,. . .e FINAL DRAFT
United States rrtn rrw n->7
Environmental Protection Cl.HU-UiN-b I c I
Agency February, 1991
SEPA Research and
Development
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR METHYLCYCLOHEXANE
Prepared for
OFFICE OF SOLID WASTE AND
EMERGENCY RESPONSE
Prepared by
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Environmental Protection Agency
Cincinnati, OH 45268
DRAFT: DO NOT CITE OR QUOTE
HOTICE
This document Is a preliminary draft. It has not been formally released
by the U.S. Environmental Protection Agency and should not at this stage be
construed to represent Agency policy. It Is being circulated for comments
on Its technical accuracy and policy Implications.
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DISCLAIMER
This report Is an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
Health and Environmental Effects Documents (HEEDs) are prepared for the
Office of Solid Waste and Emergency Response (OSWER). This document series
Is Intended to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for
emergency and remedial actions under the Comprehensive Environmental
Response, Compensation and Liability Act (CERCLA). Both published
literature and Information obtained for Agency Program Office files are
evaluated as they pertain to potential human health, aquatic life and
environmental effects of hazardous waste constituents. The literature
searched for In this document and the dates searched are Included 1n
"Appendix: Literature Searched." Literature search material Is current up
to 8 months previous to the final draft date listed on the front cover.
Final draft document dates (front cover) reflect the date the document Is
sent to the Program Officer (OSWER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include: Reference doses
(RfDs) for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfD, Is an estimate of an
exposure level which would not be expected to cause adverse effects when
exposure occurs during a limited time Interval I.e., for an Interval which
does not constitute a significant portion of the Hfespan. ThU type of
exposure estimate has not been extensively used, or rigorously defined as
previous risk assessment efforts have focused primarily on lifetime exposure
scenarios. Animal data used for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfDs 1s the same as traditionally employed for chronic estimates,
except that subchronlc data are utilized when available.
In the case of suspected carcinogens, a carcinogenic potency factor, or
q-|* (U.S. EPA, 1980), 1s provided. . These potency estimates are derived
for both oral and Inhalation exposures where possible. In addition, unit
risk estimates for air and drinking water are presented based on Inhalation
and oral data, respectively. An RfD may also be derived for the noncarclno-
genU health effects of compounds that are also carcinogenic.
Reportable quantities (RQs) based on both chronic toxlclty and
carclnogenlcUy are derived. The RQ Is used to determine the quantity of a
hazardous substance for which notification, 1s required In the event of a
release as specified under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). These two RQs (chronic toxlclty
and cardnogenldty) represent two of six scores developed (the remaining
four reflect IgnHablHty, reactivity, aquatic toxlclty, and acute mammalian
toxlclty). Chemical-specific RQs reflect the lowest of these six primary
criteria. The methodology for chronic toxlclty and cancer based RQs are
defined 1n U.S. EPA, 1984 and 1986a, respectively.
Ill
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EXECUTIVE SUMMARY
Hethylcyclohexane Is the name used by the 9th Collective Indices of the
CAS to define the cyclic hydrocarbon also known by the synonyms cyclohexyl-
methane and hexahydrotoluene and the trade name Sextone B (Chemllne, 1990;
SANSS. 1990). Methylcyclohexane Is a volatile, colorless liquid that Is
only slightly soluble In water (R1dd1ck et al., 1986; Sax and Lewis. 1987).
Phillips Petroleum Company In Borger, TX. 1s the sole U.S. producer of this
compound (SRI, 1989). Data regarding Us current production volumes are not
available. Methylcyclohexane Is derived from petroleum sources (Sax and
Lewis, 1987) and can be produced by the catalytic hydrogenatlon of toluene
(Campbell, 1987). Methylcyclohexane 1s used primarily as a component In the
feed to catalytic naphtha reformers producing high-octane gasoline. Some
methylcyclohexane Is used In organic synthesis and as a solvent for
cellulose ethers (Sax and Lewis, 1987).
In the atmosphere, methylcyclohexane Is expected to exist predominantly
In the gas phase. Experimental rate constants for the gas-phase reaction of
methylcyclohexane with photochemlcally produced hydroxyl radicals (Atkinson,
1985; Uno et al., 1985; Wellington et al.. 1988) Indicate that the half-life
for this reaction will be -2-4 days, suggesting that this may be a signifi-
cant removal process. Methylcyclohexane 1s not expected to undergo direct
photochemical degradation 1n the atmosphere or to react directly with ozone.
Removal by wet and dry deposition 1s not expected to be significant.
In water, methylcyclohexane Is expected to volatilize rapidly to the
atmosphere; however, adsorption to sediment and suspended organic matter
greatly reduced the rate of this process (Spain and Somervllle, 1985).
lv
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Various types of microorganisms Isolated from water can degrade methylcyclo-
hexane or are capable of using this hydrocarbon as a sole source of carbon
under aerobic conditions. These data Indicate that methylcyclohexane 1s
likely to blodegrade In environmental waters, although the rate of this
process has not been determined. Methylcyclohexane Is expected to adsorb to
sediment and suspended organic matter, but H 1s not expected to undergo
direct photolysis, hydrolysis or chemical oxidations In this medium.
Limited data suggest that methylcyclohexane .will undergo blodegradatlon
by acclimated organisms In soil (Cundell and Traxler, 1973). It 1s expected
to have slight to low mobility In soil, given Us physical properties. No
experimental data regarding the rate of volatilization of methylcyclohexane
from soil were located. Although this compound 1s relatively volatile, 1t
1s also expected to be adsorbed to soil. These competing processes do not
allow for an accurate estimation of how quickly methylcyclohexane will
volatilize from soil.
Methylcyclohexane may be released to the environment In fugitive
emissions during Its production, formulation or use. It may enter the
atmosphere In automobile exhaust (Nelson and Qulgley. 1984) and In stack
emissions from waste Incinerators (Junk and Ford. 1980). Methylcyclohexane
may be emitted to the atmosphere also from landfills, hazardous waste sites
(Vogt and Walsh, 1985; Young and Parker, 1984) or oil fires (Perry, 1971).
It may be released to surface water In the effluent of oil production
processes (Sauer, 1981a).
The National Occupational Exposure Survey estimated that 2925 people are
occupatlonally exposed to methylcyclohexane (NIOSH. 1989). Occupational
exposure may occur by Inhalation of methylcyclohexane vapors or by dermal
contact with the liquid. Methylcyclohexane has been detected 1n drinking
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water, surface water and groundwater samples. The general population may be
exposed to methylcyclohexane by the Ingestlon of contaminated water. The
dally mean atmospheric concentrations of methylcyclohexane In suburban areas
and urban areas was 0.4855 and 0.414 ppb. respectively (Shah and Heyerdahl.
1988). These atmospheric concentrations translate to a median dally human
Intake of 39 yg/day In suburban areas and 33.2 yg/day In urban areas,
using an average Intake of 20 m3 air/day. Some of the general population
may be exposed to higher than average levels of methylcyclohexane as a
result of Us presence In commercial products, gasoline and automobile
exhaust.
The general population may also be exposed to methylcyclohexane by
Ingesting food containing this compound. Methylcyclohexane has been
Identified In fried chicken (Tang et al., 1983), chickpeas (Rembold et al.,
1989), oysters and clams (Ferrarlo et al., 1985).
Data regarding the aquatic toxldty of methylcyclohexane were Inadequate
for deriving freshwater and saltwater criteria.
Acute studies with freshwater and saltwater organisms Indicated that £.
maqna. a freshwater crustacean, was the most sensitive species, with a
48-hour LCcQ of 1.4 mg/l (Bobra et al., 1983; Abernethy et al., 1986).
The saltwater crustaceans Artemla and C_. franclscorum and the saltwater
striped bass, M. saxatllls. were also very sensitive, with LC.-s of
2.5-4.5 mg/8. (Abernethy et al.. 1986; Benvllle et al., 1985). The fresh-
water midge, Chlronomldae. copepod, C. v1r1d1s. and golden shiner, N. cryso-
leucas. were less sensitive, with LCcrts as high as 1000 mg/l (Panlgrahl
bu
and Konar, 1989; Jenkins et al., 1977; Klein et al., 1975).
Chronic studies were performed on two freshwater fish. Egg hatchablllty
and fry development of flagflsh. J. Morldae. were not affected by
continuous-flow exposure to 0.83 mg/i methylcyclohexane for <87 days.
v1
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Mortality was significant In rainbow trout, S. qalrdnerl. exposed to >0.84
mg/l for 23 days. The LOEC was 0.80 mg/j. (Jenkins et al., 1977; Klein
et al., 1975).
B1oconcentrat1on studies with flagflsh and rainbow trout Indicate that
these animals may concentrate methylcyclohexane In concentrations up to 150
times those found 1n their environments (Jenkins et al., 1977; Klein et al..
1975). However, data were not sufficient for Independent analysis of the
study.
Photosynthesis was decreased 50% In freshwater algae. C_. vulgarls and C.
anqulosa. following exposure to -96 mg/l methylcyclohexane for 3 hours
(Hutchlnson et al., 1979). Ciliated bacteria had a toxlclty threshold of
8.6 mg/z (Rogerson et al., 1983).
Although quantitative studies of methylcyclohexane absorption were not
located, the available data Indicate that absorption occurs, to an unknown
extent, following Inhalation exposure (Chapter 6); that <89-93% of the dose
1s absorbed following oral exposure (Elliott et al., 1965) and that absorp-
tion Is probably not significant following dermal exposure (Treon et al..
1943b). In rabbits given 14C-methylcyclohexane orally, 54.2-77.4% of
radioactivity was recovered as metabolites (mostly methylcyclohexanols, and
especially those hydroxylated at the 3 and 4 positions, conjugated with
glucuronlc acid) 1n the urine within 58-68 hours (Elliott et al., 1965). A
•
significant amount of radioactivity (13-21%) was also found In the expired
air, mostly as unchanged methylcyclohexane (4.4-15.9%), but also as CO
(5.0-8.6%). Trace amounts of radioactivity (0.4-0.7%) were found In the
feces. Only 2.8-5.9% radioactivity remained In the body tissues after 58-68
hours. In rats given methylcyclohexane orally, methylcyclohexanedlols were
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the predominant urinary metabolites of methylcyclohexane. although methyl-
cyclohexanols were also present (Parnell et al., 1988). In an In vitro test
using rat, mouse, rabbit and guinea pig liver mlcrosomes. hydroxylatIon
occurred at all positions of the methylcyclohexane molecule (although
3-methylcyclohexanol was the main hydroxylatlon product, the tertiary CH
bond was the favored site), and further hydroxylatlon to dlols did not occur
(Frommer et al., 1970).
There was a marked Increase In the Incidence of nonneoplastlc kidney
lesions (medullary mineralization and papillary hyperplasla) In male rats
exposed to 2000 ppm of methylcyclohexane vapor Intermittently for 1 year and
held for an additional year before pathological examination (Klnkead et al.,
1985). No kidney lesions, or any other type of lesion (neoplastlc or
nonneoplastlc), were found In female rats, or In mice, hamsters or dogs.
Apparent reductions 1n body growth In male rats and hamsters exposed to >400
ppm were <10% of control body weights and were not statistically tested. No
other effects were reported. No effects were seen In animals exposed to
<1162 ppm of methylcyclohexane Intermittently for 10 weeks (Treon et al.,
1943a).
Acute studies Identified lethal levels of methylcyclohexane by Inhala-
tion, oral and dermal exposure In animals. In single-exposure Inhalation
studies of 1-2 hours, minimum lethal concentrations 1n animals were between
»
10,000 and 15,227 ppm (Lazarew, 1929; Treon et al., 1943a). Concentrations
as low as 7308 ppm caused death In repeated-exposure Inhalation experiments
(Treon et al., 1943a). The minimum lethal dose for oral exposure was
estimated to be between 4.0 and 4.5 g/kg; for dermal exposure 1t was
estimated to be >86.7 g/kg (Treon et al., 1943b).
vlll
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TABLE OF CONTENTS
1. INTRODUCTION 1
1.1. STRUCTURE AND CAS NUMBER 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES ' 1
1.3. PRODUCTION DATA 2
1.4. USE DATA 2
1.5. SUMMARY 2
2. ENVIRONMENTAL FATE AND TRANSPORT 4
2.1. AIR 4
2.1.1. Reaction with Hydroxyl Radicals 4
2.1.2. Reaction with Ozone 4
2.1.3. Photolysis 4
2.1.4. Physical Removal Processes 5
2.2. WATER 5
2.2.1. Hydrolysis 5
2.2.2. Oxidation 5
2.2.3. Photolysis 5
2.2.4. Mlcroblal Degradation 5
2.2.5. Adsorption 6
2.2.6. Volatilization 6
2.3. SOIL 7
2.3.1. Mlcroblal Degradation 7
2.3.2. Adsorption • 7
2.3.3. Volatilization 7
2.4. SUMMARY. 8
3. EXPOSURE 10
3.1. WATER 10
3.2. FOOD , 11
3.3. INHALATION 12
3.4. DERMAL 13
3.5. OTHER 13
3.6. SUMMARY 15
4. ENVIRONMENTAL TOXICOLOGY ' 16
4.1. AQUATIC TOXICOLOGY . . . . 16
4.1.1. . Acute Toxic Effects on Fauna 16
4.1.2. Chronic Effects on Fauna 16
4.1.3. Effects on Flora 18
4.1.4. Effects on Bacteria 18
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TABLE.OF CONTENTS (cont.)
4.2. TERRESTRIAL TOXICOLOGY 18
4.2.1. Effects on Fauna 18
4.2.2. Effects on Flora • 19
4.3. FIELD STUDIES 19
4.4. AQUATIC RISK ASSESSMENT. 19
4.5. SUMMARY 22
5. PHARMACOKINETCS 23
5.1. ABSORPTION 23
5.2. DISTRIBUTION 23
5.3. METABOLISM 23
5.4. EXCRETION 25
5.5. SUMMARY 26
6. EFFECTS 27
6.1. SYSTEMIC TOXICITY 27
6.1.1. Inhalation Exposure 27
6.1.2. Oral Exposure 29
6.1.3. Other Relevant Information 29
6.2. CARCINOGENICITY 32
6.2.1. Inhalation 32
6.2.2. Oral 33
6.2.3. Other Relevant Information 33
6.3. GENOTOXICITY 33
6.4. DEVELOPMENTAL TOXICITY 33
6.5. OTHER REPRODUCTIVE EFFECTS 33
6.6. SUMMARY 33
7. EXISTING GUIDELINES AND STANDARDS 35
7.1. HUMAN 35
7.2. AQUATIC 35
8. RISK ASSESSMENT 36
8.1. CARCINOGENICITY 36
8.1.1. Inhalation 36
8.1.2. Oral 36
8.1.3. Other Routes 36
8.1.4. Weight of Evidence 36
8.1.5. Quantitative Risk Estimates 36
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TABLE OF CONTENTS (cont.)
