ISOPHORONE
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
ISOPHORONE
CRITERIA
Aquatic Life
The data base for freshwater aquatic life is insufficient to
allow use of the Guidelines. The following recommendation is
inferred from toxicity data for saltwater organisms.
For isophorone the criterion to protect freshwater aquatic
life as derived using the Guidelines is 2,100 y.g/1 as a 24-hour
average and the concentration should not exceed 4,700 ug/1 at any
time.
For isophorone the criterion to protect saltwater aquatic
life as derived using the Guidelines is 97 ug/1 as a 24-hour
i
average and the concentration should not exceed 220 ug/1 at any
time.
Human Health
For the protection of human health from the toxic properties
of isophorone ingested through the consumption of water and fish,
the criterion is 460 ug/1.
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ISOPHORONE
Introduction
Isophorone is an industrial chemical synthesized from
acetone -and used commercially as a solvent or cosolvent
for finishes, lacquers, polyvinyl and nitro cellulose resins,
pesticides, herbicides, fats, oils, and gums. It is also
used as a chemical feedstock for the synthesis of 3,5 xylenol,
2,3,5-trimethyl-cyclohexanol, and 3,5-dimethylaniline.
Isophorone is an unsaturated, cyclic ketone or aliphatic
o
enone produced commercially by passing acetone over calcium
oxide, calcium hydroxide, calcium carbide or mixtures of
t
these at 350°C and 1 atomosphere of pressure (Mark, et al.
1963). It is also prepared by heating acetone with aqueous,
alkali metal hydroxide at approximately 150°C under pressure
(Mark, et al. 1963). Blackford (1975) has estimated isophorone
production at a level of 28 million pounds for 1973.
Isophorone (^-isophorone) has the chemical name 3,5,5-
trimethyl-2-cyclohexen-l-one, and is also known as trimethyl
cyclohexanone or isoacetophorone (Rohm and Haas,-1971).
Although isophorone is normally produced as the y-isomer,
it may exist also as a ^-isomer having the chemical name
3,5,5-trimethyl-3-cyclohexen-l-one (Schering Ag. 1972).
The technical or industrial grade of isophorone normally
contains 3.0 percent or less of the ^-isomer, causing a
slight deviation in the melting and boiling points reported
for pure isophorone (c*-isomer) (Schering Ag. 1972; Rohm
and Haas, 1971) .
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The pure compound ( £T-isophorone) is a water-white
liquid which exhibits low volatility, possesses a camphor
or peppermint-like odor, and turns yellow upon standing
(Schering Ag. 1972; Browning, 1965; Patty, 1962; Sax, 1975).
It has the empirical formula CqH140 and a molecular weight
of 138.21. The physical properties include: melting point,
-8.1°C; boiling point, 215.2°C; vapor pressure, 0.31 Hg
at 20°C and 1 mm Hg g at 38°C; and a density of 0.9229 at
20°C (Mark, 1963; Sax, 1975; Browning, 1965). The compound
is soluble in water up to 1.2 gm/100 ml at 20°C and is readily
soluble in fats, oils, and other hydrophobic substances
(Patty, 1962; Rohm and Haas, 1971; Jacob, 1949).
Isophorone is considered chemically stable (Patty,
1962). At 150°C, however, it will form salts with sulfuric
acid and a tricyclic $~-, & -unsaturated ketone in the presence
of 60 percent aqueous sodium hydroxide (Marx, 1971). Such
reactions may be of little significance since the conditions
required for their completion are generally not found in
tne environment.
In aqueous solutions, isophorone forms three different
tricyclic diketodimers when exposed to direct sunlight (Jennings,
1965) . The molecular weights of these compounds are double
that of isophorone and the melting points range from 182
to 186.5°C. Following ultraviolet irradiation for one and
ten days, conversions to the dimer were 10 and 50 percent,
respectively (Craven, 1963). In a similar study, irradiation
for 40 and 80 days resulted in dimer conversions of 76 and
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83 percent, respectively (Craven, 1962). The significance
of these laboratory studies with respect to the stability
of isophorone in the environment is not known.
The microbiological degradation of isophorone, measured
as percent biooxidation, was investigated by Price, et al.
(1974) in domestic waste water and synthetic saltwater using
a modification of the standard BOD test. The observed biooxi-
dation levels of isophorone were 13, 47, and 42 percent
in the domestic waste water at 10, 15, and 20 days, respec-
tively. The biooxidation in synthetic saltwater reached
only nine percent after 20 days incubation.
Although isophorone has been reported in drinking water,
the Delaware River, and effluents of several industrial
facilities, little or no information is available regarding
bioconcentration, persistence, or fate of isophorone under
environmental conditions. However, its broad application
as a solvent or cosolvent or chemical feedstock for industrial
and agricultural products clearly suggests that the potential
for both point source and non-point source water contamination
exists (39 FR 37195).
Isophorone has been reported to be toxic to aquatic
life, particularly saltwater invertebrate species. Isopphorone
also has been shown to be toxic to experimental mammals
in acute, subacute, and chronic toxicity tests.
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REFERENCES
Browning, E. 1965. Toxicity and metabolism of industrial
solvents, Elsevier, New York.
Craven, E.G. 1962. Isophorone. Jour. Appl. Chem. (London).
12: 120
Craven, E.G. 1963, Dimeric isophorone. Ger. 1, 143, 809.
(cl. 120) Br. Appl.
Jacob, M.B. 1949. The analytical chemistry of industrial
poisons, hazards, and solvents. Interscience, New York.
Jennings, P.w. 1965. Photochemistry of isophorone, I. Disser-
tation Abstr. 26: 698
Mark, K.F., et al. 1963. Kirk-Othmer Encyclopedia of Chemical
Technology. 2nd ed. John Wiley, New York.
Marx, J.N. 1971. Interaction of 2, ^-unsaturated ketones
with hydrogen halides. Addition vs. salt formation. Tetra.
Lett. 52: 4957. . '
Patty, F.A. 1962. ed. Industrial Hygiene and Toxicology.
2nd ed. John Wiley, New York.
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Price, K.S., et al. 1974. Brine shrimp bioassay and BOD
of petrochemicals. Jour. Water Pollut. Control Fed. 46: 63.
Rohm and Haas. 1971. The name, chemical identity, and composi-
tion of the innert ingredients for use in pesticide.
