United States Office of Water EPA 440/5-80-054
Environmental Protection Regulations and Standards October 1980
A9er|CV Criteria and Standards Division
Washington DC 20460 /> ^_
xvEPA Ambient
Water Quality
Criteria for
Hexachlorocyclohexane
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AMBIENT WATER QUALITY CRITERIA FOR
HEXACHLOROCYCLOHEXANE
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.
ii
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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 A. Brungs, ERL-Narragansett
U.S. Environmental Protection Agency
David J. Hansen, ERL-Gulf Breeze
U.S. Environmental Protection Agency
Mammalian Toxicology and Human Health Effects:
Leo Newland (author)
Texas Christian University
Steven D. Lutkenhoff (doc. mgr.)
ECAO-Cin
U.S. Environmental Protection Agency
Bonnie Smith (doc. mgr.)
ECAO-Cin
U.S. Environmental Protection Agency
Curtis Klaassen
University of Kansas Medical Center
S. D. Lee, ECAO-RTP
U.S. Environmental Protection Agency
Robert E. Menzer
University of Maryland
James Selkirk
Oakridge National Laboratory
Roy E. Albert*
Carcinogen Assessment Group
U.S. Environmental Protection Agency
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,
8.0. Quesnell, T. Highland, R. Rubinstein.
Julian Andelman
University of Pittsburgh
James V. Bruckner
University of Texas Medical School
R. W. Chadwick, HERL
U.S. Environmental Protection Agency
Edmund LaVoie
American Health Foundation
Robert G. Melton, HERL
U.S. Environmental Protection Agency
Joseph Santodonato
Syracuse Research Corporation
Jerry F. Stara, ECAO-Cin
U.S. Environmental Protection Agency
*CAG Participating Members:
Elizabeth L. Anderson, Larry Anderson, Dolph Ami car, Steven Bayard,
David Bayliss, Chao W. Chen, John R. Fowle-III, Bernard Haberman,
Charalingayya Hiremath, Chang S. Lao, Robert McGaughy, Jeffrey Rosen-
blatt, Dharm V. Singh, and Todd W. Thorslund.
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TABLE OF CONTENTS
Page
Criteria Summary
Introduction A-l
Aquatic Life Toxicology B-l
Introduction B-l
Effects B-2
Acute Toxicity B-2
Chronic Toxicity B-4
Plant Effects B-5
Residues B-6
Miscellaneous B-8
Summary B-8
Criteria B-9
References 8-27
Mammalian Toxicology and Human Health Effects C-l
Introduction C-l
Exposure C-4
Ingestion from Water C-4
Ingestion from Food C-5
Inhalation C-7
Dermal C-7
Pharmacokinetics C-8
Absorption C-8
Distribution C-9
Metabolism C-10
Excretion C-12
Effects C-16
Acute, Subacute, and Chronic Toxicity C-16
Synergism and/or Antagonism C-23
Teratogenicity C-25
Mutagenicity C-27
Carcinogenicity C-27
Criterion Formulation C-34
Existing Guidelines and Standards C-34
Current Levels of Exposure C-34
Special Groups at Risk C-35
Basis and Derivation of Criteria C-36
References C-41
Appendix C-57
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CRITERIA DOCUMENT
HEXACHLOROCYCLOHEXANE
CRITERIA
Aquatic Life
Lindane
For llndane the criterion to protect freshwater aquatic life as derived
using the Guidelines is 0.080 yg/1 as a 24-hour average and the concentra-
tion should not exceed 2.0 yg/1 at any time.
For saltwater aquatic life the concentration of lindane should not ex-
ceed 0.16 pg/1 at any time. No data are available concerning the chronic
toxicity of lindane to sensitive saltwater aquatic life.
BHC
The available data for a mixture of isomers of BHC indicate that acute
toxicity to freshwater aquatic life occurs at concentrations as low as 100
wg/l and would occur at lower concentrations among species that are more
sensitive than those tested. No data are available concerning the chronic
toxicity of a mixture of isomers of BHC to sensitive freshwater aquatic life.
The available data for a mixture of isomers of BHC indicate that acute
toxicity to saltwater aquatic life occurs at concentrations as low as 0.34
Mg/l and would occur at lower concentrations among species that are more
sensitive than those tested. No data are available concerning the chronic
toxicity of a mixture of isomers of BHC to sensitive saltwater aquatic life.
Human Health
For the maximum protection of human health from the potential carcino-
genic effects due to exposure of a -hexachlorocyclohexane through ingestion
of contaminated water and contaminated aquatic organisms, the ambient water
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concentrations should be zero based on the non-threshold assumption for this
chemical. However, zero level may not be attainable at the present time.
Therefore, the levels which may result in incremental increase of cancer
risk over the lifetime are estimated at 10~5, 10"6, and 10~ . The
corresponding recommended criteria are 92 ng/1, 9.2 ng/1, and 0.92 ng/1,
respectively. If the above estimates are made for consumption of aquatic
organisms only, excluding consumption of water, the levels are 310 ng/1,
31.0 ng/1, and 3.10 ng/1, respectively.
For the maximum protection of human health from the potential carcino-
genic effects due to exposure of s-hexachlorocyclohexane through ingestion
of contaminated water and contaminated aquatic organisms, the ambient water
concentrations should be zero based on the non-threshold assumption for this
chemical. However, zero level may not be attainable at the present time.
Therefore, the levels which may result in incremental increase of cancer
risk over the lifetime are estimated at 10" , 10"6, and 10" . The
corresponding recommended criteria are 163 ng/1, 16.3 ng/1, and 1.63 ng/1,
respectively. If the above estimates are made for consumption of aquatic
organisms only, excluding consumption of water, the levels are 547 ng/1,
54.7 ng/1, and 5.47 ng/1, respectively.
For the maximum protection of human health from the potential carcino-
genic effects due to exposure of Y-hexachlorocyclohexane through ingestion
of contaminated water and contaminated aquatic organisms, the ambient water
concentrations should be zero based on the non-threshold assumption for this
chemical. However, zero level may not be attainable at the present time.
Therefore, the levels which may result in incremental increase of cancer
risk over the lifetime are estimated at 10~ , 10 , and 10~ . The
corresponding recommended criteria are 186 ng/1, 18.6 ng/1, and 1.86 ng/1,
VII
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respectively. If the above estimates are made for consumption of aquatic
organisms only, excluding consumption of water, the levels are 625 ng/1,
62.5 ng/1, and 6.25 ng/1, respectively.
For the maximum protection of human health from the potential carcino-
genic effects due to exposure of technical-hexachlorocyclohexane through
ingestion of contaminated water and contaminated aquatic organisms, the
ambient water concentrations should be zero based on the non-threshold as-
sumption for this chemical. However, zero level may not be attainable at
the present time. Therefore, the levels which may result in incremental
increase of cancer risk over the lifetime are estimated at 10~ , 10 ,
and 10" . The corresponding recommended criteria are 123 ng/1, 12.3 ng/1,
and 1.23 ng/1, respectively. If the above estimates are made for consump-
tion of aquatic organisms only, excluding consumption of water, the levels
are 414 ng/1, 41.4 ng/1, and 4.14 ng/1, respectively.
Using the present guidelines, satisfactory criteria cannot be derived at
this time due to the insufficiency in the available data for 5- and e-hexa-
chlorocyclohexane.
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INTRODUCTION
Hexachlorocyclohexane is a broad spectrum insecticide of the group of
cyclic chlorinated hydrocarbons called organochlorine insecticides. It con-
sists of a mixture of five configurational isomers and was introduced in
1942 as a contact insecticide under the trade names BHC, benzene hexachlor-
ide, and 666. Since its introduction, both the used and production volume
of technical grade BHC have undergone dramatic changes as a result of the
discovery that virtually all of the insecticidal activity of BHC resides
with its Y-isomer. By voluntary action, the principal domestic producer of
technical grade BHC requested cancellations of its BHC registrations on
September 1, 1976. As of July 21, 1978 all registrants of pesticide prod-
ucts containing BHC voluntarily cancelled their registrations or switched
their former BHC products to lindane formulations. On the other hand, sig-
nificant commercial use of the purified Y-isomer of BHC (lindane) con-
tinues. As of January 17, 1977, there were 557 Federal registrations for
pesticide products containing lindane and 87 formerly State-registered prod-
ucts containing lindane for which Federal registration has been reauested.
Hexachlorocyclohexane, commonly referred to as BHC or benzene hexachlor-
ide, is a brownish-to-white crystalline solid with a phosgene-like odor, a
molecular formula of CgHgClg, a molecular weight of 290.0, a melting
point of 65°C, and a solubility in water of 10 to 32 mg/1 (Hardie, 1972;
Clristensen, 1976; Matsumura, 1975). BHC is the common name approved by the
International Standards Organization for the mixed configurational isomers
of 1,2,3,4,5,6-hexachlorocyclohexane, although the terms BHC and benzene
hexachloride are misnomers for this aliphatic compound and should not be
confused with aromatic compounds of similar structure, such as the aromatic
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compound hexachlorobenzene (Int. Agency Res. Cancer, 1974). Lindane is the
common name approved by the International Standards Organization for the
Y-isomer of 1,2,3,4,5,6-hexachlorocyclohexarie. BHC is synthesized by the
direct action of chlorine on benzene in the presence of ultraviolet light
(Hardie, 1972).
Technical grade BHC contains the hexachlorocyclohexane isomers in the
following ranges: a-isomer, 55 to 70 percent; s-isomer, 6 to 8 percent;
Y-isomer, 10 to 18 percent; 5-isomer, 3 to 4 percent; e-isomer, trace
amounts (Hardie, 1972). The actual content of the isomers in technical
grade BHC varies depending on the manufacturing conditions.
In addition to the hexachlorocyclohexane isomers, technical grade BHC
may contain varying quantities (three to five percent) of other chlorinated
derivatives of cyclohexane primarily heptachlorocyclohexane and octachloro-
cyclohexane.
Technical grade BHC is available in various formulations as wettable
powders, granules, dusts, and emulsifiable concentrates and can be used as a
stomach and contact poison for a wide variety of insect pests and animal
parasites. Since the Y-isomer (lindane) has been shown to be the insecti-
cidally active ingredient in technical grade BHC (Hardie, 1972), technical
grade BHC now has limited use commercially except as the raw material from
which the purified Y-isomer is extracted by a process of selective crystall-
ization.
Technical grade lindane is composed of 99 to 100 percent pure Y-BHC iso-
mer and is available in the form of emulsifiable concentrates, wettable pow-
ders, dusts, crystals, and solids for smoke generators and thermal vapor-
izers.
The physical properties of the purified BHC isomers are presented in
Table 1.
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TABLE 1
Physical Properties of BHC Isomers*
BHC
Isomer
alpha
beta
gamma
delta
Melting
Point
CC)
158
312
112.5
138
Vapor
Pressure
(mm Hg
at 50*C)
0.00087
0.000014
0.0008
—
Water
Solubility
(mg/1)
10
5
10
10
Solubility in
Relatively Non-
polar Solvent
(g/100 g ether
at 20' C)
6.2
1.8
20.8
35.4
*Source: Hardie, 1972; Ulmann, 1972
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The isomers of BHC are not susceptible to photolysis or strong acids but
are, with the exception of the e-isomer, dehydrochlorinated by alkalies to
form primarily 1,2,4-trichlorobenzene (Hardie, 1972). Lindane has been
shown to be slowly degraded (ten percent degradation after six weeks) by
soil microorganisms (Mathur and Saha, 1975) and is capable of isomerization
to a - and/or s-BHC by microorganisms and plants (Matsumura, et al. 1976;
Newland, et al. 1969; Steinwandeter, 1976).
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REFERENCES
Christensen, H.E. 1976. Registry of toxic effects of chemical substances.
U.S. Dep. Health Edu. Welfare, Rockville, Maryland.
Hardie, O.W.F. (ed.) 1972. Kirk-Othmer Encyclopedia of Chemical Technol-
ogy. Interscience Publishers, Inc., New York.
International Agency for Research on Cancer. 1974. Some organochlorine
pesticides. IARC monographs on the evaluation of carcinogenic risk of chem-
icals to man. World Health Organization, Lyon.
Mathur, S.P. and J.G. Saha. 1975. Microbial degradation of lindane-C-14 in
a flooded sandy loam soil. Soil Sci. 120: 301.
Matsumura, F. 1975. Toxicology of Insecticides. Plenum Press, New York.
Matsumura, F., et al. 1976. Factors affecting microbiol metabolism of
Y-BHC. Jour. Pestic. Sci. 1: 3.
Newland, L.W., et al. 1969. Degradation of Y-8HC in simulated lake im-
poundments as affected by aeration. Jour. Water Pollut. Control Fed.