8.2. SYSTEMIC TOXICITY.
8.2.1. Inhalation Exposure 36
8.2.2. Oral Exposure 38
9. REPORTABLE QUANTITIES 39
9.1. BASED ON SYSTEMIC TOXICITY 39
9.2. BASED ON CARCINOGENICITY 39
10. REFERENCES 43
APPENDIX A: LITERATURE SEARCHED 57
APPENDIX B: SUMMARY TABLE FOR METHYLCYCLOHEXANE 60
APPENDIX C: DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO
METHYLCYCLOHEXANE 61
xin
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LIST OF TABLES
No. TUIe Page
3-1 Methylcyclohexane In Ambient Air Samples 14
4-1 Acute Toxlclty of Methylcyclohexane to Aquatic Fauna 17
9-1 Inhalation Toxlclty Summary for Methylcyclohexane 40
9-2 Inhalation Composite Scores for Methylcyclohexane 41
9-3 Methylcyclohexane: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 42
X 1 V
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LIST OF ABBREVIATIONS
CAS Chemical Abstract Service
CS Composite score
F344 Fischer 344
HEC Human equivalent concentration
Koc Soil sorptlon coefficient standardized
with respect to organic carbon
Kow Octanol/water partition coefficient
LCso Concentration lethal to 50% of recipients
LOEC Lowest-observed-effect concentration
MATC Maximum acceptable toxicant concentration
HTO Maximum tolerated dose
NADPH N1cot1nam1de adenlne dlnucleotide phosphate
(reduced form)
NOAEL No-observed-adverse-effect level
NOEC No-observed-effect concentration
ppb Parts per billion
ppbC Parts per billion carbon
ppbv Parts per billion by volume
ppm Parts per million
RfC Reference concentration
RfD Reference dose *
RQ Reportable quantity
RVd Dose-rating value
RVe Effect-rating value
TLV Threshold limit value
TWA Time-weighted average
UV Ultraviolet
v/v Volume per volume
xv
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1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
Methylcyclohexane Is the name used by the CAS for the cyclic hydrocarbon
also known as cyclohexylmethane and hexahydrotoluene and the trade name
Sextone B (Chemllne. 1990; SANSS, 1990). The structure, CAS Registry
number, empirical formula and molecular weight of methylcyclohexane are as
follows:
CAS Registry number: 108-87-2
Empirical formula: C7H.
Molecular weight: 98.19
1.2. PHYSICAL AND CHEMICAL PROPERTIES
Methylcyclohexane Is a colorless, liquid hydrocarbon that Is only
slightly soluble In water {Rlddlck et al.. 1986; Sax and Lewis. 1983).
Selected physical properties of methylcyclohexane are as follows:
Melting point:
Boiling point:
Density (25°C):
Water solubility (25°):
Vapor pressure (25°C):
Log Kow:
Henry's Law
constant (25'C):
Flash point:
Conversion factor
(25°C):
-126.6°C
100.9°C
0.7651 g/mi
14 ppm
46 mm Hg
3.86
4.35xlO~J atm-mVmol
-3.89°C
1 mg/m3 * 0.249 ppm;
1 ppm = 4.01 mg/m3
Campbell, 1987
Campbell, 1987
Rlddlck et al.. 1986
Rlddlck et al., 1986
Rlddlck et al., 1986
Abernethy et al.,
1988
Nlrmalakhandan and
Speece, 1988
Sax and Lewis, 1987
0523d
-1-
08/22/90
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1.3. PRODUCTION DATA
According to U.S. EPA (1990). Phillips Chemical Company produced an
unreported amount of methylcyclohexane In 1977. Current data Indicate that
Phillips Petroleum Company 1n Borger, TX, Is the sole U.S. producer of this
compound (SRI, 1989). Current production volumes are not available.
Methylcyclohexane 1s derived from petroleum sources (Sax and Lewis,
1987) and 1s easily produced by the hydrogenatlon of toluene performed at
elevated pressure and temperature with the aid of a catalyst (Campbell,
1987). There 1s no current market for large-scale production of this
compound.
1.4. USE DATA
Methylcyclohexane Is used primarily as a component In the feed to
catalytic naphtha reformers, where 1t 1s readily dehydrogenated to toluene.
a high-octane gasoline component. Some methylcyclohexane Is used as a
solvent for cellulose ethers. In which H Is one component of a mixture of
compounds obtained from a narrow boiling range fraction of distilled
naphtha. Methylcyclohexane 1s used in organic synthesis (Campbell, 1987;
Sax and Lewis, 1987) and Is also a component of gasoline and missile fuels
(Jamison et al., 1976; Spain and Somervllle. 1985).
1.5. SUMMARY
Methylcyclohexane Is the name used by the 9th Collective Indices of the
CAS to define the cyclic hydrocarbon also known by the synonyms cyclohexyl-
methane and hexahydrotoluene and the trade name Sextone B (Chemllne, 1990;
SANSS. 1990). Methylcyclohexane Is a volatile, colorless liquid that 1s
only slightly soluble In water (Rlddlck et al., 1986; Sax and Lewis. 1987).
Phillips Petroleum Company In Borger, TX, Is the sole U.S. producer of this
compound (SRI, 1989)'. Data regarding Its current production volumes are not
0523d -2- 08/22/90
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available. Methylcyclohexane Is derived from petroleum sources (Sax and
Lewis, 1987) and can be produced by the catalytic hydrogenatlon of toluene
(Campbell, 1987). Methylcyclohexane Is used primarily as a component 1n the
feed to catalytic naphtha reformers producing high-octane gasoline. Some
methylcyclohexane Is used 1n organic synthesis and as a solvent for
cellulose ethers (Sax and Lewis, 1987).
0523d -3- 08/22/90
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2. ENVIRONMENTAL FATE AND TRANSPORT
2.1. AIR
The vapor pressure of methylcyclohexane, 46 mm Hg at 25°C (Rlddlck et
al., 1986), suggests that this compound will exist predominantly In the gas
phase 1n the atmosphere (Elsenrelch et al., 1981).
2.1.1. Reaction with Hydroxyl Radicals. Experimental rate constants for
the gas-phase reaction of methylcyclohexane with photochemlcally produced
hydroxyl radicals range from 3.9xlO~12 cm3/molecule-sec to l.OSxlO"11
cmVmolecule-sec at 24°C (Atkinson, 1985; Uno et al., 1985; Walllngton et
al., 1988). Given an average • atmospheric HO- concentration of 5xlOs
\
molecule/cm3 (Atkinson, 1985), the half-life for this reaction would be
1.6-4.1 days. Indicating that this will be a significant removal process.
Methylcyclohexane may be more rapidly removed 1n polluted atmospheres
because of a higher concentration of HO* under these conditions. Air
samples collected during rush hour 1n downtown Los Angeles were Irradiated
with natural sunlight. After 6 hours, methylcyclohexane decreased -45% 1n
concentration (Kopczynskl et al., 1972).
2.1.2. Reaction with Ozone. Sixty-five different organic compounds
chosen to represent those found 1n a polluted urban center were Irradiated
in a smog chamber (Yanaglhara et al., 1977). These organic compounds were
ranked In order of decreasing reactivity with ozone. Methylcyclohexane was
ranked 39th, and nonreactlve methane was last. In general, the rate
constant's magnitude for the reaction of ozone with alkanes Is such that
these reactions are negligible under environmental conditions (Atkinson and
Carter, 1984).
2.1.3. Photolysis. Pertinent data regarding the direct photolysis of
methylcyclohexane Tn the atmosphere were not located 1n the available
0523d -4- 10/15/90
-------
IHerature cHed 1n Appendix A. Alkanes do not have functional groups
capable of absorbing UV radiation. Therefore, direct photolytk degradation
of methylcyclohexane 1n the environment 1s not likely.
2.1.4. Physical Removal Processes. Pertinent data regarding the physical
removal of methylcyclohexane From the atmosphere were not located 1n the
available literature dted In Appendix A. Its limited water solubility and
expected occurrence 1n the gas phase, however. Indicate that wet and dry
deposition are not expected to be significant removal processes.
2.2. WATER
2.2.1. Hydrolysis. Pertinent dSta regarding the hydrolysis of methyl-
cyclohexane were not located '1n the available literature cited In Appendix
A. Hydrocarbons generally do not have function groups susceptible to
hydrolysis under environmental conditions (Harris, 1982).
2.2.2. Oxidation. An experimental rate constant for the reaction of
methylcyclohexane with aqueous HO- 1s 8.6xlO~13 cm3/molecule-sec under
ambient conditions (Malllngton et al., 1988). Given an average HO-
concentration of 6xl03 molecules/cm3 In natural, sunlH waters (Mill et
al., 1980), a half-life of -ISO days can be estimated for this reaction,
which Is too slow to be significant under environmental conditions.
2.2.3. Photolysis. Pertinent data regarding the photolysis of methyl-
cyclohexane 1n water were not located In the available literature dted 1n
Appendix A. It Is not, however, expected to be a significant process (see
Section 2.1.3.)-
2.2.4. HUroblal Degradation. The available data suggest that methyl-
cyclohexane may undergo mlcroblal degradation In water under aerobic condi-
tions. Resting cell suspensions of Corynebacterlum sp. raised on octane
oxidized methylcyclohexane at 1/10 the rate of octane (Buswell and Jurtshuk,
0523d -5- 08/22/90
-------
1969). Methylcyclohexane, as a component of high-octane gasoline, was
degraded by 32 different types of organisms Isolated from groundwater. At
an Initial concentration of 1 ppm (v/v), methylcyclohexane In gasoline
underwent 75% blodegradatlon In 8 days by the mixed microorganisms (Jamison
et al., 1976). A strain of Xanthobacter sp. Isolated from soil and grown on
cyclohexane as the sole source of carbon degraded methylcyclohexane at a
rate of 3.1 ymols of oxygen/hour per mg of organism (Trower et al., 1985).
Bacteria Isolated from sediment taken from the Chedabucto Bay. Nova Scotia,
grew on solid media that contained methylcyclohexane (Cundell and Traxler.
1973).
Although these studies may not Indicate the rate at which methylcyclo-
hexane degrades In the environment, they suggest that there are a variety of
mlcroblal strains capable of degrading this hydrocarbon. Given the chance
for suitable acclimation, these microorganisms may readily blodegrade
methylcyclohexane In environmental waters.
2.2.5. Adsorption. The relatively strong adsorption of methylcyclohexane
to soil and Us limited water solubility Indicate that adsorption to
sediment and suspended organic matter Is likely to be a significant fate
process. Methylcyclohexane has been detected In sediment samples taken from
natural waterways (Ste1nhe1mer et al., 1981; Whelan et al.. 1988) (Section
3.1.).
2.2.6. Volatilization. When methylcyclohexane was added as a component
of high-density missile Fuel (7.IX by weight) and Incubated with water from
a salt marsh. It volatilized completely within 5 hours (Spain and
Somervllle. 1985). When sediment was added to the water sample, the time
for complete volatilization Increased to 80 hours. When the test was
repeated with water/sediment samples from a river, methylcyclohexane could
0523d -6- 08/22/90
-------
stm be detected after 120 hours. The rate of methylcyclohexane volatili-
zation In these experiments may not represent volatilization rates In the
environment; however, the general trends observed are consistent with those
predicted from the physical properties of this compound. Its relatively
high Henry's Law constant of 4.35XKT1 at 25°C atm/m'-mol suggests that
methylcyclohexane would volatilize rapidly from water, and Us propensity to
adsorb to soil (Section 2.3.2.) Indicates that the rate of volatilization
would be attenuated as methylcyclohexane adsorbs to sediment or suspended
organic matter.
2.3. SOIL
2.3.1. Mlcroblal Degradation. Experimental data regarding the degrada-
tion of methylcyclohexane 1n soil samples were limited 1n the available
literature. Bacteria Isolated from Alaskan soil samples contaminated by an
oil spill grew on solid media containing methylcyclohexane as the sole
carbon source (Cundell and Traxler, 1973). In aquatic systems, numerous
strains of microorganisms degraded methylcyclohexane. Therefore, It appears
that this compound has the potential to blodegrade under aerobic conditions
In soil.
2.3.2. Adsorption. Pertinent data regarding the adsorption of methyl-
cyclohexane to soil were not located In the available literature cited In
Appendix A. Using a regresslonal analysis (Lyman. 1982), K values of
1022 and 2998 can be calculated for methylcyclohexane from Us water solu-
bility (R1dd1ck et al.. 1986) and K (Abernethy et al.. 1988), respec-
tively. These values suggest that methylcyclohexane will have slight to low
mobility 1n soil; therefore. It may adsorb to soil (Swann et al., 1983).
2.3.3. Volatilization. Pertinent data regarding the volatilization of
methylcyclohexane from soil were not located In the available literature
0523d -7- 08/22/90
-------
cHed 1n Appendix A. Even though methylcyclohexane can be considered a
relatively volatile organic compound, H also has the potential to be
adsorbed to soil. These competing processes are both significant In deter-
mining the rate at which methylcyclohexane would volatilize from soil to the
atmosphere; therefore, no reliable method of estimating the rate of this
process Is available.
2.4. SUMMARY
In the atmosphere, methylcyclohexane Is expected to exist predominantly
In the gas phase. Experimental rate constants for the gas-phase reaction of
methylcyclohexane with photochemlcJlly produced hydroxyl radicals (Atkinson.
1985; Uno et al.. 1985; Walllngton et al.. 1988) Indicate that the half-life
for this reaction will be -2-4 days, suggesting that this may be a signifi-
cant removal process. Methylcyclohexane 1s not expected to undergo direct
photochemical degradation In the atmosphere or to react directly with ozone.
Removal by wet and dry deposition Is not expected to be significant.
In water, methylcyclohexane 1s expected to volatilize rapidly to the
atmosphere; however, adsorption to sediment and suspended organic matter
greatly reduced the rate of this process (Spain and Somervllle. 1985).
Various types of microorganisms Isolated from water can degrade methylcyclo-
hexane or are capable of using this hydrocarbon as a sole source of carbon
under aerobic conditions. These data Indicate that methylcyclohexane Is
likely to blodegrade In environmental waters, although the rate of this
process has not been determined. Methylcyclohexane 1s expected to adsorb to
sediment and suspended organic matter, but 1t Is not expected to undergo
direct photolysis, hydrolysis or chemical oxidations 1n this medium.
Limited data suggest that methylcyclohexane will undergo blodegradatlon
by acclimated organisms In soil (Cundell and Traxler. 1973). It 1s expected
0523d -8- 08/22/90
-------
to have slight to low mobility in soil, given Us physical properties. No
experimental data regarding the rate of volatilization of methylcyclohexane
from soil were located. Although this compound 1s relatively volatile. It
1s also expected to be adsorbed to soil. These competing processes do not
allow for an accurate estimation of how quickly methylcyclohexane will
volatilize from soil.
0523d -9- 08/22/90
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3. EXPOSURE
Methylcyclohexane may be released to the environment 1n fugitive
emissions during Us production, formulation or use. It may enter the
atmosphere In automobile exhaust (Nelson and Qulgley, 1984} and In stack
emissions from waste Incinerators (Junk and Ford, I960). The amount of
methylcyclohexane emitted to the atmosphere In the California South Coast
*
Air Basin, based on a 1974 estimate, was 6.5 kg/day (Grosjean and Fung,
1984). Methylcyclohexane may also be emitted to the atmosphere from land-
fills, hazardous waste sites (Vogt^ and Walsh. 1985; Young and Parker, 1984)
or oil fires (Perry, 1971). It may be released to surface water In the
effluent of oil-production processes (Sauer. 1981a).
The National Occupational Exposure Survey estimated that 2925 people are
occupatlonally exposed to methylcyclohexane and that 100% of the exposure
results from the use of trade-name products containing this hydrocarbon
(NIOSH, 1989). Occupational exposure may occur by Inhalation of methyl-
cyclohexane vapors or by dermal contact with the liquid.
3.1. WATER
Methylcyclohexane has been detected 1n drinking water, surface water and
groundwater samples. In 1976. it was detected In drinking water supplies In
England (Fielding et al.. 1981). It was detected as a minor component in
raw water samples obtained 1n 1972 from underground wells In Waterloo. IA
(Burnham et al., 1973) and qualitatively detected In 1/17 samples taken from
the Torresdale Water Treatment Plant in Philadelphia, PA from 1975-1977
(Suffet et al., 1980). Quantitative data regarding the level of methyl-
cyclohexane 1n U.S. drinking water supplies were not located In the avail-
able literature, artd It Is not possible to quantify levels of exposure to
this compound from ingestion of contaminated drinking water.
