297 924
HEXACHLOROCYCLOHEXAN E
Ambient Water Quality Criteria
Criteria and Standards Division
Office of Water Planning and Standards
U.S. Environmental Protection Agency
Washington, D.C.
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CRITERION DOCUMENT
HEXACHLOROCYCLOHEXAN E
CRITERIA
Aquatic Life
Lindane
For lindane the criterion to protect freshwater aquatic
life as derived using the Guidelines is 0.21 ug/1 as a 24^-hour
average and the concentration should not exceed 2.9 ug/1 at any
time.
: For saltwater aquatic life, no criterion for lindane
can be derived using the Guidelines, and there are insufficient
data to estimate a criterion using other procedures.
BHC
For freshwater aquatic life, no criterion for a mixture
of isomers of BHC can be derived using the Guidelines, and there
are insufficient data to estimate a criterion using other pro-
cedures.
For saltwater aquatic life, no criterion for a mixture
of isomers of BHC can be derived using the Guidelines, and there
are insufficient data to estimate a criterion using other pro-
cedures.
Human Health
For the maximum protection of human health from the poten-
tial carcinogenic effects of exposure to o<-HCH, ^-HCH, and
2f -HCH through ingestion of water and contaminated aquatic or-
ganisms, the ambient water concentration is zero. Concentrations
of ck -HCH, & -HCH, and 2T-HCH estimated to result in additional
-------
lifetime cancer risks ranging from no additional risk to an aal
tional risk of 1 in 100,000 are presented in the Criterion Foddi-
mulation section of this document. The Agency is consideringr-
setting criteria at an interim target risk level in the range
10-5, 10-6, or 10-7 with corresponding criteria as follows: of
Isomer Criteria (ng/1) at the following risk levels
10~5 10~6 10~7
04 -HCH
X* -HCH
7T-HCH
t -HCH
16
28 .
54
21
1.6
2.8
5.4
2.1
0.16
0.28
0.54
0.21
There is insufficient data to establish criteria for the O
and . isomers of HCH.
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Introduction
Hexachlorocyclohexane is a broad spectrum insecticide
of the group of cyclic chlorinated hydrocarbons called organo-
chlorine insecticides. It consists of a mixture of five
configurational isomers and was introduced in 1942 as a
contact insecticide under the trade names BHC, benzene hexa-
chloride, and 666. Since its introduction, both the uses
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
gamma 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 products containing
BHC voluntarily cancelled their registrations or switched
their former BHC products to lindane formulations. On the
other hand, significant commercial use of the purified gamma
isomer of BHC (lindane) continues. As of January 17, 1977,
there were 557 Federal registrations for pesticide products
containing lindane and 87 formerly State-registered products
containing lindane for which Federal registration has been
requested.
Hexachlorocyclohexane, commonly referred to as BHC
or benzene hexachloride, is a brownish-to-white crystalline
solid with a phosgene-like odor, a molecular formula of
C6H6C16, 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; Cristensen, 1976; Matsumura, 1975). BHC is the common
A-l
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name approved by the International Standards Organization
for the mixed configurational isomers of 1,2,3,4,5,6-hexa-
chlorocyclohexane, although the terms BHC and benzene hexa-
chloride are misnomers for this aliphatic compound and should
not be confused with aromatic compounds of similar structure,
such as the aromatic compound hexachlorobenzene (Int. Agency
Res. Cancer, 1974). Lindane is the common name approved
by the International Standards Organization for the gamma-
isomer of 1,2,3,4,5,6-hexachlorocyclohexane. BHC is synthe-
sized 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: alpha-isomer, 55 to 70
percent; beta-isomer, 6 to 8 percent; gamma-isomer, 10 to
18 percent; delta-isomer, 3 to 4 percent; epsilon-isomer,
trace amounts (Hardie, 1972). The actual content of the
isomers in technical grade BHC varies depending on the manu-
facturing conditions.
.In addition to the hexachlorocyclohexane isomers, tech-
nical grade BHC may contain varying quantities (three to
five percent) of other chlorinated derivatives of cyclohexane,
primarily heptachlorocyclohexane and octachlorocyclohexane.
Technical grade BHC is available in various formulations
as wettable powders, granules, dusts, and emulsifiable concen-
trates and can be used as a stomach and contact poison for
a wide variety of insect pests and animal parasites. Since
the gamma-.isomer (lindane) has been shown to be the insecti-
cidally active ingredient in technical grade BHC (Hardie,
A-2
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1972) , technical grade BHC now has limited use commercially
except as the raw material from which the purified gamma-
isomer is extracted by a process of selective crystallization.
Technical grade lindane is composed of 99 to 100 percent
pure gamma-BHC isomer and is available in the form of emulsi-
fiable concentrates, wettable powders, dusts, crystals,
and solids for smoke generators and thermal vaporizers.
The physical properties of the purified BHC isomers
are presented in Table 1.
TABLE 1
Physical properties of BHC isomers
(Ulmann, 1972; Hardie, 1972)
BHC
isomer
alpha
beta
gamma
delta
Melting
point
(deg.C)
158
312
112.5
138
Vapor
pressure
(mm Hg at
50 deg.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 deg.C)
6.2
1.8
20.8
35.4
The isomers of BHC are not susceptible to photolysis
or strong acids but are, with the exception of the beta
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 alpha and/or delta BHC
by microorgamisms and plants (Matsumura, et al. 1976; Newland,
et al. 1969; and Steinwandter, 1976).
A-3
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REFERENCES
Christensen, H.E. 1976. Registry of toxic effects of chemical
substances. U.S. Dep. Health Edu. Welfare, Rockville, Md.
Hardie, D.W.F. 1972. Kirk-Othmer encyclopedia of chemical
technology. Interscience Publishers, Inc., New York.
International Agency for Research on Cancer. 1974. Some
organochlorine pesticides. IARC monographs on the evaluation
of carcinogenic risk of chemicals 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 gamma-BHC. Jour. Pestic. Sci. 1: 3.
Newland, L.W., et al. 1969. Degradation of gamma-BHC in
simulated lake impoundments as affected by aeration. Jour.
Water Pollut. Control Fed. 41: 174.
A-4
-------
Steinwandter, H. 1976. Lindane metabolism in plants. II,
Formation of alph-HCH. Chemosphere 5: 221.
Ulmann, E. 1972. Lindane: monograph of an insecticide.
Schillinger Press, Republic of Germany.
A-5
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AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
Hexachlorocyclohexane is a member of the group of cyclic
chlorinated hydrocarbons 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 should not be confused with aromatic com-
pounds of a similar structure. The aromatic compounds are also
called BHC, benzene hexachloride or hexachlorobenzene, so caution
is advised when reading reports on these chemicals.
The International Standards Organization has approved the
common name BHC for the mixed configurational isomers of 1,2,3,4,
5,6-hexachlorocyclohexane. Technical grade BHC contains five
hexachlorocyclohexane isomers. They are alpha (55 to 70 percent),
beta (6 to 8 percent), gamma (10 to 18 percent), delta (3 to 4
percent) and epsilion (trace). The gamma isomer is usually con-
sidered to be the most toxic, and preparations which contain at
least 99 percent of the gamma isomer are called lindane.
*The reader is referred to the Guidelines for Deriving Water Qual-
ity Criteria for the Protection of Aquatic Life [43 FR 21506 (May
18, 1978) and 43 FR 29028 (July 5, 1978)] in order to better
understand the following discussion and recommendation. The fol-
lowing tables contain the appropriate data that were found in the
literature, and at the bottom of each table are the calculations
for deriving various measures of toxicity as described in the
Guidelines.
B-l
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The majority of the effects data were for the gamma isomer
(lindane). A criterion was developed for this compound. There
are additional data for technical BHC, which contains varying
amounts of the gamma isomer and the alpha isomer. The data for
these compounds are included in the Tables but are insufficient
for criteria development.
Acute Toxicity
Twenty-five of the 31 acute toxicity test results reported in
Table 1 are for lindane and represent 16 species of fish. The
remaining 6 test results are for BHC. Most are 96-hour static
tests and all have been based on calculated toxicant concentra-
tions. For comparative purposes, these data have been adjusted
using the Guidelines.
The adjusted values for lindane range from 1 to 83 ug/1 for
brown trout and goldfish, respectively. These values represent an
interspecific difference in response to lindane exposure. Gener-
ally, the warmwater fish appear to be more tolerant of lindane ex-
posure than the coldwater salmonids.
The 96-hour LC50 values for BHC are much higher than those
for lindane. The difference cannot be explained by simple ratio
of the lindane content in the BHC to pure lindane. For example,
Henderson, et al. (1959) based their LC50 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 con-
centrations were so high that precipitates were observed.
B-2
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In addition, they determined a concentration of 0.1 mg/1 of
lindane alone caused 100 percent mortality of fathead minnows in
24 hours. When 3.2 mg/1 of technical BHC, a concentration that
caused no mortality, and 0.1 mg/1 lindane were added to the same
tank, no mortality occurred within 96 hours. They concluded that
the other BHC isomers either had reduced the solubility of the
gamma isomer (lindane) or had produced an antagonistic effect
reducing its toxicity.
When the geometric mean of the lindane data is divided by the
sensitivity factor (3.9), the Final Fish Acute Value is 6.9 ug/1.
Because the Final Fish Acute Value is lower than 95 percent (15 of
16 fish species) of the acute data, adjustment factors from the
Guidelines are appropriate. The Final Fish Acute Value for BHC is
740 ug/1.
Eleven toxicity tests with lindane and eight species of in-
vertebrate species are reported in Table 2. Three toxicological
groups can be formed from the data. The three cladoceran species
are the most resistant organisms tested. The LC50 concentrations
ranged from 390 to 745 ug/1 or about 10 to 100 times higher than
the LC50 concentrations for the next group. The crustaceans,
represented by the sowbugs and scud, are generally the most sensi-
tive species tested. With these animals, the LC50 value ranged
from 8 to 41 ug/1- The last group, represented by two insect
species, shows a wide range in LC50 values. The most sensitive
species of all the tested invertebrate species was the stonefly
with a LC50 of 4 ug/1. The other insect, a chironomid, had a LC50
of 175 ug/1 which is between the cladoceran and crustacean toxic
concentrations.
B-3
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The geometric mean of the adjusted values for lindane is 62
ug/1. When this value is divided by the sensitivity factor (21),
the resulting Final Invertebrate Acute Value, 2.9 ug/lf is lower
than any of the reported acute values. The cladoceran and crus-
tacean LC50 values are interspecifically consistent, whereas the
insect data show a substantial divergence. However, the stonefly
has been shown in studies with other pesticides to be a sensitive
indicator, so the acute value reported here may be close to a
minimum for insects. Because the adjusted acute value is lower
than the reported values, it should be protective on an acute
exposure basis.
Since the Final Invertebrate Acute Value for lindane (2.9
ug/1) is lower than the comparable value for fish (6.9 ug/l)» the
former value becomes the Final Acute Value for lindane.