41: 174.
A-5
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Steinwandter, H. 1976. Lindane metabolism in plants. II. Formation of
•x-HCH. Chemosphere. 5: 221.
Ulmann, 'E. 1972. Lindane: Monograph of an Insecticide. Schillinger Press,
Republic of Germany.
A-6
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Aquatic Life Toxicology*
INTRODUCTION
Hexachlorocyclohexane is a member of the group of cyclic chlorinated hy-
drocarbons called organochlorine insecticides. It is manufactured by the
chlorination of benzene and is commonly called BHC or benzene hexachloride.
Hexachlorocyclohexane is an aliphatic compound, and it should not be con-
fused with aromatic compounds of a similar structure. The aromatic com-
pounds are also called BHC, benzene hexachloride or hexachlorobenzene, so
caution is advised when reading reports on these chemicals.
Hexachlorocyclohexane primarily consists of five configurational iso-
mers, sold under the trade name BHC (benzene hexachloride) and Com-
pound-666. Technical grade BHC contains five hexachlorocyclohexane isomers
in the following ranges: alpha isomer, 55 to 70 percent; beta isomer, 6 to 8
percent; gamma isomer, 10 to 18 percent; delta isomer, 3 to 4 percent; and
epsilon isomer, trace amounts. The gamma isomer (lindane, a pesticide) is
the isomer with insecticidal properties and is usually considered to be the
isomer most toxic to aouatic organisms. Preparations which contain at least
99 percent of the gamma isomer are called lindane, and lindane is the most
important hexachlorocyclohexane isomer.
The majority of the freshwater and saltwater effects data are for the
gamma isomer, lindane, and criteria were developed for this compound. There
are additional data for technical BHC, which contains varying amounts of the
*The reader is referred to the Guidelines for Deriving Water Quality Crite-
ria 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.
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gamma and alpha isomers. The data for these compounds are included in the
tables but are insufficient for criteria development.
EFFECTS
Acute Toxicity
Of the 33 freshwater acute toxicity test results reported in Table 1,
all are with lindane; seven invertebrate and 15 fish species were tested.
Most tests were 96-hour static tests based on unmeasured concentrations; on-
ly three were tests with measured concentrations, of which only one used
flow-though procedures.
Nine toxicity tests with lindane and seven freshwater invertebrate spe-
cies are reported in Table 1. The data can be separated into three toxico-
logical groups. The three cladoceran species are the most resistant organ-
isms tested. Their species mean acute values range from 460 to 676 ug/1, or
about 10 to 70 times higher than the LCgQ concentrations for the most sen-
sitive group. The crustaceans, represented by the sowbugs and scud, are
generally the most sensitive species tested; their LCrp. values range from
10 to 48 ug/1. The middle group, represented by an insect, a chironomid,
had an IC™ of 207 ug/1, which is between the concentrations toxic to the
cladoceran and crustacean species.
Acute values for lindane with 15 freshwater fish species (Table 1) range
from 2 to 141 ug/1 for brown trout and goldfish, respectively. These values
represent differences among species in their responses to lindane exposure.
Generally, the warmwater fish species appear to be more tolerant of lindane
than do the coldwater salmonid species; this is also shown by the additional
fish acute data in Table 6. Frog and toad species were even more resistant
than warmwater fish species (Table 6).
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The 96-hour LC50 values for BHC (Table 6) are much higher than those
for lindane. The difference cannot be explained by simple ratio of the lin-
dane content in the BHC to pure lindane. For example, Henderson, et al.
(1959) based their LC5Q values for BHC on the gamma isomer content and
found that the gamma isomer in BHC was approximately 244 times less toxic to
the fathead minnow in soft water than the gamma isomer tested alone. In
fact, the BHC concentrations were so high that precipitates were observed.
In addition, they determined that a concentration of 100 yg/1 of lindane
alone cause 100 percent mortality of fathead minnows in 24 hours. When
3,200 ug/1 of technical BHC, a concentration that caused no mortality, and
100 ug/1 lindane were added to the same tank, no mortality occurred within
96 hours. They concluded that the other BHC isomers either reduced the sol-
ubility of the gamma isomer (lindane) or had an antagonistic effect,
reducing its toxicity.
The Freshwater Final Acute Value for lindane, derived from the species
mean acute values listed in Table 3 using the procedure described in the
Guidelines, is 2.2 ug/1. However, the brown trout has a species mean acute
value of 2 ug/1 (Table 3). Therefore, the Freshwater Final Acute Value for
lindane should be lowered to 2.0 ug/1 to protect this important species.
Insufficient data are available for BHC to derive a Freshwater Final Acute
Value according to the Guidelines.
Acute toxicity values for BHC and lindane with saltwater invertebrate
species range from 0.17 to 3,680 ug/1 (Table 1). Saltwater invertebrate
species are generally more sensitive than fish species to lindane. The
LCcn for the commercially important pink shrimp, Penaeus duorarum, is more
than one order of magnitude lower than the second most sensitive species.
The least sensitive invertebrate soecies was the polychaete, Neanthes aren-
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aceodentata, with a 96-hour LC5g value of 3,680 ug/1, 21,000 times greater
than that of the pink shrimp. A single LC50 value was available for a
saltwater invertebrate species and BHC. The 96-hour IC™ for pink shrimp
based on measured concentrations was 0.34 ug/1, indicating BHC to be less
toxic than lindane (Schimmel, et al. 1977).
Although saltwater fish species have a wide range of sensitivity to lin-
dane (Table 1), they are generally less sensitive than saltwater inverte-
brate species. Eleven species of fishes were tested in static and flow-
through exposures. Only two species were exposed for 96 hours under
flow-through conditions with measured concentrations. These LCgQ values
were 30.6 ug/1 for the pinfish and 103.9 ug/1 for the sheepshead minnow
(Schimmel, et al. 1977). LC5Q values, acceptable according to the Guide-
lines and including nine other species, have a range from 7.3 to 103.9 ug/1
(Table 1). Only one test was conducted on a saltwater fish species using
BHC. The 96-hour LCgQ from a flow-through test with measured concentra-
tions was 86.4 ug/1 for pinfish (Schimmel, et al. 1977). This compares to a
30.6 ug/1 LCc0 for the same species under the same conditions for lindane,
indicating a lesser toxicity for BHC (Schimmel, et al. 1977).
The Saltwater Final Acute Value for lindane, derived from the species
mean acute values listed in Table 3 using the procedure described in the
Guidelines, is 0.16 ug/1. Insufficient data were found on acute toxicity of
BHC to saltwater species to derive a Saltwater Final Acute Value for BHC.
Chronic Toxicity
Chronic data are available for three freshwater invertebrate species
(Table 2). Chronic values for Daphnia magna, Gammarus fasciatus, and Chiro-
nomus tentans are 14.5, 6.1, and 3.3 ug/1, respectively. Acute-chronic
ratios are calculable for two invertebrate species; these values are 33 for
B-4
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Daphnia magna and 63 for Chironomus tentanus. An acute-chronic ratio was
not calculated for Gammarus fasciatus because no appropriate acute value was
available.
Only one acceptable chronic test with a fish species was found (Nlacek,
et al. 1976). A chronic value of 14.6 ug/1 was calculated for the fathead
minnow (Table 2). No 96-hour IC™ values were obtained with fathead min-
nows in water of the same Quality, even though duplicate flow-through acute
toxicity tests were conducted, and lindane concentrations were measured. In
both cases the LC50 was >100 ug/1 but was not calculated. After 11 days
incipient LC5Q values of 62.5 and 75.6 yg/1 were determined. The geo-
metric mean of the three acute values for fathead minnows in Table 1 is 67.1
yg/1 which is close to the mean of the 11-day values. Thus, 110 ug/1 can
probablv be used as a reasonable estimate of the flow-through LC^Q for
fathead minnows. This results in an acute-chronic ratio of 7.5 for fathead
minnows (Table 2) and a Freshwater Final Chronic Value of 0.080 ug/1 (Table
3).
No chronic toxicity values for hexachlorocyclohexane were found for any
saltwater invertebrate or fish species.
Plant Effects
The effect of hexachlorocyclohexane on freshwater plants (Table 4) must
be estimated from only one report (Krishnakumari, 1977). Growth inhibition
of an alga, Scenedesmus acutus, was reported at 500 to 5,000 ug/1, depending
on the isomer used in the exposures. The alpha isomer was the most toxic at
500 ug/1, whereas the more commonly used gamma isomer (lindane) inhibited
growth at 1,000 ug/1. The gamma isomer effect concentration is about 10,000
times higher than the freshwater chronic value, so the plants should be
protected.
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Hexachlorocyclohexane affected saltwater plants at concentrations
greater than concentrations affecting animals (Table 4). A 28.5 percent
decrease in productivity of natural phytoplankton communities occurred at a
concentration of 1,000 yg/1 lindane (Butler, 1963). Exposure to concentra-
tions of alpha-hexachlorocyclohexane up to the solubility limit for the cul-
ture medium (1,400 ug/D showed no toxicity to the marine algae, Chlamydo-
monas sp. or Dunaliella sp. (Canton, et al. 1977, 1978).
Residues
Freshwater bioconcentration factors (BCF) (Table 5) include mean fac-
tors determined using data obtained from a small oligotrophic lentic ecosys-
tem (a flooded limestone quarry), where the fate of introduced lindane and
DOE was followed for one year by Hamelink and Waybrant (1976). They
reported average steady-state bioconcentration factors for lindane of 768
and 486 for whole bluegills and rainbow trout, respectively. They used mean
concentration data from all thermal strata under summer water conditions to
calculate their bluegill concentration factor. This value (768) was not
used because the bluegill would probably stay above the thermocline.
Seventy percent of the lindane was evenly distributed in the epilimnion, and
concentrations were relatively constant until fall turnover (destratifica-
tion). After turnover, the lindane concentrations were similar throughout
the water column. Their rainbow trout BCF data were obtained under these
conditions.
The remaining available BCF values (Table 5) are those of Macek, et al.
(1976) obtained under laboratory conditions. These BCF values are for mus-
cle tissue in bluegill (35) and brook trout (70) and for eviscerated fathead
minnows (477).
B-6
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The bioconcentration of hexachlorocyclohexane from water into the tis-
sues of saltwater organisms has been relatively well studied (Table 5).
Steady-state 8CF values are available for American oysters and pinfish
(Schirnmel, et al. 1977). Compared to many of the chlorinated insecticides,
the 8CF values at steady-state are low. American oysters exposed continu-
ously for 28 days to BHC bioconcentrated an average of 218 times the amount
measured in the exposure water. Only in the highest exposure concentration,
0.093 ug/1, did the insecticide accumulate sufficiently high for accurate
measurement. Pinfish exposed to BHC for 28 days bioconcentrated in edible
tissue an average of 130 times the amount in water. The average BCF in of-
fal (head and viscera) was 617. The relative percentages of the four iso-
mers in BHC were similar to those in pinfish offal and edible tissues. Ap-
parently, no individual isomer was stored or purged selectively. Oysters
and pinfish depurated all detectable BHC within one week after being placed
in BHC-free water.
Additional data on the bioconcentration of lindane and BHC are available
for other organisms, but it is doubtful that the concentrations in the or-
ganisms are at steady-state (Table 6). The average bioconcentration factors
after four days of exposure to lindane were 63 for grass shrimp, 84 for pink
shrimp, 490 for sheepshead minnow, and 218 for pinfish (Schimmel, et al.
1977). In the same study, the average bioconcentration factors after four
days of exposure to BHC were 80 for pink shrimp and 482 for pinfish. The
four isomers of BHC were bioconcentrated in tissues of pink shrimp and pin-
fish in approximately the same relative amounts as in the insecticide formu-
lation. Saltwater phytoplanktons rapidly accumulate and depurate BHC
(Canton, et al. 1977).
B-7
-------
No Freshwater of Saltwater Final Residue Value can be calculated because
the only maximum permissible tissue concentration is a U.S. Food and Drug
Administration (FDA) action level for frog legs.
Miscellaneous
None of the additional data included in Table 6 but not yet discussed
would alter the freshwater criteria for lindane or contribute significantly
to the derivation of a criterion for BHC or a saltwater criterion for lin-
dane.
Summary
Data are available estimating the acute toxicity of lindane to seven
freshwater invertebrate and 15 fish species. Freshwater crustaceans (sowbug
and scud) are the most sensitive invertebrate species tested, and cladoce-
rans are the most resistant. The range of species mean acute values for in-
vertebrate species is 10 to 676 ug/1. Among the fish species tested, brown
trout is the most sensitive with an acute value of 2 ug/1; goldfish is least
sensitive with a value of 141 ug/1. The Freshwater Final Acute Value for
lindane is 2.0 ug/1. No acute data are available for other hexachlorocyclo-
hexane isomers and freshwater animals.