0523d -10- . 10/15/90
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Methylcyclohexane has been found In surface water near known sources of
release. It was detected 1n 7/8 samples taken from the Gulf of Mexico,
often wHh oil platforms 1n view, at concentrations of 0.4-6.9 mg/8. for
the positive samples (Sauer et a!., 1978), and at concentrations of 5-25
ng/l near coastal areas In samples taken during a 1977 expedition (Sauer.
1981b). The concentration of methylcyclohexane 1n water near an underwater
vent from an offshore oil production platform In the Gulf of Mexico was 1280
ng/9. (Sauer, 1981a).
Methylcyclohexane has been detected also 1n surface water, where the
source of release was unknown, ft was detected (but not quantified) In
water samples from the Delaware River 1n 1976 and 1977 (Sheldon and HUes,
1978). Sediment samples from the Calcasleu River, LA, In 1979 contained a
detectable amount of methylcyclohexane (Stelnhelmer et al., 1981). It was
also found In bottom sediments from the Guaymas Basin, Gulf of California,
and sediment samples taken from a deep-sea drilling project (Whelan et al.,
1988).
Methylcyclohexane was detected also In groundwater samples obtained near
a commercial/residential and Industrial landfill 1n England during 1984-1985
(Baxter. 1985).
3.2. FOOD
The general population may be exposed to methylcyclohexane by Ingesting
food that contains the compound. Methylcyclohexane was Identified In fried
chicken (Tang et al., 1983) and chickpeas (Rembold et al., 1989). Concen-
trations of 1.3 and 0.9 ppb were detected In oysters and clams, respec-
tively, from Lake Pontchartraln, LA. 1n 1980 (Ferrarlo et al., 1985).
0523d -11- • 08/22/90
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3.3. INHALATION
The presence of methylcyclohexane 1n automobile exhaust Indicates that
the general population living In urban and suburban areas Is likely to be
exposed routinely to low levels of this compound. A concentration of 13
yg/hour methylcyclohexane was detected In the exhaled air of 1/7 nonsmok-
ing, urban subjects (Conkle et al., 1975). It was detected In 2/12 breath
samples obtained 1n 1980 from Individuals living In urban areas of New
Jersey and North Carolina (Wallace et al., 1984). In a compilation of
published and unpublished data regarding the atmospheric concentration of
volatile organic compounds determined between 1970 and 1987, Shah and
Heyerdahl (1988) reported that the dally mean concentration of methylcyclo-
hexane 1s 0.4855 ppb 1n suburban areas and 0.414 ppb 1n urban areas. These
values were determined from 220 and 465 data points, respectively. Given
this Information and an average human air Intake of 20 m3/day, the median
Intake of methylcyclohexane would be 39 yg/day In suburban areas and 33.2
yg/day 1n urban areas.
Some members of the general population may be exposed to higher than
average levels of methylcyclohexane because of Its presence In commercial
products. Methylcyclohexane was detected 1n the air of Canadian homes where
hardwood floors were recently finished with a natural oil finish, although
It could not be detected In houses finished at least 4-5 months earlier (Van
Netten et al., 1988). Methylcyclohexane was also detected In the Indoor air
of homes In northern Italy (OebortoH et al.. 1986). Methylcyclohexane was
also detected at higher than ambient levels In the air of the Allegheny
Mountain Tunnel on the Pennsylvania Turnpike during 1979 (Hampton et al.,
1982), 1n roadside air samples (Stump and Dropkln, 1985; Zweldlnger et al.,
1988) and at hazardous waste sites 1n New Jersey (LaReglna et al., 1986).
0523d -12- '. 10/15/90
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Methylcyclohexane was detected (but not quantified)•In 5/18 samples taken In
and around a high-volume service station 1n Pennsylvania (Kearney and
Dunham. 1986).
Representative atmospheric concentrations of methylcyclohexane In the
United States are reported In Table 3-1. Methylcyclohexane has been
detected 1n the air of Sydney, Australia (Mulcahy et al.f 1976), Tokyo,
Japan (Uno et al., 1985), and In cities In the Union of Soviet Socialist
Republics (loffe et al.. 1979} and South Africa (Louw et al.. 1977).
Occupational exposure to methylcyclohexane 1s expected to occur mainly
by Inhalation of Its vapors. Concentrations of 1-2 and 3-800 jig/m3
methylcyclohexane were detected 1n the vulcanization area of a shoe sole
factory and 1n the vulcanization and extrusion areas of a tire retreading
facility, respectively (Cocheo et al., 1983). The mean air concentrations
of methylcyclohexane for workers In the gasoline Industry 1n the summer of
1984 were 0.152 mg/m3 for outside operators, 0.187 mg/m3 for transport
drivers and 0.151 mg/m3 for service station attendants (Rappaport et al.,
1987). It was detected In the air of 9% of printing. 16% of painting. 65%
of car repair and 3% of various Industries of 336 businesses monitored 1n
northern Belgium (Veulemans et al., 1987). Methylcyclohexane at a maximum
concentration of 0.07-6.99 mg/m3 was found 1n the air In 8/9 small screen-
printing plants In the Netherlands (Verhoeff et al., 1988).
3.4. DERMAL
Pertinent data regarding dermal exposure to methylcyclohexane were not
located In the available literature dted 1n Appendix A.
3.5. OTHER
Pertinent data regarding other routes of exposure to methylcyclohexane
were not located In the available literature cited In Appendix A.
0523d -13- 08/22/90
-------
o
en
CJ
CL
O
CD
03
O
TABLE 3-1
Methylcyclohexane In Ambient A1r Samples
Location
Tulsa. OK
Colorado remote site
Smokey Hat. Park, TN
Los Angeles
Jones State
TX
Houston, TX
Janesvl 1 le,
, CA
Forest,
WI*
Huntlngton Park, CA:
Ground Level
1500 feet
2200 feet
Los Angeles
, CA
Year
1978
1978
1978
1981
1978
1973-
1974
1977
1968
1968
Concentration
Range
3.0-36.5 ppbC
0-2.0 ppbC
0-0.9 ppbC
3-14 ppbv
1.3-9.2 ppbC
0-260 ppbC
1-1 .5 \jg/ma
3.5-15.6 ppb
0.3 ppb
0.1 ppb
68 ppbC
Average
11.4
1.16
0.43
NR
4.3
65.2
1.13
NR
NR
NR
NR
ppbC
ppbC
ppbC
ppbC
ppbC
wg/m3
Frequency
8/8
4/5
5/9
NR
15/15
13/21*
4/4
1/2
1/1
1/1
1/1
Reference
Arnts and Heeks, 1981
Arnts and Heeks, 1981
Arnts and Meeks, 1981
Grosjean and Fung, 1984
Sella, 1979
Lonneman et al., 1979
Sexton and Westberg,
Scott Research Labs,
Inc., 1969
1980
KopczynsM et al., 1972
•Downwind of an automotive painting plant
NR = Not reported
-------
3.6. SUMMARY
Methylcyclohexane .may be released to the environment 1n fugitive
emissions during Its production, formulation or use. It may enter the
atmosphere In automobile exhaust (Nelson and Qulgley, 1984) and In stack
emissions from waste Incinerators (Junk and Ford, 1980). Methylcyclohexane
may be emitted to the atmosphere also from landfills, hazardous waste sites
(Vogt and Walsh, 1985; Young and Parker, 1984) or oil fires (Perry. 1971).
It may be released to surface water In the effluent of oil production
processes (Sauer, 1981a).
The National Occupational Exposure Survey estimated that 2925 people are
occupatlonally exposed to methylcyclohexane (NIOSH, 1990). Occupational
exposure may occur by Inhalation of methylcyclohexane vapors or by dermal
contact with the liquid. Methylcyclohexane has been detected 1n drinking
water, surface water and groundwater samples. The general population may be
exposed to methylcyclohexane by the 1ngest1on of contaminated water. The
dally mean atmospheric concentrations of methylcyclohexane 1n suburban areas
and urban areas was 0.4855 and 0.414 ppb, respectively (Shah and Heyerdahl
1988). These atmospheric concentration translate to a median dally human
Intake of 39 vig/day 1n suburban areas and 33.2 yg/day 1n urban areas.
using an average Intake of 20 m3 air/day. Some of the general population
may be exposed to higher than average levels of methylcyclohexane as a
result of Us presence In commercial products, gasoline and automobile
exhaust.
The general population may also be exposed to methylcyclohexane by
Ingesting food containing this compound. Methylcyclohexane has been
Identified In fried chicken (Tang et al.. 1983), chickpeas (Rembold et al.,
1989), oysters and clams (Ferrarlo et al.. 1985).
0523d -15- 08/22/90
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4. ENVIRONMENTAL TOXICOLOGY
4.1. AQUATIC TOXICOLOGY
4.1.1. Acute Toxic Effects on Fauna. Studies on aquatic organisms and
the resulting acute LCcns are summarized In Table 4-1. Daphnla magna was
one of the most sensitive species, with a 48-hour LC._ of 1.4 mg/l
(Bobra et al., 1983; Abernethy et al.. 1986). Other freshwater Inverte-
brates and vertebrates were less sensitive, with 96-hour LC,Qs ranging
from 78 mg/l for the golden shiner, Notemlgonus crysoleucas (Jenkins et
al.. 1977; Klein et al.. 1975). to 1000 mg/l for the midge larvae,
Ch1ronom1dae (Panlgrah! and Konar, 1989). The saltwater crustaceans Artemla
and Crangon franclscorum were very sensitive to methylcyclohexane, with
LC..S of 3.36 mg/l (48-hour) (Abernethy et al., 1986) and 2.5 mg/l
(96-hour) (Benvllle et al., 1985), respectively. Similarly, the striped
bass, Horone saxatlHs. was very sensitive, with a 96-hour LC of 4.5
mg/l (Benvllle et al., 1985).
Trout (species not reported) exposed to at 5.0 mg/l methylcyclohexane
died In 13 minutes. Sea lamprey, Petromyzon marlnus. were not affected
following exposure to 5.0 mg/l for 24 hours (Applegate et al., 1957).
Jenkins et al. (1977) reported a 7-day lethal level between 0.83 and
1.85 mg/l for the flagflsh, Jordanella florldae. There were no mortali-
ties at concentrations <0.83 mg/l; however, all of the fish exposed to
1.85 mg/l died after 7 days.
4.1.2. Chronic Effects on Fauna.
4.1.2.1. TOXICITY — Jenkins et al. (1977) and Klein et al. (1975)
reported no effects on flagflsh, Jordanella florldae. egg hatchabHUy or
fry development following continuous-flow exposure to methylcyclohexane at
0.83 mg/l. The fry were exposed for 87 days. Rainbow trout. Sal mo
0523d -16- 08/22/90
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TABLE 4-1
Acute Toxlclty of Methylcyclohexane to Aquatic Fauna
o
U-l
(NJ
CJ
Q.
1
1
08/22/90
Median Response Concentration
Test (mq/l) Temperature Hardness
Species Type Effect pH (*C) (as cng/1 CaC03)
24 Hours 48 Hours 96 Hours
FRISHWATER
Oaphnla viatic NR 1.4 NR LC$n -6-7 23 NR
nvagna
Copepod static NR NR 865 LCso 7.2 27 286
(plank tonic )
Cyclops
vlrldls
Midge static NR NR 1000 LC50 7.2 27 286
larvae
Chlrono-
mldae
Golden static NR 136 78 LC$Q NR NR 100
shiner NR 87 87 LC$Q NR NR 25
Notemlqonus
chrysoleucas •
SALTWATER
Planktonlc static 3.6 -3.6 NR LC$Q NR 20 NR
crustacean
Ar temla
Bay shrimp static 2.7 NR 2.5 LC50 NR 15-20 salinity of
Cranqon 27-37X
franc Ucorum
Striped bass static 5.4 NR 4.5 LC;o NR 15-20 salinity of
Honone 27-37X
saxatl Us
Comments
Purity of at
least 97X
NC
NC
Technical
grade
Purity of at
least 97X; no
significant
difference
between 24- and
48-hour LCso* •
99X purity
99X purity
Reference
Bobra et al.. 1983;
Abernelhy et al.. 19B6
Panlgrahl and Konar,
1989
Panlgrahl and Konar.
1989
Jenkins et al.. 1977;
Klein et al.. 1975
Abernethy et al.. 1986
Benvllle et al.. 1985
Benvllle et al.. 1985
-------
galrdnerl, exposed to methylcyclohexane at 0, 0.31, 0.80, 0.84 and 1.19
mg/i for 23 days had no significant Increase In mortality at <0.80 mg/i;
however, significant mortality occurred at >0.84 mg/i. Mortality was 40%
at the highest concentration tested. Therefore, based on a NOEC of 0.80
mg/i and a LOEC of 0.84 mg/8., the HATC for rainbow trout 1s 0.82 mg/!i.
4.1.2.2. BIOACCUMULATION/BIOCONCENTRATION -- Jenkins et al. (1977)
and Klein et al. (1975) reported that the tissues of flagflsh, Jordanella
florldae. and rainbow trout, Salmo galrdnerl. exposed to methycycolhexane
under continuous-flow conditions for up to 87 days contained the chemical at
concentrations -ISO times that of their aqueous environments. However,
equilibrium may not yet have been reached.
4.1.3. Effects on Flora.
4.1.3.1. TOXICITY — Graphed data from Hutchlnson et al. (1979)
Indicated that the freshwater algae, Chlorella vulgarls and Chlamydomonas
angulosa. exposed to ~10~7 mol/a (96 mg/i) methylcyclohexane for 3
hours had a SOX reduction In photosynthesis. This Is extrapolated data of
very low reliability.
4.1.3.2. BIOCONCENTRATION — Pertinent data regarding the bloconcen-
tratlon potential of methylcyclohexane In aquatic flora were not located In
the available literature cited 1n Appendix A.
4.1.4. Effects on Bacteria. The toxldty threshold of methylcyclohexane
to the ciliated bacteria, Tetrahymena el*l1ott1. was 89.1 mmol/m3 (8.6
mg/i) (Rogerson et al.. 1983).
4.2. TERRESTRIAL TOXICOLOGY
4.2.1. Effects on Fauna. Pertinent data regarding the effects of
exposure of terrestrial fauna to methylcyclohexane were not located In the
available literature cited In Appendix A.
0523d -18- 08/22/90
-------
4.2.2. Effects on Flora. Pertinent data regarding the effects of
exposure of terrestrial flora to methylcyclohexane were not located In the
available literature dted In Appendix A.
4.3. FIELD STUDIES
Pertinent data regarding the effects of methylcyclohexane on flora and
fauna In the field were not located 1n the available literature dted In
Appendix A.
4.4. AQUATIC RISK ASSESSMENT
The lack of pertinent data regarding the effects of exposure of aquatic
fauna and flora to methylcyclohexane precluded the development of a
freshwater criterion by the method of U.S. EPA/OWRS (1986) (Figure 4-1).
Additional data required to develop a freshwater criterion Include the
results of acute assays with a salmonld fish species, a second fish species
or an amphibian, a benthlc crustacean, a nonarthropod and nonchordate
species and an Insect or species from a phylum not previously represented.
The development of a freshwater criterion also requires data from chronic
toxiclty tests with another species of fauna and one species of algae or
vascular plant and at least one bloconcentratlon study.
The lack of pertinent data regarding the effects of exposure of aquatic
fauna and flora to methylcyclohexane precluded the development of a
saltwater criterion by the method of U.S. EPA/OWRS (1986) (Figure 4-2).
•
Additional data required to develop a saltwater criterion Include the
results of acute assays with another chordate species, a nonarthropod and
nonchordate species and two additional nonchordate species. The development
of a saltwater criterion also requires data from chronic toxldty tests with
two species of fauna and one species of algae or vascular plant and at least
one bloconcentratlon study.