Only one chronic test with fish was found. The geometric
mean of the chronic values for the fathead minnow is 14.6 ug/l«
Interpretation of this value requires a re-examination of the fish
acute data. The geometric mean of the fathead minnow acute con-
centrations is about 37 ug/1. This compares favorably with the
overall geometric mean of 27 ug/1 for all fish acute concentra-
tions. Because of the similarity, it is appropriate to consider
the fathead minnow as an average fish with regard to lindane
toxicity. The adjustment of the geometric mean of 14.6 ug/1 by
the sensitivity factor (6.7) provides a Final Fish Chronic Value
for lindane of 2.2 ug/1 which should give protection for 95 per-
cent of the species. However, one acute value (brown trout LC50 =
1 ug/1) is lower than the Final Fish Chronic Value, but this'value
is much lower than those for three other salmonids.
B-4
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Chronic data are available for three in-vertebrate species.
Fortunately, the three species are members of the three classes
already described in the invertebrate acute section. Longer ex-
posure resulted in a substantial decrease in the effect concentra-
tion for the cladoceran, Daphnia magna, (28x) and the chironomid,
Chironomus tentans, (53x) but little decrease for the scud,
Gammarus fasciatus, (1.6x).
The geometric mean of the chronic values is 6.6 ug/1. When
this value is adjusted with the sensitivity factor (5.1), the re-
sulting Final Invertebrate Chronic value for lindane is 1.3 ug/1.
The substantial decrease in effect concentrations between
acute and chronic invertebrate exposures for 2 of the 3 species
presents a concern for the safety of the final chronic value for
other untested species. If the acute to chronic ratio for other
cladocerans or insects is consistent, some untested species may
not be protected at 1.3 ug/1? since the Final Invertebrate Acute
Value is 2.9 ug/1.
Plant Effects
The effect of hexachlorocyclohexane on plants must be esti-
mated from only one report (Krishnakumari, 1977). Growth inhibi-
tion of an alga 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 while the more commonly used gamma isomer (lindane)
inhibited growth at 1,000 ug/1. The gamma isomer effect concen-
tration is about 770 times higher than the invertebrate chronic
value, so the plants should be protected.
B-5
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Residues
Bioconcentration factors (Table 6} include mean factors de-
termined using data obtained from a small oligotrophic lentic eco^
system (a flooded limestone quarry), where the fate of introduced
lindane and DDE was followed for one year (Hamelink and Waybrant,
1976). They reported average steady-state bioconcentration fac-
tors for lindane of 768 and 486 for whole bluegills and rainbow
trout, respectively. They used mean concentration data from all
thermal statra under summer water conditions to calculate their
bluegill concentration factor. This value (768) was not used be-
cause the bluegill would probably stay above the thermocline. A
bioconcentration factor (340) was calculated using their epilim-
nion lindane concentration data and is thought to reflect exposure
conditions for the bluegills. Seventy percent of the lindane was
evenly distributed in the epilimnion, and concentrations were
relatively constant until fall turnover (destratification). After
turnover, the lindane concentrations were similar throughout the
water column. Their rainbow trout bioconcentration factor data
were obtained under these conditions. The remaining bioconcentra-
tion factors (Table 6) are those of Macek, et al. (1976) and were
obtained under laboratory conditions. These values are for muscle
tissue in bluegill and brook trout and for eviscerated fathead
minnows. Their bluegill muscle factor (35) is aproximately 10
times less than that calculated for whole bluegills (340). This
difference is probably due to different lipid content.
The residue limit for consumers of aquatic life, established
by the U.S. Food and Drug Administration (FDA) for lindane in
domestic animal feed is 0.1 mg/kg, and was used to calculate the
B-6
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Residue Limited Toxicant Concentration (RLTC). This value divided
by the highest geometric mean bioconcentration factor for whole
fish tissue of any species, 486, gives a RLTC of 0.00021 mg/kg or
0.21 ug/1. The lowest of the Final Fish Chronic Value (2.2 ug/1),
Final Invertebrate Chronic Value (1.3 ug/D* Final Plant Value
(1,000 ug/D, and the RLTC (0.21 ug/1) is used to determine the
Final Chronic Value. For lindane, the Final Chronic Value is 0.21
ug/1.
Miscellaneous
Table 7 contains data on lindane, the alpha-isomer, and the
commercial trade mixture BHC. The data support the earlier find-
ings that lindane is the most toxic isomer of BHC. No data were
found that would alter the lindane Final Chronic Value of 0.21
ug/1.
B-7
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CRITERION FORMULATION
Freshwater-Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Lindane
Final Fish Acute Value = 6.9 ug/1
Final Invertebrate Acute Value = 2.9 ug/1
Final Acute Value =2.9 ug/1
Final Fish Chronic Value = 2.2 ug/1
Final Invertebrate Chronic Value =1.3 ug/1
Final Plant Value = 1,000 ug/1
Residue Limited Toxicant Concentration = 0.21 ug/1
Final Chronic Value = 0.21 ug/1
0.44 x Final Acute Value = 1.3 ug/1
BHC
Final Fish Acute Value = 740 ug/1
Final Invertebrate Acute Value = not available
Final Acute Value = 740 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = 1,000 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 1,000 ug/1
0.44 x Final Acute Value = 330 ug/1
Lindane
The maximum concentration of lindane is the Final Acute Value
of 2.9 ug/1 and the 24-hour average concentration is the Final
B-8
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Chronic Value of 0.21 ug/1. No important adverse effects on
freshwater aquatic organisms have been reported to be caused by
concentrations lower than the 24-hour average concentration.
CRITERION: For lindane the criterion to protect freshwater
aquatic life as derived using the Guidelines is 0.21 ug/1 as a
24-hour average, and the concentration should not exceed 2.9 ug/1
at any time.
BHC
No freshwater criterion can be derived for a mixture of
isomers of BHC using the Guidelines because no Final Chronic Value
for either fish or invertebrate species or a good substitute for
either value is available, and there are insufficient data to
estimate a criterion using other procedures.
B-9
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Table 1. Freshwater fish acute values for hexachlorocyclohexane
Bioaesay Test chemical Time
Organism Mstnod* Cone .** Description Ihrs)
Rainbow trout, S U Llndane 96
Salmo gairdneri
Rainbow trout, S U
Salmo gairdneri
Brown trout, S U
Salmo trutta
Brook trout, FT U
Salvellnus fontlnalls
Coho salmon, FT U
Ohcorhynchus kisutch
03 ...
' Coho salmon, S U
o Oncorhynchus kisutch
Coho salmon, S U
Oncorhynchus kisutch
Chinook salmon, S U
Oncorhynchus tshawytscha
Goldfish. S U
Carassius auratus
Goldfish, S U
Carassius auratus
Goldfish, S U
Carassius auratus
Carp, S U
Cyprinus carplo
Kr.thead minnow, S U
Pimephales promelaa
Lindane (98%)
Lindane
Llndane
BMC
Lindane
Llndane (100%)
Lindane (100%)
Lindane
Lindane (100%)
BI1C tech (15.5%
gamma isomer)
Lindane
Lindane
96
96
96
48
96
96
96
96
96
96
96
96
LCbO
(un/il
27
38
2
44.3
200
41
50
40
131
152
15.000
90
87
Adjusted
LOO
(ucj/i) heterence
15
21
1
34
154
22
27
22
72
83
8,200
49
48
Macek &
McAllister,
1970
Katz, 1961
Macek &
McAllister,
1970
Macek, et
al. 1976
Velson &
Alderdice, 1967
Macek &
McAllister,
1970
Katz. 1961
Katz. 1961
Macek &
McAllister,
1970
Henderson,
et al. 1959
Henderson,
et al. 1959
Macek &
McAllister,
1970
Macek &
McAllister,
1970
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Table 1. (Continued)
Organism
Bioassay Test Chemical Tina
flethpd* Cone.** Description fnrtj)
LCbi.
Adjusted
LCbO
fuq/il Keterence
JO
I
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelaa
Black bullhead.
Ictalurus melas
Channel catfish,
Ictalurus punctatus
Guppy.
Poecilia reticulatus
Guppy,
Poecilia reticulatus
Mosquitofish,
Gambusia affinis
Bluegill.
Lepomts macrochirug
Dluegill,
Lepomts macrochlrus
Bluegill.
Lepomls macrochlrus
Bluegill.
Lepomls macrochlrus
Ltndane (100%) 96
U
U
U
U
U
Lindane (100%) 96
BUG tech
(15.57. gamma
isomer)
BHC tech
(15.5% gamma
isomer)
Lindane
Lindane
U Lindane (100%) 96
BHC tech
(15.5% gamma
isomer)
Lindane
Tech lindane 96
62 34 Henderson.
et al. 1959
56 31 Henderson,
et al. 1959
96 15.000 8,200 Henderson,
et al. 1959
96 13,000 7,100 Henderson,
et al. 1959
96 64 35 Macek &
McAllister,
1970
96 44 24 Macek &
McAllister,
1970
138 75 Henderson,
et al. 1959
96 14,000 7,654 Henderson,
et al. 1959
48 74 33 Culley &
Ferguson, 1969
54 29 Macek. et
al. 1969
Tech lindane 96 51 28 Macek, et
al. 1969
Tech lindane 96 37 20 Macek, et
al. 1969
Lindane 96 68 37 Macek £.
McAllister.
1970
-------
Table 1. (Continued)
Organism
Bluegill.
Lepomis macrochirus
Bluegill.
Lepomis macrochirus
Redear sunfish.
Lepomis roicrolophus
Largemouth bass.
Mlcropterus salmoides
Yellow perch,
. Perca flavescens
KJ . .
Bioabsay Test
Method* <^onc .**
S U
S U
S U
S U
S U
Chemical
Description
Lindane (100%)
BUG tech (15.51
gamma laomer)
Lindane
Lindane
Lindane
Time
(f>ra)
96
96
96
96
96
LCtn.
77
5.100
83
32
68
Adjusted
LCSO
luq/.l»
42
2.788
45
17
37
heterence
Henderson.
et al. 1959
Henderson,
et al. 1959
Macek &
McAllister.
1970
Macek &
McAllister,
1970
Macek &
McAllister.
1970
* S = static, FT - flow-through
** U - unmeasured
Geometric mean of adjusted values.for- llpdane = 22 vfjl
BUG = 2.901 pa/1 2'901 - 740 pg/1
1.9
- 6,9 Mg/1
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Table 2. Freshwater invertebrate acute values for hexachlorocyclohexane
BiOdseay Test % Chemical
Of ganjam Method* Cone.** Description
Pond snail, S M Alpha HCH
Lymnaea atagnalia ,
Cladoceran, S U Lindane
Daphnia pulex
Cladoceran, S U Lindane
Daphnia giagna
Cladoceran, S U Lindane
Slrnocephalus serralatus
Cladoceran,
Simocephalus serralatus
Sowbug ,
W Asellus brevicaudus
(jj Scud,
Carnmarus lacustris
Scud.
Gammarus fasciatus
Scud.
