parenchymal cells) after about 90 days of
treatment. Ingestion of the tetra-penta mixture or the penta-hexa
mixture resulted in severe systemic disease with all animals either
dying or sacrificed in a moribund condition. Histopathological
studies showed marked swelling and vacuolization of liver cells.
Scattered necrotic cells and occasional mitotic figures were also
seen.
Unfortunately the feeding studies by Bennett, et al. (1938)
were carried out at rather high doses in order to demonstrate
effects which were often severe. Only a single dose level was
used, thus there are generally no intermediate or no-effect levels
available.
C-23
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TABLE 6
Oral Toxicity of Polychlorinated Naphthalenes
No. of
Chlorine Atoms Dose
3* 300 mg/rat/day
4,5 50 mg/rat/day
5,6 125 mg/rat/every
other day
o 5,6 100 mg/rat/day
to
if*
5,6 300 mg/rat/day
4,5,6 1.1 mg/kg/day
4,5,6 11.0-27.6
n»g/kg/day
6 11.0-16.5
«ng/kg/day
6 17.1-17.6
mg/kg/day
6 19.8-22.0
mg/kg/day
Duration
(days)
9-182
63
26
55
33
90-135
7-35
8-10
9-10
8-10
Results
Slight liver damage
All moribund or dead
Moderate liver damage
All moribund or dead
All dead
Severe liver damage
or death
All dead
No effect
Depressed vitamin A
All moribund or dead
Species
Rats
Rats
Rats
Rats
Rats
Sheep
Sheep
Pigs
Pigs
Pigs
Reference
Dennett, et al.
1938
Bennett, et al.
1938
Bennett, et al.
1938
Bennett, et al.
1938
Bennett, et al.
1938
Brock, et al.
1957
Brock, et al.
1957
Link, et al.
1958
Link, et al.
1958
Link, et al.
1958
*With traces of 4
-------
TABLE 7
Oral Toxicity of Polychlorinated Naphthalenes in Cattle
No. of Dose
Chlorine Atoms (mg/kg/day)
o
i
K>
m
2
3
4
4
5
6
6
7
8
8
8
4.4
2.4-2.6
1.6-2.7
3.4
1.7-3.3
1.1-3.2
4.6-13.9
0.69-2.4
1.0
2.4
4.9-12.3
Duration
(days)
7
7-10
10
13
5-10
5-10
20-30
7-9
11
9
13-18
Results
No effect
No effect
Slight hyperkeratosis
No effect
Severe systemic disease
Severe systemic disease
Severe systemic disease
Severe systemic disease
Mild systemic disease
Severe systemic disease
Severe systemic disease
Reference
Bell, 1953
Bell, 1953
Bell, 1953
Bell, 1953
Bell, 1953
Bell, 1953
Sikes, et al.
1952
Bell, 1953
Bell, 1953
Bell, 1953
Sikes, et al.
1952
-------
The sheep studies by Brock, et al. (1957) (Table 6) were at
dose levels only a fraction of those used by Bennett, et al (1938)
in the rat studies. Nevertheless the sheep also developed severe
liver damage and died even when only 1.1 mg/kg/day of (4,5,6)
chloronaphthalene was fed in the diet. Thus in this study also,
even though 3 dose levels were used, no intermediate or no-effect
level was determined.
Link, et al. (1958) fed hexachloronaphthalene to pigs for 8 to
10 days at dose levels ranging from 11 to 22 mg/kg/day (Table 6).
At necropsy (36 to 64 days) pigs receiving 11 mg/kg for the 10 days
had no visible effects and histological examination showed liver
and kidney to be essentially normal. At higher dose levels (19-22
mg/kg/day) for 10 days animals became moribund and were sacrificed.
These animals had hemorrhagic liver and mild gastritis. The pigs
did not develop the typical signs and symptoms seen in cattle nor
did they develop more than a minimal hyperkeratotic response. The
authors suggest that the pig is considerably more resistant to the
chlorinated naphthalenes than is the cow.