0523d -19- 08/22/90
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Family
GMAV"
TEST TYPE
GMCVa
BCF"
Chordate
Morone saxatilis
4.5
NA
NA
#2
Chordate
NA
NA
NA
S3
non-Arthropod/-Chordate
NA
NA
NA
54
Crustacean (Mysid/Panaeid)
Cranaon franciscorum
2.5E
NA
NA
a c
JTJ
non-Chordate
Artemia
non-Chordate
#7
non-Chordate
MO
ir°
other
#9
algae
#10
Vascular plant
3.6° NA NA
NA NA NA
NA NA NA
NA NA NA
XXXX NA NA *
XXXX NA NA
»NA=Not Available
b= a 96-h LC50 e= an approximate 48-h LC50
FIGURE 4-1
Organization Chart for Listing GHAVs, GMCVs and BCFs Required to Derive
Numerical Water Quall.ty Criteria by the Method of U.S.EPA/OWRS (1986) to
Protect Freshwater Aquatic Life from Exposure to Methylcyclohexane.
0523d
-20-
08/22/90
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TEST TYPE
Family
$1
Cnordate (Salmonid-f ish)
Salmo qairdneri
*2
Chordate (warnwater fish)
Notemiqonus crvsoleucas
*3
Chordate (fish or amphibian)
U f
•K *t
Crustacean (planktonic)
Daphnia magna
" ^
TT 3
Crustacean (benthic)
#6
Insectan
Chironomidae
* i
it 1
non-Arthropod/ -Chordate
JJQ
7TO
New Insectan or phylum
representative
410
ny
algae
no
Vascular plant
GMAV* GMCV3 BCF8
NA 0.82 NA
82 NA NA
NA NA NA
1.4 NA NA
NA NA NA
1000b NA NA
NA NA NA
NA NA NA
XXXX NA NA
XXXX NA NA
^
"NA=Not Available
b= a 96-h LC50
FIGURE 4-2
Organization Chart for Listing GMAVs. GMCVs and BCFs Required to Derive
Numerical Water Quality Criteria by the Method of U.S.EPA/OWRS (1986) to
Protect Saltwater Aquatic Life from Exposure to Methylcyclohexane.
0523d
-21-
08/22/90
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4.5. SUMMARY
Data regarding to the aquatic toxIcHy of methylcyclohexane were
Inadequate for deriving freshwater and saltwater criteria.
Acute studies with freshwater and saltwater organisms Indicated that £.
maqna. a freshwater crustacean, was the most sensitive species, with a
48-hour LC5Q of 1.4 mg/l (Bobra et al., 1983; Abernethy et al., 1986).
The saltwater crustaceans Artemla and C_. frandscorum and the saltwater
striped bass, M. saxatlHs. were also very sensitive, with LC.-S of
2.5-4.5 mg/l (Abernethy et al.. 1986; Benvllle et al., 1985). The fresh-
water midge, Ch1ronom1dae. copepod. C_. vlrldls. and golden shiner, N. cryso-
leucas. were less sensitive, with LC-.-S as high as 1000 mg/a. (Panlgrahl
3U
and Konar, 1989; Jenkins et al.. 1977; Klein et al., 1975).
Chronic studies were performed on two freshwater fish. Egg hatchablllty
and fry development of flagflsh, 2- florldae. were not affected by
continuous-flow exposure to 0.83 mg/j. methylcyclohexane for <87 days.
Mortality was significant In rainbow trout, S. qalrdnerl. exposed to >0.84
mg/i for 23 days. The LOEC was 0.80 mg/8. {Jenkins et al., 1977; Klein
et al., 1975).
Bloconcentratlon studies with flagflsh and rainbow trout Indicate that
these animals may concentrate methylcyclohexane In concentrations up to 150
times those found 1n their environments (Jenkins et al., 1977; Klein et al..
1975). However, data were not sufficient for Independent analysis of the
study.
Photosynthesis was decreased 50% 1n freshwater algae, C. vulqarls and C.
angulosa, following exposure to -96 mg/8. methylcyclohexane for 3 hours
(Hutchlnson et al., 1979). Ciliated bacteria had a toxldty threshold of
8.6 mg/i (Rogerson et al., 1983).
0523d -22- 08/22/90
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5. .PHARMACOKINETICS
5.1. ABSORPTION
Absorption of methylcyclohexane following oral exposure was not studied
quantitatively; Elliott et al. (1965), reported that gastrointestinal
absorption of an oral dose was <89-93%. Absorption following Inhalation
exposure was not studied quantitatively but can be Inferred from health
effects In animals exposed by this route (Section 6.1.1.). Absence of
mortality or sublethal systemic effects following high doses applied
dermally (Treon et al., 1943b) suggests that dermal absorption, 1f It occurs
at all, 1s less significant than that by the oral and Inhalation routes.
5.2. DISTRIBUTION
Elliott et al. (1965) reported that 60 hours after rabbits were treated
by gavage with "C-methylcyclohexane, unspecified tissues contained
2.8-5.9% of the dose of radioactivity.
5.3. METABOLISM
Adult female chinchilla rabbits were given a single 2.10-2.41 mmol/kg
(206-237 mg/kg) gavage dose of uniformly labeled 14C-methylcyclohexane
(containing <5% cyclohexane and <1% toluene Impurities) 1n water (Elliott et
al., 1965). Urinary excretion was the primary route of elimination of
radioactivity, accounting for 54.2-77.4% of the given dose, most of which
was contained 1n methylcyclohexanols present as conjugated glucuronldes.
[Increased glucuronlc add In the urine o*f rabbits exposed orally or by
Inhalation to methylcyclohexane was first reported by Treon et al.
(1943a,b)]. The methylcyclohexanols Identified (and the percent of dose
they represented In decreasing order of prevalence) were as follows: trans-
4-methyl-cyclohexanol (11.6-19.4%). cls-3-methylcyclohexanol (8.9-15.0%),
trans-3-methylcyclohexanol (8.5-11.9%), ds-4-methyl-cyclohexanol
(2.0-2.8%), trans-2-methylcyclohexanol (1.1-1.2%), ds-2-methylcyclohexanol
0523d -23- 10/15/90
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(0.3-0.7%). and cyclohexylmethanol (<0.2-0.3%). Other metabolites Identi-
fied In the urine were cyclohexanol (2.4-2.6%). which was probably derived
from cyclohexane contaminant present In the methylcyclohexane solution, and
benzole add (1.6-2.2%). some of which was probably derived from toluene
contaminant 1n the methylcyclohexane solution, but some of which must have
been formed from methylcyclohexane mixed with cyclohexanecarboxyllc acid.
Oxldatlve cleavage of the methylcyclohexane ring appears to be an alter-
native metabolic pathway for methylcyclohexane In rabbits, leading to the
production of C0?. Of the 13-21% of administered radioactivity recovered
1n the expired air In this study, 5.0-8.6% was present as CO.; the
remainder/was present as unchanged methylcyclohexane.
A different set of metabolites was Isolated from the urine collected for
48 hours from male F344 rats given a single dose of 800 mg/kg of methyl-
cyclohexane by gavage (Parnell et al.. 1988). Metabolites (and their
relative abundances). Identified by gas chromatography, were 2-transhydroxy-
4-c1s-methylcyclohexanol (23.4), 2-c1s-hydroxy-4-trans-methylcyclohexanol
(15.7), trans-3-methylcyclohexanol (10.1), 2-c1s-hydroxy-4-c1s-methylcyclo-
hexanol (2.1), trans-4-methylcyclohexanol (2.0), and cyclohexylmethanol
(1.0). Dlhydroxylatlon was the favored metabolic pathway In this species,
with the monoalcohols presumably serving as precursors of the cyclohexane-
dlols.
In an hi vitro study, methylcyclohexane'was added to hepatic mlcrosomes
prepared from rats, mice, rabbits and guinea pigs 1n the presence of NADPH
and oxygen (Frommer et al., 1970). In order to Induce mixed function
oxygenase activity, 50% of the rats, and all of the mice, rabbits and guinea
pigs were Injected with phenobarbHal prior to sacrifice. Gas chromato-
graphy revealed that hydroxylatlon occurred at all positions in the
molecule, although to different degrees. In contrast with the results of
0523d -24- 10/15/90
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Parnell et al. (1988), methylcyclohexanols were not further hydroxylated to
cyclohexanecMols under these conditions. The main hydroxylatlon product for
all four species was 3-methylcyclohexanol (combined els- and trans-lsomers).
This Is consistent with the results of \n vivo studies by Elliott et al.
(1965), In which combined c1s- and trans-3-methylcyclohexanol exceeded
combined 4-methylcyclohexanol In rabbits, and by Parnell et al. (1988). 1n
which 3-methylcyclohexanol was the most prevalent single hydroxylatlon
product 1n rats. The amount of hydroxylatlon at the 4 position was notice-
ably larger 1n rabbits than 1n other species, which Is also consistent with
^n vivo studies by Elliott et al. (1965) In which 4-methylcyclohexanol was
the predominant metabolite In rabbits, but not In rats (Parnell et al..
1988). Another difference among species was the occurrence of less
hydroxylatlon at the 1 position In rabbits and guinea pigs than In rats and
mice. Overall, hydroxylatlon of the secondary CH bonds (positions 2, 3 and
4) was favored significantly over hydroxylatlon of the primary CH bonds
(position w), which Is consistent with the ^ vivo results (Elliott et al.,
1965; Parnell et al., 1988). However, hydroxylatlon of the tertiary CH bond
(position 1) was greatest overall on a per bond basis. This Is In contrast
with the results of \n_ vivo studies, which did not detect the presence of
1-methylcyclohexanol following methyl eyelohexane exposure (Elliott et al..
1965; Parnell et al., 1988). Comparison of Induced and nonlnduced rats
revealed that pretreatment with phenobarbltaf had no effect on the results.
5.4. EXCRETION
The excretion of methylcyclohexane In rabbits was studied by Elliott et
al. (1965). Urine, feces and expired air were collected until activity In
the urine decreased to trace amounts (58-68 hours), at which time the
animals were sacrificed, and their tissues analyzed for radioactivity.
Total recovery of radioactivity was -90-94% In two rabbits, but only 65% In
0523d -25- 10/15/90
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one rabbit, because recovery of radioactivity In the expired air was In-
complete. Excluding . the data regarding the Incomplete recovery of
radioactivity, -13-21% of the administered radioactivity was recovered In
the expired air. Using data from all three rabbits, the recovered
radioactivity was 0.4-0.7% 1n the feces, 54.2-77.4% In the urine and
2.8-5.9% remaining 1n body tissues.
5.5. SUMMARY
Although quantitative studies of methylcyclohexane absorption were not
located, the available data Indicate that absorption occurs, to an unknown
extent, following Inhalation exposure (Chapter 6); that <89-93% of the dose
Is absorbed following oral exposure (Elliott et al., 1965) and that absorp-
tion 1s probably not significant following dermal exposure (Treon et al..
1943b). In rabbits given a«C-methylcyclohexane orally, 54.2-77.4% of
radioactivity was recovered as metabolites (mostly methylcyclohexanols, and
especially those hydroxylated at the 3 and 4 positions, conjugated with
glucuronlc add) In the urine within 58-68 hours (Elliott et al.. 1965). A
significant amount of radioactivity (13-21%) was also found In the expired
air. mostly as unchanged methylcyclohexane (4.4-15.9%). but also as CO.
(5.0-8.6%). Trace amounts of radioactivity (0.4-0.7%) were found 1n the
feces. Only 2.8-5.9% radioactivity remained In the body tissues after 58-68
hours. In rats given methylcyclohexane orally, methylcyclohexanedlols were
the predominant urinary metabolites of methylcyclohexane, although methyl-
cyclohexanols were also present (Parnell et al., 1988). In an \n vitro test
using rat, mouse, rabbit and guinea pig liver mlcrosomes. hydroxylatlon
occurred at all positions of the methylcyclohexane molecule (although
3-methylcyclohexanol was the main hydroxylatlon product, the tertiary CH
bond was the favored site), and further hydroxylatlon to dlols did not occur
(Frommer et al., 1970).
0523d -26- 10/15/90
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6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. Inhalation Exposure.
6.1.1.1. SUBCHRONIC — Groups of four rabbits (strain and sex not
specified) were .exposed to either 241 or 1162 ppm of methylcyclohexane vapor
6 hours/day. 5 days/week for 10 weeks, and observed for another 2 months
(Treon et al., 1943a). A single monkey (strain and sex not reported) was
exposed to 372 ppm according to the same experimental protocol. Liquid
methylcyclohexane In metered amounts was sprayed directly Into the air
stream to produce the vapor. The exposure concentration was determined by
passing the sampled air over platinum In a silica tube at high temperature
and weighing the carbon dioxide collected (high-dose group) or by using a
combustible gas Indicator (low-dose groups). Throughout the experiment
(exposure period and subsequent 2-month observation period), animals were
weighed, monitored for hematologlcal effects and observed for clinical signs
of toxldty. Gross and microscopic pathological examinations were performed
at the end of the 2-month observation period. Unexposed and sham-exposed
control rabbits were Included, but data from these groups were not
explicitly compared with data from test groups. No exposure-related effects
were reported 1n any subchronlc exposure group.
6.1.1.2. CHROMIC -- Klnkead et al. (1985) reported a study In which
•
groups of F344 rats (65 of each sex). C57BL/6J mice (200 females). Golden
Syrian hamsters (100 males) and purebred beagle dogs (4 of each sex) were
exposed to 0, 400 or 2000 ppm of methylcyclohexane vapor 6 hours/day, 5
days/week for 1 year. At the end of exposure. 10 rats, 20 mice and 10
hamsters from each group were sacrificed for comprehensive pathological
examination (Including hlstopathologlcal examination of -33 tissues). The
0523d -27- 10/15/90
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remaining rodents were observed for 1 year before sacrifice and patho-
logical examination; .dogs were observed for 5 years before necropsy.
Throughout the exposure and observation periods, body weight was monitored
1n rats and hamsters, and hematology and clinical chemistry parameters were
monitored In rats and dogs. Exposures were performed In large chambers (two
for each exposure concentration); vapors were generated by metering liquid
methylcyclohexane (-98% pure) directly Into the Inlet air supply stream of
the chambers. Analysis of chamber concentrations using a total hydrocarbon
analyzer revealed that actual concentrations were very close to nominal; the
mean measured concentrations differed from nominal by <1X, with standard
deviations between 0.63 and 2.6%, In each chamber.
Growth appeared to be reduced throughout the study In a dose-related
fashion 1n male rats of both exposure groups, but statistical comparisons
were not made. Time-weighted average body weights during exposure were
estimated, from data reported In the study, to be -330, 317 and 300 g 1n the
control, low- and high-dose groups, respectively. No depression of body
weight was seen In treated female rats. In hamsters (only males tested),
growth appeared to be reduced during exposure In both groups (TWA body
weights estimated from data reported 1n the study were 131. 115 and 113 g 1n
the control, low- and high-dose groups, respectively), but. as with rats, no
statistical comparisons were made. The apparent reductions In body weight
gain were all <1054 of control body weights and therefore were not considered
to be adverse. Hematology and clinical chemistry parameters were not
altered by exposure to methylcyclohexane. The pathology results Immediately
following exposure showed no exposure-related effects on the Incidence of
nonneoplastlc lesions In mice, hamsters or female rats. A renal effect 1n
high-dose male rats Was suggested by a very slight, apparent Increase In the
0523d -28- 10/15/90
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Incidence of renal tubular dilatation (4/11 at 2000 ppm versus 2/10 at 400
ppm and 1/11 at 0 ppm), which was not statistically significant. Following
an additional year of observation, high-dose male rats had significantly
Increased Incidences of medullary mineralization (36% at 2000 ppm versus
1.9% at 400 ppm and 3.6% at 0 ppm) and papillary hyperplasla (44% at 2000
ppm, vs. 1.9% at 400 ppm and 1.8% at 0 ppm) In the kidney. Indicating that
this organ Is a target of methylcyclohexane toxIcHy In male rats. Female
rats examined after the postexposure observation period did not have an
Increased Incidence of nonneoplastlc lesions In the kidney or any other
tissue. Terminal pathology results were negative In mice, hamsters and
dogs, as well.