Gammarus fasciatus
Scud,
Gammarus fasciatus
Stonefly,
Pteronarcys californica
Midge,
Chironomus tentans
S
S
S
S
S
S
S
S
U
U
U
U
U
U
U
U
Lindane
Lindane (99%)
Lindane
Lindane
Lindane (99%)
Lindane (99%)
Lindane
Lindane
Tine
IMJ)
48
48
48
48
48
96
96
48
96
96
96
48
LCbO
1,200
460
485
520
880
10
48
39
10
11
4.5
207
Adjusted
LCiO
(uq/ll Reference
568
390
411
440
745
8
41
14
8
9
4
175
Canton &
Slooff. 1977
Sanders &
Cope, 196b
Macek, et
al. 1976
Sanders &
Cope, 1966
Sanders &
Cope, 1966
Sanders ,
1972
Sanders ,
1969
Macek, et
al. 1976
Sanders ,
1972
Sanders ,
1972
Sanders &
Cope, 1968
Macek, et
al. 1976
* S = static
** U - unmeasured, M - measured
Geometric mean of adjusted values for lindane = 62 Mp-/l T 2.9 ug/1
£ O
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Table 3. .Freshwater fish chronic values for hexachlorocyclohexane* (Macek, et al. 1976)
Chronic
Limits Value
Organism Test**
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Table 4. Freshwater invertebrate chronic values for hexachlorocyclohexane* (Macek, et al. 1976)
CO
I
organism
Cladoceran,
Daphnia magna
Scud,
Gaimnarus fasciatus
Midge.
Chlronoir.us tentans
Chronic
Limits Value
Test** fuq/U (uq/ll***
LC 11-19 14.5
LC 4.3-8.6 6.1
LC 2.2-5.0 3.3
* Data for lindane
"'* LC = life cycle or partial life cycle
*** All values measured
Geometric mean of chronic values = 6.6 pg/1
Lowest chronic value » 3.3 pg/1
6.6
1.3 Mg/1
-------
Table 5. Freshwater plane e'ffects for hexachlorocyclohexane* (Krishnakumari. 1977)
Organism
Effect
Concentration
Alga.
Scenedesmus acutus
Alga.
Scenedesmus acutus
Alga.
Scenedesmus acutus
Alga.
Scenedesmus acutus
>20% growth
inhibition in
5 days
>20% growth
inhibition in
5 days
>20% growth
inhibition in
5 days
>20% growth
inhibition in
5 days
1.000 (B1IC
tech)
500 (alpha
BUG)
5,000 (beta
BHC)
1,000 (gamma
BHC)
00
I
* Tested isomer listed
Lowest plant value - Lindane - 1,000 ug/1
BHC =1.000 pg/1
-------
Table 6. Freshwater residues for hexachlorocyclohexane
DO
I
Organism
Zooplankton.
Rainbow trout,
Sal mo gairdneri
Brook trout,
Salvelinus fontinalls
Fathead minnow,
Pimephales promelas
Bluegill,
I.epomis raacrochirus
Bluegill,
Lepomis macrochirus
Organism
Domestic animals
Domestic animals
Man
* Lindane
** BIIC
Bioconcentration Factor laays;
336* 5-60
486* 108
70* *** 261
477* *** 304
35* *** 735
340* 5-81
Maximum Permissible Tissue Concentration
Concentration
Action Level or Effect (rag/kg)
Animal feed 0.1*
Animal feed 0.1**
Frog legs 0.5**
neterence
llamelink & Vtaybrant,
Hamelink 6. Waybrant.
Macek, et al. 1976
Macek. et al. 1976
Macek, et al. 1976
llamelink & Waybrant.
Reference
1976
1976
1976
U.S. FDA Admin. - Guideline
7426.04
U.S. FDA Admin. - Guideline
7426.04
U.S. FDA Admin. - Guideline
7420.08
***Muscle tissue for bluegill and brook trout and eviscerated fathead minnows.
Geometric mean whole body fish bioconcentratlon factor for lindane = 406
Lowest permissible residue concentration for lindane - 0.1 mg/kg
Ilipliest geometric mean whole body bioconcentration factor for a single species for lindane « 486
= 0.00021 mg/kg or 0.21 (,g/l
-------
Table 7. Other freshwater, data for hexnchlorocyclohexane
Orqani sm
Rainbow trout,
Salmo galrdneri
Brook trout,
Salvelinus fontlttalla
Brook trout.
Salvelinus fontinalis
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
f Bluegill.
!_. Lepomis macrochirus
00
Dluegill,
Lepomis macrochirus
Chorus frog (tadoole) ,
Pseudacrls triseriata
Toad (tadpole),
Bufo woodhousii
Tub if ex and
Llmnodrilus mixture
Chinook salmon,
Oncorhynchus
tshawytscha
Rainbow trout,
Salmo gairdneri
Toad (tadpole).
Test
Duration
6 wks
11 days
261 days
11 days
11 days
21 days
21 days
96 hrs
96 hr
96 hrs
10 hrs
44fe hrs
96 hrs
Etfect
Llndane
Lethal threshold
concentration
LC50
Reduced growth
LC50
LC50
LC50
LC50
LC50
LC50
BHC
LC50
LCI 00
LC100
LC50
Result
Jufl/H
22
26
16.6
62
76
29
31
2,700
4.400
3,150
100
100
3,200
22 Tooby fc Durhin, 1975
Macek, et al. 1976
16.6 Macek, et al. 1976
Macek, et al. 1976
Macek, et al. 1976
Macek, et al. 1976
Macek, et al. 1976
Sanders, 1970
Sanders. 1970
3,150 Whit ten & Goodnip.ht, 1966
100 Anonymous, 1960
100 Anonymous, 1960
Bufo woodhousii
-------
Table 7. (Continued)
Organism
Test
Duration
Ettect
Result
(uu/it Beterei.ce
Alpha Hexachlorocyclohexane
Pond snail.
Lymnaea stagnalis
Pond snail.
Lymnaea stagnalis
Pond snail.
Lymnaea stagnalis
Cladoceran
Daphnia magna
DO
1
40 days
40 days
40 days
25 days
EC50 egg production ,
inhibition
EC50 embryonic
development
Reproductive
inhibition
EC50 reproduction
250 Canton & Slooff. 1977
230 Canton ft Slooff. 1977
65 Canton ft Flooff. 1977
100 Canton, et al. 1975
-------
SALTWATER ORGANSMS
Introduction
Hexachlorocyclohexane is an insecticide, primarily consisting
of five configurational isomers, sold under the trade names, BHC
(benzene hexachloride) and Compound-666. Technical grade BHC con-
tains isomers in the following ranges: alpha-isomer, 55 to 70
percent; beta-isomer, 6 to 8 percent; gamma-isomer, 10 to 18 per-
cent; delta-isomer, 3 to 4 percent; and epsilon isomer, trace
amounts. Since the gamma-isomer (lindane, a pesticide) is the
isomer with insecticidal properties and is most toxic to aquatic
organisms, lindane is the most important hexachlorocyclohexane
isomer for which to establish a water quality criterion.
The data base for the toxicity of BHC or lindane to saltwater
organisms includes acute toxicity tests on 13 fish and 8 inverte-
brate species (Tables 8, 9, and 12), toxicity tests on algae
(Table 10), and bioconcentration tests with oysters, shrimp and
fish (Table 11 and 12). No data are available on the chronic
toxicity of hexachlorocyclohexane to any fish or invertebrate
species.
Acute Toxicity
Saltwater fishes have a wide range of sensitivity to l.indane.
Thirteen species of fishes were tested in static and flow-through
exposures. Only two species were tested for 96 hours under flow-
through conditions with measured concentrations. The LC50 values
for the pinfish were 30.6 ug/1 and for sheepshead minnow, 103.9
ug/1 (Schimmel, et al. 1977). The LC50 values for the 11 other
species, after adjusting for test conditions, have a range from
B-20
-------
4.9 to 149.7 ug/1 (Butler, 1963; Eisler, 1970; Katz, 1961; Korn
and Earnest, 1974) indicating considerable variation in species
sensitivity.
Only one test was conducted on a saltwater fish using BHC.
The 96-hour flow-through LC50 with measured concentrations was
86.4 ug/1 for pinfish (Schinunel, et al. 1977). This compares to a
30.6 ug/1 LC50 for the same species under the same conditions for
lindane indicating a lesser toxicity for BHC (Schimmel, et al.
1977). Adjusted LC50 values for 16 freshwater fishes exposed to
lindane, 1 to 83 ug/1 (Table 1), were similar to those of salt-
water fishes.
When the geometric mean of the adjusted LC50 values for lin-
dane is divided by the species sensitivity factor (3.7), a value
of 6.2 ug/1 is obtained. Since this value is close to, but less
than, several of the lowest adjusted LC50 values in Table 8, the
species sensitivity factor seems reasonable. The Final Fish Acute
Value is 6.2 ug/1, a value expected to be equal to or less than
the LC50 value for 95 percent of all saltwater fish species.
The 96-hour LC50 value of BHC to pinfish is the only acute
value, and when it is adjusted for species sensitivity, the Final
Fish Acute Value is 23 ug/1-
Invertebrate LC50 or EC50 values for BHC and lindane range
from 0.13 to 346 ug/1, after adjusting for test conditions (Table
9). With the exception of the American oyster, invertebrate
species are generally more sensitive than are saltwater fishes to
lindane. The commercially important pink shrimp and brown shrimp
are more than one order of magnitude more sensitive than the
B-21
-------
second most sensitive species. The American oyster has an ad-
justed 96-hour EC50 value of 346.5 ug/1 based on decreased shell
deposition (Butler, 1963). This value is over 2,000 times greater
than the value for the most sensitive species, indicating a much
greater tolerance than the other species tested and the need for a
larger species sensitivity factor for invertebrate species than
for fishes. Adjusted LC50 values for 8 freshwater invertebrate
species exposed to lindane ranged from 4 to 745 ug/1 (Table 2),
indicating that they may be slightly less sensitive than saltwater
species.
A single invertebrate LC50 was available for BHC. The LC50
value for pink shrimp of 0.34 ug/1 indicates that BHC is less
toxic than lindane (Schimmel, et al. 1977).
The geometric mean of the adjusted LC50 values for lindane
divided by the species sensitivity factor (49) gives a Final
Invertebrate Acute Value of 0.076 v.g/1, which is about one-half
the lowest value. Since there are data for only 7 species, the
"''"
calculated Final Invertebrate Acute Value of 0.076 ug/1 appears
reasonable and becomes the Final Acute Value for lindane.
The 96-hour LC50 of BHC for the only species tested, pink
shrimp, was 0.34 ug/1. Since this species is exceptionally more
sensitive to lindane than the other invertebrate species, it .would
be unreasonable to divide the single LC50 for the pink shrimp and
BHC by the sensitivity factor. Thus the Final Invertebrate Acute
Value for BHC would be 0.34 ug/1.
B-22
-------
Plant Effects
Only three published studies were found on the effect of
hexachlorocyclohexane on plants (Table 10). The first was con-
cerned with the effects of lindane on the marine alga, Aceta-
bularia mediterranea (Borghi, et al. 1973). Concentrations of
10,000 ug/1 inhibited cell growth and morphogenesis following at
least 3 days exposure. Exposures of 2 days or less showed no ef-
fect on the alga. The growth inhibition that occurred was revers-
ible when the alga was removed from lindane. The growth inhibi-
tion was apparently related to the fact that the alga appeared to
become dormant during exposure.