Sax, N.I. 1976. Dangerous Properties of Industrial Materials.
4th ed. Van Nostrand Reinhold Co., New York.
Schering, Ag. 1972. Isophorone. Specif. No. 276. Agric.
Chem. Div. Berlin, E. Germany.
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AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
Static acute toxicity tests have been reported for isophorone
in the bluegill, Daphnia magna, and alga, Selenastrum capricornu-
tum. The 50 percent effect concentrations were between 117,000
and 224,000 ug/1. A bioconcentration test indicated negligible
uptake of isophorone.
Acute Toxicity
The 96-hour LC50 for the bluegill (224,000 g/1) after
adjustment for test methods and species sensitivity results in a
Final Fish Acute Value for isophorone of 31,000 y.g/1 (Table 1).
Daphnia magna has been tested and the 48-hour EC50 is 117,000
ug/1 (Table 2) which indicates little, if any, difference in
sensitivity with the bluegill. The Final Invertebrate Acute Value
(4,700 ug/D also becomes the Final Acute Value since the former
is lower than the comparable value for fish.
*The reader is referred to the Guidelines for Deriving Water
Quality 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
following tables contain the appropriate 'data that were found in
the literature, and at the bottom of each table are the calcula-
tions for deriving various measures of toxicity as described in
the Guidelines.
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Chronic Toxicity
(
No chronic studies have been reported on the effects of
isophorone on freshwater organisms.
Plant Effects
The 96-hour EC50 values for cell number production and
inhibition of chlorophyll a by the alga, Selenastrum capricornutum,
are 122,000 and 126,000, respectively (Table 3). These effect
concentrations are essentially the same as for the bluegill and
Daphnia magna.
Residues
A 28-day exposure (U.S. EPA, 1978) to 14C-isophorone
resulted in bioconcentration by the bluegill to 7 times that in
the water (Table 4). The half life of isophorone in the whole
body was one day. Thin-layer chroraatography was used to verify
the analytical results.
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CRITERION FORMULATION
Freshwater-Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Final Fish Acute Value = 31,000 ug/1
Final Invertebrate Acute Value = 4,700 ug/1
Final Acute Value = 4,700 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = 120,000 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 120,000 ug/1
0.44 x Final Acute Value = 2,100 ug/1
No freshwater criterion can be derived for isophorone using
the Guidelines because no Final Chronic Value for either fish or
invertebrate species or a good substitute for either value is
available.
Results obtained with isophorone and saltwater organisms
indicate how a criterion may be estimated.
For isophorone and saltwater organisms, 0.44 times the Final
Acute Value is less than the Final Chronic Value derived from
results of an embryo-larval test with the sheepshead minnow.
Therefore, it seems reasonable to estimate a criterion for iso-
phorone and freshwater organisms using 0.44 times the Final. Acute
Value.
The maximum concentration of isophorone is the Final Acute
Value of 4,700 ug/1 and the estimated 24-hour average concentra-
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tion is 0.44 times the Final ^Icute Value. 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 isophorone the criterion to protect fresh-
water aquatic life as derived using procedures other than the
Guidelines is 2,100 ug/1 as a 24-hour average and the concentra-
tion should not exceed 4,700 u.g/1 at any time.
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Table 1 Freshwater fish acute values for isophorone (U S EPA, 1978)
Adjusted
Bioaseay Test Time LC50 LC50
Organism Method;.- Cone.** (hrs) (ug/l> lug/l>
Bluegill. S U 96 224,000 122,000
Lepomis macrochirus
" S = static
** U = unmeasured
Geometric mean of adjusted values = 122,000 ug/1 = 31,000 yg/1
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TaDle 2 Freshwater invertebrate acute values for isophorone (U.S. EPA, 1978)
Organism
Cladoceran.
Daphnia magna
faioassay Test time
leu-ou* Cone.** 1/irs)
48
Adjusted
LC50 LCbO
(uq/i) luq/i)
117.000 99.100
* S = static
** U = unmeasured
Geometric mean of adjusted values = 99,100 wg/1
99
- 4.700 wg/1
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Table 3 Freshwater plant effects for isophorone (U S. EPA, 1978)
Concentration
Organism Effect (ug/i)
Alga. EC50 96-hr 122,000
Selenastrum cell numbers
capncomutum
Alga, EC50 96-hr 126,000
Selenastrum chlorophyll a
capricornutum ~
Lowest plant value = 122,000
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Tatle 4. Freshwater residues for isophorone (U.S. EPA. 1978)
Time
Organism Bioconcentration Factor (days;
Bluegill. 7 28
Leponus macrochirus
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SALTWATER ORGANISMS
Introduction
As with freshwater organisms, most of the available data for
the effects of isophorone on saltwater organisms result from
static tests with unmeasured concentrations. An embryo-larval
test has been conducted with the sheepshead minnow.
Acute Toxicity
The 96-hour LC50 for the sheepshead minnow (U.S. EPA, 1978)
was determined to be between 166,000 and 295,000 ug/1 (Table 8).
No Final Fish Acute Value can be derived but it would be higher
than the equivalent value for invertebrate species (220 ug/1)
which is derived-from an unadjusted 96-hour LC50 value of 12,900
g/1 for the mysid shrimp, Mysidopsis bahia (Table 5).
Chronic Toxicity
The chronic value for the sheepshead minnow obtained from an
embryo-larval test (U.S. EPA, 1978) is 51,614 ug/1 (Table 6). The
limits on this test were 74,000 to 144,000 ug/1 which is about 0.5
of the LC50 range (Table 8). The Final Fish Chronic Value, and
the Final Chronic Value since no invertebrate species has been
tested, is 7,700 ug/1.
Plant Effects
Chlorophyll a_ was inhibited and cell numbers were reduced by
50 percent after 96-hour exposures of the alga, Skeletonema
costatum (U.S. EPA, 1978), to isophorone concentrations of 110,000
and 105,000 ug/1, respectively (Table 7).
