March 31, 1987
n-HEXANE
Health Advisory
Office of Drinking Water
U.S. Environmental Protection Agency
I. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Drinking
Water (ODW), provides information on the health effects, analytical method-
ology and treatment technology that would be useful in dealing with the
contamination of drinking water. Health Advisories describe nonregulatory
concentrations of drinking water contaminants at which adverse health effects
would not be anticipated to occur over specific exposure durations. Health
Advisories contain a margin of safety to protect sensitive members of the
population.
Health Advisories serve as informal technical guidance to assist Federal,
State and local officials responsible for protecting public health when
emergency spills or contamination situations occur. They are not to be
construed as legally enforceable Federal standards. The HAs are subject to
change as new information becomes available.
Health Advisories are developed for One-day, Ten-day, Longer-term
(approximately 7 years, or 10% of an individual's lifetime) and Lifetime
exposures based on data describing noncarcinogenic end points of toxicity.
Health Advisories do not quantitatively incorporate any potential carcinogenic
risk from such exposure. For those substances that are known or probable
human carcinogens, according to the Agency classification scheme (Group A or
B), Lifetime HAs are not recommended. The chemical concentration values for
Group A or B carcinogens are correlated with carcinogenic risk estimates by
employing a cancer potency (unit risk) value together with assumptions for
lifetime exposure and the consumption of drinking water. The cancer unit
risk is usually derived from the linear multistage model with 95% upper
confidence limits. This provides a low-dose estimate of cancer risk to
humans that is considered unlikely to pose a carcinogenic risk in excess
of the stated values. Excess cancer risk estimates may also be calculated
using the One-hit, Weibull, Logit or Probit models. There is no current
understanding of the biological mechanisms involved in cancer to suggest that
any one of these models is able to predict risk more accurately than another.
Because each model is based on differing assumptions, the estimates that are
derived can differ by several orders of magnitude.
-------
n-Hexane March 31, 1987
-2-
II. GENERAL INFORMATION AND PROPERTIES
CAS No. 110-54-3
Structural Formula
H H H H H H
MINI
H-C-C-C-C-C-C-H
I I I.I I I
H H H H H H
Synonyms
0 Esani, Heksan, Hexahen (NIOSH, 1978)
Uses
0 Hexane is used commercially as a solvent in glues, varnishes, cements
and inks (NIOSH, 1977).
0 Hexane also is used in the seed oil industry to extract the natural
oils from various seeds, including soybeans and cotton seeds.
Properties (Windholz, 1983)
Chemical Formula 013(^2)4^3
Molecular Weight 86.18
Physical State Liquid
Boiling Point 68.7°C
Melting Point
Density
Specific Gravity 0.655 at 25°C
Vapor Pressure 150 mm at 25°C
Water Solubility 23 mg/liter
Log Octanol/Water Partition
Coefficient
Taste Threshold
Odor Threshold
Conversion Factor 1 ppm = 2.78 mg/m3
Occurrence
0 Hexane has not been included in Federal and State surveys of drinking
water and no other information on the occurrence of hexane has been
located.
III. PHARMACOKINETICS ' •' ,;
•• .' » .. f.
Absorption • - .
0 Bus et al. (1983) studied the'absorption of n-hexane in rats following
a single 6-hour inhalational exposure to 1,000 (2,780 mg/m3), 3,000
(8,340 mg/m3) or 10,000 (-27,800 mg/m3) ppm c1 4-n-hexane. Total
-------
n-Hexane March 31, 1987
-3-
radioactivity collected in the various excreta fractions was approxi-
mately 98% of the total administered dose levels.
Distribution
0 No information was found in the available literature on distribution
of n-Hexane.
Metabolism
0 DiVincenzo et al. (1976) studied the metabolism of n-hexane in
guinea pigs. The chemical was dissolved in corn oil and injected
intraperitoneally in a single 'dose of 450 mg/kg body weight in male
guinea pigs. Blood samples were collected 1, 2, 4, 6, 8, 12 and 16
hours after the dose was administered. The two major metabolites of
n-hexane in the serum were identified as 2,5-hexanedione and 5-hydroxy-
2-hexanone; however, they were not quantified.