6.1.2. Oral Exposure. Pertinent data regarding the subchronlc and
chronic oral toxldty of methylcyclohexane were not located In the available
literature cited In Appendix A.
6.1.3. Other Relevant Information. Acute Inhalation exposures to methyl-
cyclohexane were performed by Treon et al. (1943a) as part of the same study
described In Section 6.1.1.1. Groups of four rabbits were exposed to 2886
ppm for 3 weeks, 5567 ppm for 4 weeks, 7308 ppm for 2 weeks, 10.054 ppm for
2 weeks or 15,227 ppm for 70 minutes. The lowest concentration to cause
death was 7308 ppm (1/4 dead); exposure to higher concentrations resulted 1n
100% mortality. Sublethal effects progressed from mild, unspecified hlsto-
»
pathological lesions In the liver and kidney at 2886 ppm to slight lethargy
at 5567 ppm, lethargy and Incoordlnatlon at 7308 ppm, convulsions and light
narcosis at 10.054 ppm and severe convulsions and rapid narcosis at 15,227
ppm. Other effects In the two highest dose groups Included conjunctiva!
congestion, salivation, labored breathing, diarrhea and weight loss.
Hematology parameters, monitored In rabbits exposed to <10,054 ppm, were not
affected by exposure.
0523d -29- 10/15/90
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Klnkead et al. (1979) conducted a series of 1-hour Inhalation exposures
to methylcyclohexane, using rats, mice and dogs. In the first experiment,
20 male Sprague-Dawley rats and 20 female ICR mice were exposed to a mean
measured concentration of 6564 ppm and compared with untreated controls. In
each exposure group, 10 animals were sacrificed Immediately following
exposure, and the rest were observed for signs of stress and changes In body
weight for 28 days before sacrifice. Results were similar In both species.
HyperactWHy was noted Immediately after the start of exposure and was
followed by loss of coordination and eventually prostration. No signs of
stress were noted after the 1-hour exposure period. Body weight gain during
the 28-day observation period was comparable with that of controls. No
gross or microscopic lesions attributable to exposure were observed In rats
after the exposure or observation period.
After the first experiment, rats and mice were exposed to either 4172 or
4758 ppm, respectively, following the same protocol. Hyperactlvlty was the
only sign of stress noted In these animals. Body weight gain was not
affected. Upon necropsy, convoluted tubule adenomas of the kidney were
found In two of the rats exposed to 4172 ppm and held for 28 days, but these
lesions were not considered treatment-related since they were not seen In
rats exposed to a higher concentration. Some of the exposed mice had mild.
reversible cytoplasmlc changes In the liver.
Based on the results 1n rodents, four* purebred beagle dogs (sex not
specified) were exposed to a mean measured concentration of 4071 ppm for 1
hour and compared with a similar untreated control group. Following
exposure, the dogs were tested for ability to perform tasks they had been
taught previously, examined for neurological effects (a series of reflexes
were checked), monitored for hematology and serum chemistry changes, weighed
0523d -30- 10/15/90
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and, after the 28-day observation period, sacrificed for gross and
hlstopathologlcal examination. No exposure-related effects were reported.
Lazarew (1929) exposed mice to methylcyclohexane vapor for 2 hours In
hermetically sealed glass vessels. Experimental details-were not provided.
The minimum nominal concentration that caused the mice to assume a lateral
position was between 7500 and 10,000 ppm, and the minimum lethal concentra-
tion was between 10,000 and 12.500 ppm.
The acute oral toxlclty of methylcyclohexane In rabbits was studied by
Treon et al. (1943b). Four rabbHs survived single gavage doses of 1.0-4.0
g/kg, but four rabbits given 4.5-10.0 g/kg died within 84 hours. Based on
these data, the minimum lethal dose was estimated to be 4.0-4.5 g/kg.
Severe diarrhea occurred within 3 hours of dosing at lethal levels. No
convulsions, narcosis or other neurological effects were seen In the exposed
rabbits at any dose. Pathology results revealed the occurrence of severe
widespread vascular damage at lethal doses (fIbrlnocellular thrombi 1n the
capillaries and venules, and toxic coagulation necrosis In the heart, liver.
spleen and kidneys). Similar, but less extensive lesions were seen In
rabbHs that survived exposure to lower doses. Hematologlcal parameters,
which were monitored for 2 months following exposure, were not affected by
treatment.
The renal toxldty of methylcyclohexane following oral exposure was
•
studied by Parnell et al. (1988). Eight male F344 rats given 800 mg/kg by
gavage every other day for 2 weeks were compared with six control rats
treated with water. Rats were sacrificed 24 hours after exposure for
hlstopathologlcal examination of the kidneys. Special attention was paid to
hyaline droplet formation, tubular cysts and papillary calcification.
Results were not reported 1n detail, but the Investigators stated that only
slight traces of nephropathy were observed In the treated rats.
0523d -31- 02/20/91
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The toxlclty of methylcyclohexane following dermal application to
rabbits was studied by Treon et al. (1943b). Methylcyclohexane (60 mi)
was applied to a clipped 24-Inch area of the abdomen on 6 successive days.
Each day the chemical was allowed to remain In contact with the skin for 1
hour. Tests were conducted under a hood to prevent Inhalation of the
chemical. No deaths were reported; the minimum lethal dose was >86.7 g/kg.
Skin Irritation appeared on the second day and Increased over the course of
the experiment. Hardening, thickening and ulceratlon of the skin were seen
after several days. Unspecified lesions were found 1n the heart, liver and
kidney, but may have been caused by Intercurrent severe pulmonary Infection.
Methylcyclohexane produced severe membrane damage, leading to Increased
membrane permeability, 1n human dlplold embryonic lung flbroblasts tested \j\
vitro (Thelestam et al., 1980).
6.2. CARCINOGENICITY
6.2.1. Inhalation. Rats, mice, hamsters and dogs were Intermittently
exposed for 1 year to 0, 400 or 2000 ppm of methylcyclohexane (Klnkead et
al., 1985) (see Section 6.1.1.2.). Approximately 10% of the rodents were
necropsled at the end of the exposure period; the remaining rodents were
held for 1 year before necropsy. Dogs were examined after a 5-year
observation period. Sacrificed animals were given a thorough pathological
examination that Included hlstopathologlcal examination of -33 body tissues.
There was no exposure-related effect on the Incidence of any neoplastlc
lesion 1n any species at either time point. This study Is not considered
adequate for evaluation of cardnogenlclty, however, because H appears that
the MTD had not been reached In female rats, In mice, hamsters and dogs, and
the duration of exposure was considerably less than the llfespan of the
animals tested.
0523d -32- 10/15/90
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6.2.2. Oral. Pertinent data regarding the cardnogenlclty of methyl-
cyclohexane following oral exposure were not located 1n the available
literature dted In Appendix A.
6.2.3. Other Relevant Information. Other relevant Information regarding
the cardnogenlclty of methylcyclohexane was not located 1n the available
literature cited In Appendix A.
6.3. GENOTOXICITY
Pertinent data regarding the genotoxldty of methylcyclohexane were not
located In the available literature cited 1n Appendix A.
6.4. DEVELOPMENTAL TOXICITY
Pertinent data regarding the developmental toxlclty of methylcyclohexane
were not located In the available literature cited 1n Appendix A.
6.5. OTHER REPRODUCTIVE EFFECTS
Pertinent data regarding the other reproductive effects of methylcyclo-
hexane were not located 1n the available literature dted 1n Appendix A.
6.6. SUMMARY
There was a marked Increase 1n the Incidence of nonneoplastlc kidney
lesions (medullary mineralization and papillary hyperplasla) In male rats
exposed to 2000 ppm of methylcyclohexane vapor Intermittently for 1 year and
held for an additional year before pathological examination (Klnkead et al..
1985). No kidney lesions, or any other type of lesion (neoplastlc or
nonneoplastlc). were found 1n female rats* or In mice, hamsters or dogs.
Apparent reductions 1n body growth In male rats and hamsters exposed to >400
ppm were <10% of control body weights and were not statistically tested. No
other effects were reported. No effects were seen In animals exposed to
<1162 ppm of methylcyclohexane Intermittently for 10 weeks (Treon et al.,
1943a).
0523d -33- 10/15/90
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Acute studies Identified lethal levels of methylcyclohexane by Inhala-
tion, oral and dermal exposure In animals. In single-exposure Inhalation
studies of 1-2 hours, minimum lethal concentrations In animals were between
10,000 and 15,227 ppm (Lazarew, 1929; Treon et al., 1943a). Concentrations
as low as 7308 ppm caused death 1n repeated-exposure Inhalation experiments
(Treon et al., 1943a). The minimum lethal dose for oral exposure was esti-
mated to be between 4.0 and 4.5 g/kg; for dermal exposure It was estimated
to be >86.7 g/kg (Treon et al., 1943b).
Acute studies also described systemic effects not seen at the lower dose
levels tested 1n long-term studies. Systemic effects following Inhalation
exposure Included central nervous system effects (progressing from hyper-
activity at -4000 ppm, to Incoordlnatlon and prostration at -6500 ppm, to
convulsions and narcosis at -10,000 ppm) and other signs of stress (saliva-
tion, labored breathing and diarrhea at -10,000 ppm) (Klnkead et al., 1979;
Lazarew, 1929; Treon et al., 1943a). Following oral exposure, thrombus
formation In capillaries and coagulation necrosis In heart, liver, spleen
and kidneys were severe at lethal levels, and less extensive at lower dcses
(Treon et al., 1943b). Slight nephropathy was observed In male rats In an
acute oral study designed specifically to Investigate renal effects (Parnell
et al., 1988). Repeated dermal application of 60 ml produced local skin
Irritation and ulceratlon but no systemic evidence of toxlclty (Treon et
al.. 1943b).
No evidence of carcinogenic!ty from Inhalation exposure to methylcyclo-
hexane was observed In rats, mice, hamsters or dogs exposed Intermittently
for 1 year (Klnkead et al., 1985); however, the study was not adequate to
test the cardnogenlclty of the compound. Data were not located regarding
the cardnogenlclty of other routes of exposure or the genotoxlcl ty,
developmental toxlclty or other reproductive effects of methylcyclohexane.
0523d -34- 08/22/90
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7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
The TWA/TLV for exposure to methylcyclohexane during an 8-hour workday
and 40-hour workweek Is 400 ppm (ACGIH, 1989). This value was derived by
analogy to heptane, which has comparable acute toxldty (ACGIH, 1986). The
transitional OSHA permissible exposure limit Is 500 ppm, and the final rule
limit Is 400 ppm (OSHA, 1989).
7.2. AQUATIC
Guidelines and standards to protect aquatic life from exposure to
methylcyclohexane were not located In the available literature cited In
Appendix A.
0523d -35- 08/22/90
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8. RISK ASSESSMENT
8.1. CARCINOGENICITY
8.1.1. Inhalation. Intermittent 1-year exposure to methylcyclohexane
vapor at concentrations <2000 ppm had no effect on the Incidence of
neoplastlc lesions In rats, mice, hamsters or dogs examined 1 year (rodents)
or 5 years (dogs) after the exposure period ended (Klnkead et al.. 1985).
This study, however, was not adequate to test the cardnogenlclty of the
compound.
8.1.2. Oral. Pertinent data regarding the cardnogenlclty of methyl-
cyclohexane following oral exposure were not located In the available
literature cited In Appendix A.
8.1.3. Other Routes. Pertinent data regarding the cardnogen1c1ty of
methylcyclohexane by other routes of exposure were not located 1n the
available literature cited 1n Appendix A.
8.1.4. Weight of Evidence. No data were available regarding the cardno-
genlclty of methylcyclohexane In humans. An Inadequate 1-year study using
rats, mice, hamsters and dogs found no evidence of cardnogenlclty 1n
animals. Because of the lack of human data and Inadequate animal data,
methylcyclohexane was assigned to U.S. EPA (1986b) welght-of-evidence Group
D — not classifiable as to human cardnogenldty.
8.1.5. Quantitative Risk Estimates. The lack of positive data regarding
the cardnogenlclty of methylcyclohexane precluded quantitative estimation
of carcinogenic risk.
8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposure.
8.2.1.1. LESS THAN LIFETIME (SUBCHRONIC) — Treon et al. (1943a)
found no effects In groups of four rabbits exposed Intermittently to methyl-
cyclohexane at 241 or 1162 ppm (corresponding to adjusted concentrations of
0523d -36- 10/15/90
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173 or 833 mg/m3} (Rec. #6, Appendix C.2.1.) or In a monkey exposed Inter-
mUtently to 372 ppm (corresponding to an adjusted concentration of 267
mg/m3) (Rec. #7, Appendix C.2.1.) for 10 weeks. These data were not
considered adequate for deriving a subchronlc Inhalation RfC because of the
small number of animals tested. Therefore, the chronic RfC of 3 mg/m3 was
adopted as a conservative estimate for the subchronlc RfC. Confidence In
this RfC 1s medium (Section 8.2.1.2.).
8.2.1.2. CHRONIC — Klnkead et al. (1985) reported an Increase 1n the
Incidence of medullary mineralization and papillary hyperplasla In the
kidneys of male rats exposed Intermittently to methylcyclohexane at 2000 ppm
(equivalent adjusted concentration of 1434 mg/m3) for 1 year (Rec. #2,
Appendix C.2.1.). This effect was not found In male rats exposed to 400 ppm
(equivalent adjusted concentration of 287 mg/m3) (Rec. #1, Appendix
C.2.1.). Although reduced body weight gain was reported In male rats and
hamsters exposed to adjusted concentrations of >287 mg/m3 (Recs. #1 and 3,
respectively. Appendix C.2.1.), statistical comparisons with controls were
not made. Because the estimated TWA body weight 1n test animals differed
from controls by <10% In each group, these apparent changes were not
considered adverse.
The study by Klnkead et al. (1985) Identified the male rat as the most
sensitive species tested and as an appropriate model for the toxlclty of
methylcyclohexane. The adjusted NOAEL of 287 mg/m3 derived from this
study was used as the basis for the chronic RfC. Since pharmacoklnetlc data
to the contrary were not located. It was assumed that periodicity (net
uptake during each exposure Interval 1s equal to the amount eliminated In
the period between exposures) occurred and that blood/gas partition coeffi-
cients for methylcyclohexane are Identical In rats and humans. Therefore,
0523d -37- 05/07/91
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the NOAELHEC is Identical to the adjusted NOAEL of 287 mg/m3. An RfC of
3 mg/m3 was calculated by dividing the HEC by an uncertainty factor of 100
to account for Interspedes extrapolation and variation in sensitivity among
humans, and rounding to one significant digit.
Confidence In this study Is high; the study appears to have been
generally well designed and conducted. Confidence In the data base Is low
because no other chronic studies and no developmental and reproduction
studies were located. Overall confidence 1n the RfC Is medium.
8.2.2. Oral Exposure. The lack of subchronlc or chronic oral toxldty
data for methylcyclohexane precluded derivation of RfDs for oral exposure.
0523d -38- . 04/03/91
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9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The toxlclty of methylcyclohexane Is discussed 1n Chapter 6. Data
appropriate for the derivation of candidate CSs are summarized In Table 9-1.