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CRITERION FORMULATION
Saltwater-Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Final Fish Acute Value = not available
Final Invertebrate Acute Value = 220 ug/1
Final Acute Value = 220 ug/1
Final Fish Chronic Value = 7,700 ug/1
Final Invertebrate Chronic Value = not available
Final Plant Value = 110,000 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 7,700 ug/1
0.44 x Final Acute Value = 97 ug/1
The maximum concentration of isophorone is the Final Acute
Value of 220 ug/1 and the 24-hour average concentration is 0.44
times the Final Acute Value, No important adverse effects on
saltwater organisms have been reported to be caused by concentra-
tions lower than the 24-hour average concentration.
CRITERION: For isophorone the criterion to protect saltwater
aquatic life as derived using the Guidelines is 97 ug/1 as a
24-hour average and the concentration should not exceed 220 ug/1
at any time.
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"aole 5 Marine invertebrate acute values for Isophorone (U S EPA, 1978)
Adjusted
Bioassay Test Time ix:50 LCbO
Or>ja-usm Metiiog* Cone. ** (nts) (ug/1) (uq/H
Mysid shrimp, S U 96 12,900 10,926
Mysidopsis bahia
* S - static
** U = unmeasured
10 926
Geometric mean of adjusted values - 10,926 yg/1 =-+5— - 220 Mg/1
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to
Tafcle 6 Marine fish chronic values for isophorone (U S. EPA. 1978)
Chronic
Limits Value
organism Test* tug/ij fug/lfr
Sheepshead minnow, E-L 74,000- 51,614
Cyprinodon variegatus 144,000
* E-L = embryo-larval
Geometric mean of chronic values = 51,614 wg/1 51t6¥ = 7,700 pg/1
o. /
Lowest chronic value = 51,614 vg/1
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Table 7 Marine plant effects for isophoi^B (U S EPA, 1978)
Concentration
Organism Effect (aq/i)
Alga, EC50 96-hr 110,000
Skeleconema costatum chlorophyll a
Alga, ECSO 96-hr 105,000
SVeletonema costatum cell number
Lowest plant value = 105,000 Mg/1
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Table 8. Other marine data for isophorone (U S. EPA, 1978)
Test Result
- Organism Duration Effect (ug/ll
Sheepshead minnow, 96 hrs LC50 >166,000
Cyprinodon variegatus . <295,000
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ISOPHORONE
REFERENCES
U.S. EPA. 1978. In-depth studies on health and environmental
impacts of selected water pollutants. Contract No. 68-01-
4646.
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Mammalian Toxicology and Human Health Effects
Introduction
Isophorone is a high-boiling colorless liquid of low
volatility with an odor resembling peppermint. Its salient
physical properties are summarized in Table 1. Isophorone is
an excellent solvent for many oils, fats, gums and natural
and synthetic resins (Rowe and Wolf, 1963), but it is used
mainly as a solvent for vinylic resins applied by roller
coating (Blackford, 1975). Isophorone is also used as a sol-
vent for cellulose derivatives, lacquers, and pesticide for-
mulations, particularly anilide and carbomate herbicides.
Because of its structure, isophorone is useful as a chemical
intermediate, and is utilized in the synthesis of 3,5-
xylenol, 3,3,5- trimethyl cyclohexanol, and plant growth
retardants (Haruta, et al. 1974).
Isophorone is prepared commercially by two methods, both
of which require acetone as a starting material (Rowe and
Wolf, 1963). Acetone is passed over calcium oxide, hydrox-
ide, carbide, or mixtures of these at 350°C, or is heated at
200-250°C under pressure. The isophorone is separated from
the resultant products by distillation. Because less than
three companies manufacture isophorone, production figures
are not published by the U.S. Tariff Commission. The produc-
tion of isophorone can, however, be estimated from acetone
consumption data. In 1973, 35 million pounds of acetone were
consumed for isophorone production (Blackford, 1975). Black-
ford estimated that, for every pound of Methyl Isobutyl
Ketone produced, 1.25 pounds of acetone are required. This
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TABLE 1
Physical Properties of Isophorone
(EPA, 1979a; Union Carbide, 1968; NIOSH, 1978)
Empirical Formula
Molecular Weight
Freezing Point
Boiling Point (760 nun)
Specific Gravity (20/20°C)
Refractive Index nD(20°C)
Vapor Pressure (25°C)
Air Saturation
Evaporation Rate (ether =1)
Water Solubility (weight % at 20°C)
Commercial Puritya (weight %)
Impurities:
6 -isophorone
mes itylene (1,3,5-1rimethyIbenzene)
mesityl oxide (2-methyl-2 pertene-
4-one)
phorone (2,6-dimethyl-2,5-
heptachiene-4-one)
isoxylitones
water
Structure
C9H140
138.21
215. 2°C
0.9229 g/cc
1.4781
0.44 mm
0.06%
200
1.2
96-98%
2-4%
trace
trace
trace
trace
trace
3,5,5-trimethyl-2-cyclo-
hexene-1-one
'Isophorone plus trimethylcyclohexenone
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corresponds to a yield of slightly above 90 percent. Assum-
ing a 90 percent yield, and an acetone consumption figure of
35 million pounds/ the estimated 1973 production of iso-
phorone was 28 million pounds.
NIOSH (1978) estimates that more than 1.5 million work-
ers are exposed to isophorone. In the industrial handling of
isophorone inhalation of the vapors is the most likely mode
of contact, although skin and eye contact with the liquid may
also occur. Because of the odor and taste of isophorone, in-
gest ion is not expected unless by accident. In the environ-
ment, isophorone has been detected in a few samples of drink-
ing water, but not in ambient air, soil, or food.
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EXPOSURE
Ingestiort from Water
Isophorone has been detected in several samples of
* j
drinking water (Table 2), but these identifications cannot be
used to imply a continuous occurrence. The sources of the
isophorone contamination were not identified, but they would
appear to be of industrial origin.
The Environmental Protection Agency has quantified
levels .of isophorone in finished drinking water in the New
Orleans area (EPA, 1974a). At the Carrollton Water Plant
(City of New Orleans), and at two water treatment sites in
Jefferson Parish, the highest measured isophorone concentra-
tions were 1.5, 2.2 and 2.9 ug/1, respectively.
The National Organics Reconnaissance Survey/ initiated
in 1974, was designed to provide an estimate of the nation-
wide distribution of organic compounds in drinking water
(EPA, 1975). In a comprehensive organic analysis of the
finished drinking waters of ten cities, isophorone was
identified only in Cincinnati, at a level of 0.02 ug/1. The
Cincinnati water source was categorized as being contaminated
with industrial discharges. Isophorone was not found in the
waters of Miami (FL), Seattle (WA), Ottumwa (IA), Philadel-
phia (PA), Tucson (AR), New York (NY), Lawrence (MA), Grand
Forks (ND), or Terrebonne Parish (LA).