0 Studies in shoe factory workers show that n-hexane is metabolized to
2-hexanol, 2,5-hexanedione, 2,5-dimethylfuran and O-valerolactone
(Perbillini et al., 1980).
0 Baker and Rickert (1981) studied metabolism of n-hexane in the
Fischer-344 rat following inhalation of n-hexane. Male F-344 rats
were exposed to 500 (1,390 mg/m3), 1,000 (2,780 mg/m3), 3,000 (8,340
mg/m3) or 10,000 (27,800 mg/m3) ppm n-hexane in the air. n-Hexane and
its metabolites, methyl-n-butyl ketone (MBK), 2,5-dimethylfuran (DMFU),
2,5-hexanedione (2,5-HD), 2-hexanol and 1-hexanol, were quantified by
GC/MS in several tissues at time intervals during and following a
single 6-hr exposure to n-hexane. Urinary metabolites were quantified
following a single n-hexane exposure. n-Hexane concentrations achieved
an apparent steady state within two hours in all tissues. Peak blood
concentrations of n-hexane were 1, 2, 8 and 12 ug/ml and peak sciatic
nerve concentrations were 12, 48, 130 and 430 ug/g at 500 (1,390 iag/m3),
1,000 (2,780 mg/m3), 3,000 (8,340 mg/m3) and 10,000 (27,800 mg/m3) ppm,
respectively. The halflives of n-hexane and MBK were on the order of
1 to 2 hours in all tissues except the kidneys (K1/2 = 5 to 6 hrs).
The data showed a complex relationship between n-hexane exposure and
peak concentrations of the remaining metabolites. Tissue concentrations
of 2,5-HD were not proportional to dose. Highest 2,5-HD concentrations
were found following exposure to 1,000 ppm n-hexane in the blood,
kidneys and sciatic nerve (6.1, 55 and 25 ug/g, respectively). The
data indicated that the metabolism and elimination of n-hexane were
dependent upon exposure concentration. Consequently,'n-hexane exposure
concentration cannot be directly correlated with tissue 2,5-HD concen-
trations.
Excretion
The metabolites of n-hexane in urine and their concentrations following
n-hexane (commercial) exposure of shoe factory workers were: 2-hexanol
(0.5 mg/liter), 2,5-hexanedione (10.1 mg/liter), O-valerolactone (2.4
mg/liter) and 2,5-dimethylfuran (5.2 mg/liter) (Perbillini et al.,
1980).
-------
n-Hexane March 31, 1987
-4-
IV. HEALTH EFFECTS
Humans
Hershkowitz et al. (1971) reported the effects of inhalation of
n-hexane vapor on three female employees who worked in a furniture
factory. n-Hexane concentrations in the room averaged 650 (1,807
mg/m3) ppm with peaks up to 1,300 (3,614 mg/m3) ppm. The first
symptoms appeared 2 to 4 months after the beginning of exposure and
the three employees were hospitalized 6 to 10 months later when they
complained of one or more of the following symptoms: headache,
burning sensation of the face, abdominal cramps, numbness and weakness
of the distal extremities. Physical examination revealed bilateral
foot-drop gait, bilateral wrist drop and absence of Achilles tendon
reflexes. Electromyographic examination of these patients indicated.
fibrillation potentials in the small muscles of the hands and feet.
Biopsies of the anterior tibial muscle and sural nerves of two of the
patients revealed that the muscles contained small angulated fibers
and other fibers with clear central zones (denervation type injury).
Small bundles of axons from the muscle sections were studied by
electron microscopy and found to contain dense bodies and fibrous
formations, increased numbers of neurofilaments and abnormal membranous
structures with clumped and degenerated mitochondria. Motor-end
plates also were damaged, with swollen terminal axoplasmic expansions,
an increased number of degenerated mitochondria and an increased
number of glycogen granules, dense bodies, large osmophilic membranes,
synaptic folds and vesicles. The investigators reported that the
health of these employees improved after leaving their employment.