These data were obtained from a single chronic Inhalation 'study using rats,
hamsters, mice and dogs (Klnkead et al,, 1985). The reported effects were
Irreversible kidney lesions (RV =6) In male rats and reduced body growth
(RV =4) In male rats and hamsters. Effects on body weight were Included
In this analysis, even though they were small (<10% change) and not verified
statistically, because they were reported by the authors. The candidate CSs
for the lowest human equivalent doses associated with each effect are
derived In Table 9-2. The CS for kidney lesions (6.00} was greater than
that for reduced growth (4.00). The RQ of 1000 derived from this CS 1s
presented In Table 9-3. This RQ represents the hazard associated with the
chronic (noncancer) toxlclty of methylcyclohexane.
9.2. BASED ON CARCINOGENICITY
Because of the lack of carclnogenlcUy data In humans, and the lack of
positive results In an Inadequate carclnogenldty study using animals
(Klnkead et al., 1985), methylcyclohexane 1s assigned to U.S. EPA
we1ght-of-ev1dence Group D. Hazard ranking and assignment of an RQ based on
carclnogenlcHy Is not performed for Group D compounds.
0523d -39- 10/15/90
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T'"E 9-1
Inhalation ToxIcHy Summary for Methylcyclohexanea»b
O
cn
CO
o.
Species/ Sex
Strain
Rat/F344 M
Rat/F344 H
I
-^*
o
1 Hamster/ H
Golden
Syrian
Average
No. at Weight0
Start (kg)
65 0.300
65 0.317
100 0.115
Transformed Equivalent
Exposure Animal Oosed Human Dose6
(mg/kg/day) (mg/kg/day)
2000 ppm 1424.05 231.31
for 1 year
6 hours/day,
5 days/week
(1434 mg/m3)
400 ppm 282.01 46.66
for 1 year
6 hours/day,
5 days/week
(287 mg/m3)
400 ppm 177.40 20.93
for 1 year
6 hours/day,
5 days/week
(287 mg/m3)
Response
Kidney lesions
Reduced growth
Reduced growth
o
CD
aSource: Klnkead et al., 1985
blhe vehicle/physical state was air and the purity of the compound was 98%.
Estimated from data provided by Investigators
^Calculated from the adjusted equivalent continuous exposure concentration, dividing by the estimated
average body weight, and multiplying by the Inhalation rate, which was calculated using the allometrlc
equations In U.S. EPA (1987).
Estimated by multiplying the animal dose by the cube root of the ratio of the animal body weight to the
reference human body weight (70 kg), which assumes that dose/unit surface area 1s equivalent across
species and that surface area 1s a function of body welght^/3 (Mantel and Schnelderman, 1975)
-------
TABLE 9-2
Inhalation Composite Scores for Methylcyclohexane
Chronic *
Species Animal Dose Human MEDb RVd Effect RVe CS RQ
(mg/kg/day) (mg/day)
Rat 1424.05
Hamster 177.40
16.191.87 1.00 kidney 6 6.00 1000
lesions
1.465.30 1.00 reduced 4 4.00 5000
growth
aSource: Klnkead et al., 1985
bHuman equivalent dose (mg/kg/day) from Table 9-1 multiplied by 70 kg to
express MED 1n mg/day for a 70 kg human
0523d
-41-
08/22/90
-------
TABLE 9-3
Methylcyclohexane
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: Inhalation
Species/Sex: rat/male
Dose*: 16.191.87 mg/day
Duration: 1 year
Effect: kidney lesions
RVd: 1.00
RVe: 6
CS: 6.00
RQ: 1000
Reference: Klnkead et al.t 1985
*Equ1valent human dose
0523d -42- 08/22/SO
-------
10. REFERENCES
Abernethy, S, A.M. Bobra. W.Y. Sh1u, P.G. Wells and D. Mackay. 1986. Acute
lethal toxldty of hydrocarbons and chlorinated hydrocarbons to two plank-
tonic crustaceans: The key role of organism-water partitioning. Aquat.
Toxlcol. (Amst). 8(3): 163-174.
Abernethy, S.6., D. Mackay and L.S. McCarty. 1988. "Volume fraction"
correlation for narcosis 1n aquatic organisms: The key role of partitioning.
Environ. Toxlcol. Chem. 7: 469-^48?.
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1986.
Documentation of the Threshold Limit Values and Biological Exposure Indices,
5th ed. Cincinnati, OH. p. 384.
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1989.
Threshold Limit Values and Biological Exposure Indices for 1989-1990.
Cincinnati, OH. p. 29.
Applegate, V.C., J.H. Howell. A.E. Hall, Jr. and M.A. Smith. 1957.
Toxldty of 4.346 chemicals to larval lampreys and fishes. Spec. Sd.
Rep.-Msh. No. 207, F1sh W1ldl. Serv. USOI, Washington, DC. p. 2, 48-49.
Arnts. R.R. and S.A. Heeks. 1981. Blogenlc hydrocarbon contribution to the
ambient air of selected areas. Atmos. Environ. 15: 1643-1651.
0523d -43- 08/22/90
-------
Atkinson, R. 1985. Kinetics and mechanisms of the gas-phase reactions of
hydroxyl radical with.organic compounds under atmospheric conditions. Chem.
Rev. 85: 69-201.
Atkinson. R. and W.P.L. Carter. 1984. Kinetics and mechanisms of the
gas-phase reactions of ozone under atmospheric conditions. Chem. Rev. 84:
437-470.
Baxter, K.H. 1985. The effects of a hazardous and a domestic waste
landfill on the trace organic quality of chalk groundwater at a site In East
Anglla. Scl. Total Environ. 47: 93-98.
Benvllle, P.E., Jr., J.A. Whlpple and H.B. Eldrldge. 1985. Acute toxldty
of seven allcycllc hexanes to striped bass, Horone saxatllls. and bay
shrimp, Cranqon franclscorum. In seawater. Calif. F1sh Game. 71(3):
132-140.
Bobra, A.M., W.Y. Shlu and D. Hackay. 1983. A predictive correlation for
the acute toxldty of hydrocarbons and chlorinated hydrocarbons to the water
flea (Daphnla maqna). Chemosphere. 12(9-10): 1121-1129.
Burnham, A.K., G.V. Calder, J.S. Fritz, G.A. Junk. H.J. Sulc and J. V1ck.
1973. Trace organlcs In water; their Isolation and Identification. AWWA J.
65: 722-725.
Buswell, J.A. and P. Jurtshuk. 1969. Mlcroblal oxidation of hydrocarbons
measured by oxygraphy (using a dark oxygen electrode). Arch. Mlkroblol.
64: 215-222.
0523d -44- 08/22/90
-------
Campbell, H.L. 1987. Cyclohexane. Ii±: Ullman's Encyclopedia of Industrial
Chemistry. Vol. A8. H. Gerhartz, Y.S. Yamamoto and L. Knudy, Ed. VCH
Publishers, New York, NY. p. 209-215.
Chemllne. 1990. National Library of Medicine Chemllne Data Base. Online
3/29/90.
Cocheo. V.. H.L. BeHomo and G.G. Bombl. 1983. Rubber manufacture:
Sampling and Identification of volatile pollutants. Am. Ind. Hyg. Assoc. J.
44: 521-527.
Conkle, J.P., B.J. Camp and B.E. Welch. 1975. Trace composition of human
respiratory gas. Arch. Environ. Health. 30: 290-295.
Crockett. P.W., B. Klllan. K.S. Crump and R.B. Howe. 1985. Descriptive
methods for using data from dissimilar experiments to locate a no-adverse-
toxic-effects region In the dose-duration plane. Prepared by K.S. Crump and
Company, Inc., Ruston, LA under Contract No. 68-01-6807 for the Environ-
mental Criteria and Assessment Office, U.S. EPA, Cincinnati, OH.
Cundell, A.M. and R.W. Traxler. 1973. Mlcroblal degradation of petroleum
at low temperature. Marine Poll. Bull. 4: 125-127.
Debortoll, M.. H. Knoeppel. E. Pecchlo et al. 1986. Concentrations of
selected organic pollutants In Indoor and outdoor air. Northern Italy.
Environ. Int. 12: 343-350.
0523d -45- 08/22/90
-------
Durkln, P. and W. Meylan. 1989. Users Guide for D2PLOT: A program for
dose/duration graphs: Version 2.02. Prepared by Syracuse Research Corpora-
tion, Syracuse. NY. under Contract No. 68-C8-0004 for the Environmental
Criteria and Assessment Office. U.S. EPA, Cincinnati, OH.
Elsenrelch, S.J.. B.B. Looney and J.O. Thornton. 1981. Airborne organic
contaminants In the Great Lakes ecosystem. Environ. Sd. Technol. 15:
30-38.
Elliott, T.H.. C. Rosaline. C. Taw and R.T. Williams. 1965. The metabolism
of methylcyclohexane. Blochem. J. 95(1): 70-76.
FerraMo, J.B., G.C. Lawler, I.R. Deleon and J.L. Laseter. 1985. Volatile
organic pollutants In biota and sediments of Lake Pontchartraln. Bull.
Environ. Contain. Toxlcol. 34: 246-255.
Fielding, H., T.H. Gibson. H.A. James, K. McLoughln and C.P. Steel. 1981.
Organic mlcropollutants In drinking water. TR-159. Water Research Center,
Medmenham, England. 49 p.
Frommer, U., V. Ulllrch and H. Staudlnger. 1970. Hydroxylatlon of
aliphatic compounds by liver mlcrosomes. I. The distribution pattern of
Isomerlc alcohols. Hlppe-Seyler's 2. Physlol. Chem. 38(8): 903-912.
Grosjean. 0. and K. Fung. 1984. Hydrocarbons and carbonyls In Los Angeles
air. J. Air Pollut. Control Assoc. 34: 537-543.
0523d -46- 08/22/90
-------
Hampton, C.V., W.R. Plerson, T.M. Harvey. N.S. Updegrove and R.S. Marano.
1982. Hydrocarbon gases emitted from vehicles on the road. I. A qualita-
tive gas chromatography/mass spectrometry survey. Environ. Scl. Techno!.
16: 287-298.
Harris, J.C. 1982. Rate of hydrolysis. In: Handbook of Chemical Property
Estimation Methods. W.J. Lyman. W.F. Reehl, D.H. Rosenblatt. Ed. McGraw
Hill Book Co.. New York, NY. Chapter 7.
Hutchlnson. T.C.. J.A. Hellebust* D. Mackay, D. Tarn and P. Kauss. 1979.
Relationship of hydrocarbon solubility to toxlclty 1n algae and cellular
membrane effects. Am. Pet. Inst. Publ. 4308: 541-547.
loffe, B.V., V.A. Isldorus and I.G. Zerkevlch. 1979. Certain regulatorles
1n the composition of volatile organic pollutants In the urban atmosphere.
Environ. Scl. Technol. 13: 864-868.
Jamison, V.W., R.L. Raymond and J.O. Hudson. 1976. Blodegradatlon of
high-octane gasoline. In: Proc. Int. Blodeg. Symp., 3rd ed., J.M. Sharpley
and A.M. Kaplan. Ed. Essex, England, p. 187-196.
Jenkins, D., S.A. Klein and R.C. Cooper. 1977. Fish toxlclty of Jet fuels.
I. The toxlclty of the synthetic fuel JP-9 and Us components. Water Res.
11: 1059-1067.
Junk, G.A. and C.S. Ford. 1980. A review of organic emissions from
selected combustion-processes. Chemosphere. 9: 187-230.
0523d -47- 08/22/90
-------
Kearney, C.A. and D.B. Dunham. 1986. Gasoline vapor exposures at a high
volume service station. Am. Ind. Hyg. Assoc. J. 47: 335-339.
Klnkead. E.R.. R.S. Bowers, H.G. Schneider and A.I. Hall. 1979. Methyl-
cyclohexane one-hour emergency exposure limit. Aerosp. Med. Res. Lab. ISS
AHRL-TR-79-68 Proc. Conf. Environ. Toxlcol. p. 154-160.
Klnkead. E.R., C.C. Haun, M.G. Schneider, E.H. Vernot and J.D. MacEwen.
1985. Chronic Inhalation exposure of experimental animals to methylcyclo-
hexane. Govt. Reports Announcements and Index. Issue 21. 29 p.
Klein, S.A., D. Jenkins and R.C. Cooper. 1975. The toxlclty to fish of the
Jet fuel JP-9. Us components RJ-4, RJ-5 and methylcyclohexane (HCH). Tech.
Rep. AMRL-TR-75-125, Aerosp. Med. Res. Lab. Paper No. 24: 429-455.
Kopczynskl, S.L., W.A. Lonneman, F.D. Sutterfleld and P.E. Darley. 1972.
Photochemistry of atmospheric samples 1n Los Angeles. Environ. Scl.
Technol. 6: 342-347.
LaReglna, J., J.W. Bozzell, R. Harkov and S. G1ant1. 1986. Volatility of
organic compounds at hazardous waste sites and a sanitary landfill In New
Jersey. An up-to-date review of the present situation. Environ. Prog. 5:
18-27.
Lazarew, N.W. 1929. ToxIcHy of various hydrocarbon vapors. Arch. Exp.
Path. Pharmakol. 143: 223-233. (German with English translation)
0523d -48- 08/22/90
-------
Lonneman, W.A., G.R. Namle and J.J. Bufallnl. 1979. Hydrocarbons In
Houston air. U.S. EPA, Research Triangle Park, NC. EPA/600/3-79/018.
p. 1-36.
Louw, C.W., J.F. Richards and P.K. Faure. 1977. The determination of
volatile organic compounds In city air by gas chromatography combined with
standard addition, selective subtraction. Infrared spectrometry and mass
spectrometry. Atmos. Environ. 11: 703-717.
Lyman, W.J. 1982. Adsorption coefficient for soils and sediments, Iji:
Handbook of Chemical Property Estimation Methods, U.J. Lyman, W.F. Reehl and
D.H Rosenblatt. Ed. HcGraw Hill Book Co.. New York', NY. Chapter 4.
Mantel. N. and M.A. Schnelderman. 1975. Estimating "safe" levels, a
hazardous undertaking. Cancer Res. 35: 1379-1386.
Mill, T.f O.C. Hendry and H. Richardson. 1980. Free radical oxldants In
natural waters. Science, p. 207, 886-887.
Mulcahy, M.F.R., P.F. Nelson. H.Y. Smith, K.E. Hurray and F.B. UhUfleld.
1976. Smog forming hydrocarbons In urban air. In: Occurrence Control
Photochemical Pollution, Proc. Symp. Workshop Sess., PAP No. IV. p. 1-17.
Nelson. P.F. and S.M. Qulgley. 1984. The hydrocarbon composition of
exhaust emitted from gasoline fueled vehicles. Atmos. Environ. 18: 79-87.
0523d -49- 08/22/90
-------
NIOSH (National Institute for Occupational Safety and Health). 1989.
National Occupational .Exposure Survey (NOES), p. 31.
Nlrmalakhandan, N.N. and R.E. Speece. 1988. QSAR model for predicting
Henry's Constant. Environ. Sd. Technol. 22: 1349-1357.
OSHA (Occupational Safety and Health Administration). 1989. 29 CFR Part
1910. Final Rule for Air Contaminants. Federal Register. 54: 2944.
Pan1grah1, A.K. and S.K. Konar.t 1989. Acute toxldty of some petroleum
pollutants to plankton, fish and bentMc organism. Environ. Ecol. 7(1):
44-49.
Parnell. M.J.. 6.M. Hennlngsen, C.J. Hlxson, K.O. Yu, G.A. McDonald and M.P.
Serve. 1988. The metabolism of methylcyclohexane 1n Fischer 344 rats.
Chemosphere. 17(7): 1321-1327.
Perry, R. 1971. Mass spectrometry 1n the detection and Identification of
air pollutants. Int. Symp. Ident. Heas. Environ. Pollut. p. 130-137.