Acute toxicity data for lindane are available for eight saltwater inver-
tebrate and 11 fish species. Acute values for invertebrate species range
from 0.17 to 3,680 ug/1. Pink shrimp are the most sensitive species tested,
and the polychaete, Neanthes arenaceodentata, is the least sensitive. Salt-
water fish species tested have a wide range of sensitivity to lindane and
are generally less sensitive than the invertebrate species; LC™ values
range from 7.3 to 104 ug/1. The Saltwater Final Acute Value for lindane is
0.16 ug/1. Data are available for BHC with one saltwater invertebrate and
one fish species and indicate that BHC is less toxic than lindane.
-------
Chronic values for lindane are available for three freshwater inverte-
brate species and range from 3.3 ug/1 for the midge, Chironomus tentans, to
14.5 ug/1 for Daphnia magna. A chronic value of 14.6 ug/1 is available for
the fathead minnow. Acute-chronic ratios range from 7.5 for fathead minnow
to 63 for the midge, and the Freshwater Final Chronic Value for lindane is
0.080 ug/1. No chronic data are available for any other hexachlorocyclohex-
ane isomers nor for any saltwater species.
Acute tests with a freshwater alga and three different BHC isomers indi-
cated that the alpha isomer is more toxic than are gamma (lindane) and
beta. Both freshwater and saltwater algal species were much more resistant
to hexachlorocyclohexane than were the invertebrate and fish species tested.
Bioconcentration factors for lindane with a variety of freshwater fish
species ranged from 35 to 486; bioconcentration factors for saltwater spe-
cies ranged from 130 to 617. No useful FDA action level or result of a
chronic feeding study with wildlife is available for calculation of a Final
Residue Value.
CRITERIA
Lindane
For lindane the criterion to protect freshwater aquatic life as derived
using the Guidelines is 0.080 ug/1 as a 24-hour average, and the concentra-
tion should not exceed 2.0 ug/1 at any time.
For saltwater aquatic life the concentration of lindane should not
exceed 0.16 ug/1 at any time. No data are available concerning the chronic
toxicity of lindane to sensitive saltwater aquatic life.
BHC
The available data for a mixture of isomers of BHC indicate that acute
toxicity to freshwater aquatic life occurs at concentrations as low as 100
B-9
-------
ug/1 and would occur at lower concentrations among any species that are more
sensitive than those tested. No data are available concerning the chronic
toxicity of a mixture of isomers of BHC to sensitive freshwater aquatic life.
The available data for a mixture of isomers of BHC indicate that acute
toxicity to saltwater aquatic life occurs at concentrations as low as 0.34
ug/1 and would occur at lower concentrations among any species that are more
sensitive than those tested. No data are available concerning the chronic
toxicity of a mixture of isomers of BHC to sensitive saltwater aquatic life.
B-10
-------
Table 1. Acute values for hexacMorocyclohexane
f i _- Method*
Species iwinuu
C ladoceran, S, U
Oaphnla put ex
Cladoceran, s. M
Daphnia magna
Cladoceran, S, U
SI mocepha 1 us serra 1 atus
Cladoceran, S, U
SI mocepha 1 us serra 1 atus
Sowbug, s» u
Asel lus brevlcaudus
Scud, s« u
Gammarus lacustrlj
Scud, s« u
Gammarus fasclatus
Scud, s» u
Gammarus fasciatus
Midge, s» M
Chironomus tentans
Rainbow trout, S, U
Sal mo fla i rdner 1
Rainbow trout, S, U
Sal mo oal rdner i
Brown trout, S, U
Salmo trutta
Brook trout, FT • M
Species Mean
LC50/EC50 Acute Value
Chemical (ug/(>
FRESHWATER SPECIES
Llndane
Lindane 460 460
Lindane 485 485
Lindane 520
Llndane 880 676
Lindane (99%) 10 1°
Llndane 48 48
Lindane (99$) 10
Llndane (99%) 11 10'5
Llndane 207 207
Llndane 27
Lindane (98J) 38 32
Llndane 2 2
Lindane 44.3 44.3
Reference
Sanders 4 Cope
Macek, et al .
Sanders 4 Cope
Sanders 4 Cope
Sanders, 1972
Sanders, 1969
Sanders, 1972
Sanders, 1972
Macek, et al.
Macek 4 McAl 1
1970
Katz, 1961
Macek 4 McA 1 1
1970
Macek, et al.
, 1966
1976
, 1966
, 1966
1976
Ister,
ister.
1976
Salvellnus fontlnalIs
-------
Table 1. (Continued)
Spec 1 es
Coho salmon,
Oncorhynchus klsutch
Coho salmon,
Oncorhynchus klsutch
Chinook salmon,
Oncorhynchus tshawytscha
Goldfish,
Car ass 1 us auratus
Goldfish,
Carasslus auratus
Carp.
*- Cyprlnus carplo
I Fathead minnow,
|^ Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Black bul (head,
Ictalurus me las
Channel catfish,
Ictalurus punctatus
Guppy,
Poecllia retlculata
Blueglll,
Lepomls macrochirus
Method*
S, U
S, U
s, u
s, u
s, u
S, 0
s, u
s, u
s, u
s, u
s, u
s, u
s, u
Chemical
L 1 ndane
Llndane (lOOf)
Llndane (100JO
Llndane
LI ndane (100*)
Lindane
Li ndane
Llndane ( lOOf)
Lindane (100JO
Lindane
Lindane
Lindane (100*)
Technical II ndane
LC50/EC50
(Ufl/D
41
50
40
131
152
90
87
62
56
64
44
138
54
Species Mean
Acute Value
(tig/I)
-
45.3
40
141.1
90
-
-
67.1
64
44
138
Blueglll,
Lepomls macrochirus
S, U Technical 11ndane
51
Reference
Macek & McA I 11 ster
1970
Katz, 1961
Katz, 1961
Macek 4 McAI lister,
1970
Henderson, et at.
1959
Macek & McAI lister,
1970
Macek 4 McAllister,
1970
Henderson, et al.
1959
Henderson, et al.
1959
Macek & McA I lister,
1970
Macek & McAI lister,
1970
Henderson, et al.
1959
Macek, et al. 1969
Macek, et al. 1969
-------
Table 1. (Continued)
Species
B 1 ueg ill,
Lepomis macrochirus
Bluegi 1 1,
Lepomis macrochirus
Bluegi 1 1,
Lepomis macrochirus
Redear sunfish,
Lepomis mlcrolophus
Largemouth bass,
Micropterus sal mo Ides
Yel low perch,
Perca flavescens
01
1
Method* Chemical
S, U Technical llndane
S, U Llndane
S, U Lindane (100?)
S, U Llndane
S, U Llndane
S, U Llndane
SALTWATER
Species Mean
LC50/EC50 Acute Value
(ug/l) (ug/l)
37
68
77 55.6
83 83
32 32
68 68
SPECIES
Reference
Macek, et al. 1969
Macek & McA 1 1 1 ster ,
1970
Henderson, et al.
1959
Macek & McAl lister,
1970
Macek & McA 1 1 1 ster ,
1970
Macek 4 McAl 1 ister,
1970
Lindane
American oyster,
Crassostrea virgin lea
Mysid,
Mysidopsis bah la
Sand shrimp,
Crangon septemsp 1 nosa
Hermit crab,
Pagurus longl carpus
Grass shrimp.
Pal aemonetes pugio
Grass shrimp,
Pa 1 aemonetes vulgar is
Pink shrimp,
FT, U Technical 1 indane
FT, M Technical 1 indane
S, U Lindane***
S, U Lindane***
FT, M Technical 1 indane
S, U Llndane***
FT, M Technical llndane
450** 450
6.28 6.28
5.0 5.0
5.0 5.0
4.44 4.44
10.0 10.0
0.17 0.17
Butler, 1963
Schinmel, et al. 1977
Eisler, 1969
Eisler, 1969
Schimmel, et al. 1977
Eisler, 1969
Schinmel, et al. 1977
Penaeus duorarum
-------
Table 1. (Continued)
Species
Polychaete,
Neanthes arenaceodentata
Ameri can eeI,
Angullla rostrata
Sheepshead minnow,
Cyprlnodon varlegatus
Mummlchog,
Fundulus heterociItus
Striped kl Illfish,
Fundu I us majalIs
Atlantic sllverslde,
Men Id la men Id I a
Threesplne stickleback,
Gasterosteus aculeatus
Threespine stickleback,
Gasterosteus aculeatus
Striped bass,
Morone saxatlI Is
Plnflsh,
Lagodon rhomboldes
B luehead,
Thalassoma blfasclatum
Striped mullet,
Mug I I cephalus
Northern puffer,
Sphaeroides maculatus
Method*
Chemical
S, M Technical llndane
S, U Technical llndane
FT, M
S, U
S, U
FT, U
FT, M
Lindane***
S, U Technical llndane
S, U Technical llndane
S, U Technical llndane
Llndane***
Llndane***
Llndane***
Llndane***
S, U Technical llndane
S, U Technical lindane
S, U Technical llndane
LC50/EC50
(ug/l)
3,680
56.0
103.9
60.0
28.0
9.0
44.0
50.0
7.3
30.6
14.0
66.0
35.0
Species Mean
Acute Value
3,680
56.0
103.9
60.0
28.0
9.0
47.0
7.3
30.6
14.0
66.0
35.0
Reference
U.S. EPA, I960
Elsler, 1970
Schimmel, et al. 1977
Elsler, 1970
Eisler, 1970
Eisler, 1970
Katz, 1961
Katz, 1961
Korn 4 Earnest, 1974
Schimmel, et al. 1977
Eisler, 1970
Elsler, 1970
Elsler, 1970
-------
Table 1. (Continued)
ft)
H-"
Ln
Species
Pink shrimp,
Penaeus duorarum
Plnf ish,
Lagodon rhomboldes
LC50/EC50
Method* Chemical
-------
Table 2. Chronic values for llndane (Macek, et al. 1976)
Limits Chronic Value
Species Test* (t»g/!> (ug/l)
ro
H1
en
FRESHWATER SPECIES
Cladoceran,
Daphnla magna
Scud,
Gammarus fasciatus
Midge,
Chlronomus tentans
Fathead minnow,
Plmephales promelas
LC 11-19
LC 4.3-8.6
LC 2.2-5.0
LC 9.1-23.5
14.5
6.1
3.3
14.6
* LC = life cycle or partial life cycle
Acute-Chronic Ratios
Species
Cladoceran,
Daphnla magna
Midge,
Chlronomus tentans
Fathead minnow,
Plmephales promelas
Acute Chronic
Va 1 ue Va 1 ue
(ug/l) (ug/l)
485 14.5
207 3.3
HO* 14.6
Ratio
33
63
7.5
* Estimated (see text)
-------
Table 3. Species mean acute values and acute-chronic ratios for hexachlorocyclohexane
ui
i
tank*
Species
FRESHWATER
Species Mean
Acute Value
(UQ/I)
SPECIES
Species Mean
Acute-Chron 1 c
Ratio
Llndane
22
21
20
19
18
17
16
15
14
13
12
11
10
Cladoceran,
Simocepha lus serralatus
Cladoceran,
Daphnla maqna
Cladoceran,
Daphnla pulex
Midge,
Chlronomus tentans
Goldfish,
Carasslus auratus
Guppy,
Poecl 1 la reticulata
Carp,
Cyprlnus carplo
Redear sunflsh,
Lepomls mlcrolophus
Yel low perch,
Perca flavescens
Fathead minnow,
Plmephales promelas
Black bul (head,
Ictalurus me las
Bluegl 1 1,
Lepomls macroch 1 rus
Scud,
676
485
460
207
141.1
138
90
83
68
67.1
64
55.6
48
33
63
7.5
Gammarus lacustrls
-------
Table 3. (Continued)
O)
i
oo
Rank*
9
8
7
6
5
4
3
2
1
Species
Coho salmon,
Oncorhynchus klsutch
Brook trout.
Salve) Inus fontinalis
Channel catfish,
Ictaturus punctatus
Chinook salmon,
Oncorhynchus tshawytscha
Largemouth bass,
Micropterus sal mo Ides
Rainbow trout.
Sal mo galrdneri
Scud,
Gammarus fasclatus
Sowbug,
Asellus brevlcaudus
Brown trout.
Sal mo trutta
SALTWATER
Species Mean Species Mean
Acute Value Acute-Chronic
(ug/l) Ratio
45
44
44
40
32
32
10.5
10
2
SPECIES
Lindane
19
18
17
16
Poly chaste,
Neanthes arenaceodentata
American oyster,
Crassostrea virglnlca
Sheepshead minnow,
Cyprlnodon varlegatus
Striped mullet.