Animals
Short-term Exposure
Kimura et al. (1971) studied the oral toxicity of a single dose of
n-hexane in different age groups of rats: newborn (1 to 2 days old,
5 to 8 g), 14 days old (16 to 50 g), young adult (80 to 160 g) and
older adult (300 to 470 g). The undiluted solvents were administered
orally to non-fasted rats. A precise LDso value for n-hexane could not
be determined for the newborn rats because of measurement limitations,
but doses of less than 1 ml/kg body weight were lethal. The acute
oral LD5Q was 24.0 ml/kg (15.7 g/kg) for 14-day old rats, 49.0 ml/kg
(32.1 gAg) for young adults and 43.5 ml/kg (28.9 g/kg) for older
adult rats.
Hewett et al. (1980) carried out experiments in which groups of
male adult Sprague-Dawley rats were given a single oral dose of
1,290 mg/kg of n-hexane solubilized in corn oil (control animals
received corn oil alone). This segment of the experiment was to
provide evidence of potentiation of chloroform toxicity in rats
pretreated with n-hexane, methyl n-butyl ketone or 2,5-hexanedione.
n-Hexane-induced hepatotoxicity was estimated 42 hours later by
measuring enzyme activity of glutamic-pyruvic transferase (GPT) and
ornithine carbamyl transferase (OCT) in the plasma of animals.
-------
n-Hexane March 31, 1987
-5-
The extent of cell damage was assessed by observing histological
changes in the liver and nephrotoxicity was evaluated by monitoring
the ability of renal cortical slices to accumulate an organic anion
(p-aminohippurate) and cation (tetraethylammonium) and by deter-
mining the blood urea nitrogen content. The investigators reported
.that the 1,290 mg/kg dose of n-hexane produced no measurable effects
either on organ weight (liver, kidney) or on any parameters described
earlier. However, a single oral dose of n-hexane in rats produced
minimal changes in renal histology as indicated by the presence of
degenerated tubules in sections from these animals.
0 Howd et al. (1982) studied the relation between schedules of exposure
to n-hexane and plasma levels of 2,5-hexanedione. Male Fischer rats
were exposed repeatedly to high concentrations of n-hexane: 4,000 ppm
for 8 hours/day for 5 days/week; 48,000 ppm for 10 minutes every half
hour for 8 hours/day, 5 days/week; 40,000 ppm for 10 minutes every
half hour, on a background of 4,000 ppm continuous, for 8 hours/day,
. 5 days/week. Concentrations of n-hexane in blood and brain were
linearly related to the concentrations of n-hexane in the chamber
after a 10-minute exposure, and declined thereafter, with half-lives
of about 2-1/2 and 4 minutes in blood and brain, respectively. Despite
the rapid elimination of n-hexane, neurotoxic levels of 2,5-hexanedione
(2,5-HD) were formed from repeated 10-minute exposures to a high con-
centration of n-hexane when the"inter-exposure interval was 20 minutes.
Neurotoxic levels of 2,5-HD also resulted from continuous exposure to
much lower concentrations of n-hexane. Both exposure schedules (4,000
ppm for 8 hours/day and 10 minutes every half hour exposure) caused
an increase in 2,5-HD concentrations in blood after repeated daily
treatments. The authors suggested that the minimal sustained plasma
2,5-HD concentration that will result in neurotoxicity appears to be
less than 50 ug/ml in the rat.
0 In vitro toxicity of n-hexane and 2,5-hexanedione using isolated
perfused rabbit hearts is reported (Raye, 1983). The hearts were
perfused using Langendorf's procedure and modified Anderson's coronary
perfusion apparatus. The force of cardiac contraction was significantly
reduced following one hour perfusion with 9.6 mg/L concentration of
n-hexane and with 0.35% v/v concentration of 2,5-hexanedione.