The second study (Canton, et al. 1977) reported that alpha-
hexachlorocyclohexane showed no toxicity to the marine alga
Chlamydomonas sp., at concentrations up to the solubility limit
for the culture medium.
The third study (Butler, 1963) observed a 28.5 percent de-
crease in productivity of natural phytoplankton communities at a
concentration of 1,000 ug lindane/1.
Residues
The bioconcentration of hexachlorocyclohexane from water into
the tissues of saltwater organisms has been relatively well
studied (Table 11,) . Probable steady-state bioconcentration fac-
tors (BCF's) are available for American oysters and pinfish
(Schimmel, et al. 1977). Additional BCF data (Table 12) probably
are not at steady-state from two-hour exposures of two species of
algae (Canton, et al. 1977) and from 4-day exposures of grass
shrimp, pink shrimp, sheepshead minnow, and pinfish (Schimmel et
al. 1977).
B-23
-------
Compared to many of the chlorinated insecticides, the biocon-
centration factors at steady-state are low. American oysters ex-
posed continuously 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/l» did the insecti-
cide accumulate sufficiently high for accurate measurement. Pin-
fish exposed to BHC for 28 days bioconcentrated in edible tissue
an average of 130 times the amount in water. The average BCF in
offal (head and viscera) was 617. The relative percentages of the
four isomers in BHC were similar to those in pinfish offal and
edible tissues. Apparently, 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. The
Residue Limited Toxicant Concentration is 0.27 ug/1 based on an
average fish BCF of 374 and a FDA limit of 0.1 mg/kg for animal
feed.
Additional data on the bioconcentration of BHC and lindane
are available for other organisms, but it is doubtful that the
concentrations in the organisms, are at steady-state. The average
bioconcentration factors after 4 days of exposure to lindane were
63 for grass shrimp, 84 for pink shrimp, 450 for sheepshead min-
now, and 218 for pinfish (Schimmel, et al. 1977). In the same
study, the average bioconcentration factors after 4 days of expo-
sure to BHC were 80 for pink shrimp and 482 for pinfish. The four
isomers of BHC were bioconcentrated in tissues of pink shrimp and
pinfish in approximately the same relative amounts as in the in-
secticide formulation. Saltwater phytoplankters rapidly accumu-
late and depurate BHC (Canton, et al. 1977).
B-24
-------
Miscellaneous
Other data included in the tables but not yet discussed do
not contribute significantly to the derivation of a criterion for
BHC or lindane.
B-25
-------
CRITERION FORMULATION
Saltwater-Aquatic Life
Summary of Available Data
Lindane
Final Fish Acute Value = 6.2 ug/1
Final Invertebrate Acute Value = 0.076 ug/1
Final Acute Value = 0.076 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = 1,000 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 1,000 ug/1
0.44 x Final Acute Value = 0.033 ug/1
BHC
Final Fish Acute Value = 23 ug/1
Final Invertebrate Acute Value = 0.34 ug/1
Final Acute Value = 0.34 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = not available
Residue Limited Toxicant Concentration = 0.27 ug/1
Final Chronic Value = 0.27 ug/1
0.44 x Final Acute Value = 0.15 ug/1
Lindane
No saltwater criterion can be derived for lindane using the
Guidelines because no Final Chronic Value for either fish or in-
vertebrate species or a good substitute for either value is avail-
able, and there are insufficient data to estimate a criterion
using other procedures.
B-26
-------
BHC
No saltwater criterion can be derived for a mixture of
isomers of BHC using the Guidelines because no Final Chronic Value
for either fish or invertebrate species or a good substitute for
either value is available, and there are insufficient data to
estimate a criterion using other procedures.
B-27
-------
Table 8. Marine fish acute values for hexachlorocyclohexane
Bioassay Test
Organism Mttnod* Cone.**
American eel.
Annul 1 la rostrata
Sheepshead minnow,
Cyprinodon variegatua
Mummichog,
Fundulus heteroclitus
Striped killifish.
Fundulus majalis
Longnose killifish.
Fundulus similis
Atlantic silverside,
? Menidia menidia
to
oo Threespine stickleback,
Gasterosteus aculeatus
Threespine stickleback,
Gasterosteus aculeatus
Striped bass,
Morone saxatilis
Pinfish,
Lat-odon rhomboides
Pinfish,
I.agodon rhomboides
-
Bluehead,
Thalassoma bifasciatum
White mullet,
MuRil curema
Striped mullet.
Muj;il cephalus
S
FT
S
S
FT
S
S
S
FT
FT
FT
S
FT
S
U
M
U .
U
U
U
U
U
U
M
M
U
U
U
Chemical
Time
LCbu
Adjusted
LCbO
Description (hrfi) (uy/1) (»q/i)
***
****
***
***
****
***
****
****
****
*****
****
***
****
***
96
96
96
96
48
96
96
96
96
96
96
96
48
96
56.0
103.9
60.0
28.0
240.
9.0
44.0
50.0
7.3
86.4
30.6
14.0
30.0
66.0
30.6
103.9
32.8
15.3
149.7
4.9
24.1
27.3
5.6
86.4
30.6
7.7
18.7
36.1
heterence
Eisler.
1970
Schimmel,
et al.
1977
Eisler.
1970
Eisler.
1970
Butler,
1963
Eisler.
1970
Katz, 1961
Katz. 1961
Korn &
Earnest,
1974
Schimmel,
et al.
1977
Schimmel,
et al.
1977
Eialer,
1970
Butler.
1963
Eisler.
1970
-------
Table 8. (Continued)
1
I
co
10
Organism
Northern puffer,
Sphaeroides macula CDS
Biodcsay
{Ittflod*
S
Test
Cone .**
U
Chemical
Description
***
Time LCbo
96 35.0
Adjusted
U.'i>o
19.1
hetereuce
Eisler,
1970
* S = static; FT - flow-through
** M " measured; U - unmeasured
*** Entomol. Soc. Am. Reference Standard for Lindane
**** Technical grade Lindane
*****BHC (21% a-BHC. 39% Y-BHC. 2.17. B-BIIC. 23% A-BHC. 14.9% unidentified compounds)
23 0
Geometric mean of adjusted values: lindane » 23.0 ng/1 ~TT7 ** '"^ ^8^
BHC = 86.4 Mg/l ^-j - 23 pg/1
Lowest value from a flow-through test with measured concentrations: lindane - 30.6 pg/1
BUG = 86.4 tig/1
-------
Table 9. Marine invertebrate acute values for hexachlorooyclohexane
Adjusted
to
1
U)
o
Biddssay Test
Qrganiani B£thSd*_ £2Q£j.**
American oyster, FT U
Crassostrea virginica
Mysid. FT M
Mystdopsis bahia
Sand Bhrlrop, S U
Crangon septemapinosa
Hermit crab. S U
Pagurua longtcarpus
Grass ahrimp, FT. M
Paiaemonetes pugio
Grass shrimp, S U
Paiaemonetes vulgaris
Brown shrimp, FT U
Penaeus aztecus
Pink shrimp. FT M
Penaeus duorarum
Pink shrimp, ' FT M
Penaeus duorarum
Chemical Time LCbu LCL.O
Description (In a) (uii/l| (ug/1) Keterence
*** 96 450****** 346.5 Butler,
, 1963
*** ' 96 6.28 6.28 Schimmel,
et al.
1977
**** 96 5.0 4.2 Eisier,
1969
**** 96 5.0 4.2 Elsler.
1969
*** 96 4.44 4.44 Schimmel,
et al.
1977
**** 96 10.0 8.5 Elsler.
1969
*** 48 o.4****** 0.13 Butler,
1963
*** 96 0.17 0.17 Schimmel.
et al.
1977
***** 96 0.34 0.34 Schiramel,
et al.
1977
* S = static; FT - flow-through
** M = measured; U - unmeasured
*..-* Technical grade lindane (100% y-BllC)
**** Entomol. Soc. Am. Reference Standard for Lindane
***** BIIC (212 a-BHC, 39% y-BHC, 2.1% fl-BHC. 23% 4-BIIC, 14.9% unidentified compounds)
******EC50: decreased shell growth In oysters or loss of equilibrium in pink shrimp.
Geometric mean of adjusted values: lindane - 3.7 Mg/1 jrn = 0.076 Mg/1
- « 0.0069 Mg/1
BIIC = 0.34 Mg/1
Lowest value from a flow-through test with, measured concentrations: lindane - 0.17 Mg/1
BIIC = 0.34 i.g/1
-------
Table 10. Marine plant effects for hexachlorocyclohexane
Organism
Effect
Concentration
(uq/41
Natural phytoplankton 28.57. decrease 1,000*
communities in productivity.
ftef erfcnce
Butler, 1963
Alga,
Acetabularia
medi terranea
Alga.
Chlamydomonaa sp.
Inhibition of 10,000*
cell growth and
cell morphogenesis,
reversible.
No effect in Solubility
short term limit**
toxicity (45 hr)
Borghi. et al. 1973
Canton, et al. 1977
CD
I
LO
* Lindane
**u-BHC
Lowest plant value for lindane - 1.000 Mg/1
-------
Table 11. Marine residues for hexachlorocyclohexane (Schimmel. et al. 1977)
(days)
American oyster,
Crassostrea virginica
Pinfish.
Lagodon rhombotdes
Pinfish.
Lagodon rhomboides
Bioconcentration Factor
218* 28
130*. ** 28
617*, *** 28
Maximum Permissible Tissue Concent:ration
CO
1
u>
N9
Organs iro
Domestic animals
Man
Domestic animals
Action Level or Effect
Animal feed
Frog legs (meat only)
Animal feed
Concentration
(mg/kg)
0 . 1****
0 . 5*****
0 . i*****
Reference
U.S. FDA Admin. .
Guideline 7426.04
U.S. FDA Admin. .
Guideline 7420.08
U.S. FDA Admin . .
Guideline 7426.04
* Technical grade BHC (21% a-BHC, 39% Y-BHC, 2.1% 0-BHC. 23% A-BHC, 14.9% unidentified compounds)
** Edible tissue
*** Offal tissue
**** Lindane
***** BUC
Average fish bioconcentration factor for BHC = 374. .
Lowest residue concentration for BHC - 0.1 mg/kg
°'1 - 0.00027 mg/kg or 0.27 ug/1
-------
Table 12. Other marine data for hexachlorocyclohexane
03
Organism
Alga.
Chlamydomonas
Alga.
Chlamydomonaa
Alga.
Dunaliella
Grass shrimp,
Palaemonetes pugio
Brown shrimp,
Penaeus aztecus
Pink shrimp,
Penaeus duorarum
Pink' shrimp.