3,680
450
103.9
66.0
Mug11 cephalus
-------
Table 3. (Continued)
Rank*
15
14
13
12
11
10
9
8
7
6
5
4
3
2
Species
Mummlchog,
Fundulus heteroclltus
American eel,
Anguilla rostrata
Threespine stickleback,
Gasterosteus aculeatus
Northern puffer,
Sphaeroldes maculatus
Plnflsh,
Lagodon rhombo 1 des
Striped killiflsh,
Fundulus majal Is
81 uehead,
Thalassoma bifasciatum
Grass shrimp,
Palaemonetes vulgar is
Atlantic sllverslde,
Men Id la men id la
Striped bass.
Moron e saxat ills
Mysld,
Mysidopsis bahia
Hermit crab,
Pagurus longlcarpus
Sand shrimp,
Crangon septecnsp 1 nosa
Grass shrimp,
Species Mean Species Mean
Acute Value Acute-Chronic
(ug/l) Ratio
60.0
56.0
47
35.0
30.6
28.0
14.0
10.0
9.0
7.3
6.28
5.0
5.0
4.44
Palaemonetes puglo
-------
Table 3. (Continued)
Rank*
Pink shrimp,
Penaeus duorarum
Species Mean
Acute Value
(ug/l)
0.17
Species Mean
Acute-Chronic
Ratio
2
1
BHC
Plnflsh, 86.4
Lagodon rhomboldes
Pink shrimp, 0.34
Penaeus duorarum
* Ranked from least sensitive to most sensitive based on species mean
acute value.
CO
I
NJ
o
Final acute-chronic ratio for llndane = 25
Freshwater Final Acute Value for llndane = 2.2 ug/l
Revised Freshwater Final Acute Value for llndane (see text) = 2 ug/l
Freshwater Final Chronic Value for llndane = 2 ug/l r 25 = 0.080 ug/l
Saltwater Final Acute Value for llndane = 0.16 ug/l
-------
Table 4. Plant values for ttexachloroeyclohexane
Species
Alga,
Scenedesmus acutus
Alga,
Scenedesmus acutus
Alga,
Scenedesmus acutus
tt, Alga,
I Scenedesmus acutus
IvJ
!-•
Natural phy top lankton
communities
Alga,
Acetabularla med i terranea
Alga,
Chlamydomonas sp.
Alga,
Dunaliella sp.
Chemical Effect
FRESHWATER SPECIES
Technical BHC >20% growth inhi-
bition In 5 days
Alpha BHC >20* growth inhi-
bition in 5 days
Beta BHC >20% growth inhi-
bition In 5 days
Gamma BHC >20% growth Inhi-
bition In 5 days
SALTWATER SPECIES
Llndane 28.5)1 decrease In
productivity, 14C
Llndane Inhibition of eel
growth and ce 1 1
morphogenesis.
reversible
Alpha BHC No short-term
(48-hr)
toxic effect
Alpha BHC No effect on
growth after
2 and 4 days
Result
(1*9/0
1,000
500
5,000
1,000
1,000
1 10,000
Solubility
limit (1,400)
Solubility
limit (1,400)
Reference
Krishnakumari, 1977
Krlshnakumari, 1977
Krishnakumarl, 1977
Krishnakumarl, 1977
Butler, 1963
Borghl, et al. 1973
Canton, et al. 1977
Canton, et al. 1978
-------
Table 5. Residues for hexachlorocyclohexone
f
K)
KJ
Species
Zooplankton
Rainbow trout.
Sal mo galrdnerl
Brook trout,
Salvel Inus fontlnal Is
Fathead minnow,
Plmephales promelas
Blueglll,
Lepomis macrochlrus
American oyster,
Crassostrea virgin lea
Plnflsh,
Laqodon rhomboldes
Pint ish,
Laqodon rhomboides
* Technical grade BHC
Llpld
Tissue (|) Chemical
B ioconcentrnt ion
Factor
Durat ion
(days) Reference
FRESHWATER SPECIES
Whole body - Llndane 336
HWe body ~ Llndane 486
m
Muscle - Llndane 70
Eviscerated - Llndane 477
Muscle - Lindane 35
SALTWATER SPECIES
All soft - Technical BHC*
tissue
Edible tissue - Technical BHC*
Offal tissue - Technical BHC*
(21* alpha BHC, 39? gamma BHC, 2. If beta BHC, 23*
Maximum Permissible Tissue
Concentration
Action Level (mg/kg)
218
130
617
5-60 Hamelink &
1976
108 Hamel Ink &
1976
261 Macek, et
304 Macek, et
735 Macek, et
28 Schlmmel,
28 Sch I rime) ,
28 Schlmnel,
Way brant.
Way brant,
al. 1976
al. 1976
al. 1976
et al. 1977
et al. 1977
et al. 1977
delta BHC, 14.9? unidentified compounds)
Concentrat Ion
Reference
Frog legs
0.5
U.S. FDA Guide) Ine
7420.08, 1978
-------
Table 6. Other data for bexachlorocyclohexane
Species
DO
NJ
OJ
FRESHWATER
SPECIES
Llndane
Scud,
Gammarus fasclatus
Rainbow trout,
Salmo galrdneri
Brook trout,
Salvelinus fontlnalis
Brook trout,
Salvelinus fontlnalis
Fathead minnow,
Plmephales proroelas
Fathead minnow,
Plmephales promelas
Mosqultofish,
Gamubusia aftlnls
Blueglll,
Lepomls macrochlrus
Bluegill,
Lepomls macrochlrus
Chorus frog (tadpole),
Pseudacris trlseriata
Toad (tadpole),
Bufo woodhousl 1
Pond sna 1 1 ,
48 hrs
6 wks
It days
261 days
11 days
11 days
46 hrs
21 days
21 days
96 hrs
95 hrs
48 hrs
LC50
Lethal threshold
concentrat Ion
LC50
Reduced growth
LC50
LC50
LC50
LC50
LC50
LC50
LC50
alpha BHC
LC50
Lymnaea staqna11s
Result
(lig/l) Reference
39 Macek, et al. 1976
22 Tooby & Durbln, 1975
26 Macek, et al. 1976
16.6 Macek, et al. 1976
62 Macek, et al. 1976
76 Macek, et al. 1976
74 Cut ley & Ferguson,
1969
29 Macek, et al. 1976
31 Macek, et al. 1976
2,700 Sanders, 1970
4,400 Sanders, 1970
1,200 Canton & Slooff, 1977
-------
Table 6. (Continued)
w
Species
Pond sna 1 1 ,
Lymnaea stagna 1 1 s
Pond snal 1,
Lymnaea stagna 1 1 s
Pond sna 1 1 ,
Lymnaea stagna 1 1 s
Cladoceran,
Daphnla magna
Tub If ex and
Llmnodrllus mixture
Coho salmon,
Oncorhynchus klsutch
Chinook salmon,
Oncorhynchus tshawytscha
Rainbow trout,
Sal mo galrdnerl
Goldfish,
Carassius auratus
Fathead minnow,
PI mepha les promelas
Fathead minnow,
PI mepha les promelas
Guppy,
Poecllla retlculata
Blueglll,
Lepomls macrochlrus
Toad (tadpole),
Duration
40 days
40 days
40 days
25 days
96 hrs
48 hrs
10 hrs
44.5 hrs
96 hrs
96 hrs
96 hrs
96 hrs
96 hrs
96 hrs
Effect
EC50 egg produc-
tion Inhibition
EC 50 embryonic
deve lopment
Reproduct 1 ve
inhibition
EC 50 reproduction
BHC
LC50
LC50
LCIOO
LC100
LC50
LC50
LC50
LC50
LC50
LC50
Result
(yg/D
250
230
65
100
3,150
200
too
100
15,000
15,000
13,000
14,000
5,100
3,200
Reference
Canton A Slooff, 1977
Canton & Slooff, 1977
Canton & Slooff, 1977
Canton, et al. 1975
Whit ten & Goodnight,
1966
Vet son & Alderdioa,
1967
Anonymous, 1960
Anonymous, 1960
Henderson, et al.
1959
Henderson, et al.
1959
Henderson, et al.
1959
Henderson, et al.
1959
Henderson, et al.
1959
Sanders, 1970
Bufo woodhousi I
-------
Table 6. (Continued)
Spec Ies
Duration
Effect
td
NJ
cn
SALTWATER SPECIES
Grass shrimp,
Palaemonetes puglo
Pink shrimp,
Penaeus duorarum
Sheepshead minnow,
Cyprinodon variegatus
Plnflsh,
Lagodon rhomboldes
Longnose kl 1 1 if Ish,
Fundulus sim! 1 Is
White mullet.
Mug II curema
Brown shrimp,
Penaeus aztecus
Alga,
Chlamydomonas
Alga,
Chlamydomonas
Alga,
Ounal lei la
Pink shrimp,
Penaeus duorarum
Pinfish,
4 days
4 days
4 days
4 days
48 hrs
48 hrs
48 hrs
2 hrs
2 hrs
2 hrs
4 days
4 days
Lindane
B loconcentrat ion
factor = 63
B 1 oconc entr at i o n
factor = 84
Bloconcentratlon
factor = 490
Bloconcentration
factor = 218
LC50
LC50
EC 50*
alpha BHC
f 310**
f 2,700**
f 1,500»»
BHC***
B loconcentrat ion
factor = 80
B loconcentrat ion
Result
(tig/1) Reference
Schlmmel, et al. 1977
Schlnmel, et al. 1977
Schirrmel, et al. 1977
Schlmmel, et al. 1977
Lagodon rhomboldes
factor = 482
240 Butler, 1963
30 Butler, 1963
0.40 Butler, 1963
10 Canton, et al. 1977
1,000 Canton, et al. 1977
1,000 Canton, et al. 1977
Schlmmel, et al. 1977
Schimmel, et al. 1977
-------
Table 6. (Continued)
Species
Brown shrimp,
Penaeus aztecus
White and brown shrimp,
Penaeus setlferus
Penaeus aztecus
Result
Duration Effect (ug/l)
Tri-6 Dust No. 30****
24 hrs LC50 35
24 hrs LC50 400
Reference
Chin & Al len, 1957
Chin 4 Allen, 1957
* EC50 - loss of equilibrium In brown shrimp.
** f-Freundlich isotherm: concentration (alpha BHC) in algae (ug/g)/concentration (alpha BHC)
in water phase (ug/ml).
*** Technical grade BHC (21$ alpha BHC, 39$ gamma BHC, 2.1$ beta BHC, 23$ delta BHC, 14.9%
a unidentified compounds).
KJ *tt»*Trl_6 Dust No. 30 (3.0? gamma BHC, 5.1$ other isomers BHC, 91.9$ inert). Result based on
ug/l Tri-6 Dust No. 30.
-------
REFERENCES
Anonymous. 1960. Toxic effects of organic and inorganic pollutants on
young salmon and trout. Washington Dep. Fish. Res. Bull. 5: 278.
Borghi, H., et al. 1973. The effects of lindane on Acetabularia mediter-
ranen. Protoolasma. 78: 99.
Butler, P.A. 1963. Commercial fisheries investigations, pesticide-wildlife
studies: A review of Fish and Wildlife Service investigations during 1961-
1962. U.S. Oep. Int. Fish Wild!. Circ. 167: 11.
Canton, J.H. and W. Slooff. 1977. The usefulness of Lymnaea stagnalis L.
as a biological indicator in toxicological bioassays (model substance
a-HCH). Water Res. 11: 117.
Canton, J.H., et al. 1975. Toxicity, accumulation and elimination studies
of alpha-hexachlorocyclohexane (alpha-HCH) with freshwater organisms of dif-
ferent tropic levels. Water Res. 9: 1163.
Canton, J.H., et al. 1977. Accumulation and elimination of a-Hexachlorocy-
clohexane (a-HCH) by the marine algae Chlamydomonas and Dunaliella. Water
Res. 11: 111.
Canton, J.H., et al. 1978. Toxicity, accumulation and elimination studies
of a-Hexachlorocyclohexane (a-HCH) with saltwater organisms of different
trophic levels. Water Res. 12: 687.
B-27
-------
Chin, E. and D.M. Allen. 1957. Toxicity of an insecticide to two species
of shrimp, Penaeus aztecus and Penaeus setiferis. Texas Jour. Sci. 9: 270.
Culley, D.O., Jr. and D.E. Ferguson. 1969. Patterns of insecticide resis-
tance in the mosquitofish, Gambusia affinis. Jour. Fish. Res. Board Can.
26: 2395.
Eisler, R. 1969. Acute toxicities of insecticides to marine decapod crus-
taceans. Crustaceana. 16: 302.