Dermal/Ocular Effects
0 Jakobson et al. (1982) reported results of uptake via the blood and
elimination of n-hexane (one of 10 organic solvents) following
epicutaneous exposure of anesthetized guinea pigs. The concentration
of n-hexane in the blood was monitored over a 6-hour period of n-hexane
exposure of anesthetized guinea pigs. A glass ring chamber (area:
3.1 cm2) 4 mm in thickness and 10 mm in height was glued to a clipped
area of skin on the back of the guinea pigs. This glass ring chamber
contained 1.0 ml.of n-hexane solvent for the study. With n-hexane,
the concentrations in the blood at 0.5 and 6 hrs were 0.58 and 0.23
ug/ml of n-hexane, respectively.
-------
n-Hexane March 31, 1987
-6-
0 Nomiyama and Nomiyama (1975) investigated the absorption rates of
n-hexane and toluene through the skin of humans. 'An unspecified
number of subjects immersed their hands up to the wrists in a dish
containing analytically pure n-hexane (95% n-hexane) for 1 minute.
At intervals following skin exposure, breath, blood and urine samples
were analyzed for n-hexane by gas chromatographs. The authors were
unable to detect hexane in either the breath or the blood of any of
the subjects following exposure to n-hexane. The detection limit for
n-hexane was 1 ppm in the breath and 3.5 ppm in blood. The authors
did not describe any physiological effects.
Long-term Exposure
0 Krasavage et al. (1980) studied the relative neurotoxicities of
n-hexane by the appearance of hind-limb weakness. Charles River male
rats were given oral doses of. n-hexane at 570 mg/kg (6.6 mmol/kg)
5 days/week for 90 days or 1,140-or 4,000 mg/kg doses for 120 days.
As soon as hind-limb weakness clinical signs occurred, the animals
were killed and the tissues were examined for histopathological
changes. No clinical or histological signs of neuropathy were observed
in the animals at dose levels of 570 or 1,140 mg/kg n-hexane (although
body weights were depressed at all three dose levels compared to
controls). At a dose level of 4,000 mg/kg n-hexane, the clinical and
histological signs of neuropathy occurred at approximately 101 days.
The histological changes included multi-focal axonal swellings,
adaxonal myelin infolding and paranodal myelin retraction. In addition
to neuropathy, histological examination of testicular tissue revealed
varying stages of atrophy of the germinal epithelium following the
administration of 4,000 mg/kg n-hexane.
0 Takeuchi et al. (1980) studied the neurotoxicity of n-hexane in
Wistar strain male rats following inhalation exposure to 3,000 ppm
(8,340 mg/m3) of n-hexane for 12 hours a day for 16 weeks. The nerve
conduction velocity and the distal latency measured before the
beginning of the exposure and after the experiment showed that
(1) n-hexane disturbed the conduction velocity of the motor nerve and
the mixed nerve and prolonged the distal latency in the rat's tail
and (2) the neuromuscular junction and the muscle fiber of the rats
exposed to n-hexane were impaired severely as seen by light and
electron microscopy.
0 Cavender et al. (1984) reported the results of a 13-week vapor
inhalation study of n-hexane in rats with emphasis on neurotoxic
effects. Male and female Fischer-344 rats were exposed to 0, 3,000
(8,340 mg/m3), 6,500 (18,070 mg/m3) or 10,000 (27,800 mg/m3) ppm
n-hexane vapors 6 hours per day, 5 days per week, for 13 weeks. The
13-week exposures had no adverse effect on the growth of female rats.
However, the mean body weight gain of male rats in the 10,000 (27,800
mg/m3)' ppm was significantly lower than for controls at 4 weeks of
exposure and thereafter. In addition to the depression in body weight
gain, the males exposed to 10,000 (27,800 mg/m3) ppm had slightly but
significantly lower brain weights at necropsy. No adverse testicular
effects were noted. Axonopathy was observed in the tibial nerve in
-------
n-Hexane March 31, 1987
-7-
four of five male rats from the 10,000 ppm group and one of five male
rats in the 6,500 (18,070 mg/m3) ppm group and in the medulla from
one male rat in the 10,000 (27,800 mg/m3) ppm group. These axonal
changes were detectable only in teased nerve fiber preparations or in
Epon embedded specimens. Histopathologic studies on Formalin fixed
tissues did not reveal any lesions that were attributed to n-hexane
exposure.