Penaeus duorarum
White and brown shrimp
Penaeus setiferus
Penaeus aztecus
Sheepshead minnow,
Cyprinodon variegatua
Pinfish,
LaKodon rhomboides
Pinfish,
LuKodon rhomboides
Test
Duration Ettect
2 hrs
2 hrs
2 hrs
4 days
24 hrs
4 days
4 days
.24 hrs
4 days
4 days
4 days
f*310
f*2700
f*1500
Bioconcentration
factor » 63
LC50
Bioconcentration
factor = 84
Bioconcentration
factor = 80
LC50
Bioconcentration
factor = 490
Bioconcentration
factor = 218
Bioconcentration
factor = 482
Result
-------
HEXACHLOROCYCLOHEXANE
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B-34
-------
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B-35
-------
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B-36
-------
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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 insecticides to tubificids. Jour. Water Pollut.
Control Fed. 38: 227.
B-3 7
-------
Mammalian Toxicology and Human Health Effects
Introduction
Hexachlorocyclohexane (HCH) was first synthesized in
1825 by Faraday. The insect icidal 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 hexachlor ide) . This
is obviously a misnomer since HCH is a saturated chlorinated
hydrocarbon and, therefore, has no aromaticity. The common
"misname", BHC, probably came from the original method of
preparation of HCH, i.e., the chlorination of benzene.
4-
3C1
..
Radiation
HCH
This preparation method yields technical grade HCH which \
is a mixture of the five basic isomers (see Figure 1) .
The composition of technical HCH is approximately as follows
I some r
alpha
beta
gamma
delta
epsilor
( <* )
( ^ )
( V )
( S )
i ( )
Percent
60-70
5-12
10-15
6-10
3-4
The gamma isomer ( "jf -HCH) has the lowest melting point
(112. 8°C) and the highest acute toxicity and is commonly
called lindane.
C-l
-------
O
O
a
B
Y
5
c
r
A
e
Vi In loctin. BHC
60-70
5-12
10-15
6-10
3- 4
e
a.
a
i
157.5-158.5
309
112.8
138-139
218,8
68 * 88
89.8- S0.5
124-125
io
O
if
0.02
O.C05
0.03
0.02
3
222:
0
Z8:
3,6
2,2:
(2.17:
2.32)
0
Roliucllon Index
nOZO
1,60 -1,626
1,630
1,60 -1.635
1,576-1.674
1,00 -1,635
£ 2
?1 s-
£0 =
1| f
$§ u
1253 ^z;
1
1
1346 -~Zr
1322 ^
T7
1131 ^
1396 7*
i '
u
~f^- monoclinic
"^T" prisms
^ * i cubic
^1^ (octahedral)
^-s.;:-^ monoclinic
^^ crystals
^, i crystals or
^/^ * fing
1 platelets
^ ^e.}- monoclinic
"^p needles or
hexagonal
monoclinic
crystals
Figure 1. Comparison of the Physical Constants
of Lindane and some of the other BHC Isomers
(Ulmann, 1972)
Lindane, named after the Belgian chemist, van der Linden,
has been marketed under a number of trade names as an insecti-
cide including the following registered trademarks:
Jacutin
Lindafor 90
Lindamul 20
Nexit-Staub
Prodactic
(emulsifiable concentrate)
(wettable powder)
(emulsifiable concentrate)
(0.8 percent dust)
(wettable powder)
Other names for #-HCH include Y-BHC, TT-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 literature. In this docu-
ment, HCH will be used,as an abbreviation for hexachlorocyclo-
C-2
-------
hexane and its synonyms. However, the various isomers will
be designated by the appropriate Greek letter. Lindane
will be referred to as 2T-HCH. The technical product will
be t-HCH.
The major commercial usage of HCH is based upon its
insecticidal properties. As indicated previously, the - "8*
isomer has the highest acute toxicity, but the other isomers
are not without activity. It is generally advantageous
to purify the o-isomer from the less active isomers. The
7f -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 mosqui-
toes, 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 princi-
pally from two sources:
(1) direct application of 2f-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 pollution of HCH occasionally occurs
during its manufacture. HCH-containing waste water can
be generated during the synthesis, crystallization, 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 insec-
ticides, such as DDT, endrin, aldrin, heptachlor, etc.,
due to HCH's high water solubility. Solubility of "if-HCH
is 7.3 ppm at 25°C, 12 ppm at 35°C and 14 ppm at 45°C (Gunther,
et al. 1968). However, the different HCH isomers exhibit
different solubilities at a constant temperature, e.g.,
Sol, e ?0°C Vapor Pressure
alpha 10 ppm 0.06 torr
beta 5 ppm 0.17 torr
gamma 10 ppm 0.14 torr
Jf-HCH has been detected in the finished water of Streator,
Illinois at 4 jug/liter (U.S. EPA, 1975). 2f-HCH has a low
residence time in the aquatic environment and the principal
routes by which 7f~HCH disappears are sedimentation, metabo-
C-4
-------
lism, and volatilization. ^-HCH is generally found to
contribute less to aquatic pollution than the other HCH
isomers (Henderson, et al. 1971).
Ingestion from Foods
Duggan and Duggan (1973) tabulated the human daily
intake for ^-HCH and other HCH isomers. For ^-HCH the
daily intake was 1 to 5 jjg/kg body weight/day and was 1
to 3 jug/kg/day for all other isomers of HCH. Assuming a
70-year lifespan for a 70 kg man, his lifetime ingestion
would be 1.8 to 8.9 grams of tf-HCH, and 1.8 to 5.4 grams
of all other isomers of HCH. Engst, et al. (1976) in a
study of German citizens, determined that a male of 65 kg
would consume 0.25 mg of ^-HCH in 70 years. Reasons for
the large difference in the two investigations are apparently
due to exposure and consumption of fish products.
The chief sources of HCH residues in the human diet
are milk, eggs, and other dairy products. Seafood as a
source of HCH for humans is usually minor, which may be
attributed to the relatively high rate of dissipation of
HCH in the aquatic environment. ^-HCH and other HCH isomer
residues have generally been of low order of magnitude.
A bioconcentration factor (BCF) relates the concentration
of a chemical in water to the concentration in aquatic orga-
nisms, but BCF's are not available for the edible portions
of all four major groups of aquatic organisms consumed in
the United States. Since data indicate that the BCF for
lipid-soluble compounds is proportional to percent lipids,
BCF's can be adjusted to edible portions using data on percent
C-5
-------
lipids and the amounts of various species consumed by Americans,
A recent survey on fish and shellfish consumption in the
United States (Cordle, et al. 1978) found that the per capita
consumption is 18.7 g/day. From the data on the nineteen
major species identified in the survey and data on the fat
content of the edible portion of these species (Sidwell,
et al. 19.74) , the relative consumption of the four major
groups and the weighted average percent lipids for each
group can be calculated:
Consumption Weighted Average
Group (Percent) Percent Lipids
Freshwater fishes 12 4.8
Saltwater fishes 61 2.3
Saltwater molluscs 9 1.2
Saltwater decapods 18 1.2
Using the percentages for consumption and lipids for each
of these groups, the weighted average percent lipids is
2.3 for consumed fish and shellfish.
A measured steady-state bioconcentration factor of
340 was obtained for lindane using bluegills containing
about one percent lipids (Hamelink and Waybrant, 1976).
An adjustment factor of 2.3/1.0 = 2.3 can be used to adjust
the measured BCF from the 1.0 percent lipids of the bluegill
to the 2.3 percent lipids that is the weighted average for
consumed fish and shellfish. Thus, the weighted average
bioconcentration factor for lindane and the edible portion
of all aquatic organisms consumed by Americans is calculated
to be 340 x 2.3 = 780.
C-6
-------
Inhalation
Little is known about the concentration and distribution
of tf-HCH in the atmosphere. Abbott, et al. (1966) found
only traces of HCH in air in central and suburban London.
According to an investigation by Barney (1969) the 7f-HCH
intake by inhalation is 0.002 jug/kg/day, while the FAO/WHO
A.D.I, limit is 1 jug/kg/day (Natl. Acad. Sci., 1977). Hesse,
et al. (1976) showed that short term inhalation of HCH
by men did not lead to a significant increase of the compound
in the blood and urine and had no influence on serum enzymes
either immediately or within 21 to 24 days after exposure.
Voitenko (1978) described a synergistic action for 2T-HCH
administered through both the gastrointestinal (1.5 mg/kg/day)
and respi-ratory (0.84 mg/m ) tracts for four months in
albino rats.
Dermal
7f-HCH has been used in human and veterinary dermatology
against ectoparasites for more than 25 years. Many publica-
tions express good dermal tolerance and there is little
mention of adverse skin reaction. In a few cases, dermal
reactions after contact with #"-HCH preparations have been
described as local irritation and an occasional case of
eczema has been described. The adverse experiences with .^
man have usually been with concentrated liquid formulations.
All these reactions healed after scab formation.
PHARMACOKINETICS
Absorption
The rapidity of V-HCH absorption is enhanced by lipid
mediated carriers. For an organochlorine insecticide, lindane
is unusually soluble in water, another factor contributing
C-7
-------
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 rag administered orally, only 0.1 to 4 jug Tf-HCH was
found in the urine, representing 0.005 to 0.2 percent of
intact $ -HCH. However, 2 to 5 percent of the original
Tf* -HCH was found in the feces (Chadwick, 1971; Chadwick,
1979) . It can be concluded from these data that 2T-HCH
is not generally excreted in the urine but is in the feces.
Excretion from the feces comprises only a small percentage
of the original orally administered dose.
An oil solution containing 40 mg 2T-HCH per kg body
weight was injected intraperitonally to rats, resulting
in 35 percent absorption. At the end of,a 24 hour period,
10 percent of the original amount still remained in the
abdominal cavity (Koransky, et al. 1963). Low lindane levels
in the intestinal wall indicated a very rapid absorption
process.
Ginsburg, et al. (1977) studied the dermal absorption
of lindane in infants and children. Twelve children with
infection caused by Sarcoptes scabiei and eight non-infected
siblings for whom prophylactic tf*-HCH had been prescribed
were included in the investigation. Blood specimens were
obtained at 2, 4, 6, 8, 12, 24, and 48 hours after the topical
application of one percent Zf-HCH lotion. b^-HCH was detected
in the blood at all times,- with peak concentration noticed
six hours after application. An absorption half-life of
17.9 hours in the blood of infected children was recorded
C-8
-------
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
has reached detectable levels in the brain,
liver, skin, and musculature of mice in as little as three
hours after administration (van Asperen, 1958). Carbon-
14 tagged "2^-HCH administered to rats intraperitoneally
in a dose of 14 mg/kg body weight was noticed very quickly
in the fatty tissues. At least 75 percent of the labeled
"£* -HCH was consistently found in the skin, muscle, and
fatty tissue (Koransky, et al. 1963) . Another experiment
14
utilizing C labeled HCH isomers revealed a uniform distribu-
tion in adipose tissue throughout the body of mice (Nakajima,
et al. 1970). On the other hand, concentration of 0-HCH
in the brain at a level higher than other organs is supported
in the literature (Laug, 1943; Davidou and Frawley, 1951;
Koransky, et al. 1963; Huntingdon, 1971) .