Data reported by Schoettle, et al. (1955) suggest that the
hamster appears to be more resistant to chlorinated naphthalenes
than the rat. This study also demonstrated decreased vitamin A
levels in the treated animals. A subsequent study of vitamin A
levels in rats treated with 90 percent octachloronaphthalene fed at
levels as low as 0.002 percent of the diet resulted in rapid loss of
vitamin A from the liver, but blood levels were essentially un-
changed (Deadrick, et al. 1955). This is in contrast to the report
of decreased vitamin A levels in plasma of calves treated with wood
C-26
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preservative containing chlorinated naphthalenes (Hansel, et al.
1951).
Bell (1953) reported the effects of a series of chlorinated
naphthalenes in cattle (Table 7). In some instances several dose
levels were utilized. These were all short-term dosing studies (5-
13 days) with period of subsequent observation ranging up to sever-
al months prior to sacrifice depending on the condition of the
animal. These dosage levels are much lower than those used in
Bennett's rat studies (Table 6) and are more comparable to those
used in sheep and pigs (Table 6). No effects were noted in cattle
fed di- or trichloronaphthalene at dosages approximately 2 to 4
mg/kg/day for 7 to 10 days. Minimal systemic effects and hyper-
keratosis developed in cattle fed tetrachloronaphthalene. With all
other more highly chlorinated naphthalenes severe systemic effects
were noted in cattle receiving 1.1 to 3.3 mg/kg/day for 5 to 10
days.
Sikes and Bridges (1952) fed pentachloronaphthalene to two
cows at increasing dose levels of 2, 4, 6, and 8 g/day. Each dose
level was fed for a 10-day period then increased for the next 10
days. Animals were sacrificed at 40 days showing hyperkeratosis
and severe systemic distress, diarrhea, salivation, cough, and
weight loss. The livers showed severe central lobular degenera-
tion. A subsequent study, Table 7 (Sikes, et al. 1952), at high
dose levels of hexa- and octachloronaphthalene also produced simi-
lar toxic results. One nursing calf, kept separate from the mother
except when nursing, also developed hyperkeratosis suggesting
transfer of the octachloronaphthalene through the milk.
C-27
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An additional study by Vlahos, et al. (1955) examined the
effect of penta- and hexachloronaphthalene on a bull fed 2 to 8
itig/kg/day for 21 days. Five days after the first dose plasma vita-
min A levels had dropped by 50 percent. Four months after the final
dose vitamin A levels were approaching normal. An examination of
semen indicated that the concentration of sperm dropped from
400,000 to 5,000 per mm within 3 months after the administration
of the chlorinated naphthalene. For the following 4 months the
sperm count was 0 to 200 per mm . Recovery was gradual and the
count was at 300,000 per mm nine months after the initial dose.
Ten days after the final dose the left epididymis and testis was
surgically removed from the treated bull and a control bull. This
treatment did not significantly alter sperm count or sperm motility
of the control animal. The seminiferous epithelium of the treated
bull had degenerated and there was pronounced squamous metaplasia
in the head of the epididymis.
Bennett, et al. (1958) along with their oral feeding studies
carried out a relatively long-term inhalation study with trichloro-
naphthalene and with a penta-hexachloronaphthalene mixture. The
results are shown in Table 8. Rats exposed to trichloronaphthalene
at 1.31 mg/m or 10.97 mg/m for approximately four months, 16
hours per day, developed slight to moderate liver damage. The
lower dose level may be close to a no-effect level by the inhala-
tion route. Three exposure levels were chosen for the penta-
hexachloronaphthalene study. At an exposure level of 8.88 mg/m
for 16 hr/day all animals died or were sacrificed in extremis. At
1.16-mg/m for 16 hr/day animals had developed in about 30 days a
C-28
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moderate degree of liver damage described as swollen and granular
liver cells with a moderate excess of small fat droplets. These
abnormalities increased slightly during the next 30 days of expo-
sure, but were then unchanged even though exposure continued for
several additional months. Rats exposed for 105 days then removed
from exposure for a period of two months still showed liver changes
similar to those present when they were removed from the exposure.