EPA also maintains an inventory of organic compounds
that have been isolated and identified in drinking water in
the United States (EPA, 1975). Two hundred and fifty-three
compounds were compiled from an extensive search of the
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TABLE 2
Water Types Contaminated with Isophorone
Finished
Drinking
Water
Effluent from
River
Latex
Plant
Chemical
Plant
Tire
Plant
Concentration
Reference
o
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9.5 ug/1 highest concen-
tration reported in a
nationwide survey
1.5-2.9 ug/1, treated
river water, New Orleans
area
trace (<0.01 ppb),
Delaware River
0.04 mg/1
EPA (1975)
EPA (1974)
Sheldon and Hites
(1978)
Shackelford and
Keith (1976)
Jungclaus, et al.
(1976)
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chemical literature and from EPA reports generated from the
Agency's analytical activities. Although the compounds in-
cluded in the inventory were based upon an analysis of only a
few (unspecified) public water supplies, isophorone was
nevertheless detected at concentrations as high as 9.5 ug/1.
In a primarily qualitative study, Sheldon and Kites
(1978) recently found trace quantitites (<0.01 ppb) of iso-
phorone in water samples from the Delaware River near a
highly industrialized region. Isophorone was also identified
as a contaminant (approximate concentration, 0.04 mg/1) in
the wastewater from a tire manufacturing plant (Jungclaus, et
al. 1976). Shackelford and Keith (1976) have reported that
isophorone has been detected in the effluents from latex and
chemical plants in Alabama, but no levels were reported.
Ingestion from ,Foods
No reports have been published concerning the possible
presence of isophorone in food.
A bioconcentration factor (BCF) relates the concentra-
tion of a chemical in water to the concentration in aquatic
organisms, but BCF's are not available for the edible portion
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
lipids and the amounts of various species consumed by Ameri-
cans. A recent survey on fish and shellfish consumption in
the Uni'ted States (Cordle, et al. 1978) found that the per
capita consumption is 18.7 g/day. From the data on the nine-
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teen major species identified in the survey and data on the
fat content of the edible portion of these species (Sidweli,
et al. 1974), 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.
i
A measured steady-state bioconcentration factor of 7 was
obtained for isophorone using bluegills containing about one
percent lipids (U.S. EPA, 1978). 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 iso-
phorone and the edible portion of all aquatic organisms con-
sumed by Americans is calculated to be 7 x 2.3 = 16.
Inhalation
No iponitoring information is available on the levels of
isophorone in ambient air.
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Dermal
No direct information is available on the importance of
dermal absorption in total human exposure to isophorone. It
has been demonstrated that isophorone can be absorbed across
the skin of rabbits (see Acute, Sub-acute, and Chronic
Toxicity section). For those humans exposed only to back-
ground levels of isophorone, however, dermal absorption is
not likely to be a significant route of entry.
PHARMACOKINETICS
Absorption
No direct quantitative information is available on the
absorption of isophorone in animals or man. The demonstrated
toxicity of isophorone by oral, inhalation and dermal expo-
sures (Acute, Sub-acute, and Chronic Toxicity section) in-
dicates that it is capable of passage across epithelial
membranes.
Distribution
•«^MM^_BMMV^^M^M_^^MM^W>—A V
The tissue distribution and accumulation of isophorone
has not been studied.
Metabolism and Excretion
Isophorone appears to undergo oxidation at the 3-methyl
group following oral administration of 1 g/kg to rabbits
(Truhaut, et al. 1970). This reaction, shown below, precedes
glucuronide conjugation and urinary elimination.
CM
i. ^"^ I .I"1 -.
COOH
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The complete reaction sequence for isophorone biotransforma-
tion has not been determined and no quantitative data on the
extent of glucuronic acid conjugation are available.
Isophorone has been detected as a urinary metabolite of
3,5,5-trimethylcyclohexanone in rats and rabbits (Truhaut, et
al. 1973). A large percentage of the metabolite was present
as a glucuronide conjugate.
EFFECTS
Acute, Sub-acute, and Chronic Toxicity
Effects on Experimental Mammals: The acute toxicology
of isophorone is summarized in Table 3. Oral LDso values in
the area of 2 gm/kg body weight have been reported for rats
and mice by several authors.
The Union Carbide Corporation reported a single skin
penetration LD5Q value of 1.39 g/kg in rabbits in a 1975
technical data1 booklet. Single skin penetration refers to a
24-hour covered skin contact with the isophorone, but no de-
tails regarding the number of animals exposed nor any other
aspects of the experimental protocol were presented.
Smyth and Seaton (1940) reported that 750 ppm was the
highest concentration of isophorone to which rats and guinea
pigs could be exposed for several hours with no symptoms
other than slight eye and nose irritation. The symptoms ex-
hibited by the animals following exposures to higher concen-
trations included eye and nose irritation, lacrimation,
swelling of the nose, instability, respiratory difficulty or
irregularity, marked increase in intestinal peristalsis and
light sarcosis (Table 4). Exposures lasting 12 hours or more
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resulted in increased heart rates. Opacity of the cornea or
corneal necrosis, as revealed by Fluorescin staining, was
found in the guinea pigs following exposures to 840 ppm iso-
phorone lasting four hours or more. Corneal effects were
never observed in the rats.
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TABLE 3
Acute Toxicology of Isophorone
Route Animal
Oral Rats
Rats
Rats
n Rats
i
»-•
t^
r^
Mice
Dermal Rabbits
Inhalation'3 Rats and
Guinea Pigs
Rats
Guinea Pigs
Rats
Number Treated
per dose level3 Dose
n.s. 1.87 gAg
5 2.10 gAg
5 2.12 gAg
n.s. 2.37 gAg
n.s. 2.00 gAg
n.s. 1.39 gAg
n.s. 750 ppm
n.s. 1B40 ppro
n.s. 4600
6 Air saturated
with isophorone
Duration Mortality
LD50
14 day LD5o
14 day LDjn
U>50
LD50
LD50
"several" No death or
hours serious symptoms
4 hrs. Caused death in
some animals
8 hrs. No deaths
8 hrs. One death
Reference
Union Carbide
(1975)
Smyth, et al.