A 17 mg/kg body weight dose of lindane in rape oil
given orally to calves showed a 0.62 ppm blood level after
three hours, 2.0 ppm after 24 hours and 0.124 ppm after
seven days. Only barely detectable levels were found at
three and six weeks subsequent to application (Kadis and
Jonasson, 1965) .
0 -HCH has also been noted to enter the fetus through
the placenta. Residue levels of various pesticides, includ-
ing lindane, were found in the fatty tissue of pregnant
women and in the vernix careosa of their newborn babies.
In some women with a normal course of pregnancy, pesticide
C-9
-------
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 detectable
levels of
-------
and Chadwick, 1973; Chadwick and Freal, 1972). These metabo-
lites have been found in the blood, liver, kidneys, spleen,
heart, and brain of rats fed 0-HCH, but were not detected
in the intestine or feces (Engst, et al. 1976) . Freal and
Chadwick (1973) originally suggested 2f-HCH is metabolized
in the rat to a series of metabolites ranging from pentachloro-
cyclohexenes to trichlorobenzenes and resulting in chlorophe-
nols. Chadwick, et al. (1975) later demonstrated that tf'-HCH
undergoes metabolism to an intermediate hexachlorocyclo-
hexene, from which further degradation yields PCCOL, two
tetrachlorophenols and three trichlorophenols. This metabolic
pathway was not observed for the other hexachlorocyclohexane
isomers. Freal and Chadwick (1973) also noted an enhanced
metabolism of 2T-HCH upon pretreatment with the other BHC
isomers. This enhancement decreased in the order of alpha-
delta-gamma-beta. DDT, mirex, chlordane, and HCB also stimu-
late the metabolism of Zf-HCH significantly (Chadwick, et
al. 1977a). The preapplication of K -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 O-HCH metabolism. Three days after
exposure to 14 7S-HCH, the control rats excreted significant-
ly more radioactivity than the Cd-treated groups. Cd-exposure
altered the distribution of neutral and polar
0 -HCH metabolites, as well as inhibiting the dehydrogenation
of V-HCK to hexachlorocyclohexene (Chadwick, et al. 1978).
The administration of dimethyl sulfoxide with 5-HCH
to female rats led to impaired o-HCH metabolism and lowered
C-ll
-------
specific microsomal phospholipid content indicated some
interaction between tf'-HCH, dimethyl sulfoxide, and dietary
lipids (Chadwick, et al. 1977b).
Dietary fibers are known to have protective effects
against a variety of chemical toxicants through metabolic
alterations. Chadwick, et al. (1977c) demonstrated that
rats fed diets supplemented with fiber showed a higher dehy-
drogenation and dechlorination of 2T-HCH and suggests a sub-
stantial alteration in the excretion and metabolism of
O -HCH and its metabolites in mammals.
Trichlorophenols also result from the metabolism of
isomers other than ^-HCH, although it seems that tetra-
chlorophenols are not produced. The excretion of mercapturic
acid conjugates has also been noted (Kurihara, 1977). Using
rat liver preparation, Portig, et al. (1973) detected the
direct glutathione dependent conversion of °*--HCH. Eliminated
products of HCH metabolism, both free and conjugated chloro-
phenols, are far less toxic, however, than the parent compounds
(Natl. Acad. Sci., 1977). A recent proposed degradation
scheme is shown in Figure 2 (Chadwick, 1978, in press).
Excretion
Continual administration of' Tf-HCH to an organism will
lead to an equilibrium concentration and stabilization.
This equilibrium concentration occurs as continuing intake
is offset by degradation and elimination of the y~HCH.
Kitamura, et al. (1970) has investigated the rate of
elimination of y*-HCH as compared to v^-HCH. Figure 3 shows
that ^-HCH is excreted at a much slower rate. Since the
pure r-isomer seems to persist in the body, there is justifi-
C-12
-------
R a-CH2CHCOOHNHCOCH3
B-S. , Q US* , CJ B-S
14.5-TC?
Figure 2. Metabolism of Lindane.
C-13
-------
<0 days
Figure 3. Reduction of HCH concentration in the total mouse
body, excluding the skin and the digestive tract, after
a single oral dose of 500 meg 2T-HCH and 500 meg ^
(Kitamura, et al. 1970)
C-14
-------
cation for the use of only the pure form of the 2^-isomer
in situations that might lead to absorption. The rapid
biological deterioration of £"-HCH is self-induced and mini-
mizes the health hazards presented by hexachlorocyclohexanes
(Sieper, 1972; Chadwick, et al. 1971; Chadwick and Fr'eal,
1972).
Even prolonged 2T-HCH administration results in complete
elimination when application has been terminated. In one
experiment a £f-HCH concentration in rat fatty tissues of
102 ppm was achieved. One week subsequent to cessation
of administration, the concentration had dropped to zero.
Similar results were obtained when it was found that 281
ppm fatty tissue was eliminated within two weeks (Frawley
and Fitzhugh, 1949; Lehman, 1952). After rats were fed
100 ppm of O -HCH over a ten day period, it was found that
three days following discontinuation of treatment quantities
in the body had diminished to 0.1 ppm. Similarly, 24 hours
after cessation of feeding rats 10 ppm cT-HCH for 20 days,
no residue could be detected using gas chromatography with
an electron capture detector (Kitamura, et al. 1970).
Only very slight amounts of unaltered "2T-HCH are excreted.
Dietary intake by rats for one month revealed only about
four percent in the urine at the end of feeding period (Laug.,
1948). No excretory traces of unchanged lindane have been
noticed with intraperitoneal injections. The main excretory
products in urine are water soluble conjugates of glucuronide,
mercapturic acid, conjugates, and sulfate. Single oral
administrations to rats of 50 to 100 mg lindane per kg body
weight resulted in 1.5 mg per day increase of urinary glu-
C-15
-------
curonic 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 secretions. It commonly exists in low concen-
trations in human milk. Usually the ^-isomer accounts
for 90 percent of the HCH present. The o< and *& isomers
account for the remaining 10 percent (Herbst and Bodenstein, 1972).
EFFECTS
Acute, Sub-acute, and Chronic Toxicity
Of the various isomers of HCH, o exhibits the greatest
acute toxicity to mammalian organisms. This toxicity varies
with the species subject. Toxicity also varies with route
of administration which in turn controls absorption. Intrave-
nous administration produces the most severe injury, followed
by intraperitoneal, subcutaneous, oral and dermal exposure
(Shirakowa, 1958) . As a general rule, formulations of HCH
in oil and fat induce a higher toxicity than most, while
the least toxic form is the pure crystalline'chemical.
Toxicity variations 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 "&*-HCH than adults of
the same species (Shirakowa, 1959; Radaleff and Bushland,
1960) . The increased sen'sitivity of young mammals to intoxi-
cation, at least to the age of weaning, is a result of low
C-16
-------
production of liver enzymes affecting detoxification at
an early age (Pouts and Adamson, 1959). Diseased and dis-
tressed animals show a similar pattern (Chen, 1968).
"^-HCH has a higher acute toxicity than many other chlorinated
hydrocarbons since absorption is rapid, and visible clinical
symptoms are quickly revealed (Lehman, 1951). Rapid uptake
as well as a higher water solubility account for the narrow
range between lowest toxic and lethal doses of #*-HCH relative
to similar compounds like DDT (Gunther, et al. 1968; Martin, 1971).
A case of acute poisoning with $" -HCH in a 42-year-
old male worker revealed an array of symptoms: depression,
headache, emesis, asthemia, epileptiform attacks, sleepless-
ness, profuse perspiration, 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. The blood
contained £-HCH between 0.1 and 0.5 ppm, and the cerebro-
spinal fluid contained 0.2 ppm £"-HCH several weeks after
poisoning. This patient was therapeutically treated with
barbituates, sedatives, glucose, and vitamins C and B12,
which elicited a favorable response (Pernov and Kyurkchiyev,
1974) .
Another case describes a 35-year-old man who ingested
O -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, myoglobinuria, acute renal failure and anemia
were also experienced. Pancreatitis developed on the 13th
day after ingestion, and on the 15th day, a muscle biopsy
C-17
-------
revealed widespread necrosis and muscle fiber regeneration.
Characteristic symptoms which occurred during the year follow-
ing exposure included recent memory loss, loss of libido/
and easy fatigability (Munk and Nantel, 1977). Topical
application of o -HCH in a child caused irritability and
hyperactivity (Wheeler, 1977). Subsequent accidental oral
administration of ^T-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 £ -HCH poisoning in man by oral intake are shown in
Table 1.
Alterations in liver function are also significant
toxicological effects of HCH. Rats fed both the Js and
$* isomers showed an increase in alanine aminotransferase,
and a decrease in aspartate aminotranferase, alkaline phos-
phatase, and acid phosphatase (Srinivasan and Radhakrishnamurty,
1977). After short-term oral administration of ^"-HCH to
rats, (5 to 20 mg/kg), an increase in the ascorbic acid
in the urine and blood serum was noted. Electron microscopy
revealed an increase in smooth endoplasmic reticulum in
liver hepatocytes of the intermediary zone. Free ribosomal
increase was probably related to the intensified formation
of microsomal protein. Individual cell glycogen content
was also observed and explained by increased glucuronic
and ascorbic acid syntheses (Herbst, et al. 1974) . Histo-
chemical studies, following daily administration of 7.5 mg
C-18
-------
Table 1
Accidental acute tf"-HCH poisoning in man
(oral intake)
Panon«
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
?
(?) ca. 30
ca. 50-1 20
ca. 6- 80
up to 65
?
?
?
?
?
?
7
?
?
?
?
?
? '
1 X48-
4x?
152
?
Fatal
casea
3
4
4
2
1
1
1
1
1
Formulation
Involved
50 % WP
20 °/o EC
crystalline in coffee
*highgradeBHC(?)
(p.o. -f p.c. T inhal.)
dust formulation
smoke sticks
smoke sticks
smoke sticks
in alcohol
smoke sticks
smoke tablets
20 % EC
Vs smoke tablet
10°/oor20%EC
powder in pudding
vermicide tablets
smoke tablet
?
4-5 smoke tablets
V: smoke tablet
*1xinhalation, 4xp.o.
7
?
crystalline, dust
smoke tablets
Remark!
7 survived on therapy
j
survived on therapy i
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
C-19
-------
of the zT-isomer to albino rats revealed disturbances in
the carbohydrate metabolism activation lytic processes (Shilina,
1973). High concentrations of the ^-isomers have been
detected in humans with various liver diseases. 7$"-HCH
may also modify the metabolism of drugs in the liver (Vrochinskii,
et al. 1976) .
Dikshith, et al. (1978) gave daily dermal applications
of HCH in 100, 200, and 500 mg/kg doses for 30 days. No
mortality occurred in response to the 100 mg/kg/day, but
significant pathologic and biochemical changes occurred
in the vital organs. Massive congestion and thickened blood
vessels were seen in the liver of the 100 mg HCH treated
animals as compared to the controls. Biochemically, the
activity of glutamic oxaloacetic transaminase, glutamic
pyruvic transaminase and alkaline phosphatase in the liver
and serum revealed significant changes from that of the
controls. All animals exposed to the high doses (200 and
500 mg) died within 5 to 12 days.