Thus recovery was extremely slow. Animals exposed to 1.44 mg/m3
for 8 hr/day for 143 days had liver damage comparable to that of the
animals exposed to 1.16 mg/m for 16 hours daily. Thus, in this
study also a no-effect level was not demonstrated.
Dichloronaphthalene was found to be non-toxic at a dose of 4.4
mg/kg/day in calves (Bell, 1953). Although ingestion of trichloro-
naphthalene did not result in any toxic effects in cattle, inhala-
tion of this chemical by rats at a concentration producing an aver-
age daily dose of 0.78 mg/kg resulted in mild liver changes (Table
8). Tetrachloronaphthalene, when given in doses of 1.6 to 3.4
nig/kg/day to calves, caused no systemic effects but did produce a
mild hyperkeratosis in some animals. Exposures to penta- and hexa-
chloronaphthalene, either alone or as a mixture, did result in
severe systemic disease except at very small doses. Rats inhaling
a mixture of these two compounds equivalent to a dose of 0.48
mg/kg/day developed slight liver changes, while more severe changes
or death were found at 5.97 mg/kg/day dose levels (Table 8).
Although sheep and cattle also developed severe systemic disease
when treated with low doses of penta- and/or hexachloronaphthalene,
swine appeared to be more resistant to the effects of hexachloro-
C-29
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TABLE 8
Inhalation Toxicity of Polychlorinated Naphthalenes in Rats*
o
I
No. of
Chlorine No. of Air Level Exposure
Atoms Animals (mg/m ) Days Hr/day
3b
3b
5,6
5,6
5,6
80 1.31 134 16
50 10.97 102 16
80 1.44 143 8
80 1.16 134 16
80 8.88 52 16
Dosea Results
(mg/kg/day)
0.78 Very slight liver damage
7.37 Moderate liver damage
0.48 Slight to moderate liver
damage
0.68 Slight to moderate liver
damage
5.97 All moribund or dead
*Source: Bennett, et al. 1938
Calculated using a respiratory rate for rats of 42 ml/hr/gm body weight (Altman and Ditmer
1974) and assuming 100 percent absorption.
With traces of 4
-------
naphthalene. Bell (1953) found that a suspension of octachloro-
naphthalene was considerably less toxic than solutions of this com-
pound when administered orally to calves.
Chloracne and liver disease similar to that found in indivi-
duals exposed to high levels of chlorinated naphthalenes are also
seen in individuals exposed to polychlorinated biphenyls. Much of
the toxicity of polychlorinated biphenyls has been attributed to
contamination of the biphenyls by chlorinated dibenzofurans
(Cordle, et al. 1978). Although chlorinated naphthalenes and
chlorinated dibenzofurans have been found as co-contaminants of
polychlorinated biphenyls (Vos, et al. 1970), chlorinated dibenzo-
furans have not been identified in samples of chlorinated naphtha-
lenes or implicated in disease states associated with exposure to
chlorinated naphthalenes.
Synergism and/or Antagonism
Drinker, et al. (1937) exposed rats to an average of 1.31
mg/m of trichloronaphthalene or to 1.16 mg/m of a penta-/hexa-
chloronaphthalene mixture in air for 6 weeks with only minor liver
effects. When a similarly exposed group of rats was challenged
with a sublethal dose of an ethanol/carbon tetrachloride mixture,
no effect was seen in the trichloronaphthalene-exposed rats, but 7
of the 10 penta-/hexachloronaphthalene-exposed rats died. No other
data are available on potentially synergistic or antagonistic
effects.
C-31
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Teratogenicity, Mutagenicity, and Carcinogenicity
No animal or human studies have been completed on the Carcino-
genicity, mutagenicity, or teratogenicity of polychlorinated naph-
thalenes.
C-32
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CRITERION FORMULATION
Existing Guidelines and Standards
The only standards that presently exist for polychlorinated
naphthalenes are the Occupational Safety and Health Administration
(OSHA) standards which were adopted from and are identical to the
American Conference of Governmental Industrial Hygienists (ACGIH)
Threshold Limit Values (TLVs). These TLVs were developed to pre-
vent the occurrence of chloracne or liver changes among workers
with potential exposures to chlorinated naphthalenes (ACGIH, 1971).