Reproductive Effects
0 Bus et al. (1979) studied the effects of maternal inhalation ex-
posure to n-hexane on the size and survival of newborn Fischer 344
rats. Pregnant rats were exposed for 6 hours per day to 1,000 (2,780
mg/m3) ppm (3.5 g/m3) n-hexane on days 8 to 12, 12 to 16, or 8 to 16
of gestation. No significant changes in fetal resorption, body
weights, visible anomalies or the incidence of soft tissue and skeletal
anomalies were noted in any of the treatment groups. The post-natal
growth of pups born to dams exposed to n-hexane at 1,000 (2,780 mg/m3)
ppm (3.5 g/m3) 6 hours/day on days 8 through 16 of gestation was
depressed significantly (P < 0.05) compared to controls for up to 3
weeks after birth. However, litter weights of treated pups had
returned to control values by 7 weeks after birth. No anatomic
defects or neuropathic symptoms were noted in treated pups.
Developmental Effects
0 Marks et al. (1980) stated that n-hexane was not teratogenic'in mice
up to a dose level of 9.90 g/kg/day. In this experiment, pregnant
outbred albino mice (CD-1) received n-hexane once daily by gavage at
doses up to 2.20 g/kg/day on days 6-15 of gestation. Other pregnant
mice received higher hexane doses (up to 9.90 g/kg/day), employing a
three times a day injection schedule. At the lower, once-daily doses
only one dam died and no teratogenic effects occurred. Higher hexane
doses were toxic: 2 of 25 dams treated with 2.83 g/kg/day, 3 of 34
treated with 7.92 g/kg/day and 5 of 33 treated with 9.90 g/kg/day
died. At the 7.92 and 9.90 g/kg/day doses, the average fetal weight
was significantly (P <0.05) reduced, but the incidence of malformations
in treated and vehicle (cottonseed oil) control groups did not differ
significantly. Thus, n-hexane was not teratogenic even at doses
toxic .to the dam.
Mutagenicity
0 No information was found in the available literature on the mutagenic
effects of n-hexane.
Carcinogenicity
0 No information was found in the available literature on the carcinogenic
effects of n-hexane.
-------
n-Hexane March 31, 19874
-8-
V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS
Health Advisories (HAs) are generally determined for One-day, Ten-day,
Longer-term (approximately 7 years) and Lifetime exposures if adequate data
are available that identify a sensitive noncarcinogenic end point of toxicity.
The HAs for noncarcinogenic toxicants are derived using the following formula:
HA = (NOAEL or LOAEL) x (BW) = /L ( /L,
(UF) x ( L/day)
where:
NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
in mg/kg bw/day.
BW = assumed body weight of a child (10 kg) or
an adult (70 kg).
UF = uncertainty factor (10, 100 or 1,000), in
accordance with NAS/ODW guidelines.
L/day = assumed daily water consumption of a child
(1 L/day) or an adult (2 L/day).
One-day Health Advisory
The results of the Hewlett et al. (1980) study in which a group of
Sprague-Dawley male rats were given a single oral dose of 1,290 mg/kg n-hexane
can be used for the derivation of a One-day HA, even though these studies (in
which other chemicals also were screened) were not designed specifically to
examine the toxicity of n-hexane. This dose produced no measurable effects
on the following parameters after 42 hours: relative liver weight, relative
kidney weight, plasma glutamic-pyruvic transaminase, plasma ornithine carbamyl
transferase, hepatic and renal histological changes, uptake of p-aminohippurate
and tetraethylammonium ion by kidney slices, and blood urea nitrogen. These
negative findings (except for body weight at the single data point are con-
sistent with the results reported by Krasavage et al. (1980) in a 90-day
study. However, a single oral dose of n-hexane in rats produced minimal
changes in renal histology as indicated by the presence of degenerated tubules
in sections from these animals.