Rappaport, S.H., S. Selvln and H.A. Waters. 1987. Exposure to hydrocarbon
components of gasoline In the petroleum Industry. Appl. Ind. Hyg. 2:
148-154.
Rembold, H., P. Wallner, S. NHz, H. Kollmannsberger and F. Drawert. 1989.
Volatile components of chickpea (Clcer arletlnum L.) seed. J. Agrlc. Food
Chem. 37(3): 6S9-6&2.
0523d -50- 08/22/90
-------
Roddick, J.A., W.B. Bunger and T.K. Sakakano. 1986. Organic Solvents.
John Wiley and Sons, New York, NY. p. 100-101.
Rogerson, A., W.Y. Shlu, L. Huang, D. Mackay and J. Berger. 1983. Determi-
nation and Interpretation of hydrocarbon toxlclty to dilate protozoa.
Aquat. Toxlcol. (AMST). 3(3): 215-228.
SANSS (Structure and Nomenclature Search System). 1990. Data base. Online
3/30/90. p. 1-2.
Sauer, T.C., Jr. 1981a. Volatile liquid hydrocarbons characterization of
underwater hydrocarbon vents and formation waters from offshore production
operations. Environ. Sd. Technol. 15: 917-923.
Sauer, T.C., Jr. 1981b. Volatile organic compounds 1n open ocean and
coastal surface waters. Org. Geochem. 3: 91-101.
Sauer, T.C., Jr., W.M. Sackett and L.H. Jeffrey. 1978. Volatile liquid
hydrocarbons 1n the surface coastal waters of the Gulf of Mexico. Mar.
Chem. 7: 1-16.
Sax. N.I. and R.J. Lewis. 1987. Hawley's Condensed Chemical Dlctonary,
llth ed. Van Nostrand Relnhold Co., New York, NY. p. 765.
Scott Research Labs, Inc. 1969. Atmospheric reaction studies In the Los
Angeles basin. Phase 1. Vol. 1. Plumsteadvllle, PA. NTIS PB-194-058.
43 p.
0523d -51- 10/15/90
-------
Sella, R.L. 1979. Non-urban hydrocarbon concentrations In ambient air
north of Houston, Texas. U.S. EPA, Research Triangle Park, NC.
EPA-500/3-79-010. p. 38.
Sexton. K. and H. Westberg. 1980. Ambient hydrocarbon and ozone measure-
ments downwind of a large automotive painting plant. Environ. Sd. Technol.
14: 329-332.
Shah J.J. and E.K. Heyerdahl. 1988. National ambient volatile organic
compound data base update. N^ro and Associates. EPA Project No.
600/3-88/010(3). p. 56.
Sheldon, L.S. and R.A. HUes. 1978. Organic compounds 1n the Delaware
River. Environ. Sc1. Technol. 12: 1188-1194.
Spain, J.C. and C.C. Somervllle. 1985. Fate and toxldty of high density
mlssle fuels RJ-5 and JP-9 In aquatic test systems. Chemosphere. 14:
239-248.
SRI (Stanford Research Institute). 1989. 1989 Directory of Chemical
Producers. SRI International, Menlo Park, CA. p. 782.
Stelnhelmer, T.R., W.E. Perelra and S.M. Johnson. 1981. Application of
capillary gas chromatography mass spectrometry/computer techniques to
synoptic survey of organic material In bed sediment. Anal. Chlm. Acta.
129: 57-67.
0523d -52- 10/15/90
-------
Stump, P.O. and D.L. Oropkln. 1985. Gas chromatbgraphlc method for quanti-
tative determination of C2 to C13 hydrocarbons In roadway vehicle emissions.
Anal. Chem. 57: 2629-2634.
Suffet, I.H., L. Brenner and P.R. Cairo. 1980. Gas chromatography-mass
spectrometry Identification of trace organlcs In Philadelphia, Pennsylvania,
USA drinking water during a two-year period. Water Res. 14: 853-867.
Swann. R.L., O.A. Laskowskl. P.J. HcCall, K. Vander-Kuy and H.J. DUhburger.
1983. A rapid method for the estimation of the environmental parameters
octanol/water partition coefficient, soil sorptlon constant, water to air
ratio and water solubility. Res. Rev. 85: 17-28.
Tang, J., Q.2. Jin, G.H. Shen, C.T. Ho and S.S. Chang. 1983. Isolation and
Identification of volatile compounds from fried chicken. 3. AgrU. Food
Chem. p. 1287-1292.
Thelestam, M., H. Curvall and C.R. Enzell. 1980. Effect of tobacco smoke
compounds on the plasma membrane of cultured human lung flbroblasts.
Toxicology. 15(3): 203-217.
Treon, J.F., W.E. Crutchfleld, Jr. and K.V. Kltzmlller. 1943a. The physio-
logical response of animals to cyclohexane, methylcyclohexane, and certain
derivatives of these compounds. II. Inhalation. J. Ind. Hyg. Toxlcol.
25(8): 323-347.
0523d -53- 08/22/90
-------
Treon. J.F.. W.E. Crutchfleld. Jr. and K.V. KHzrall.ler. 1943b. The physio-
logical response of rabbits to cyclohexane. methylcyclohexane and certain
derivatives of these compounds. I. Oral administration and cutaneous
application. J. Ind. Hyg. Toxlcol. 25(6): 199-214.
Trower, M.K., R.M. Buckland. R. Hlgglns and M. Griffin. 1985. Isolation
and characterization of a cyclohexane-metabol1z1ng xanthobacterla sp. Appl.
Environ. Mlcroblol. 49: 1282-1289.
Uno, I.. S. Wakamatsu, R.A. Uaddei, S. Konno and H. Koshl. 1985. Evalua-
tion of hydrocarbon reactivity In urban air. Atmos. Environ. 19: 1283-1293.
U.S. EPA. 1980. Guidelines and Methodology Used In the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Criteria
Documents. Federal Register. 45(231): 77347-79357.
U.S. EPA. 1984. Methodology and Guidelines for Ranking Chemicals Based on
Chronic ToxUHy Data. Prepared by the Office of Health and Environmental
Assessment. Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1986a. Methodology for Evaluating Reportable Quantity Adjust-
ments Pursuant to CERCLA Section 102. Prepared by the Carcinogen Assessment
Group. Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH for the Office of Emergency and
Remedial Response. Washington, DC.
0523d -54- 10/15/90
-------
U.S. EPA. 1986b. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
U.S. EPA. 1987. Recommendations for and Documentation of Biological Values
for Use In Risk Assessment. Prepared by the Office of Health and Environ-
mental Assessment, Environmental Criteria and Assessment Office, Cincinnati,
OH for the Office of Solid Waste, Washington, OC.
U.S. EPA. 1990. Computer print-out of nonconfIdentlal production data from
TSCA Inventory OTS, CID. U.S. EPA? Washington, DC. Online 3/30/90.
U.S. EPA/OWRS (Office of Water Regulations and Standards). 1986. Guide-
lines for Deriving Numerical National Water Quality for the Protection of
Aquatic Organisms and their Uses. U.S. Environmental Protection Agency,
Washington, DC. GRA18522.
Van Netten, C., C. Shlrtllffe and J. Svec. 1988. Formaldehyde release
characteristics from a Swedish floor finish. Bull. Environ. Contain.
Toxlcol. 40: 672-677.
Verhoeff, A.P., J. Suk and J.H. Vanmljnen. 1988. Residential Indoor air
contamination by screen printing plants. Int. Arch. Occup. Environ. Health.
60: 201-209.
Veulemans H., D. Groeseneken, R. Hasscheleln and E. Vanvlem. 1987. Survey
of ethylene glycol ether exposure 1n Belgian Industries and workshops. Am.
Indust. Hyg. Assoc. J. 48: 671-676.
0523d -55- 08/22/90
-------
Vogt, W.G. and J.J. Walsh. 1985. Volatile organic compounds In gases from
landfill simulators. In.: Proc. - APCA Annu. Meet. 78th (vol. 6): 17.
Wallace, L.A., £. PelUzzaM. T. Hartwell et al. 1984. Personal exposure
to volatile organic compounds. I. Direst measurements In breathing-zone
air, drinking water, food, and exhaled breath. Environ. Res. 35: 293-319. -
Walllngton, T.J., P. Oagaut and M.J. Krylo. 1988. Correlation between
gas-phase and solution-phase reactivities of hydroxyl radicals towards
saturated organic compounds. J. Phys. Chem. 92: 5024-5028.
Whelan. J.K., B.R.T. S1mone1t and M.E. Tarafa. 1988. C1-C8 hydrocarbons In
sediments from Guaymas Basin, Gulf of California - comparison to Peru
Margin, Japan Trench and California borderlands. Org. Geochem. 12(2):
171-194.
Yanaglhara. S., I. Shlmada, E. Shlnoyatna, F. Chlsaka and K. SaUo. 1977.
Photochemical reactivities of hydrocarbons. Proc. Int. Clean Air Congr. 4:
472-477.
Young, P. and A. Parker. 1984. Vapors, odors, and toxic gases from land-
fills. In: ASTM Spec. Tech. Publ. 851(Hazard. Ind. Waste Manage. Test):
24-41.
Zueldlnger, R.B., J.E. Slgsby, Jr., S.B. Tejada et al. 1988. Detailed
hydrocarbon and aldehyde mobile source emissions from roadway studies.
Environ. Sc1. Technol. 22: 956-962.
0523d -56- 08/22/90
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APPENDIX A
LITERATURE SEARCHED
This HEED 1s based on data Identified by computerized literature
searches of the following:
CHEHLINE
TSCATS
CASR online (U.S. EPA Chemical Activities Status Report)
TOXLINE
TOXLIT
TOXLIT 65
RTECS
OHM TADS
STORET
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
CAS ONLINE (Chemistry and Aquatic)
HSDB
SCISEARCH
Federal Research In Progress
These searches were conducted In January, 1990. and the following secondary
sources were reviewed:
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices, 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1987. TLVs: Threshold Limit Values for Chemical Substances In the
Work Environment adopted by ACGIH with Intended Changes for
1987-1988. Cincinnati. OH. 114 p.
Clayton,. G.O. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed.. Vol. 2A. John Wiley and
Sons, NY. 2878 p.
Clayton, G.O. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 28. John Wiley and
Sons. NY. p. 2879-3816.
0523d
-57-
10/15/90
-------
Clayton, G.O. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed.. Vol. 2C. John Wiley and
Sons. NY. p. 3817-5112.
Grayson, M. and 0. Eckroth, Ed. 1978-1984. Klrk-Othmer Encyclo-
pedia of Chemical Technology, 3rd ed. John Wiley and Sons, NY. 23
Volumes.
Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed.
Publishing Sciences Group, Inc., Littleton, HA. 575 p.
IARC (International Agency for Research on Cancer). IARC Hono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to
Humans. IARC, WHO, Lyons, France.
Jaber, H.H., H.R. Ha bey. A.T. Lieu. T.W. Chou and H.L. Johnson.
1984. Data acquisition for environmental transport and fate
screening for compounds of Interest to the Office of Solid Waste.
EPA 600/6-84-010. NTIS PB84.-243906. SRI International, Menlo
Park, CA.
NTP (National Toxicology Program). 1987. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
Status.
Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide.
Register. McGraw-Hill Book Co., NY.
Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th
ed. Van Nostrand Relnhold Co., NY.
SRI (Stanford Research Institute). 1987. Directory of Chemical
Producers. Menlo Park, CA.
U.S. EPA. 1986. Report on Status Report In the Special Review
Program, Registration Standards Program and the Data Call 1n
Programs. Registration Standards and the Data Call In Programs.
Office of Pesticide Programs, Washington. DC.
USITC (U.S. International Trade Commission). 1986. Synthetic
Organic Chemicals. U.S. Production and Sales, 1985. USITC Publ.
1892, Washington, DC.
Verschueren. K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Relnhold Co.. NY.
Wlndholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co..
Inc.. Rahway, NJ.
Worthing. C.R. and S.6. Walker. Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
0523d -58-
-------
In addition, approximately 30 compendia of aquatic toxlclty data were
reviewed, Including the following:
Battelle's Columbus Laboratories. 1971. Water Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data from the Literature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Johnson. W.W. and H.T. Flnley. 1980. Handbook of Acute Toxlclty
of Chemicals to F1sh and Aquatic Invertebrates. Summaries of
Toxlclty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, Fish and Wildlife
Serv. Res. Publ. 137, Washington, DC.
McKee. J.E. and H.W. Wolf. 1963. Water Quality Criteria. 2nd ed.
Prepared for the Resources Agency of California, State Water
Quality Control Board. Publ. Mb. 3-A.
Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA. Washington. DC. PB-269605.
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
EPA, Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876.
0523d -59- 08/22/90
-------
O
if
rvJ
O>
Q.
APPENDIX B
Summary Table for Methylcyclohexane
O
CD
Species
Inhalation Exposure
Subchronlc rat
Chronic rat
Carclnogenld ty ID
Oral Exposure
SuhchronVr II)
Chronic II)
Cardnogenldty ID
REPORTABLE QUANTITIES
Based on chronic toxldty:
Based on carclnogenld ty:
Exposure Effect RfD or qi*
400 ppm, 6 hours/day and NOAEL for 3 mg/m3
5 days/week for 1 year kidney lesions
(HEC=287 mg/m3)
400 ppm, 6 hours/day and NOAEL for 3 mg/m3
5 days/week for 1 year kidney lesions
(HEC=287 mg/m3)
10 ID ND
II) II) ND
II) ID ND
ID ID ND
1000
ND
Reference
Klnkead
et al. ,
Klnkead
et al.,
NA
NA
NA
NA
Klnkead
et al..
1985
1985
1985
ID = Insufficient data; NO = not derived; NA = not applicable
-------
APPENDIX C
DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO METHYLCYCLOHEXANE
C.I. DISCUSSION
Dose/duration-response graphs for Inhalation and oral exposure to
methylcyclohexane generated by the method of Crockett et al. (1985) using
the computer software by Durkln and Heylan (1989) developed under contract
to ECAO-C1nc1nnat1 are presented \n Figures C-l through C-4. Data used to
generate these graphs are presented In Section C.2. In the generation of
these figures all responses are classified as adverse (PEL. AEL or LOAEL) or
nonadverse (NOEL or NOAEL) for plotting. The ordlnate expresses Inhalation
exposure In either of two ways. In Figures C-l and C-2, the experimental
concentration, expressed as mg/m3. was multiplied by the time parameters
of the exposure protocol (e.g., hours/day and days/week), and Is presented
as expanded experimental concentration [expanded exp cone (mg/m3)]. In
Figure C-3 the expanded experimental concentration was multiplied by the
animal Inhalation rate In m'/day and divided by the animal body weight 1n
kg to calculate a dally dose 1n mg/kg/day. The dally dose was then multi-
plied by the cube root of the ratio of the an1mal:human body weight to
adjust for species differences In metabolic rate (Mantel and Schnelderman.