The rigor of these standards increases as the number of chlorine
atoms present increases based on the assumption that vapor toxicity
is proportional to the number of chlorine atoms present in each
compound. The present Threshold Limit Values (ACGIH, 1979) are:
Trichloronaphthalene 5.0 mg/m
Tetrachloronaphthalene 2.0 mg/m
Pentachloronaphthalene 0.5 mg/m
Hexachloronaphthalene 0.2 mg/m
Octachloronaphthalene 0.1 mg/m
There are no state or federal water quality or ambient air quality
standards for chlorinated naphthalenes.
Current Levels of Exposure
Polychlorinated naphthalenes have not been identified in
drinking water samples, market basket food samples, or at standard
ambient air stations. Near point sources, concentrations in water
can range as high as 7.0 ug/1 (Crump-Wiesner, et al. 1973) and con-
centrations in air as high as 2.9 jug/m3 (Erickson, et al. 1978).
Near a point source one fish sample had a level of 39 jug/kg for the
whole fish, and a sample of apples contained 90 ug/kg of
C-33
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polychlorinated naphthalenes (Erickson, et al. 1978). Polychlor-
inated naphthalenes have been detected in several samples of PCBs,
compounds that are known to be widely distributed in the aquatic
environment. Measurements of chlorinated naphthalenes in environ-
mental samples have not been widely performed using current sensi-
tive measurement techniques for these compounds.
Special Groups at Risk
Because of the possible potentiation of the toxicity of higher
chlorinated naphthalenes by ethanol and carbon tetrachloride, indi-
viduals who ingest enough alcohol to result in liver disfunction
would be a special group at risk. Individuals who are routinely
exposed to carbon tetrachloride or other hepatotoxic chemicals
(e.g., analytical and synthetic chemists, mechanics, and cleaners)
would also be at a greater risk than a population without such an
exposure. Individuals involved in the manufacture, utilization, or
disposal of polychlorinated naphthalenes would be expected to have
higher levels of exposure than the general population.
Basis and Derivation of Criteria
The chlorinated naphthalenes have not been tested for terato-
genicity, mutagenicity, or carcinogenicity.
Although these compounds have been associated with the develop-
ment of chloracne and, in some instances, fatal liver disease, little
quantitative data is available. This is particularly true with
respect to the oral route of exposure which is of major concern in
the development of water criterion. Both animal and human studies
provide evidence that the less highly chlorinated naphthalenes
appear., less toxic than the highly chlorinated ones.
C-34
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With respect to trichloronaphlalene the oral studies by Bell,
(1953), were of short duration (7-10 days) at a daily dose level of
2 to 3 mg/kg/day in cattle. No effects were noted. However, the
treatment period is too brief to be useful in developing a criter-
ion. The Bennett, et al. (1938) study in ten rats was a a high dose
level (750 mg/kg/day) and exposure extended up to 182 days for some
animals. Minimal liver damage was noted, thus even in this limit-
ed study, a no-effect level was not achieved. The inhalation study
by Bennett, et al. (1938) summarized in Table 8 provided approxi-
mately a four-month exposure period for two groups of rats at 0.68
mg/kg/day and at 7.37 mg/kg/day. At the termination of the study,
the rats (80) at the .low-dose level had minimal liver damage while
the high-dose level had more severe liver damage. Thus the low
exposure level did not define a no-effect level. Additionally, the
effects noted in rats at the low level inhalation study appear
comparable to the effects seen in rats fed approximately 1,000
times that dose by the oral route. One might question the degree of
absorption of the compound when incorporated into the diet. Bell
(1953) fed three cows 2.4 to 2.6 mg/kg/day of trichloronaphthalene
in solution also without effect. This and subsequent studies make
the rat appear to be more resistant to the effects of chloronaph-
thalenes, but the rat studies involve ingestion of the solid mater-
ial. Bell (1953) reported that in one study compounds suspended in
mineral oil were not as toxic as when the material was fed in solu-
tion (Table 7). Overall, the lack of a no-effect level in any
study, the short exposure time of the oral feeding studies, and the
C-35
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apparent species differences in response preclude the use of these
data for developing a criterion for trichloronaphthalene.