Hexicid (1 percent tf"-HCH) is highly effective in the
treatment of scabies. Toxic side effects with irritation
of the central nervous system have been reported after im-
proper or prolonged use (Lee, et al. 1976). Side effects
have included nausea, vomiting, spasms, weak respiration
with cyanosis and blood dyscrasia. The absorption of TT-HCH
has been shown to be in the order man< pig< rat< rabbit
and the permeability characteristics of pig skin were closest
to that of man (Bartek and LaBudde, 1975).
C-20
-------
Extensive data regarding the chronic toxicity of
O -HCH to rats were revealed by several investigators in
the early 1950's (Fitzhugh, et al. 1950; Lehman, 1952a,b).
These studies involved the administration of 7T-HCH in the
crystalline form at 0, 10, 100, and 800 ppm, and as an oil
solution at 0, 5, 10, 50, 100, 400, 800, and 1600 ppm.
No clinical or pathological changes were detected at levels
of 400 ppm or lower; however, liver weight increase was
noticed at 100 ppm, 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 concentrations of 400, 800, and 1600
ppm decreased lifespan by 20 to 40 percent, although a concen-
tration of 800 ppm crystalline form did not yield similar
effects.
Inhaled administration of 2f-HCH to rats with varying
exposure times resulted in little or no organ alterations.
Inhalations of 0.78 mg/m for seven hours, five days a week
for 180 days did show some liver cell enlargement although
no clinical symptoms were noticed. Rats exposed to three
percent o -HCH dust for seven hours a day, five times a
week for 218 days revealed some doubtful liver and kidney
changes in two of 20 animals exposed (Heyroth, 1952). In
1954, the United States and most western countries, as a
result of these and other inhalation experiments, established
a maximum allowable concentration of 0.5 mg/m (Ball, 1956).
C-21
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The addition of y~HCH at 10 ppm 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 increased ascorbic acid levels in
the urine along with variable modification of the content
in the blood were noted. Ascorbic acid was decreased in
both the liver and adrenals (Petrescu, et al. 1974). Experi-
mental data regarding the toxicity of various isomers of
HCH are shown in Table 2.
Male and female beagle dogs were fed ^f-HCH in the
diet at concentrations of 25, 50, and 100 for 104 weeks.
Friable and slightly enlarged livers were noted at 100 ppm,
but no histopathological changes were noticed. The negative
findings at 50 ppm 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 disturbances of carbohydrate and lipid metabo-
lism. 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.
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TABLE 2
Toxicity of HCH Isomers
Chemical Form and Duration
Animal Species of Study
Rat
t-HCH
t-HCH,
f -HCH
X-HCH
tf-HCH
4 -HCH
7" -HCH
-------
A study involving 59 females and 29 males with occupa-
tional 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 percent being chronic pancreatitis.
Some form of biochemical abnormality was noted in 60 percent
of all cases (Sasinovich, et al. 1974).
Synergism and/or Antagonism
The daily pretreatment of beagle dogs with phenobarbital
for 60 days prior to the administration of "ZT-HCH brought
about a reduction of Tf-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 "^-KGB/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 7^-HCH. As compared with
the control group, the brains of the phenobarbital pretreated
group contained a much smaller amount of the total 2T-HCH
administered. It seems that phenobarbital pretreatment
leads to decreased convulsion effect of 2T-HCH (Litterst
and Miller, 1975).
Various substances have been found to have antagonistic
effects on "6"-HCH poisoning and offer potential as treatment
or antidotes. The administration of silymarin to 2T-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
C-24
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for a three month period resulted in disruption of lipid
metabolism and a decreased serum cholesterol/lecithin ratio.
However, methionine, galascorbin, and vitamin B12, individ-
ually 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 ^f-HCH has revealed
a reduction in the teratogenic effect of some compounds.
Preliminary treatment weakened the teratogenic and embryo-
toxic action of the carbamate insecticide given in a dose
of 400 mg/kg and of sodium acetylsalicylate administered
in a dose of 400 mg/kg (Shtenberg and Torchinskii, 1977).
The chlorination of water containing various organochlo-
rine pesticides, including HCH, decreases the LD50 level
of mice and rats by conversion of the compounds to more
toxic products. This effect was determined by changes in
blood erythrocytes, enzymes, and -SH levels, disruption
of protein synthesis by the liver, and a decreased rate
of weight gain (Shtannikov, et al. 1977) .
"ZJf-HCH has also showed to be synergistic or antagonistic
with other substances. The sensitivity of mice to pentylene-
tetrazol at concentrations of 1, 3, 4, 6, and 12 mg/kg
body weight was increased by pretreatment of 2T-HCH at 10,
7.5, 5, 2.5, and 1.2 mg/kg body weight. The results showed
a significantly higher frequency of convulsions than expected
from pentylenetetrazol alone. Therefore, the convulsive
dose threshold is lowered by small, single oral doses of
2T-HCH in the mouse (Hulth, et al. 1976). S"-HCH administered
C-25
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in sublethal doses to rabbits resulted in immunosoppression
of antibody formation in response to Salmonella typhi injec-
tions (Desi, 1976).
The toxic effects of ZT-HCH have also been antagonized
by various tranquilizers (Ulmann, 1972).
Teratogenicity
A study regarding the potential teratogenic effects
of tf-HCH involved the p.o. administration in a vegetable
oil solution in 4 groups of rats. Groups 1 through 3 were
fed 25 mg. if-HCH/kg body weight/day while Group 4 was fed
12 mg "jf-HCH/kg body weight/day. Group numbers 1 and 4
received 7f-HCH throughout pregnancy (days 1 to 20), while
Group 2 received lindane throughout placentation and orogenesis
(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 experimental 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 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
C-26
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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 F2 and F3 generations. These results are indicative
of altered sexual maturation and function and suggest that
exposure to lindane during pregnancy causes reduced repro-
ductive capacity in parents and subsequent generations.
An increase in the proportion of stillbirths with succeeding
generations of lindane-fed animals was also noted in this
study:
Generation Number of Stillbirths
Control 5, 10, 15 mg/kg
F1 0/50 1/104
F2 1/45 25/64
F3 0/56 3/6
In addition, F, and F2 animals of the lindane-fed group
exhibited spastic paraplegia, 17/119 and 7/52, respectively.
Mutagenicity
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 LD50) and later mated with females during a seven
day period. No mutations or reproductive effects were noted
(cited in U.S. EPA, 1973). Mutagenic rates too low to be
considered positive were found in host-mediated testing
(Buselmair, et al. 1973). Some alterations in mitotic activity
C-27
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and the karyotype of human lymphocytes cultivated in vitro
with o -HCH at concentrations between 0.1 and 10.0 mg/ml
have been reported by Tsoneva-Maneva, et al. (1971).
Carcinogenicity
Experimentation with #-HCH in the early 1950's yielded
little or no data in support of carcinogenic activity.
Accumulation of epidemiological data (Hans, 1976), however,
initiated more recent 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 revealed acute
leukemia which apparently was associated with occupational
exposure to the insecticides HCH and DDT. It was believed
that the 44-year-old patient had inhaled the chemicals for
eight years of his employment, never having worn protective
face masking. The diagnosis on autopsy was acute leukemia
with hypoplastic marrow and hemosiderosis. The author specu-
lates that the absorption of DDT and t-HCH via the alveoli
led to aplastic anemia, which was then probably transformed
into leukemia (Hoshizaki, et al. 1970).
When y~HCH was administered orally at 800 ppm and
more to rats tumor incidence was not greater than controls,
although average life spans were reduced (Fitzhugh, et al.
1950). It is important to note, however, that all organs
were not microscopically examined. Truhant (1954) supported
these findings by feeding diets containing 2T-HCH at 25,
C-28
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50, or 100 ppm 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 660 ppm dietary t-
HCH for 24 weeks. 66.0 and 6.6 ppm did not induce tumors
but did increase liver weights. The 66.0 ppm dietary level
also revealed some cellular hyperplasia. Excessive amounts
of <* and ^9-HCH accumulated in the liver at the 660 ppm
level. ~y and
-------
Multiple nodules were found in the liver, although no perito-
neal invasion or distinct metastasis was found. The -G-
isomer-treated animals had no tumors.
Goto, et al. (1972) reported on feeding eight groups
of five-week-old male mice of the ICR-JCL strain diets con-
taining 600 ppm of the following compounds: Group 1, t-HCH;
Group 2, ^--HCH; Group 3, #-HCH; Group 4, ^-HCH; Group
5, a mixture of O -HCH and 6-HCH; Group 6, 1,2,4-tr ichloro-
benzene; Group 7, 2,3,5-trichlorophenol; Group 8, 2,4,5-
trichlorophenol. A 9th group received 300 ppm 2T-HCH.
After 26 weeks, no increase in weight of the heart, liver,
and kidneys was noticed for Groups 6 to 9; however, a marked
increase in liver weight was noticed in mice of Groups 1
to 5.
Macroscopic examination of the livers revealed 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 offer support that
t-HCH and «<-HCH frequently cause malignant liver tumors
in mice subjected to oral administration of high doses (600.
ppm) for six months. The same experimental conditions involv-
ing £ -HCH or "3"-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
-------
of cytoplasmic endoplasmic reticulum as well as nuclear
and mitochondrial changes were noticed in the region of
hepatocellular carcinomas.
The feeding of mice 500 ppm «* -HCH for a 24-week period
resulted in nodular hyperplasias of the liver (Sugihara,
et al. 1975). These nodules began to disappear after discon-
tinuation of the compound, but after 24 more weeks, hepatocar-
cinomas developed. 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 discontinuation, active phagocytotic processes
appeared between nodular cells. Although the number of
nodular cells decreased after cessation of poisoning, the
ones remaining after 12 weeks showed tumorous growth. Appar-
ently, the remaining nodular cells are responsible for the
development of the hepatocellular carcinomas (Sugihara,
et al. 1975).
Some contradiction appears in the literature with respect
to the carcinogenic action of the "^"-HCH isomer. Thorpe
and Walker (1973) noticed tumorigenic action caused by the
#*-isomer in the CF1 strain mice. However, the dose admin-
istered in this experiment of 400 ppm "S"-HCH may be higher
than the maximum tolerated dose. Associated liver enlarge-
ment and hepatomas may have also resulted from non-specific
toxic effects, since only 3 percent of the females and 17
percent of the males fed tf-HCK survived the duration of
the experiment. Additionally, the administered dose was
70 percent of the acute oral LD5Q.
C-31
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The National Cancer Institute conducted a bioassay
for the possible carcinogenicity of 2T-HCH to Osborne-Mendel
rats and B6C3F1 mice. Administration continued for 80 weeks
at 2 dose levels: time-weighted average dose for male rats
was 236 and 472 ppm; for female rats, 135 and 270 ppm; and
for all mice, 80 and 160 ppm. No statistically significant
incidence of tumor occurrence was noted in any of the experi-
mental rats as compared to the controls. At the lower dose
concentration in male mice, the incidence of hepatocellular
carcinoma was significant when compared to the controls,
but not significant in the higher dose males. "Thus, the
incidence of hepatocellular carcinoma in male mice cannot
clearly be related to treatment." The incidence of hepato-
cellular carcinoma among female mice was not significant.