The One-day HA for the 10-kg child is calculated as follows:
One-day HA = (1• 29° mg/kg/day) (10 kg) = 12.9 mg/L (13,000 ug/L)
(1 L/day) (1,000)
where:
1,290 mg/kg/day = LOAEL based on minimal adverse effect in male rats.
1 0 kg = assumed body weight of a child.
-------
n-Hexane March 31, 1987
-9-
•
1,000 = uncertainty factor, chosen in accordance with NAS/ODW
•guidelines for use with a LOAEL from an animal study.
1 L/day = assumed daily water consumption of a child.
Ten-day Health Advisory
Appropriate studies for the derivation of a Ten-day HA are not available.
Use of the Longer-term HA for the 10-kg child of 4 mg/L is recommended.
Longer-term Health Advisory
The inhalation study by Takeuchi et al. (1980) was not considered because
the parameters were not examined in detail. However, a Longer-term HA can be
derived from a study (Krasavage et al., 1980) in which Charles River rats
were given oral doses of 570 mg/kg n-hexane 5 days/week for 90 days, 1,140
mg/kg or 4,000 mgAg for 120 days. Clinical and histological signs of neuro-
pathy were absent in the animals at dose levels of 570 and 1,140 mg/kg n-hexane
(although body weights were depressed at all three dose levels compared to
control). The lowest dose administered (570 mg/kg) can be considered a
LOAEL. A safety factor of 1,000 will be used since only one species was
considered in the study and the data obtained were part of a broader study
dealing with relative neurotoxicity of n-hexane, methyl n-butyl ketone and
their metabolites.
The Longer-term HA for a 10-kg child is calculated as follows:
Longer-term HA = (570 mg/kg/day)(10 kg) (5) = 4<07 mg/L (4 000 ug/L)
(1,000) (1 L/day) (7)
where:
570 mg/kg/day = LOAEL based on depressed body weight in animals.
10 kg = assumed body weight of a child.
5/7 = conversion of 5 day/week dosing schedule to 7 day/week.
1,000 = uncertainty factor, chosen in accordance with NAS/ODW
for use with a LOAEL from an animal study.
1 L/day = assumed daily water consumption of a child.
The Longer-term HA for a 70 kg adult is:
Longer-term HA = (570 mg/kg/day) (70 kg) (5) =14.3 mg/L (14,000 ug/L)
(1,000) (2 L/day) (7)
where:
570 mg/kg/day = LOAEL based on depressed body weight in rats.
70 kg = assumed body weight of an -adult.
-------
n-Hexane March 31, 1987
-10-
1,000 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a LOAEL from an animal study.
2 L/day = assumed daily water consumption of an adult.
Lifetime Health Advisory
The Lifetime HA represents that portion of an individual's total exposure
that is attributed to drinking water and is considered protective of noncar- .
cinogenic adverse health effects over a lifetime exposure. The Lifetime HA
is derived in a three step process. Step 1 determines the Reference Dose
(RfD), formerly called the Acceptable Daily Intake (ADI). The RfD is an esti-
mate of a daily exposure to the human population that is likely to be without
appreciable risk of deleterious effects over a lifetime, and is derived from
the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided
by an uncertainty factor(s). From the RfD, a Drinking Water Equivalent Level
(DWEL) can be determined (Step 2). A DWEL is a medium-specific (i.e., drinking
water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the assumed body
weight of an adult and divided by the assumed daily water consumption of an
adult. The Lifetime HA is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC). The RSC from drinking
water is based on actual exposure data or, if data are not available, a
value of 20% is assumed for synthetic organic chemicals and a value of 10%
is assumed for inorganic chemicals. If the contaminant is classified as a
Group A or B carcinogen, according to the Agency's classification scheme of
carcinogenic potential (U.S. EPA, 1986), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.
Appropriate studies for the derivation of a Lifetime HA are not avail-
able at this time. The Krasavage et al. (1980) study was not considered
because the data obtained were part of a broader study dealing with other
chemicals.