With respect to the more highly chlorinated naphthalene, the
oral feeding data in animals provides evidence that these compounds
are reasonably toxic, since, with two exceptions, no-effect levels
were not achieved in the studies on cattle, rats, sheep, or pigs
(Tables 6 and 7). In one exception Bell (1953) found no-effect in
one cow fed 3.6 mg/kg/day of tetrachloronapthalene, however two
other cows fed only 2.6 mg/kg/day for 10 days developed mild symp-
toms of hyperkeratosis. Link, et al. (1958) found no effect in
pigs fed 11-16 mg/kg/day of hexachloronaphthalene for 8-10 days.
However, no histopathological studies were done, thus liver damage
may not have been detected.
One must keep in mind that none of the oral studies were
designed to examine dose-response relationships with respect to
establishing safe levels of exposure. Most were designed to study
the nature of the response in the several species, because of the
established potential for this compound to produce hyperkeratosis
in cattle.
The inhalation study of a mixture of hexa- and pentachloro-
naphthalene by Bennett, et al. (1938) comprised three dose levels
with exposures continuing for 52 to 143 days. At the high dose
level, calculated to be a maximum of 5.97 mg/kg/day, all animals
died or were sacrificed in a moribund condition. At the two lower
dose levels animals survived approximately four months of exposure,
but exhibited slight to moderate liver damage at autopsy. These
dosage levels, calculated at 0.48 and 0.68 mg/kg/day with slight to
C-36
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moderate liver damage, are not inconsistent with the level of 1.1
mg/kg/day that produced severe liver damage in sheep (Table 6).
Again in the rat inhalation study, these animals appear much more
susceptible to the inhaled penta-hexachloronaphthalene than do the
orally fed rats that survived dosages of 250 to 750 mg/kg/day for
33 to 55 days.
Thus the inconsistencies in the data, the lack of a no-effect
level, and what may be marked differences in the response by the
oral versus the inhalation route make it extremely difficult to
interpret these data. One is forced to the decision that insuffi-
cient data is available to develop a rational criteria for these
compounds.
It must be emphasized that the failure to derive any criteria
for the chlorinated naphthalenes is due solely to the lack of appro-
priate data. By comparison of their chemical and physical proper-
ties, one might predict that persistence in the environment could
be comparable to that of the polychlorinated biphenyls.
C-37
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REFERENCES
Altman, P.L. and D.S. Ditmer (eds). 1974. Biology Data Book.
Vol. 3. Federation of American Societies for Experimental Biology,
Bethesda, Maryland, p. 1581.
American Conference of Governmental Industrial Hygienists. 1971.
Documentation of the Threshold Limit Values for substances in work-
room air. Cincinnati, Ohio.
American Conference of Governmental Industrial Hygenists. 1979.
TLVs: Threshold Limit Values for chemical substances and physical
agents in the workroom environment with intended changes for 1979.
Cincinnati, Ohio.
Bell, W.S. 1953. The relative toxicity of the chlorinated naph-
thalenes in experimentally produced bovine hyperkeratosis (X-dis-
ease). Vet. Met. 48: 135.
Bennett, G.A., et al. 1938. Morphological changes in the livers
of rats resulting from exposure to certain chlorinated hydrocar-
bons. Jour. Ind. Hyg. Toxicol. 20: 97.
Bowes, G.W., et al. 1975. Identification of chlorinated dibenzo-
furans in American polychlorinated biphenyls. Nature. 256: 305.
C-38
-------
Brinkman, U.A. and H.G.M. Reymer. 1976. Polychlorinated naphtha-
lenes. Jour. Chromatog. 127: 203.
Brock, W.E., et al. 1957. Chlorinated naphthalene intoxication in
sheep. Am. Jour. Vet. Res. 18: 625.
Chu, I., et al. 1977a. Metabolism and tissue distribution of
(1,4,5,- C)-l,2-dichloronaphthalene in rats. Bull. Environ.
Contain. Toxicol. 18: 177.
Chu, I., et al. 1977b. Metabolism of chloronaphthalenes. Jour.