Eisler, R. 1970. Acute toxicities of organochlorine and organophosphorous
insecticides to estuarine fishes. Bur. Sport Fish Wild!. Tech. Pap. 46.
Hamelink, J.L. and R.C. Waybrant. 1976. DOE and lindane in a large-scale
model lentic ecosystem. Trans. Am. Fish. Soc. 105: 124.
Henderson, C.t et al. 1959. Relative toxicity of ten chlorinated hydrocar-
bon insecticides to four species of fish. Trans. Am. Fish. Soc. 88: 23.
Katz, M. 1961. Acute toxicity of some organic insecticides to three spe-
cies of salmonids and to the threespine stickleback. Trans. Am. Fish. Soc.
90: 264.
Korn, S. and R. Earnest. 1974. Acute toxicity of twenty insecticides to
striped bass, Morone saxatilis. Calif. Fish Game. 60: 128.
Krishnakumari, M.K. 1977. Sensitivity of the alga Scenedesmus acutus to
some pesticides. Life Sci. 20: 1525.
B-28
-------
Macek, K.J. and W.A. McAllister. 1970. Insecticide susceptibility of some
t
common fish family representatives. Trans. Am. Fish. Soc. 99: 20.
Macek, K.J., et al. 1969. The effects of temperature on the susceptibility
of bluegills and rainbow trout to selected pesticides. Bull. Environ.
Contam. Toxicol. 4: 174.
Macek, K.J., et al. 1976. Chronic toxicity of lindane to selected aquatic
invertebrates and fishes. EPA 600/3-76-046, U.S. Environ. Prot. Agency.
Sanders, H.O. 1969. Toxicology of pesticides to the crustacean Gammarus
lacustris. Bur. Sport Fish. Wild!. Tech. Pap. 25.
Sanders, H.O. 1970. Pesticide toxicities to tadpoles of the western chorus
frog, Pseudacn's triseriata, and Fowler's toad, Bufo woodhousii fowleri.
Copeia. 2: 246.
Sanders, H.O. 1972. Toxicity of some insecticides to four species of mala-
costracan crustaceans. Bur. Sport Fish. Wild!. Tech. Pap. 66.
Sanders, H.O. and O.B. Cope. 1966. Toxicities of several pesticides to two
species of cladocerans. Trans. Am. Fish. Soc. 95: 165.
Schimmel, S.E., et al. 1977. Toxicity and bioconcentration of BHC and lin-
dane in selected estuarine animals. Arch. Environ. Contam. Toxicol. 6: 355.
B-29
-------
Tooby, I.E. and F.J. Durbin. 1975. Lindane residue accumulation and elimi-
nation in rainbow trout (Salmo gairdneri Richardson) and roach (Rutilus
rutilus Linnaeus). Environ. Pollut. 8: 79.
U.S. EPA. 1980. Unpublished laboratory data. Environ. Res. Lab., Gulf
Breeze, Florida.
U.S. Food and Drug Administration. 1978. Administrative Guideline 7420.08,
Attachment B, October, 5.
Velson, F.P.J. and D.F. Alderdice. 1967. Toxicities of two insecticides to
young coho salmon. Jour. Fish. Res. Board Can. 24: 1173.
Whitten, O.K. and C.J. Goodnight. 1966. Toxicity of some common insecti-
cides to tubificids. Jour. Water Pollut. Control Fed. 38: 227.
B-3u
-------
Mammalian Toxicology and Human Health Effects
INTRODUCTION
Hexachlorocyclohexane (HCH) was first synthesized in 1825 by
Faraday. The insecticidal properties of HCH were demonstrated by
the American chemist Bender in 1933 and later by the French chemist
Dupire in 1940. One of the common names for HCH is BHC (benzene
hexachloride). This is obviously a misnomer since HCH is a satu-
rated chlorinated hydrocarbon and, therefore, has no aromaticity.
The common misnomer, BHC, probably came from the original method of
preparation of HCH, i.e., the chlorination of benzene. Cl
Cl
T T
3C12
Radiation
Benzene
This preparation method yields technical grade HCH which is a mix-
ture of the five basic isomers (see Figure 1). The composition of
technical HCH is approximately as follows:
Isomer Percent
alpha ( cX ) 60-70
beta (£ ) 5-12
gamma (
-------
JOUIOI)
a
P
Y
5
s
^
"
e
•/• In todin. OMC
60-70
5-12
10-15
6-10
3- 4
Moiling point
157,5-153,5
309
112,8
138-139
218,8
68 - 88
89,8- S0,5
124-125
O
5
SO
O •
543
I?
II
0,02
0,005
0,03
0,02
"w
4
1
2,22:
0
2.3:
3,6
2,2:
(2,17:
2.32)
0
1 ^
£ 55.
i ii r
S« s| t
li 55 3
1.60 -1,626 1253 ^
f
1,630 1345 ^
1,60 -1,635 1322 ^
'•
1,576-1,674 1131 ^
t
1.00 -1,635 1396 ^h
\ S
-^^•- monoclinic
' — ?• prisms
^^y_L» cubic
=:::^^ (octahedral)
j-^^L monoclinic
^T crystals
, crystals or
' platelets
-~^*— monoclinic
~^T* needles or
hexagonal
monoclinic
crystals
FIGURE 1
Comparison of the Physical Constants of Lindane
and some of the other BHC Isomers
Source: Ulmann, 1972
C-2
-------
Lindane, named after the Belgian chemist, van der Linden, has
been marketed under a number of trade names as an insecticide in-
cluding the following registered trademarks:
Jacutin (emulsifiable concentrate)
Lindafor 90 (wettable powder)
Lindamul 20 (emulsifiable concentrate)
Nexit-Staub (0.8 percent dust)
Prodactic (wettable powder)
Other names for ^-HCH include ^-BHC, ^-lindane, purified BHC,
and technical lindane. The common names in Sweden, Denmark, and
the USSR are hexaklor, 666, and hexachloran, respectively. It is
important to recognize the various synonyms for HCH and its isomers
due to the extensive use and misuse of these names in the litera-
ture. In this document, HCH will be used as an abbreviation for
hexachlorocyclohexane and its synonyms. However, the various iso-
mers will be designated by the appropriate Greek letter. Lindane
will be referred to as ^-HCH. The technical product will be
t-HCH.
The major commercial usage of HCH is based upon its insecti-
cidal properties. As indicated previously, the <^-isomer has the
highest acute toxicity, but the other isomers are not without
activity. It is generally advantageous to purify the ^-isomer
from the less active isomers. The j'-isomer acts on the nervous
system of insects, principally at the level of the nerve ganglia
(Block and Newland, 1974). As a result, lindane has been used
against insects in a wide range of applications including treatment
of animals, buildings, man for ectoparasites, clothes, water for
mosquitoes, living plants, seeds and soils. Some applications have
been abandoned due to excessive residues, e.g., stored foodstuffs.
C-3
-------
EXPOSURE
Ingestion from Water
The contamination of water with HCH has occurred principally
from two sources:
(1) direct application of ^-HCH or technical HCH to
aquatic systems for the control of mosquitoes
(2) the use of HCH in agriculture and forestry.
The contamination of water supplies from agriculture and forestry
comes usually from HCH associated with soil or sediment particles
(Lotse, et al. 1968). The only other major source of aquatic pol-
lution of HCH occasionally occurs during its manufacture. HCH-
containing waste water can be generated during the synthesis, crys-
tallization, and isomer separation. These HCH contaminated waste-
waters are usually cleaned up prior to discharge, but occasionally
some contamination occurs.
The occurrence of HCH in water supplies is potentially more of
a problem than for many other organochlorine insecticides, such as
DDT, endrin, aldrin, heptachlor, etc., due to HCH's high water
solubility. Solubility of
-------
-------
ingestion 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 the weighted average percent
lipids for consumed freshwater and estuarine fish and shellfish is
3.0 percent.
No measured steady-state bioconc<=ntration factor (BCF) is
available for hexachlorocyclohexane or any of its isomers, but the
equation "Log BCF = (0.85 Log P) - 0.70" can be used (Veith et al. ,
1979) to estimate the BCF for aquatic organisms that contain about
7.6 percent lipids (Veith, 1980) from the octanol-water partition
coefficient (P). Based on an average measured log P value of 3.80
(Hansch and Leo, 1979), the steady-state bioconcentration factor
for hexachlorocyclohexane is estimated to be 339. An adjustment
factor of 3.0/7.6 = 0.395 can be used to adjust the estimated 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. Thus, the weighted average bioconcentration factor
for hexachlorocyclohexane and the edible portion of all freshwater
C-6
-------
and estuarine aquatic organisms consumed by Americans is calculated
to be 339 x 0.395 = 130.
Inhalation
Little is known about the concentration and distribution of
/-HCH in the atmosphere. Abbott, et al. (1966) found only traces
of HCH in air in central and suburban London. According to an in-
vestigation by Barney (1969) the
-------
PHARMACOKINETICS
Absorption
The rapidity of tf-HCH absorption is enhanced by lipid medi-
ated carriers. For an organochlorine insecticide, lindane is
unusually soluble in water, another factor contributing to its
rapid absorption and excretion (Herbst and Bodenstein, 1972).
Fisher 344 rats were treated with daily oral injections of
peanut oil spiked with $ -HCH which was C-labeled. For 2 mg
administered orally, only 0.1 to 4 jug ^ -HCH was found in the
urine, representing 0.005 to 0.2 percent of the administered
# -HCH. However, 2 to 5 percent of the original
-------
peak concentration noticed six hours after application. An absorp-
tion half-life of 17.9 hours in the blood of infected children was
recorded and 210.4 hours in children with normal skin. These
findings support previous observations in animals and adult human
volunteers that lindane is absorbed through the skin.
Distribution
-------
caseosa of their newborn babies. In some women with a normal
course of pregnancy, pesticide concentrations were extraordinarily
high, but did not cause premature termination of the pregnancy or
noticeably affect intrauterine fetal development (Poradovsky, et
al. 1977). Analysis of macroscopically normal appearing human
embryos and fetuses obtained from abortion cases revealed detect-
able levels of ^-HCH (Nishimura, et al. 1977). Higher concentra-
tions were found in the skin than in the brain. Levels in the skin
of more highly developed fetuses were greater as a result of a more
highly developed skin fat content. Concentration never exceeded
the corresponding values of normal adult organs.
In an accidental case of human poisoning, 0.29 mg/1 T-HCH was
found in the blood plasma during the convulsive phase, and de-
creased to a 0.02 mg/1 level seven days later (Dale, et al. 1967).
Several authors have reported on the level of ^-HCH in human milk
(Savage, et al. 1973; Curley and Kimbrough, 1968). Bakken and Siep
(1977) found that approximately 56 percent of those persons exam-
ined in Norway showed milk levels of HCH greater than the maximum
approved concentration for cows' milk by the World Health Organiza-
tion.
Metabolism
The biological transformation of various hexachlorocyclo-
hexane isomers in mammals results in the formation of various chlo-
rophenols including: 2,4,5- and 2,3,5-trichlorophenol; 2,3,4,5-
tetrachlorophenol; 2,4,6-trichlorophenol; 3,4-dichlorophenol;
2,3 ,4,6-tetrachlorophenol; 2,3 ,4 ,5^-pentachloro^-cyclohexene-l-
ol (PCCOL); and 3,4-dichlorophenylmercapturic acid. These are
C-10
-------
commonly excreted in the urine as conjugates of sulfuric and glu-
curonic acid (Grover and Sims, 1965; Freal and Chadwick, 1973;
Chadwick and Freal, 1972). These metabolites have been found in
the blood, liver, kidneys, spleen, heart, and brain of rats fed
/-HCH, but were not detected in the intestine or feces (Engst, et
al. 1976). Freal and Chadwick (1973) originally suggested /-HCH
is metabolized in the rat to a series of metabolites ranging from
pentachlorocyclohexenes to trichlorobenzenes that result in chlo-
rophenols. Chadwick, et al. (1975) later demonstrated that /-HCH
undergoes metabolism to an intermediate hexachlorocyclohexene,
from which further degradation yields PCCOL, two tetrachlorophenols
and three trichlorophenols. This metabolic pathway was not ob-
served for the other hexachlorocyclohexane isomers. Freal and
Chadwick (1973) also noted an enhanced metabolism of $ -HCH upon
pretreatment with the other BHC isomers. This enhancement de-
creased in the order of alpha-delta-gamma-beta. DDT, Mirex^,
chlordane, and HCB also stimulate the metabolism of / -HCH signifi-
cantly (Chadwick, et al. 1977a). The preapplication of X -HCH has
also been shown to stimulate its own biodegradation in rats (Noack,
et al. 1975).