(1969)
Smyth, et al.
(1970)
Bukhalovskii,
et al. (1976)
Bukhalovskii,
et al. (1976)
Union Carbide
(1975)
Smyth and Seaton
(1940)
Smyth and Seaton
(1940)
Smyth and Seaton
(1940)
Union Carbide
(1975)
an.s. = not specified.
b600 ppm is the maximum attainable concentration of Isophorone in air (see discussion on page C-13 and appendix).
-------
o
I
H
to
Symptoms Resulting From Acute Exposure of. buinea Pigs to isbphoron'e Vapors9'"3
(Smyth and Seatonj i§40)
Concentration in PPM
Symptoms
Maximum exposure period (minutes)
Nasal irritation (rub nose)
Eye irritation (blink)
Lacrimation
Nose swollen
Instability
Respiratory difficulty
Diarrhea
Light narcosis
First death
4 , 600
480
(1)
(1)
5
8
40
60
120
180
(2)
1,840
360
U)
(1)
is
20
50
120
180
200
(2)
1>370
480
(1)
(i)
20
30
80
180
240
255
(2)
880
720
(1)
(i)
71,
75
135
360
480
600
(2)
750
1,440
15
15
(2}
(2)
(2)
(2)
(2)
(2)
(2)
300
1,440
(2)
(2)
(2)
(2)
(2)
'(2)
(2)
M
(2)
(1) At very start of Exposure.
(2) Not observed within maximum exposure period.
aNumbers are time in minutes for first animal to display symptom indicated. Time required
for similar effects to be displayed by rats was about 2/3 of that for guinea pigs.
b600 ppm is the maximum attainable concentration of Isophorone in air (see discussion on
page C-13 and appendix).
-------
Eight hour inhalation exposures to 4600 ppm isophorone
did not result in any deaths to guinea pigs, but in rats a
four hour exposure to 1840 ppm was the minimum lethal level
(Smyth and Seaton, 1940). When death occurred it was usually
during the exposure period due to paralysis of the respira-
tory center (narcosis). A few deaths were attributed to lung
irritation.
It must be noted that Rowe and Wolf (1963) have indi-
cated that the isophorone vapor concentrations reported by
Smyth and Seaton in this study (1940), and those in a related
subacute study described subsequently (Smyth, et al. 1941;
1942), could not have been attained under the conditions
employed. Later investigation led to the conclusion that the
material used in the Smyth studies was an impure commercial
product containing appreciable amounts of material(s) more
volatile than isophorone (Rowe and Wolf, 1963). Smyth main-
tained vapor concentrations in a flow-through chamber by
bubbling air through the solvent in a constant temperature
bath and diluting the vapor stream with pure air, and moni-
tored the concentrations with an interferometer. Since the
concentration of vapors within the exposure chamber was
measured by means of an interferometer calibrated against
pure isophorone, it was apparently assumed that the vapors
present in the chamber were isophorone.
A calculation of the maximum attainable concentration of
isophorone in air at standard temperature and pressure, pre-
sented in the appendix, yields a value of approximately 600
ppm. This calculation indicates that the allegation of Rowe
C-13
-------
and Wolf is probably correct and implies that the value of
the Smyth data is seriously compromised.
The microscopic pathology of those animals surviving
acute exposure by 14 days was almost never severe and was
essentially reversible (Smyth and Seaton, 1940). Pathologi-
cal findings were reported for 95 percent of the lungs
(general congestion; alveolar and bronchiolar secretion, red
cell leakage and epithelial cell desquamation; secondary
pneumonia), 56 percent of the kidneys (cloudy swelling, dila-
tion, granular detritis and hyaline casts in convoluted
tubules; dilation of Bowman's capsule; general congestion),
30 percent of the hearts (dilation of coronary vessels), 17
percent of the livers (congestion; hemorrhages into parenchy-
ma; cloudy swelling) and 10 percent of the spleens (conges-
tion). The typical hematologic response to acute isophorone
intoxication was a temporary drop1 in red cells and hemo-
globin, with white cells appearing to be unchanged.
Union Carbide (1975) reported that a single eight hour
innalation exposure to air saturated with isophorone (calcu-
lated concentration approximately 600 ppm) killed one of six
rats.
Iri 1942, Smyth and coworkers compared the subacute in-
halation toxicity of isophorone in rats and guinea pigs. The
mortality and pathological details of this study were origi-
nally reported by Smyth (1941). Groups of ten rats and ten
quinen piqs were reportedly exposed to isophorone vapors at
concentrations ranging from 25 to 500 ppm for eight hrs/day,
five days a week for six weeks, but the experimental methods
C-14
-------
utilized were similar to those described for the Smyth and
Seaton (1940) study. Since it appears that this experiment
was also conducted with impure material and that the concen-
tration of the isophorone tested is not accurately known
(Rowe and Wolf, 1963), these results are also of limited ,
value. The dose-related effects produced by the 25 to 500
ppm exposures are summarized in Table 5. Although about half
the animals exposed to isophorone at 500 ppm died before the
thirtieth exposure; no guinea pigs died from exposures at 100
ppm or less, and no rats died from inhalation of vapors at 50
ppm or less.
When death resulted from subacute inhalation exposure it
appeared to be due to a combination of kidney and lung
damage, although none of the surviving animals showed any-
severe grade of injury to these organs (Smyth, et al. 1941;
1942). The microscopic picture of various tissues from the
survivors was rather uniform, varying in degree with the con-
centration breathed. The lungs were frequently injured,
showing primarily congestion and leakage of red blood cells
into alveoli. Cloudy swelling with increased secretion and
dilation of Bowman's capsule was a common finding in the kid-
ney, but the action of isophorone on the liver, heart and
spleen was negligible. Guinea pigs exposed to 500 ppm showed
an increase in polymorphonuclear white cells and a corres-
ponding fall in lymphocytes, but no other consistent changes
in hematologic parameters were found.