Agr. Food Chem. 25: 881.
Cordle, F., et al. 1978. Human exposure to polychlorinated bi-
phenyls and polybrominated biphenyls. Environ. Health Perspect.
24: 157.
Cornish, H.H. and W.D. Block. 1958. Metabolism of chlorinated
naphthalenes. Jour. Biol. Chem. 231: 583.
Cotter, L.H. 1944. Pentachlorinated naphthalenes in industry.
Jour. Am. Med. Assoc. 125: 373.
Crow, K.D. 1970. Chloracne: a critical review including a com-
parison of two series of cases of acne from chlornaphthalene and
pitch fumes. Trans. St. John's Hosp. Derm. Soc. 56: 79.
C-39
-------
Crump-Wiesner, H.J., et al. 1973. A study of the distribution of
polychlorinated biphenyls in the aquatic environment. Jour. Res.
U.S. Geol. Survey. 1: 603.
Cuozzo, R. 1978. Personel communication. Halochem, Inc.
Deadrick, R.E. 1955. Effects of octachloronaphthalene on vitamin
A metabolism in the rat. Jour. Nutr. 57: 287.
Drinker, C.K., et al. 1937. The problem of possible systemic ef-
fects from certain chlorinated hydrocarbons. Jour. Ind. Hyg.
Toxicol. 19: 283.
Elkins, H.B. 1959. Iin: The Chemistry of Industrial Toxicology.
2nd ed. John Wiley and Sons, Inc., New York, p. 151.
Erickson, M.D., et al. 1978. Sampling and analysis for polychlor-
inated naphthalenes in the environment. Jour. Assoc. Off. Anal.
Chero. 61: 1335.
Green, F.A., Jr. and J.M. Neff. 1977. Toxicity, accumulation, and
release of three polychlorinated naphthalenes (Halowax ® 1000,
1013, and 1099) in postlarval and adult grass shrimp, Palaemonetes
pugio. Bull. Environ. Contam. Toxicol. 14: 399.
C-40
-------
Greenburg, L. , et al. 1939. The systemic effects resulting from
exposure to certain chlorinated hydrocarbons. Jour. Ind. Hyg.
Toxicol. 21: 29.
Hambrick, G.W. 1957. The effects of substituted naphthalenes on
the pilosebaceous apparatus of rabbit and man. Jour. Invest. Derm.
28: 89.
Hansch, C. and A.J. Leo. 1979. Substitute Constants for Correla-
tion Analysis in Chemistry and Biology. Wiley-Interscience, New
York. p. 339.
Hansel, W., et al. 1951. The effects of two causative agents of
hyperkeratosis in Vitamin A metabolism. The Cornell Vet. 41: 367.
Hardie, D.W. 1964. Chlorocarbons and Chlorohydrocarbons: Chlori-
nated Naphthalenes. In; D.F. Kirk and D.E. Othmer (eds.), Encyclo-
pedia of Chemical Toxicology, 2nd ed. John Wiley and Sons, Inc.
New York. p. 297.
Jones, A.T. 1941. The etiology of acne with special reference to
acne of occupational origin. Jour. Ind. Hyg. Toxicol. 23: 290.
Kimbrough, R.D. and M.D. Chamblee. 1972. Toxicity of chlorinated
hydrocarbons and related compounds. Arch. Environ. Health.
25: 125.
C-41
-------
Kleinfeld, M., et al. 1972. Clinical effects of chlorinated naph-
thalene exposure. Jour. Occup. Med. 14: 377.
Law, L.M. and D.P. Goerlitz. 1974. Selected chlorinated hydrocar-
bons in bottom material from streams tributary to San Francisco
Bay. Pest. Monitor. Jour. 8: 33.
Link, R.P., et al. 1958. Toxic effect of chlorinated naphthalenes
in pigs. Jour. Am. Vet. Med. Assoc. 133: 83.
Mayers, M.R. and A.H. Smith. 1942. N.Y. Ind. Bull. January: 30.
In; American Conference of Governmental Industrial Hygienists.