Consequently, the carcinogenic activity of 'S'-HCH in mice
is questionable (Natl. Cancer Inst., 1977).
Experiments by Nagasaki, et al. (1972a,b) with other
strains produced negative results. According to Miura,
et al. (1974), the toxicity of t-HCH and HCH isomers varies
significantly among different strains of mice, with the
CFl strain being particularly susceptible. Feeding 500
mice of the Chbi:NMRI(SPF) strain 2*-HCH at levels of 12.5,
25, and 50 ppm in the food for 80 weeks revealed no compound-
induced lymphatic leukemia, no malignant hemangioendotheliomas,
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 o -HCH-induced
fine structural hepatocellular alterations (Weisse and Herbst,
1977) .
C-32
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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 ** -HCH isomer was administered at 500, 1000,
and 1500 ppm, ^-HCH at 500 and 1000 ppm, TT-HCH at 500
ppm and cf -HCH at 500 and 1000 ppm. The 500 ppm 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 «*>-HCH-treated group revealed tumor
development. No metastasis were seen and no tumorous growths
developed in any of the other dietary groups (Ito, et al.
1975).
One instance of carcinogenic synergism of ^f-HCH in
combination with leupeptin showed a fivefold increase in
hepatic nodular hyperplasia (Arai, et al. 1978). Other
experiments have shown 2"-HCH to have an antagonistic effect
on the hepatocellular carcinoma induction by aflatoxin Bl
in male albino rats (Angsubhakorn, et al. 1978).
No data are currently available in the scientific liter-
ature on the carcinogenicity of the & and the 6 isomers
of HCH. Furthermore, the cT and isomers are rarely
detected in the environment.
C-33
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CRITERION FORMULATION
Existing Guidelines and Standards
The FAO/WHO Allowable Daily Intake (ADI) is set at
1 /ag/kg/day and was revised down to that figure from 12.5
mg/kg/day originally set by FAO/WHO in 1972. Barney (1969)
showed the average daily intake of HCH for U.S. citizens
to be 0.002 jjg/kg/day from the air and 0.07 pg/kg/day for
foodstuffs, clearly below the established level of 1 ;ug/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 vegetables. Finished drinking water should
contain no more than 0.004 ppm. The maximum air concentration
that is allowed by the EPA is 0.5 mg/m of air. Cases of
HCH poisoning in Japan have shown concentrations of 23 and
59 mg/m at factories involved in the manufacture 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 organochlo-
rine 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 ( #"-
HCH). It is strongly believed by many that 2T-HCH does
C-34
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not represent a pollution problem. It is recognized by
the same scientists that o<- and ^-HCH do represent a signifi-
cant hygienic problem. «* and <^-HCH are accumulated up
the food chain, e.g., Japanese rice * rice straw >
cattle > cattle products > man. t-HCH contains a
significant amount^of the *** and ^-isomers, so production
of t-HCH should be restricted and only production of2T-HCH
allowed. The presence of the °< and ^-isomers has in part
given rise to the hypothesis that the 2T-isomer can be trans-
formed 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 overlooked that °<-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 "JT-HCH had been used), residues of »*>
and & -HCH were found for many years. It is known that
in such cases, the relative share of i^-HCH of the total
HCH residues is going up. If "V -HCH is used exclusively
in an area, then the share of 2T-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
No t-HCH or tf"-HCH is currently manufactured in the
U.S. Use of t-HCH has been banned but 2f-HCH is still approved
for usage. All y-HCH used in the U.S. is currently imported;
C-35
-------
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 2^-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
during handling and planting of the seed and during application
to crops.
Basis and Derivation of Criterion
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 &< , & , Q, and technical HCH, respectively. These criteria
have been developed by the Carcinogens Assessment Group
of EPA. The assessment is given in Appendix I.
Under the Consent Decree in NRDC vs. 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." «< -HCH, ^-HCH, 2T*-HCH and t-HCH are suspected
of being human carcinogens. Because there is no recognized
safe concentration for a human carcinogen, the recommended
concentration of«*.-HCH, /0-HCH, V-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 concentrations of -HCH, -HCH, -HCH
and t-HCH corresponding to several incremental lifetime
C-36
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cancer risk levels have been estimated. 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 additional
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
ambient water quality criteria, EPA stated that it is consid-
ering setting criteria at an interim target risk level of
10 , 10" , or 10 as shown in the tables below.
<=**» -HCH
Exposure Assumptions Risk Levels and Corresponding Criteria (1)
(per day)_7 _, _,
£ 1£ 10. IP.
2 liters of drinking water 0 0.16 ng/1 1.6 ng/1 16 ng/1
and consumption of 18.7
grams fish and shellfish. (2)
Consumption of fish and 0 0.18 ng/1 1.8 ng/1 18 ng/1
shellfish only.
j^-HCH
Exposure Assumptions Risk Levels and Corresponding Criteria (1)
(per day)_7 _fi _,
0 1£ ' 1£ b 1£ 5
2 liters of drinking water 0 0.28 ng/1 2.8 ng/1 28 ng/1
and consumption of 18.7
grams fish and shellfish.(2)
Consumption of fish and 0 0.32 ng/1 3.2 ng/1 32 mg/1
shellfish only.
C-37
-------
Exposure Assumptions
2 liters of drinking water
and consumption of 18.7
grams fish and shellfish (2)
Consumption of fish
and shellfish only.
Exposure Assumptions
2 liters of drinking water
and consumption of 18.7
grams fish and shellfish (2)
Consumption of fish
and shellfish only.
-HCH
Risk Levels and Corresponding Criteria
,-7
.-6
-5
0 1£ ' 10 " 10
0 0.54 ng/1 5.4 ng/1 54 ng/1
0 0.61 ng/1 6.1 ng/1 61 ng/1
-HCH
Risk Levels and Corresponding Criteria
0 1£~7 1£~6 1£~5
0 0.21 ng/1 2.1 ng/1 21 ng/1
0 0.24 ng/1 2.4 ng/1 24 ng/1
(1) Calculated by applying a modified "one-hit" extrapo-
lation model described in the FR15926, 1979. Appropriate
bioassay data used in the calculation of the model are pre-
sented 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, 1000, and so forth.
(2) Approximately 88 percent of the«*>-HCH, <<3 -HCH, y-
HCH and t-HCH exposure results from the consumption of
aquatic organisms which exhibit ah average bioconcentration
potential of 780 fold. The remaining 12 percent of
-------
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 corresponding HCH concen-
trations. 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
factored into ambient water quality criteria formulation
until additional analyses can be made. The criteria presented,
therefore, assume an incremental risk from ambient water
exposure only.
Water quality criteria for the , 21 ng/1
*At a risk level of one in 100,000.
C-39
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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 (
-------
al. 1972; Thorpe and 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 mixture
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. 1972a). It is concluded that the water concentration
of technical HCH should be less than 21 nanograms per liter
in order to keep the lifetime cancer risk below 10~ .
The water quality criterion for alpha-HCH is based
on the induction of liver tumors in male DDY mice fed 500
ppm alpha-hexachlorocyclohexane for 24 weeks (Ito, et al.
1976) . It is concluded that the water concentration of
alpha-HCH should be less than 16 nanograms per liter to
keep the lifetime risk below 10.
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The water quality criterion for beta-HCH is based on
the induction of liver tumors in male ICR-JCL mice fed 600
ppm beta-hexachlorocyclohexane for 26 weeks (Goto, et al.
1972). It is concluded that the water concentration of
beta-HCH should be less than 28 nanograms per liter 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 CFl mice fed 400
ppm gamma-hexachlorocyclohexane for 110 weeks (Thorpe and
Walker, 1973). It is concluded that a water concentration
of gamma-HCH should be less than 54 nanograms per liter
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 hexachlorocyclohexane.
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Summary of Pertinent Data
The water quality criterion of alpha-hexachlorochyclo-
hexane 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. 1976). The time-weighted average dose
of 65 mg/kg/day was given in the feed for 24 weeks. The
liver tumor incidence was 0/18 and 20/20 in the control
and treated groups, respectively. Assuming a fish bioconcen-
tration factor of 780, the criterion is calculated from
the following parameters:
n = 20 (used 19.5 for d = 500 ppm X 0.13 = 65 mg/kg/day
calculation)
Nfc = 20 R = 780
n = 0 L = 90 weeks '
c
Nc = 18 w = 0.0357 kg
le = 24 weeks F = 0.0187 kg/day
Le = 90 weeks
Based on these parameters, the one-hit slope, BH, is
2.6637. The resulting water concentration of alpha-hexachloro-
cyclohexane calculated to keep the individual lifetime cancer
risk below 10 is 16 nanograms per liter.
-------
Summary of Pertinent Data
The water quality criterion for beta-hexachlorocyclo-
hexane 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
liver tumor incidence was 0/10 and 10/10 in the control
and treated groups, respectively. Assuming a fish bioconcen-
tration factor 780, the criterion is calculated from the
following parameters:
n. = 10 (used 9.5 for d = 600 ppm X 0.13 = 78 mg/kg/day
calcuation)
Nfc = 10 R = 780
n_ = 0 L = 90 weeks
C
NC = 10 w = 0.0475 kg
le = 26 weeks F =0.0187 kg/day
Le = 90 weeks
Based on these parameters, the one-hit slope, BH is
1.5129. The resulting water concentration of beta hexachloro-
cyclohexane calculated to keep the individual lifetime cancer
risk below 10~ is 28 nanograms per liter.
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Summary of Pertinent Data
The water quality criterion for gamma-hexachlorocyclo-
hexane is derived from the oncogenic effects observed in
the liver of male CFl 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 liver tumor incidence was 11/45 and 27/28 in the control
and treated groups, respectively. Assuming a fish bioconcen-
tration factor of 780, the criterion is calculated from
the following parameters:
n = 27 d = 400 ppm x 0.13 = 52 mg/kg/day
Nfc = 28 R = 780
n =11 L = 110 weeks
N = 45 w = 0.030 kg
c
le = 110 weeks F = 0.0187 kg/day
Le = 110 weeks
Based on these parameters, the one-hit slope, BH/ is
7.7844 x 10 . The resulting concentration of gamma-hexachloro-
cyclohexane calculated to keep the individual lifetime cancer
risk below 10~ is 54 nanograms per liter.
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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 liver tumor incidnce was 0/14 and 20/20 in the control
and treated groups, respectively. Assuming a fish bioconcen-
tration factor of 780, the criterion is calculated from
the following parameters:
nt = 20 (used 19.5 for d = 660 ppm x 0.13 = 85.8 mg/kg/day
calculation)
Nt = 20 R = 780
nc = 0 L = 90 weeks
N = 14 w = 0.0364 kg
c
le = 24 weeks F = 0.0187 kg/da
Le = 90 weeks
Based on these parameters, the one-hit slope, BH is
2.0050. The resulting water concentration of technical
hexachlorocyclohexane calculated to keep the individual
lifetime cancer risk below 10~ is 21 nanograms per liter.
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