C-15
-------
TABLE 5
Subacute Inhalation Toxicity of Isophorone
(Smyth, 1941)
Animal
Concentration3
(ppro) Hr/Day
Duration
(Days)
Mortalityb
Details
I
h-
a\
Rats
male, Wistar,
90-120 g
Guinea Pigs
both sexes,
250-300 g
25
50
100
200
25
100
200
500
8
8
8
42 (30 exposures,
5 days/wk x 6 wks)
42 (30 exposures,
5 days/wk x 6 wks)
42 (30 exposures,
5 days/wk x 6 wks)
42 (30 exposures,
5 days/wk x 6 wks)
42 (30 exposures,
5 days/wk x 6 wks)
42 (30 exposures,
5 days/wk x 6 wks)
42 (30 exposures,
5 days/wk x 6 wks)
42 (30 exposures,
5 days/wk x 6 wks)
0%
0%
20%
10%
0%
0%
25%
40%
No apparent signs of toxicity
Evidence of lung and kidney
pathology
Evidence of lung, spleen and
kidney pathology
Evidence of lung, spleen and
kidney pathology} conjunctivitis
and nasal irritation} urine
albumin
No apparent signs of toxicity
Evidence of lung and kidney
pathology} weight loss
Evidence of lung and kidney
pathology} weight loss
Evidence of lung, kidney and
liver pathology; conjunctivitis
and nasal irritation; weight
loss; increase in polymorpho-
nuclear white cells with a cor-
responding fall in lymphocytes
aRowe and Wolf
trations are
bPercentage of
(1963) have indicated that the isophorone used in this study was impure and that the reported concen-
higher than actually present (see discussion on page C-13 and appendix).
animals dying; usually 10 animals were tested at each dosage.
-------
Smyth (1941) indicated that during the course of the
study, both control and exposed animals, especially the
guinea pigs, were troubled with infections (parasites, intes-
tinal protozoa and bacteria). Although the affected animals
were reportedly eliminated from consideration, the signifi-
cance of the infection on the other animals is difficult to
ascertain.
Subacute (90 day) feeding studies on isophorone in rats
and dogs have also been conducted (EPA, 1979a).
In the rat study, CFE albino weanlings were divided into
4 groups of 20 males and females each and fed 0, 750, 1500 or
3000 ppm isophorone in the daily diet (EPA, 1979a). Individ-
ual body weights, food and compound consumption were tabu-
lated weekly. After four weeks and at 90 days, five rats/
sex/group were killed and blood was collected for hematologi-
cal and clinical chemistry determinations. Urine was col-
lected from an additional five males and five females per
t
group at the same time and was also comprehensively analyzed.
The rats sacrificed after four weeks were examined for gross
pathology only, but after 90 days tissues from ten rats of
each sex from the control and 3000 ppm groups were examined
histologically. The livers and kidneys from five rats/sex
from the 750 and 1500 ppm groups were also examined.
Two rats died during the study, one in the control group
and one in the 3000 ppm group, of an unspecified infection
unrelated to the administration of isophorone. The body
weights and food consumption were not significantly affected
at the end of the study by feeding isophorone although the
C-17
-------
body weight of the 3000 ppm male group was significantly
depressed for several weeks during the study. There was no
significant difference between the treated and control groups
regarding hematology, blood chemistry or urinalysis, and no
pathological lesions were observerd by either gross or micro-
scopic examination.
In the dog study, four male and four female beagles were
fed isophorone for 90 days at doses of 0, 35, 75 and 150
mg/kg/day, in gelatin capsules (food containing isophorone
was refused). The dogs were weighed weekly and bled monthly
»
for hematological blood chemistry evaluation, and urine was
collected and analyzed on the same schedule as the blood.
All the animals survived the study and were killed after 90
days and examined grossly. Twenty-eight selected tissues
from the control and high level (150 mg/kg) groups were ex-
amined histologically, as were liver and kidney specimens
from the intermediate exposure groups.
All dogs survived the study in excellent condition (EPA,
1979a). Food consumption was within normal limits and body
weight was not affected by treatment.
The hematology, biochemical, and urinalyses tests indi-
cated a lack of untoward effect of 90 doses of isophorone.
All organs appeared normal at gross examination and no sig-
nificant changes in organ weight were produced with the
ingestion of isophorone. There was no evidence of any de-
finitive signs of cellular change in any of the tissues
examined.
C-18
-------
Isophorone has been shown to be weakly irritating to the
skin of rabbits, but its effect was stronger on the ocular
mucosa where it induced reversible irritation of the conjunc-
tiva and corneal opacity (Truhaut, et al. 1972). These lat-
ter results are consistent with the moderate rabbit eye irri-
tation ratings for isophorone reported by Carpenter and Smyth
(1946) and Union Carbide (1963).
Effects on Humans: The most significant consequence of
human exposure to low levels of isophorone vapor is irrita-
tion of mucosal membranes. In this respect isophorone is
probably the most irritating of all ketonic solvents. Smyth
and Seaton (1940) reported that groups of 11 or 12 human
subjects exposed for a few minutes to measured concentrations
of 40, 85, 200 and 400 ppm isophorone in a small room experi-
enced eye, nose and throat irritation, but it appears that
these exposure concentrations were higher than actually
present (see discussion on page C-13). A few complaints of
nausea, headache, dizziness, faintness, inebriation and a
feeling of suffocation resulted from inhalation of isophorone
at 200 and 400 ppm in air. However, the symptoms of irrita-
tion and narcotic action were less severe at concentrations
of 40 and 85 ppm.
In a sensory threshold study, Silverman, et al. (1946)
exposed humans to the vapors of several industrial solvents
including isophorone. Twelve unconditioned subjects of both
sexes were exposed to the vapors for 15 minute periods in a
1200 ft3 chamber. They found that exposure to 25 ppm iso-
phorone produced irritation of the eyes, nose, and throat,'
C-19
-------
and that isophorone vapors were considered by the subjects to
be the most irritating of all the ketonic solvents tested.
The highest tolerable level for an eight hour isophorone ex-
posure was judged to be 10 ppm by a majority of the subjects.
It should be noted that the concentration of isophorone in
the exposure chamber was calculated (nominal) rather than
measured analytically, so the true concentration may have
been different than reported (NIOSH, 1978).
Union Carbide (1963) indicated that one-minute exposures
to 200 ppm isophorone are intolerable for humans. A concen-
tration of 40 ppm was intolerable to half of an unspecified
number of human volunteers after four minutes. Union Carbide
also noted that isophorone did not cause allergic contact
sensitization in any of the ten human volunteers.