1971. Documentation of the thresholds limit values for substances
in workroom air. Cincinnati, Ohio.
Minagawa, K. 1976. Polychlorinated naphthalenes in the surround-
ing environment of a reproduction factory of used transformer oil.
Jap. Jour. Ind. Health. 18: 416.
Olson, C. 1969. Bovine Hyperkeratosis. (X-diseases, Highly Chlor-
inated Naphthalene Poisoning). Historical Review. In: C.A. Bradly
and C.E. Cornelius (eds.), Advances in Veterinary Science and Com-
parative Medicine. Academic Press, New York, p. 101.
Roach, J.A. and I.H. Pomerantz. 1974. The finding of chlorinated
dibenzofurans in a Japanese polychlorinated biphenyl sample. Bull.
Environ. Contam. Toxicol. 12: 338.
C-42
-------
Ruzo, L. , et al. 1976. Metabolism of chlorinated naphthalenes.
Jour. Agr. Food Chem. 24: 581.
Schoettle, M.S., et al. 1955. Experimental production of hyper-
keratosis in rats and hamsters. Am. Jour. Vet. Res. 16: 183.
Schwartz, L. 1943. An outbreak of halowax acne ("cable rash")
among electricians. Jour. Am. Med. Assoc. 122: 158.
Shelley, W.B. and A.M. Kligman. 1957. The experimental production
of acne by penta- and hexachloronaphthalenes. A.M.A. Arch. Derm.
75: 689.
Sikes, D. , et al. 1952. The experimental production of "X-dis-
ease" (hyperkeratosis) in cattle with chlorinated naphthalenes and
petroleum products. Jour. Am. Vet. Med. Assoc. 121: 337.
Sikes, D. and M.E. Bridges. 1952. Production of hyperkeratosis
("X-disease") of cattle with a chlorinated naphthalene. Science.
116: 506.
Stephan, C.E. 1980. Memorandum to J. Stara. U.S. EPA. July 3.
Strauss, N. 1944. Hepatotoxic effects following occupational ex-
posure to Halowax^ (chlorinated hydrocarbons). Rev. of Gastroen-
terol. 11: 381.
C-43
-------
Sundstrom, G., et al. 1975. Methods for the study of metabolism of
toxic and persistent chemicals in aquatic organisms as exemplified
by chloronaphthalenes. I_n: Proc. Swedish Netherland Symposium,
Elsevier, Amsterdam, p. 177.
U.S. EPA. 1973. Preliminary environmental hazard assessment of
chlorinated naphthalenes, silicones, fluorocarbons, benzenepoly-
carboxylates, and chlorophenols. EPA Publ. No. 560/2-74-001.
Washington, D.C.
U.S. EPA. 1975. Environmental hazard assessment report: Chlor-
inated naphthalenes. EPA Publ. No. 560/8-75-001. Washington, D.C.
U.S. EPA. 1980. Seafood consumption data analysis. Stanford
Research Institute International. Menlo Park, California. Final
Report, Task 11, Contract No. 68-01-3887.
Vannucchi, C., et al. 1978. Residues of chlorinated naphthalenes,
other hydrocarbons and toxic metals (Hg, Pb, Cd) in tissues of
Mediterranean seagulls. Chemosphere. 6: 483.
Veith, G.D. 1980. Memorandum to C.E. Stephan. U.S. EPA.
April 14.
Veith, G.D., et al. 1979. Measuring and estimating the bioconcen-
tration factors of chemicals in fish. Jour Fish Res. Board Can.
36: 1040.
C-44
-------
Vlahos, K., et al. 1955. Destruction and restoration of sperma-
togenesis in a bull experimentally poisoned with high chlorinated
naphthalene. Cornell Vet. 45: 198.
Vosf J.G., et al. 1970. Identification and toxicological evalua-
tion of chlorinated dibenzofurans and chlorinated naphthalenes in
two commercial polychlorinated biphenyls. Food. Cosmet. Toxicol.
8: 625.
Walsh, G.E., et al. 1977. Effects and uptake of chlorinated naph-
thalenes in marine unicellular algae. Bull. Environ. Contain.
Toxicol. 18: 297.
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