1975). The result was multiplied by an absorption coefficient of 0.5 to
adjust to an equivalent absorbed dose and then multiplied by 70 kg, the
reference human body weight, to express the human equivalent dose as mg/day
for a 70 kg human [human equivalent dose (mg/day)]. For oral exposure (see
Figure C-4) the ordlnate expresses dose as human equivalent dose. The
animal dose In mg/kg/day Is multiplied by the cube root of the ratio of the
animal:human body weight to adjust for species differences in basal meta-
bolic rate (Mantel and Schnelderman, 1975). The result Is then multiplied
0523d -61- 08/22/90
-------
iHCHINHUL.W
(Inhalation Exposure)
0.001 o.oi e.i
CQUIV DURATION (fraction lifespan)
EHVELOP! HETHOD
Key: F = FEL
A - AEL
L - LOAEl
n = NOAEL
N - NOEL
Solid line = Adverse-Effects Boundary
Dashed line = No-Adverse-Effects Boundary
FIGURE C-l
Dose/Ourat1on-Response Graph for Inhalation Exposure to
Methylcyclohexane: Envelope Method (Expanded Experimental Concentration)
0523d
-62-
08/22/90
-------
1893 T
100-
8.8801
(Inhalation Exposure)
e.eei 0.01 Q.I
HUNAN EQUIV DURATION (fraction lifespan)
CIHSORO MIA METHOD
Key: F - FEL
A * AEL
L - LOAEl
n - NOAEL
N « NOCL
Solid line * Adverse-Effects Boundary
Dashed line - No-Adverse-Effects Boundary
FIGURE C-2
Dose/Duration-Response Graph for Inhalation Exposure to Hethylcyclohexane:
Censored Data Method (Expanded Experimental Concentration)
0523d
-63-
08/22/90
-------
1938033
1009
8.0901
0.801
HCHINHHL.D2
(Inhalation Exposure)
0.1
EQUIV DURATION (fraction lifespan)
ENVELOP! KTTHOD
Key: F = PEL
A - AEL
L = LOAEL
n = NOAEL
N - NOEL
Solid line = Adverse-Effects Boundary
Dashed line = No-Adverse-Effects Boundary
FIGURE C-3
Dose/Duration-Response Graph for Inhalation Exposure to Methylcyclohexane:
Envelope Method (Human Equivalent Dose)
0523d
-64-
08/22/90
-------
mm
A
t'
<
•5
\
I
i
V
a
ti
0
a 10883-
5
4
3
5
z
c
I
a
1990-
a
1 ; Ji i i , , , | \ 1 — ! l l l i 1 1 1 1 — i Miii,
; 1
•
«
.
~
•
•
,
u
•
'
•
i i i 1 1 * * 1 1 i i i 1 1 1 1 i i i 1 1 1 1 1
eeei 0.001 0.01 0-i
HUMAN EQUIV DURATION {fraction lifespan)
(Oral Exposure) »W>ri'
Key: F = FEL
L = LOAEL
Solid line « Adverse-Effects Boundary
Dashed line * No-Adverse-Effects Boundary
FIGURE C-4
Dose/Duration-Response Graph for Oral Exposure to
Methylcyclohexane: (Human Equivalent Dose)
0523d
-65-
08/22/90
-------
by 70 kg, the reference human body weight, to express the human equivalent
dose as mg/day For a 70 kg human [human equW dose (mg/day)].
The adverse effects boundary (solid line) Is drawn by Identifying the
lowest adverse effect dose or concentration at the shortest duration of
exposure at which an adverse effect occurred. From this starting point an
Infinite line 1s extended upward parallel to the dose axis. The starting
point Is then connected to the lowest adverse-effect dose or concentration
at the next longer duration of exposure that has an adverse-effect dose or
concentration equal to or lower than the previous one. This process Is
continued to the lowest adverse «effect dose or concentration. From this
point a line parallel to the duration axis Is extended Infinitely to the
right. The adverse effects region lies above the adverse effects boundary.
Using the envelope method, the no adverse effects boundary (dashed line)
Is drawn starting with the point representing the highest no adverse effects
dose or concentration. From this point a line parallel to the duration axis
1s extended to the dose or concentration axis. The starting point Is then
connected to the next equal or lower no adverse effect dose or concentration
at a longer duration of exposure. When this process can no longer be
continued, a line parallel to the dose or concentration axis Is dropped to
the duration axis. The no adverse effects region lies below the no adverse
effects boundary. At either ends of the graph between the adverse effects
and no adverse effects boundaries are regions of ambiguity. The area (1f
any) resulting from Intersections of the adverse effects and no adverse
effects boundaries 1s defined as the region of contradiction.
In the censored data method, all no adverse effect points located In the
region of contradiction are dropped from consideration and the no adverse
effects boundary Is redrawn so that H does not Intersect the adverse
0523d -66- 08/22/90
-------
effects boundary and no region of contradiction 1s generated. This method
results \r\ the most conservative definition of the no adverse effects region.
In Figure C-l, the adverse effects boundary Is defined by a 1-hour FEL
for convulsions, narcosis, and death In rabbits (Rec. #12, Section C.2.I.),
a 1-hour LOAEL for hyperactWHy 1n rats (Rec. #13, Section C.2.I.), an FEL
for mortality In rabbits exposed for 2 weeks (Rec. #10. Section C.2.I.), a
LOAEL for lethargy In rabbits exposed for 4 weeks {Rec. #9, Section C.2.1.)
and a LOAEL for slightly reduced body weight and kidney lesions In male rats
exposed for 1 year (Rec. #2, Section C.2.I.). The latter point (on the far
right of the graph) 1s obscured'by points for Recs. #3 and 4. The no
adverse effects boundary 1s defined by a NOEL 1n dogs exposed for 1 hour
(Rec. #17, Section C.2.I.), 3-week NOAEL 1n rabbits (Rec. #8, Section
C.2.I.). a 1-year NOEL In mice (Rec. #4. Section C.2.I.), and a 1-year NOAEL
In rats (Rec. #1. Section C.2.I.), which served as the basis for the chronic
Inhalation RfD. The point for Rec. #4 1s obscured by Recs. #2 and 3. A
very small region of contradiction 1n this figure results from the location
of the NOEL for mice (Rec. #4. Section C.2.1.) slightly above the LOAEL for
rats (Rec. #2. Section C.2.1.) In the 1-year study by Klnkead et al. (1985).
In Figure C-2, the region of contradiction Is eliminated by using the
censored data method to re-draw the no adverse effects boundary, which 1s
defined as described above, except that the NOEL In the 1-year study In mice
(Rec. #4. Section C.2.1.) Is replaced by the NOAEL associated with slightly
reduced body weights In hamsters (Rec. #3, Section C.2.1.).
In Figure C-3. the adverse effects and no adverse effects boundaries are
defined by the same points as 1n Figure C-l. Scaling the exposure concen-
tration to a human equivalent dose sufficiently elevates the LOAEL for
reduced body weight -and kidney lesions 1n the 1-year study In rats (Rec. #2,
0523d -67- 08/22/90
-------
Section C.2.1.) above the NOEL In the 1-year study In mice {Rec. #4, Section
C.2.1.) that the region of contradiction observed In Figure C-l no longer
exists.
Figure C-4 presents the oral data for exposure to methylcyclohexane.
Two data points are displayed; a PEL associated with mortality In rabbits
and a LOAEL associated with kidney lesions In rats. Data were Insufficient
for generation of adverse and no adverse effects regions.
C.2. DATA USED TO GENERATE DOSE/DURATION-RESPONSE GRAPHS
C.2.1. Inhalation Exposure.
Chemical Name: Methylcyclohexane
CAS Number: 108-87-2
Document THle: Health and Environmental Effects Document on
Methylcyclohexane
Document Number: pending
Document Date: pending
Document Type: HEED
RECORD #1: Species: Rats
Sex: Both
Effect: NOAEL
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
65
NR
WGTDC
BODY
4
0.317 kg
400 ppm
287 mg/m3
1 year
2 years
98.19
6.00
5.00
Comment: Exposed to 0, 400, 2000 ppm. Small effect on growth In males
only (not tested statistically). Basis for chronic and
subchronic RfDs. Body weight estimated from data provided.
CHaUon: Klnkead et al.. 1985
0523d
-68-
08/22/90
-------
RECORD #2:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
Both
LOAEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
65
NR
PATHO
KIONY
6
65
NR
WGTOC
BODY
4
0.3 kg
2000 ppm
1434 mg/m3
1 year
2 years
98.19
6.00
5.00
See previous record. Increased Incidence of kidney lesions In
males only. Body weight estimated from data provided.
Klnkead et al.. 1985 *
RECORD #3: Species: Hamsters
Sex: Male
Effect: NOAEL
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
100
NR
WGTDC
BODY
4
0.113 kg
2000 ppm
1434 mg/m3
1 year
2 years
98.19
6.00
5.00
Comment: Exposed to 0, 400, 2000 ppm. Small effect on body growth at
both levels (not tested statistically). Body weight estimated
from data provided.
Citation: Klnkead et al., 1985
0523d
-69-
08/22/90
-------
RECORD #4:
RECORD #5:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Mice
F ema1e
NOEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
200
0
0.0353 kg
2000 ppm
1434 mg/m3
1 year
2 years
98.19
6.00
5.00
Comment:
Citation:
Exposed to 0, 400, 2000 ppm.
Klnkead et al.. 1985
Species:
Sex:
Effect:
Route:
Dogs
Both
NOEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Exposed to 0, 400, 2000 ppm.
Klnkead et al.. 1985
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
8
0
10.45 kg
2000 ppm
1434 mg/m3
1 year
5 years
98.19
6.00
5.00
0523d
-70-
08/22/90
-------
RECORD #6:
Comment:
Citation:
Species: Rabbits Body Weight: 2.98 kg
Sex: NR Reported Dose: "1162 ppm
Effect: NOEL Converted Dose: 833 mg/m3
Route: Inhalation Exposure Period: 10 weeks
Duration Observation: 18 weeks
Molecular Weight: 98.19
Inhalation hours/day: 6.00
Inhalation days/week: .5.00
# Inhal. Exp. days:
4
0
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Exposed to 241, 1162 ppm.
Treon et al., 1943a «
RECORD #7: Species:
Sex:
Effect:
Route:
Monkeys
NR
NOEL
Inhalation
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
9.45 kg
372 ppm
267 mg/m3
10 weeks
18 weeks
98.19
6.00
5.00
Comment:
Citation:
Number Exposed: 1
Number Responses: 0
Type of Effect:
SHe of Effect:
Severity Effect: 3
Exposed only to 372 ppm.
Treon et al.. 1943a
0523d
-71-
08/22/90
-------
RECORD #8:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rabbits
NR
NOAEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
4
NR
HISTO
LIVER
3
4
NR
HISTO
KIDNY
3
2 kg
2886 ppm
2070 mg/m3
3 weeks
11 weeks
98.19
6.00
5.00
Exposed only to 2886 ppm. Very mild
logical lesions In liver and kidney.
Treon et a!., 1943a «
unspecified hlstopatho-
RECORD #9:
Comment:
Citation:
Species: Rabbits
Sex: NR
Effect: LOAEL
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Exposed only to 5567
Treon et al., 1943a
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
4
NR
BEHAV
CNS
7
ppm. Slight lethargy.
2 kg
5567 ppm
3992 mg/m3
4 weeks
12 weeks
98.19
6.00
5.00
0523d
-72-
08/22/90
-------
RECORD #10:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rabbits
NR
FEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Exposed to 7308.
death.
Body Weight:
Reported Dose:
Converted Oose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
4
NR
BEHAV
CNS
8
4
1
DEATH
BODY
10
2 kg
7308 ppm
5241 mg/m3
2 weeks
10 weeks
98.19
6.00
5.00
10,054 ppm. Lethargy and 1ncoord1nat1on; 1
Treon et al.. 1943a
RECORD #11:
Comment:
Citation:
Species: Rabbits
Sex: NR
Effect: FEL
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
See previous record.
Treon et al.. 1943a
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
4
4
DEATH
BODY
10
Convulsions and narcos
2 kg
10.054 ppm
7210 mg/m3
2 weeks
2 weeks
98.19
6.00
5.00
Is; all died.
0523d
-73-
08/22/90
-------
RECORD #12:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rabbits
NR
PEL
.Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
4
4
DEATH
BODY
10
2 kg
15,227 ppm
6.12e*004 mg/m3
1 day
1 day
98.19
1.17
1.00
Exposed only to 15,227 ppm. Convulsions and narcosis; all died.
Treon et al., 1943a
RECORD #13:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
Hale
LOAEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
20
NR
BEHAV
CNS
7
0.6 kg
4172 ppm
1.68e+004 mg/m3
1 day
28 days
98.19
1.00
1.00
Exposed to 0, 4172. 6564 ppm. Hyperactlvlty.
Klnkead et al.. 1979
0523d
-74-
08/22/90
-------
RECORD #14:
Species:
Sex:
Effect:
Route:
Rats
Male
AEl
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
SHe of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
20
NR
BEHAV
CNS
8
0.6 kg
6564 ppm
2.64e*004 mg/m3
1 day
28 days
98.19
1.00
1.00
Comment: See previous record.
Citation: Klnkead et al., 1979
RECORD #15: Species: Mice
Sex: Female
Effect: LOAEL
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
HyperactWHy, 1ncoord1nat1on, prostration
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
20 20
NR NR
BEHAV HISTO
CNS LIVER
7 5
0.035 kg
4758 ppm
1.91e+004 mg/m3
1 day
28 days
98.19
1.00
1.00
Comment: Exposed to 0, 4758, 6564 ppm.
cytoplasmlc changes In liver.
Citation: Klnkead et al., 1979
Hyperactlvlty; mild reversible
0523d
-75-
08/22/90
-------
RECORD #16:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Mice
F ema1e
AEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
20
NR
BEHAV
CNS
8
0.035 kg
6564 ppm
2.64e+004 mg/m3
1 day
28 days
98.19
1.00
1.00
See previous record. HyperactlvHy, Incoordlnatlon, prostration.
Klnkead et al.. 1979
RECORD #17:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Dogs
NR
NOEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Exposed only to 4071 ppm.
Klnkead et al., 1979
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
4
0
14 kg
4071 ppm
1.64e«-004 mg/m3
1 day
28 days
98.19
1.00
1.00
0523d
-76-
08/22/90
-------
RECORD #18:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Mice
NR
AEL
Inhalation
Number Exposed:
Number Responses:
Type of Effect:
SHe of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
NR
NR
BEHAV
CNS
8
0.038 kg
7500 ppm
3.01e+004 mg/rn3
1 day
1 day
98.19
2.00
1.00
Exposed to 7500-12,500 ppm.
to assume lateral position.
Lazarew. 1929
Minimum concentration causing mice
RECORD #19: Species:
Sex:
Effect:
Route:
Mice
NR
PEL
Inhalation
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
Molecular Weight:
Inhalation hours/day:
Inhalation days/week:
# Inhal. Exp. days:
0.038 kg
10,000 ppm
4.02e*-004 mg/m3
1 day
1 day
98.19
2.00
1.00
Comment:
Citation:
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
See previous record. Minimum lethal concentration.
Lazarew, 1929
C.2.2. Oral Exposure.
Chemical Name:
CAS Number:
Document Title:
Document Number:
Document Date:
Document Type:
Methylcyclohexane
108-87-2
Health and Environmental Effects Document on
Methylcyclohexane
pending
pending
HEED
0523d
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08/22/90
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RECORD #1
Comment:
Citation:
Species:
Sex-
Effect:
Route:
Rabbits
NR
PEL
Gavage
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
1
1
DEATH
BODY
10
2 kg
4500 other
4500 mg/kg/day
1 day
60 days
Exposed
necrosis
to 1-10 g/kg.
1n heart, liver,
Minimum lethal
spleen, kidney.
dose. Coagulation
Treon et al., 1943b
RECORD #2:
Species:
Sex:
Effect:
Route:
Rats
Hale
LOAEL
Gavage
Body Weight:
Reported Dose:
Converted Dose:
Exposure Period:
Duration Observation:
0.307 kg
800 other
400 mg/kg/day
14 days
14 days
Comment:
Citation:
Number Exposed: 8
Number Responses: NR
Type of Effect: HISTO
Site of Effect: KIDNY
Severity Effect: 5
Exposed to 0 or 0.8 g/kg every other day for 2 weeks.
slight traces of nephropathy.
Parnell et al., 1988
Very
NR = Not reported
0523d
-78-
08/22/90
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