Synergism and/or Antagonism
Smyth and coworkers (1969, 1970) have examined the joint
toxic action of isophorone with 26 industrial liquid chemi-
cals based on acute LDso's from oral intubations of female
albino rats. In the initial study (Smyth, et al. 1969),
LDso's were determined for each of the compounds alone and
for 1:1 (v/v) mixtures of the compounds. Based on the as-
sumption' of simple similar action, isophorone evidenced
greater than additive toxicity in combination with nine com-
pounds and less than additive toxicity in combination with 17
compounds. The significance of the interactions was deter-
mined by modifying the interactive ratios (predicted/observed
LC50) so' that the distribution approximated normality. Sig-
C-20
-------
nificant interaction was then defined as those ratios which
were beyond 1.96 standard deviations from the mean ratio. By
this criterion, none of the mixtures containing isophorone
deviated significantly from the assumption of simple similar
action. In a subsequent study (Smyth, et al. 1970), equal
volume mixtures of isophorone and propylene oxide showed
markedly less than additive toxicity but equitoxic mixtures
showed slightly greater than additive toxicity.
Teratogenicity
Isophorone has apparently not been tested for terato-
genicity.
Mutagenicity
No mutagenicity data for isophorone were encountered in
the published literature.
Carcinogenicity
Isophorone has tentatively been selected for carcino-
genesis testing in rats and mice by gavage by the National
Cancer Institute (NCI, 1979). Apparently, isophorone was
selected on the basis of its reported presence in municipal
water supplies, the large number of workers exposed indus-
trially (>1,500,000), a projected increase in production
levels (>25 million pounds are currently being produced), and
the existing paucity of epidemiological, animal and metabolic
information (Personal communication, 1979).
C-21
-------
CRITERION FORMULATION
Existing Guidelines and Standards
The current eight-hour time-weighted average threshold
limit value (TLV) for isophorone established by the American
Conference of Governmental Industrial Hygienists (1977) is 5
ppm (~ 28 mg/m3). The TLV was lowered from 25 ppm (<-*140
mg/m3) to 5 ppm in response to a June 1973 communication
from the Western Electric Company to the TLV committee re-
garding fatigue and malaise among workers exposed to levels
of 5 to 8 ppm for one month (Am. Conf. Gov. Ind. Hyg., 1974).
When isophorone levels in air were lowered to 1 to 4 ppm
(/^ 6-23 mg/m3) by increasing exhaust ventilation, no fur-
ther complaints were received.
The current U.S. Federal standard for occupational expo-
sure to isophorone is 25 ppm (140 mg/m3) as an eight-hour
time-weighted average concentration limit in the air of the
working environment (Occup. Safety Health Admin., 1974).
This standard is based on the TLV adopted by the ACGIH in
1968, and is intended to prevent irritative and narcotic ef-
fects. The National Institute for Occupational Safety and
Health (NIOSH) currently recommends a permissible exposure
limit of 4 ppn (23 mg/m3) as a TWA concentration for up to
a 10-hour workshift, 40-hour work week (Natl. Inst. Occup.
Safety Health, 1978). The NIOSH recommended standard is es-
sentially based on the 1974 ACGIH TLV documentation.
Isophorone was exempted from the requirement of a toler-
ance und?er the Federal Food, Drug and Cosmetic Act when used
as an inert solvent or cosolvent in pesticide formulations
C-22
-------
before a crop emerges from the soil, and for post-emergence
use both on rice before the crop begins to head and on sugar
and table beets (U.S. EPA, 1974b).
Current Levels of Exposure
As detailed in the Exposure section of this report, only
limited monitoring data are available regarding levels of
isophorone in water, and virtually no information is avail-
able on ambient levels in air or food. Since there is a lack
of extensive monitoring data on isophorone levels in drinking
water, it is difficult to predict the magnitude or extent of
human population exposure.
Although isophorone has been detected at levels of less
than 3 ppt in several water samples, a maximum daily intake
can be calculated from the highest reported level (9.5 y.g/1;
U.S. EPA, 1975) by assuming that 100 percent exposure comes
from the ingestion of water and fish and shellfish from con-
taminated waters. Assuming: (a) an average daily consump-
tion of 2 liters of water plus 18.7 grams fish/shellfish; (b)
a bioconcentration factor of 16 (U.S. EPA, 1979b); and (c)
100 percent gastrointestinal absorption of the ingested iso-
phorone; then the daily intake of isophorone from water would
be 21.8 ug/day (9.5 y.g/1 x [2 liters + (16 x 0.0187)] x
1.0).
Special Groups at Risk
Certain occupations (particularly individuals who are
exposed to isophorone as a solvent) have elevated levels of
exposure relative to the general population.
C-23
-------
Basis and Derivation of Criterion .
Based on the available data on the toxicological effects
of isophorone absorption in both man and experimental ani-
mals, a calculated water quality criterion for isophorone can
only be based upon a non-carcinogenic end point. Water
quality criteria may therefore be derived from the TLV, acute
oral LDso values, or from subacute oral toxicity data using
non-carcinogenic biological responses. Criteria derivations
based on all three approaches are presented below.
Criterion Based on TLV: Stokinger and Woodward (1958)
presented a method for calculating equivalent water quality
levels from TLV's. Essentially, this method consists of
deriving an acceptable daily intake (ADI) from the TLV by
making assumptions on breathing rate, and respiratory and
gastrointestinal absorption. Stokinger and Woodward assumed
that the daily total pollutant uptake from air at the TLV
concentration can be safely tolerated, and that this safe
quantity of pollutant per day can-be similarly tolerated via
oral exposure. The ADI is then partitioned into permissible
amounts from drinking water and from other sources.