Pretreatment of male Wistar rats with cadmium also has been
noted to alter /-HCH metabolism. Three days after exposure to 14C
/-HCH, the control rats excreted significantly more radioactivity
than the Cd-treated groups. Cd-exposure altered the distribution
of neutral and polar ^T-HCH metabolites, as well as inhibiting the
dehydrogenation of
-------
The administration of dimethyl sulfoxide with #-HCH to female
rats led to impaired
-------
Cl B-S, /Cl
R = -CHjCHCOOHNMCOCHj
TCPMAX TCPMA\ OCPMA
2456 TCCOLX L_l /O 124STCCOL
^_y
^ OH C,
<>•
H^S. O
MO
Z 3 5 TCP
136.451 »CCM
•U
I =°«
*
LVj
o
FIGURE 2
Metabolism of Lindane
Source: Chadwick, et al. 1975
C-13
-------
40 days
FIGURE 3
Reduction of HCH concentration in the total mouse
eluding the skin and the digestive tract, after a single
of 500 ug JT-HCH and 500 ug ^
Source: Kitamura, et al. 1970
body
oral
, ex-
dose
C-14
-------
excreted at a much slower rate. Since the pare p -isomer seems to
persist in the body, there is justification for the use of only the
pure form of the ^-isomer in situations that might lead to absorp-
tion. The rapid biological deterioration of <3"-HCH is self-induced
and minimizes the health hazards presented by hexachlorocyclohex-
anes (Sieper, 1972; Chadwick, et al. 1971; Chadwick and Freal,
1972).
Even prolonged $ -HCH administration results in complete elim-
ination when application has been terminated. In one experiment a
-------
50 to 100 mg lindane per kg body weight resulted in 1.5 mg per day
increase of urinary glucuronic acid excretion within about two
weeks. Organic sulfur compound excretion was enhanced by about 35
to 58 percent (Rusiecki and Bronisz, 1964). When given at 20 mg/kg
body weight, an increase in glucuronic acid excretion was noticed
after two days (Chadwick, et al. 1971; Chadwick and Freal, 1972).
HCH is eliminated not only by urinary excretion, but also via
milk secretion. It commonly exists in low concentrations in human
milk. Usually the^-isomer accounts for 90 percent of the HCH
present. The - and JT-isomers account for the remaining 10 per-
cent (Herbst and Bodenstein, 1972).
EFFECTS
Acute, Subacute, and Chronic Toxicity
Of the various isomers of HCH, tf exhibits the greatest acute
toxicity to mammalian organisms. This toxicity varies with the
species subject. Toxicity also varies with route of administra-
tion. Intravenous administration produces the most severe injury,
followed by intraperitoneal, subcutaneous, oral and then dermal
(Shirakowa, 1958). As a general rule, formulations of HCH in oil
and fat are associated with higher toxicities; the least toxic form
is the pure crystalline chemical. Variations in toxicity are also
noted among different types of oils or solvents (Starek and
Zabinski, 1970).
It has been demonstrated that young animals are more sensitive
to the toxic effects of if -HCH than adults of the same species
(Shirakowa, 1959; Radaleff and Bushland, 1960). The increased sen-
sitivity of young mammals to intoxication, at least to the age of
C-16
-------
weaning, is a result of low production of liver enzymes affecting
detoxification at an early age (Fouts and Adamson, 1959). Diseased
and distressed animals show a similar sensitivity (Chen, 1968).
^T-HCH has a higher acute toxicity than many other chlorinated
hydrocarbons since absorption is rapid; and visible clinical symp-
toms quickly develop (Lehman, 1951). This rapid uptake as well as
a higher water solubility account for the narrow range between low-
est toxic and lethal doses of ^f-HCH relative to similar-compounds
like DDT (Gunther, et al. 1968; Martin, 1971).
A case of acute poisoning with ^f-HCH in a 42-year-old male
worker revealed an array of symptoms: depression, headache, erne-
sis, asthenia, epileptiform attacks, sleeplessness, profuse per-
spiration, pathologically increased tendon reflex, tremor of the
fingers, oral automatism, bilateral Marinesiu-Radovici reflex,
Romberg's sign, and Hoffmann's and Troemmer's signs in the upper
extremities. Several weeks after poisoning the blood contained
fl"-HCH between 0.1 and 0.5 mg/1, and the cerebrospinal fluid con-
tained 0.2 mg/1 ff-HCH. This patient was therapeutically treated
with barbituates, sedatives, glucose, and vitamins C and B,_, which
elicited a favorable response (Pernov and Kyurkchiyev, 1974).
Another case describes a 35-year-old man who ingested ^-HCH
contaminated food. Grand mal seizures which recurred for nearly
two hours, developed rapidly as well as severe acidemia. Muscle
weakness and pain, headaches, episodic hypertension, myoglobin-
uria, acute renal failure and anemia were also seen. Pancreatitis
developed on the 13th day after ingestion, and on the 15th day, a
muscle biopsy revealed widespread necrosis and muscle fiber
C-17
-------
regeneration. Characteristic symptoms which occurred during the
year following exposure included recent-memory loss, loss of
libido, and easy fatigability (Munk and Nantel, 1977). Topical
application of ^T-HCH in a child caused irritability and hyper-
activity (Wheeler, 1977). Subsequent accidental oral administra-
tion of ^-HCH induced sporadic vomiting. Central nervous system
stimulation seems to be the major toxic function of HCH, regardless
of the absorption mechanism (Wheeler, 1977). This manifestation is
of primary clinical importance. In most animals, initial symptoms
of poisoning include an aggressive and excited state. Some cases
of accidental acute tf'-HCH poisoning in man by oral intake are
shown in Table 1.
Alterations in liver function are also significant toxic ef-
fects of HCH. Rats fed both the /? - and
-------
TABLE 1
Accidental Acute 2f -HCH Poisoning
(oral intake)
in Man
o
Persons
Involved
10
1
11
8
1
7
6
3
5
2
3
2
1
1
5
1
1
1
1
1
4
5
1
1
Age
adults &
children
adult
adults
children
child
children
children
children
adults
infants
children
adults
child
child
adults
-
child
child
child
child
1 child,
3 adults
7
adult
child
Dose
(mg/kg)
up to 300
ca. 90
ca. 10
7
(?) ca. 30
ca. 50-120
ca. 6-80
up to 65
7
?
7
7
7
7
7
?
7
•p
?
?
7
1 x 48
4 x ?
152
7
Fatal
cases
3
-
-
4
-
-
-
-
4
2
-
1
1
-
-
1
-
1
1
-
-
-
_
Formulation
Involved
50% WP
20% EC
crystalline in coffee
highgrade BHC (?)
(p.o. + p.c. + inhal. )
dust formulation
smoke sticks
smoke sticks
smoke sticks
in alcohol
smoke sticks
smoke tablets
20% EC
h smoke tablet
10% or 20% EC
powder in pudding
vermicide tablets
smoke tablet
7
4-5 smoke tablets
h smoke tablet
1 x inhalation
4 x p.o.
7
7
crystalline, dust
smoke tablets
Remarks
7 survived on therapy
survived on therapy
survived on therapy
4 survived on therapy
all undernourished
no symptoms
survived on therapy
survived on therapy
survived on therapy
1 survived on therapy
-
survived on therapy
survived on therapy
-
no therapy, severe
after effects
survived on therapy
undernourished, sur-
vived on therapy
-
survived on therapy
-
-
1 x urticaria, all
survived on therapy
-
survived on therapy
survived on therapy
*Source: Ulman, 1972
-------
processes (Shilina, 1973).
-------
at levels of 400 mg/1 or lower; however, liver weight increase was
noticed at 100 mg/1, particularly with respect to the oil forms.
This was a dose-related effect and increased with concentration.
At higher doses, liver cell hypertrophy (fat degeneration and
necrosis) and nephritic changes were noted. Oil solution concen-
trations of 400, 800, and 1,600 mg/1 decreased lifespan by 20 to 40
percent, although a concentration of 800 mg/1 crystalline form did
not yield similar effects.
Inhalation of (^-HCH by rats for varying times resulted in
little or no organ alterations. For example, inhalations of 0.78
mg/m3 for seven hours, five days a week for 180 days showed some
liver cell enlargement although no clinical symptoms were noticed.
Two out of 20 rats exposed to three percent ff-HCH dust for seven
hours a day, five times a week for 218 days developed some doubtful
liver and kidney changes (Heyroth, 1952). As a result of these and
other inhalation experiments, the United States and most western
countries, in 1954 established a maximum allowable air concentra-
tion of 0.5 mg/m3 (Ball, 1956).
The addition of <^-HCH at 10 mg/kg to the diet of rats for one
to two years revealed noxious effects to them and their offspring.
Body weight decreased after five months of administration, and in-
creased ascorbic acid levels in the urine along with changes in the
ascorbic acid levels of the blood were noted. Ascorbic acid was
decreased in both the liver and adrenals (Petrescu, et al. 1974).
Experimental data regarding the toxicity of various isomers of HCH
are shown in Table 2.
C-21
-------
TABLE 2
Toxicity of HCH Isoraers*
O
l
K>
NJ
_ .
Chemical Form and
Animal Species
Hat
t-HCll
-------
Male and female beagle dogs were fed tf-HCH at concentrations
of 25, 50, and 100 mg/kg in the diet for 104 weeks. Friable and
slightly enlarged livers were noted at 100 mg/kg/diet, but no
histopathological changes were noticed. The negative findings at
50 mg/kg/diet are consistent with a no-effect level for this
species (Rivett, et al. 1978). The no-effect levels after chronic
poisoning to several other mammals are shown in Table 2.
Kazakevich (1974) has reported that production workers with
exposure to t-HCH have exhibited a variety of symptoms including
headache, vertigo, irritation of the skin, eyes and respiratory
tract mucosa, etc. In some instances, there were apparent distur-
bances of carbohydrate and lipid metabolism. Dysfunction of the
hypothalamo-pituitary-adrenal system was also reported by the
authors. Besughyi, et al. (1973) reported similar findings in 88
persons having headache, vertigo, and irritation of the skin, eyes
and respiratory tract mucosa.
A study involving 59 females and 29 males with occupational
exposure to HCH for periods ranging from 11 to 23 years revealed
biochemical manifestations of toxic hepatitis. Fifty-five percent
of the workers showed pathological changes in the hepatobiliary
system, 33 percent of the total being chronic hepatitis, and 5 per-
cent being chronic pancreatitis. Some form of biochemical abnor-
mality was noted in 60 percent of all cases (Sasinovich, et al.
1974).
Synergism and/or Antagonism
The daily treatment of beagle dogs with phenobarbital for
60 days prior to the administration of % -HCH brought about a
C-23
-------
reduction of ^-HCH concentrations in the brain. The control dogs
(without pretreatment) were found to convulse after 27 minutes of
i.v. infusion of 7.5 mg ^T-HCH/minute, while the phenobarbital-
pretreated group did not convulse within 60 to 70 minutes. By the
end of the infusion period, the phenobarbital pretreated group
showed significantly higher concentration of blood $ -HCH. As com-
pared with the control group, the brains of the phenobarbital pre-
treated group contained a much smaller amount of the total cf-HCH
administered. It seems that phenobarbital pretreatment leads to
decreased convulsion effect of ^-HCH (Litterst and Miller, 1975).
Various substances have been found to have antagonistic ef-
fects on <3T-HCH poisoning and offer potential as treatment or anti-
dotes. The administration of silymarin to <2f-HCH-intoxicated mice
resulted in a prolonged survival time (Szpunar, et al. 1976). An
oral application mixture of HCH and Rogor ^ at concentrations of
3.2 and 3.8 mg/kg body weight to rabbits for a three month period
re suited in disruption of lipid metabolism and a decreased serum
cholesterol/lecithin ratio. However, methionine, galascorbin, and
vitamin B,-' individually aided the recovery of disrupted lipid
metabolism, although a combination of the three was more effective
(Karimov, 1976). Alterations in the serum cholestrol levels may be
indicative of chronic poisoning by these pesticides.
Pretreatment of Wistar rats with #-HCH has revealed a reduc-
tion in the teratogenic effect of some compounds. Preliminary
treatment weakened the teratogenic and embryotoxic action of a
carbamate insecticide given in a dose of 400 mg/kg and of sodium
C-24
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acetylsalicylate administered in a dose of 400 mg/kg (Shtenberg and
Torchinskii, 1977).