The International Commission on Radiological Protection
(1974) has estimated that the "reference man" breathes 7.6 m3
of air during eight-hours of "light activity." Since respi-
ratory absorption rates are unknown, 50 percent absorption of
inhaled'isophorone will be assumed. In addition, the five
day per week TLV may be converted to a seven day per week
equivalent to reflect the more continuous pattern of exposure
C-24
-------
via drinking water. An ADI for man can be thus calculated
from the TLV by multiplying by these factors:
28 mg/m^ x7.6m^x0.5x5 days/7days = 76 mg/day
Since es-timates of isophorone exposure from non-water sources
are not available, it will be assumed that total isophorone
exposure is attributable to the ingestion of drinking water
and fish and shellfish. For the purpose of estimating a cri-
terion it will be further assumed that the maximal daily in-
take of water is 2 liters, that the consumption of fish/shell
fish amounts to 18.7 grams/day, and that the gastrointestinal
absorption of isophorone is 100 percent. Also a bioconcentra
tion factor of 16 has been calculated for fish (U.S. EPA,
1979b). A water quality criterion may then be calculated as:
76 mg/man _, ,. \
(21+ [16 x 0.0187]) x 1.0 ~ JJ mg/J-
It should be noted that the TLV is based on the preven-
tion of the irritant effects of isophorone from inhalation
exposures, rather than on chronic effects. Consequently, the
development of a criterion by this approach probably has
little validity in this case.
Criterion Based on Acute Oral Toxicity Data: McNamara
(1976) has suggested that data from acute exposures can be
used to estimate chronic no-effect levels for toxic responses
to chemical absorption. Based on an extensive review of the
literature comparing the results of acute and chronic toxicity
bioassays, McNamara noted that "for 95 percent of chemical
compounds...[on which data were available]...LD5Q/1000 will
C-25
-------
produce no effects in a lifetime." Using this approximation
for isophorone, and an average oral LD5Q value of 2 g/kg
(Effects section), the no-observable-effect level for iso-
phorone in rats can be estimated at 2 mg/kg/day. This value
may be converted into an ADI by applying an appropriate uncer-
tainty factor to account for species extrapolation and limita-
tions of the data. Since the chronic no-effect dose is merely
an estimate based on observed relationships between acute and
chronic toxicity, an uncertainty factor of 1,000 is recommended
(see Natl. Acad. Sci., 1977, p. 804). Thus, the estimated ADI
for man is ug/kg or 140 ug/roan, assuming a 70 kg body weight.
By assum ing that man consumes 2 liters of water per day, that
man is additionally exposed daily to 18.7 grams of fish and
shellfish which bioaccumulate isophorone from water by a factor
of 16, and that gastrointestinal absorption is 100 percent, the
corresponding no-adverse-effect level in water can be calcu-
lated as follows:
140 ug/day _ fi, .,
(21+ [16 x 0.0187]) x 1.0 ~ bl ug/1
Based on these calculations, the criterion for isophorone
should not exceed 0.06 mg/1.
Criterion Based on Subacute Oral Data: As summarized in
the Effects section, no significant effects were produced in
beagle dogs by feeding isophorone in gelatin capsules at
levels up to 150 mg/kg/day for 90 days (U.S. EPA, 1979a). Due
L
to the fact that this study did not involve a truly chronic ex-
C-26
-------
posure, the Natl. Acad. Sci. (1977) guidelines for establising
an acceptable daily intake for man are not directly applicable
McNamara (1976) has suggested, however, that subacute exposures
r
can be used to estimate chronic no-effect exposure levels.
McNamara (1976) found that for 95 percent of chemical 'com-
pounds for which data were available, a three-month no-effect
dose/10 will yield a level which should produce no adverse ef-
fects in a lifetime. By using this relationship, the chronic
no-effect dose for dogs is calculated to be:
150 ^ = 15 mg/kg
The application of an uncertainty factor of 1000 is suggested
to convert this value to an ADI (see Natl. Acad. Sci., 1977,
p. 804). Therefore, an estimated ADI for man is 15 ug/kg or
1,050 ug/man, assuming a 70 kg body weight. Consumption of 2
liters of water daily and of 18.7 grams of contaminated aquatic
organisms which have a bioconcentration factor of 16 would
result in, assuming 100 percent gastrointestional absorption of
isophorone, a maximum permissible concentration of 0.46 mg/1
for the ingested water:
1050 ug/dav
(21+ [16 x 0.0187]) x 1.0 *D/ ug/J-
In conclusion, criterion levels for isophorone can be esti-
mated on the basis of a TLV (33 mg/1), acute oral toxicity data
(0.06 mq/1), and a 90-day feeding study in dogs (0.46 mg/1).
C-27
-------
The most prudent approach at this time would be to
recommend only an interim criteria level pending the results of
future research, including the planned NCI bioassay. An in-
terim criterion of 0.46 mg/1 could be recommended in cases
where ambient water is the sole source of exposure to iso-
phorone, because the basis for this value is a well defined
no-effect level derived from a higher vertebrate species (dog)
subjected to subchronic oral exposure. Since current levels
of isophorone in water are usually less than 3 v.g/1, although
amounts as high as 9.5 ug/1 have been reported, an ample
margin of safety apparently exists.
In summary, based on the use of subchronic dog toxico-
logical data and an uncertainty factor of 1,000, the criterion
level of isophorone corresponding to an acceptable daily in-
take of 15 ug/kg/day, is 0.46 mg/1. Drinking water contrib-
utes 87 percent of the assumed exposure while eating contami-
nated fish products accounts for 13 percent. The criterion
level can similarly be expressed as 3.5 mg/1 if exposure is
assumed to be from the consumption of fish and shellfish pro-
ducts alone.
C-28
-------
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C-30
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«
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C-31
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Appendix
Calculation of appropriate isophorone concentration ThT
saturated air.
For a sample of ideal gas,
PV = nRT
where
P = pressure
V = volume
n = number of moles
R = universal gas constant
T = absolute temperature
Since n = - - , the ideal gas equation can be rearranged
mw
as follows to calculate the approximate number of grams of
compound contained in a particular volume of gas at a speci-
fied temperature and pressure:
PV - -2- RT
mw
_ PV(mw)
y RT
At 25°C, the vapor pressure of isophorone is 0.44mm.
Assuming a 1 liter volume of air,
0.44mm , ,.. ._„ ^,
x 1 liter x 138.21
760mm
g =
0.082 : x 2.98 «K
= 0.00327 g = 3.27 mg
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The approximate ppm equivalent concentration of iso-
phorone in saturated air can then be calculated from the
relationship:
(mg/1) (24,450 ml/mole)
mw ppm
(3.27 mg/1) (24,450 ml/mole) __a
138.21 g/mole = 578 ppm
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