The chlorination of water containing various organochlorine
pesticides, including HCH, decreases the subsequent LD levels in
mice and rats presumably by conversion of these compounds to more
toxic products. This effect was determined by changes in blood
erythrocytes, enzymes, and -SH levels, disruption of protein syn-
thesis by the liver, and a decreased rate of weight gain (Shtan-
nikov, et al. 1977).
ft-HCH has also shown to be synergistic or antagonistic with
other substances. For example, the sensitivity of mice to pentyl-
enetetrazol at concentrations of 1, 3, 4, 6, and 12 mg/kg body
weight was increased by pretreatment of /T-HCH at 10, 7.5, 5.0,
2.5, and 1.2 mg/kg body weight. Specifically, the results showed a
significantly higher frequency of convulsions than expected from
pentylenetetrazol alone; the convulsive dose threshold was lowered
by small, single oral doses of ^f-HCH (Hulth, et al. 1976). ,^-HCH
administered in sublethal doses to rabbits resulted in the suppres-
sion of antibody formation in response to Salmonella typhi injec-
tions (Desi, 1976).
The toxic effects of ^-HCH have also been antagonized by var-
ious tranquilizers (Ulmann, 1972).
Teratogenicity
A study regarding the potential teratogenic effects of ,^-HCH
involved the p.o. administration in a vegetable oil solution to 4
groups of rats. Groups 1 through 3 were fed 25 mg /-HCH/kg body
weight/day while Group 4 was fed 12 mg /-HCH/kg body weight/day.
C-25
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Group numbers 1 and 4 received #-HCH throughout pregnancy (days 1
to 20), while Group 2 received it throughout placentation and
organogenesis (days 7 to 15) and Group 3 during preimplantation
period (days 1 to 7). All animals were sacrificed on day 20 and
examined. No teratogenic effects were noticed in any of the exper-
imental groups. Females in Group 1 did show, however, increased
postimplantation death of embryos: 25.6 percent compared with 11.2
percent in Group 2, 7.6 percent in Group 3, and 9.5 percent in Group
4, and 13.2 percent in nontreated controls (Mametkuliev, 1978).
Similar results were obtained by Palmer, et al. (1978) with white
rabbits. The effects of lindane on reproductive capacity were also
examined by Petrescu, et al. (1974). Four generations of rats (327
animals total) were studied. The investigators reported that 5,
10, or 15 mg/kg body weight administered in the diet resulted in an
increase in the average duration of pregnancy from 21 to 22 days in
the control animals to 21 to 24 days in the lindane-fed animals.
Also, the dosage 15 mg/kg decreased the number of births compared
to the number of animals in the parental generation. Numbers fell
from 100 births per control parental population to 60 births in
lindane-fed animals per parental population. Also noted were
delayed opening of the vagina, delayed initiation of first estrous
in offspring of experimental groups, and longer estrous cycles in
F~ and F, generations. These results are indicative of altered
sexual maturation and function and suggest that exposure to lindane
during pregnancy causes reduced reproductive capacity in parents
and subsequent generations. An increase in the proportion of
C-26
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stillbirths with succeeding generations of lindane-fed animals was
also noted in this study:
Generation Number of Stillbirths
Control 5, 10, 15 mg/kg
Pi 0/50 1/104
F^ 1/45 25/64
Fj 0/56 3/6
In addition, F^ and F~ animals of the lindane-fed group exhib-
ited spastic paraplegia, 17/119 and 7/52, respectively.
Mutagenicitff
Male mice were administered single intraperitoneal doses of
12.5, 25, and 50 mg tf-HCH/kg (1/8, 1/4, and 1/2 of the LD5Q) and
later mated with females during a seven day period. No mutations
or reproductive effects were noted (U.S. EPA, 1973). Mutagenic
rates too low to be considered positive were found in host-mediated
testing (Buselmair, et al. 1973). However, both the dominant
lethal assay and the host mediated assay have been shown to be less
sensitive in detecting chemical mutagens than the standard bacter-
ial plate incorporation assay. Many compounds demonstrating no
mutagenic activity in the first two assay systems are positive in
the latter (Hollstein and McCann, 1979; Poirier and deSerres,
1979). In addition, some alterations in mitotic activity and the
karyotype of human lymphocytes cultivated iin vitro with <3T-HCH at
concentrations between 0.1 and 10.0 mg/ml have been reported by
Tsoneva-Maneva, et al. (1971).
Carcinogenicity
Experimentation with tf-HCH in the early 1950s yielded little
or no data in support of carcinogenic activity. Accumulation of
epidemiological data (Hans, 1976), however, initiated more recent
C-27
-------
investigations into the potential carcinogenic action of HCH. This
shift was also prompted by an increase in agricultural use of HCH
in Japan. One case report of a Japanese sanitation employee re-
vealed acute leukemia which apparently was associated with occupa-
tional exposure to the insecticides HCH and DDT (Hoshizaki, et al.
1970).
When #-HCH was administered to rats at 800 mg/kg or more in
the diet the tumor incidence was not greater than in controls,
although average lifespans were reduced (Fitzhugh, et al. 1950).
It is important to note, however, that all organs were not micro-
scopically examined. Truhant (1954) supported these findings by
feeding diets containing ^ -HCH at 25, 50, or 100 mg/kg to rats for
two years. Again, no significant increase in tumors was observed.
Nagasaki (1972a) reported the development of liver tumors in
all male mice which were fed t-HCH at 660 mg/kg in the diet for 24
weeks. Doses of 66.0 and 6.6 mg/kg/diet did not induce tumors but
did increase liver weights. The 66.0 mg/kg dietary level also re-
vealed some cellular hyperplasia. Excessive amounts of cA- and
£ -HCH accumulated in the liver at the 660 mg/kg level. # - and
/-HCH were found only in trace amounts.
A later experiment involved feeding the °* - , p -, <•> -, and
-------
any tumors with respect to the other isomers (Nagasaki, et al.
1972b). Pathomorphological investigations by Didenko, et al.
(1973) established that the ^-isomer did not induce tumors in mice
given intragastric administration at doses of 25 mg/kg twice a week
for five weeks.
Hanada, et al. (1973) fed six-week-old mice a basal diet con-
taining 100, 300, and 600 mg/kg of t-HCH or the c* -, £ -, Or
^-isomers for a period of 32 weeks followed by 6 weeks of chemical
free diet. At this time, animals were killed and liver tumors were
found in 44 percent of the males and 44 percent of the females fed
t-HCH. Multiple nodules were found in the liver, although perito-
neal invasions or distinct metastases were not found. Liver tumors
were found in 68 and 42 percent respectively of the males and
females fed the o^-isomer. In males and females fed the
-------
tumors in all mice of Groups 1 and 2; eight of ten mice in Group 5;
and five of ten mice in Group 4.
The results of these experiments support the observations that
t-HCH and <=^-HCH frequently cause malignant liver tumors in mice
subjected to oral administration of high doses (600 mg/kg) for six
months. The same experimental conditions involving X-HCH or
^-HCH produced benign tumors. Malignant tumors were also produced
in mice of Group 5, although it was not established whether » -,
£-, or the mixture was responsible for the hepatomas.
The combination of #'-, /-, or & -HCH with the highly car-
cinogenic o<-HCH revealed no synergistic or antagonistic effect on
the production of tumors by cX-HCH for dd strains of mice (Ito, et
al. 1973). Proliferation of cytoplasmic endoplasmic reticulum as
well as nuclear and mitochondrial changes were noticed in the
region of hepatocellular carcinomas.
The feeding of o(-HCH at 500 mg/kg in the diet to mice for a
24-week period resulted in nodular hyperplasias of the liver (Sugi-
hara, et al. 1975). At the end of initial administration, the
ultrastructure of the nodular cells was characterized by large,
oval shaped nuclei with clear nucleoplasm. Four weeks after dis-
continuation, active phagocytotic processes appeared between nodu-
lar cells. Although the number of nodular cells decreased after
cessation of poisoning, the ones remaining after 12 weeks showed
tumorous growth; after 24 weeks, hepatocarcinomas developed.
Apparently, the remaining nodular cells are responsible for the
development of the hepatocellular carcinomas (Sugihara, et al.
1975).
C-30
-------
Some contradiction appears in the literature with respect to
the carcinogenic action of the <2f-HCH isomer. Thorpe and Walker
(1973) noticed tumor igenic action caused by the
-------
different strains of mice, with the CFX strain being particularly
susceptible. Feeding 500 mice of the Chbi:NMRI(SPF) strain X -HCH
at levels of 12.5, 25, and 50 mg/kg in the food for 80 weeks re-
vealed no compound-induced lymphatic leukemia, no malignant heman-
gioendotheliomas, and no liver cell adenomas (Herbst, et al. 1975).
Electron-microscopical examinations of SPF mice which were fed the
same concentrations, provided no evidence of X -HCH-induced fine
structural hepatocellular alterations (Weisse and Herbst, 1977).
In a study by Ito, et al. (1975) male Wistar-derived rats were
fed several isomers of HCH in the diet for 72 weeks. The oC-HCH
isomer was administered at 500, 1,000, and 1,500 mg/kg of diet,
^-ECE at 500 and 1,000 mg/kg, ^-HCH at 500 mg/kg and <5~-HCH at 500
and 1,000 mg/kg. The 500 mg/kg level of all isomers produced no
neoplastic changes, cell infiltration, fatty changes, fibrosis, or
bile duct proliferation, but liver weights did increase in all
groups except the /-HCH-treated rats. Only the o<-HCH-treated
group revealed tumor development. No metastases were seen and no
tumorous growths developed in any of the other dietary groups (Ito,
et al. 1975).
One instance of carcinogenic synergism of ^-HCH in combina-
tion with leupeptin showed a 5-fold increase in hepatic nodular
hyperplasia (Arai, et al. 1978). Other experiments have shown
#-HCH to have an antagonistic effect on the hepatocellular car-
cinoma induction by aflatoxin Bl in male albino rats (Angsubhakorn,
et al. 1978).
No pertinent data are currently available in the scientific
literature on the carcinogenicity of the £ - and the £-isomers of
C-32
-------
HCH. Furthermore, the o - and £-isomers are rarely detected in
the environment.
C-33
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CRITERION FORMULATION
Existing Guidelines and Standards
The FAO/WHO ADI is 1 jug/kg/day and was revised downward to
that figure from 12.5 mg/kg/day originally set by FAO/WHO in 1972
(NAS, 1977). Barney (1969) showed the average daily intake of HCH
for U.S. citizens to be 0.002 jug/kg/day from the air and 0.07
ug/kg/day from foodstuffs, clearly below the established level of 1
ng/kg/day.
The EPA set the tolerance for animal fats at 7 ppm, and 0.3 ppm
for milk. One ppm is the tolerance level for most fruits and vege-
tables. Finished drinking water should contain no more than 0.004
ppm. The maximum air concentration that is allowed by the rlPA is
0.5 mg/m of air. Cases of HCH poisoning in Japan have shown con-
centrations of 23 and 59 mg/m at factories involved in the manu-
facture of HCH. In both cases a number of workers became ill with
convulsions. It is clear that research is needed concerning the
effects of long-term, low-level air concentrations of the HCH
isomers.
Current Levels of Exposure
Considering the steady decline in the use of organochlorine
insecticides, it is likely that HCH concentrations will continue to
fall. This should also lower the amount of human exposure of HCH by
oral ingestion. Dermal and inhalation, however, are recognized
sources of contamination for those involved in the manufacture,
use, and formulation of HCH and its isomers.
There is considerable pressure in the European countries to
ban all organochlorine insecticides except lindane ( <5 -HCH). It is
C-34
-------
strongly believed by many that v -HCH does not represent a pollu-
tion problem. It is recognized by the same scientists that °^- and
ft -HCH do represent a significant hygienic problem. <=* - and/2 -HCH
are accumulated up the food chain, e.g., Japanese rice —^ rice
straw —> cattle —> cattle products —> man. Technical grade
HCH (t-HCH) contains a significant amount of the o< - and
jl -isomers, so production of t-HCH should be restricted and only
production of ft -HCH allowed. The presence of the c/ - and
^-isomers has in part given rise to the hypothesis that the
ft -isomer can be transformed to the unwanted isomers. Experimental
isomerization has occurred (Newland, et al. 1969), but only under
anaerobic aquatic conditions and probably by microorganisms. There
is a lack of bioisomerization in mammals. It should not be over-
looked thato^-HCH, despite its relatively short half-life, will be
detected for a long time following the use of t-HCH, in which it is
present in high proportion (60 to 70 percent). Practical proof of
this theory is shown by the fact that in countries where the use of
t-HCH was terminated (and no ft -HCH had been used), residues of o* -
and ^-ECU were found for many years. It is known that in such
cases, the relative share of /^-HCH of the total HCH residues is
increasing. If 2T -HCH is used exclusively in an area, then the
share of $ -HCH of the total HCH residues will vary in accordance
with the extent of application, and the other isomers will show a
downward trend.
Special Groups at Risk
t-HCH or ft-HCH is not currently manufactured in the U.S. Use
of t-HCH has been banned, but # -HCH is still approved for use. All
C-35
-------
/-HCH used in the U.S. is currently imported; there is no exposure
during manufacture in this country. Formulators, distributors and
users of the product certainly represent a special risk group. The
major use of %-HCH in recent years has been to pretreat seeds (42
percent in 1974), representing a source of exposure for employees
of the seed companies. Agricultural workers could be exposed dur-
ing handling and planting of the seed and during application to
crops.
Basis and Derivation of Criteria
The animal carcinogenicity data from Ito, et al. (1976), Goto,
et al. (1972), Thorpe and Walker, (1973), and Nagasaki, et al.
(1972a) have been used to develop water quality criteria for o< -,
£-t 3T-, and technical-HCH, respectively. These criteria have
been developed by the Carcinogen Assessment Group of EPA. The
assessment is given in Appendix I.
Under the Consent Decree in NRDC v. Train, criteria are to
state "recommended maximum permissible concentrations (including
where appropriate, zero) consistent with the protection of aquatic
organisms, human health, and recreational activities." c^-HCH,
$ -HCH, ft -HCH and t-HCH are suspected of being human carcinogens.
Because there is no recognized safe concentration for a human car-
cinogen, the recommended concentration of oi-HCH, /d'-HCH, ^-HCH,
and t-HCH in water for maximum protection of human health is zero.
Because attaining a zero concentration level may be infeasible
in some cases and in order to assist the Agency and States in the
possible future development of water quality regulations, the con-
centrations of oUHCH, ^-HCH, J-HCH, and t-HCH corresponding to
C-36
-------
several i.-creme Retime cancer risk levels have been estimat-
ed. A cancer risk level provides an estimate of the additional
incidence of cancer that may be expected in an exposed population.
A risk of 10 for example, indicates a probability of one addi-
tional case of cancer for every 100,000 people exposed, a risk of
10 indicates one additional case of cancer for every million
people exposed, and so forth.
In the Federal Register notice of availability of draft ambi-
ent water quality criteria, EPA stated that it is considering set-
ting criteria at an interim target r:
10 as shown in the tables following.
ting criteria at an interim target risk level of 10 ,10 , or
Exposure Assumptions
(per day)
2 liters of drinking water
and consumption of 6.5 g
fish and shellfish.(2)
Consumption of fish and
shellfish only.
Exposure Assumptions
(per day)
2 liters of drinking water
and consumption of 6.5 g
fish and shellfish.(2)
Consumption of fish and
shellfish only.
o^-HCH
Risk Levels and Corresponding Criteria (1)
0. i°_~7 IP_~6 IP."5
0 0.92 ng/1 9.2 ng/1 92 ng/1
0 3.10 ng/1 31.0 ng/1 310 ng/1
/-HCH
Risk Levels and Corresponding Criteria (1)
o. IP-"7 IP.'6 IP.'5
0 1.63 ng/1 16.3 ng/1 163 ng/1
0 5.47 ng/1 54.7 ng/1 547 ng/1
C-37
-------
Exposure Assumptions
(per day)
2 liters of drinking water
and consumption of 6.5
g fish and shellfish.(2)
Consumption of fish
and shellfish only.
Exposure Assumptions
(per day)
2 liters of drinking water
and consumption of 6.5
g fish and shellfish.(2)
Consumption of fish
and shellfish only.
2 -HCH
Risk Levels and Corresponding Criteria(l)
2 1£~7 10."6 10."5
0 1.86 ng/1 18.6 ng/1 186 ng/1
0 6.25 ng/1 62.5 ng/1 625 ng/1
t-HCH
Risk Levels and Corresponding Criteria(l)
£ 10_"7 lOf6 10."5
0 1.23 ng/1 12.3 ng/1 123 ng/1
0 4.14 ng/1 41.4 ng/1 414 ng/1
(1) Calculated by applying a linearized multistage model as dis-
cussed in the Human Health Methodology Appendices to the
October 1980 Federal Register notice which announced the
availability of this document. Appropriate bioassay data used
in the calculation of the model are presented in Appendix I.
Since the extrapolation model is linear at low doses, the
additional lifetime risk is directly proportional to the water
concentration. Therefore, water concentrations corresponding
to other risk levels can be derived by multiplying or dividing
one of the risk levels and corresponding water concentrations
shown in the table by factors such as 10, 100, 1,000, and so
forth.
C-38
-------
(2) Approximately 30 percent of the o(-HCH, s#-HCH, /-HCH, and
t-HCH exposure results from the consumption of aquatic organ-
isms which exhibit an average bioconcentration potential of
130-fold. The remaining 70 percent of o<-HCH, X-HCH, /-HCH,
and t-HCH exposure results from drinking water.
Concentration levels were derived assuming a lifetime exposure
to various amounts of HCH (1) occurring from the consumption of
both drinking water and aquatic life grown in waters containing the
corresponding HCH concentrations and, (2) occurring solely from
consumption of aquatic life grown in the waters containing the cor-
responding HCH concentrations. Although total exposure information
for HCH is discussed and an estimate of the contributions from
other sources of exposure can be made, these data will not be fac-
tored into ambient water quality criteria formulation until addi-
tional analyses can be made. The criteria presented, therefore,
assume an incremental risk from ambient water exposure only.
Water quality criteria for the
-------
Criteria
<=><-isomer 92 ng/1*
/-isomer 163 ng/1*
r-isomer 186 ng/1*
d -isomer none
C-isomer none
technical 123 ng/1
*At a risk level of one in 100,000.
C-40
-------
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APPENDIX I
Summary and Conclusions Regarding the Carcinogenicity
of Hexachlorocyclohexane
Hexachlorocyclohexane (HCH;BHC) is a saturated chlorinated
hydrocarbon which has insecticidal properties. Technical grade HCH
is composed of five basic isomers including the alpha (°<), beta
(j£ ), gamma ( $ ), delta (S ), and epsilon (£ ) isomers. The gamma
isomer (gamma-HCH; tf-BHC; Lindane) has the lowest melting point
(112 C) and also has the highest acute toxicity of these five iso-
mers of HCH.
So far, 2,4,6-trichlorophenol is the only metabolite of gamma-
HCH shown to be an animal carcinogen (National Cancer Institute,
1979).
Reports concerning the mutagenicity of hexachlorocyclohexane
relate to the gamma isomer. Although gamma-HCH was found to be
mutagenic in microbial tests using Salmonella typhimurium TA 1535
and TA 1538 with metabolic activation (Ames test), the host-medi-
ated assay, and the dominant lethal test in rats, other reports
indicate that it does not have significant mutagenic activity.
Numerous reports concerning the Carcinogenicity of technical
hexachlorocyclohexane and its isomers are in the literature. An
increased incidence of liver tumors was reported in male and/or
female mice of various strains fed technical HCH (Goto, et al.
1972; Hanada, et al. 1973; Nagasaki, et al. 1972a), alpha-HCH
(Goto, et al. 1972; Hanada, et al. 1973; Ito, et al. 1973, 1976;
Nagasaki, et al. 1972b), beta-HCH (Goto, et al. 1972; Thorpe and
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Walker, 1973) and gamma-HCH (Goto, et al; 1972; Hanada, et al.
1973; National Cancer Institute, 1977; Thorpe and Walker, 1973).
Male rats fed alpha-HCH for up to 72 weeks also developed liver
tumors (Ito, et al. 1975). One report in the literature (Goto, et
al. 1972) detailed an increase of liver tumors in mice fed a mix-
ture of delta and epsilon isomers of HCH, but there were no studies
which used individual delta or epsilon isomers.
The induction of liver tumors in male and female mice from the
administration of either technical HCH, alpha-HCH, beta-HCH, or
gamma-HCH and the induction of liver tumors in male rats from the
administration of alpha-HCH indicates that technical, alpha-,
beta-, and gamma-HCH are likely to be human carcinogens.
The water quality criterion for technical HCH is based on the
induction of liver tumors in male dd mice fed 660 ppm technical
hexachlorocyclohexane for 24 weeks (Nagasaki, et al. L972a). It is
concluded that the water concentration of technical HCH should be
less than 123 ng/1 in order to keep the lifetime cancer risk below
io-5.
The water quality criterion for alpha-HCH is based on the
induction of liver tumors in male DDY mice fed 500 ppm alpha-hexa-
chlorocyclohexane for 24 weeks (Ito, et al. 1975). It is concluded
that the water concentration of alpha-HCH should be less than 92
ng/1 to keep the lifetime risk below 10
The water quality criterion for beta-HCH is based on the in-
duction of liver tumors in male ICR-JCL mice fed 600 ppm beta-hexa-
chlorocyclohexane for 26 weeks (Goto, et al. 1972). It is
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concluded that the water concentration of beta-HCH should be less
than 163 ng/1 in order to keep the lifetime risk below 10 .
The water quality criterion for gamma-HCH is based on the
induction of liver tumors in male CF, mice fed 400 ppm gamma-hexa-
chlorocyclohexane for 110 weeks (Thorpe and Walker, 1973). It is
concluded that a water concentration of gamma-HCH should be less
than 186 ng/1 in order to keep the lifetime cancer risk below 10 .
Because of insufficient data, a water quality criterion cannot
be established for either the delta or epsilon isomer of hexa-
chlorocyclohexane.
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Summary of Pertinent Data
The water quality criterion of alpha-hexachlorochyclohexane
is derived from the oncogenic effects observed in the liver of male
DDY mice fed 500 ppm alpha-HCH in the diet (Ito, et al. 1975). The
time-weighted average dose of 65 mg/kg/day was given in the feed
for 24 weeks. The criterion is calculated from the following para-
meters:
DOSe Incidence
(mg/kg/day) (no. responding/no, tested)
0 0/18
65 20/20
le = 24 weeks w = 0.0357 kg
Le = 90 weeks R = 130 I/kg
L = 90 weeks
With these parameters the carcinogenic potency factor for
humans, q^, is 2.67 (mg/kg/day)"1. The resulting water concentra-
tion of alpha-hexachlorocyclohexane calculated to keep the individ-
ual lifetime cancer risk below 10" is 92 ng/1.
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Summary of Pertinent Data
The water quality criterion for beta-hexachlorocyclohexane is
derived from the oncogenic effects observed in the liver of male
ICR-JCL mice fed 600 ppm beta-HCH in the diet (Goto, et al. 1972).
The time-weighted average dose of 78 mg/kg/day was given in the
feed for 26 weeks. The criterion is calculated from the following
parameters:
Dose Incidence
(mg/kg/day) (no. responding/no, tested)
0 0/10
78 10/10
le = 182 days w = 0.0475 kg
Le = 630 days R = 130 I/kg
L = 630 days
With these parameters the carcinogenic potency factor for
humans, q1*f is 1.514 (mg/kg/day)'1. The resulting water concen-
tration of beta-hexachlorocyclohexane calculated to keep the indi-
vidual lifetime cancer risk below 10~5 is 163 ng/1.
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Summary of Pertinent Data
The water quality criterion for gamma-hexachlorocyclohexane
is derived from the oncogenic effects observed in the liver of male
CF, mice fed 400 ppm gamma-HCH in the diet (Thorpe and Walker,
1973). The time-weighted average dose of 52 mg/kg/day was given in
the feed for 110 weeks. The criterion is calculated from the
following parameters:
Dose Incidence
(mg/kg/day) (no. respond ing/no. tested)
0 11/45
52 27/28
le = 770 days w = 0.030 kg
Le - 770 days R « 130 I/kg
L = 770 days
With these parameters the carcinogenic potency factor for
humans, q^*, is 1.326 (mg/kg/day)"1. The resulting concentration
of gamma-hexachlorocyclohexane calculated to keep the individual
lifetime cancer risk below 10" is 186 ng/1.
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Summary of Pertinent Data
The water quality criterion for technical hexachlorocyclo-
hexane is derived from the oncogenic effects observed in the liver
of male dd mice fed 660 ppm technical HCH in the diet (Nagasaki, et
al. 1972a). The time-weighted average dose of 85.8 mg/kg/day was
given in the feed for 24 weeks. The criterion is calculated from
the following parameters:
Dose Incidence
(mg/kg/day) (no. responding/no, tested)
0 0/14
85.8 20/20
le = 24 weeks w = 0.0364 kg
Le = 90 weeks R = 130 I/kg
L = 90 weeks
With these parameters the carcinogenic potency factor for
humans, q.^*, is 2.0 (mg/kg/day) . The resulting water concentra-
tion of technical hexachlorocyclohexane calculated to keep the
individual lifetime cancer risk below 10 is 123 ng/1.
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