Evaluation of Carcinogenic Potential
0 No information was found in the available literature on the carcino-
genic effects of n-hexane.
0 According to the EPA classification scheme (U.S. EPA, 1986), n-hexane
may be classified as Group D.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 An occupational threshold limit value (TLV) of 100 ppm was set by
ACGIH (1976).
VII. ANALYTICAL METHODS
0 There is no standardized method for the determination of hexane in
drinking water samples. However, hexane may be determined by a
-------
n-Hexane March 31, 1987
-1 1-
purge-and-trap gas chromatographic/mass spectrometric procedure used
for the determination of volatile organic compounds in water (U.S. EPA,
1985). This method calls for the bubbling of an inert gas through
the sample and trapping hexane on an adsorbant material. The adsorbant
material is heated to drive off n-hexane onto a gas chromatographic
column. The gas chromatograph is temperature programmed to separate
the method analytes which are then detected by the mass spectrometer.
VIII. TREATMENT TECHNOLOGIES
0 No data are available on the removal of n-hexane by conventional or
other treatment technologies. However, the physical properties and
structure of the compound, as well as its similarity to other straight
chain aliphatic hydrocarbons, suggest that several treatment methods
may be effective in removing n-hexane.
0 ESE [(1982) considered adsorption a potential treatment technique for
hexane on the basis of its structure and low solubility. According
to McGuire and Suffet (1980), non-polar saturated hydrocarbons such
as hexane should be adsorbed on granulated activated carbon (GAG).
However, only limited data demonstrating hexane removal by GAG is
available. In a full-scale study, average hexane concentrations in
water were reduced from 0.2 ppb to 0.1 ppb on passage through each of
two 5 ft diameter (1.6 m), 11 ft (3.4 m) GAG contactors containing
Westvaco 12 x 40 GAG. The hydraulic loading for each contactor was
7.4 gpm/ft^ and the Empty Bed Contact Time was 15.2 min.
0 Packed column aeration also may remove n-hexane from drinking water.
McCarty et al. (1979) found that the Henry's Law Constant for a
chemical is a good indicator of the relative amenability of that
chemical to aeration. Accordingly, the Henry's Law Constant for
n-hexane (1 x 10~1 atm-mVmole) suggests that this substance will be
amenable to removal from solution by air stripping. For example, this
value is significantly higher than that for chloroform (3.4 x 10-3
atm-m-3/mole), a substance known to be amenable to air stripping
(Singley and Bilello, 1981). Air stripping is an effective, simple
and relatively inexpensive process for removing many organics from
water. However, this process transfers the contaminant directly to
the air stream. When considering use of air stripping as a treatment
process, it is suggested that careful consideration be given to the
overall environmental occurrence, fate, route of exposure and potential
health hazards associated with the chemical.
0 The boiling point of n-hexane (69°C) and of its azeotropic mixture
with water [94.4% n-hexane, 61.6°C CCRC, 1979)] suggest that boiling
would be an effective means of removing n-hexane from aqueous systems.
However, the potential health hazard from hexane inhalation would
have to be considered.
0 A study reported by Quentin et al. (1977) removed n-hexane in water
from 7.3 mg/L to 0.3 mg/L after treatment with alum and a polymeric
flocculant. This suggests that a conventional treatment process such
as coagulation/sedimentation may be effective in reducing n-hexane.
-------
n-Hexane March 31, 1987
-12-
IX. REFERENCES
ACGIH. 1976. American Conference of Governmental Industrial Hygienists:
TLVs—threshold limit values for chemical substances in workroom air
adopted by ACGIH for 1976. Cincinnati, OH. pp. 1-54.
Baker, T.S., and D.E. Rickert. 1981. Dose-dependent uptake, distribution,
and elimination of inhaled n-hexane in the Fischer-344 rat. Toxicol.
Appl. Pharmacol. 61:414-422.
Bellar, T.A.> and J.J. Lichtenberg. 1974. Determining volatile organics
at microgram-per-liter levels by gas chromatography. Journal AWWA.
66:739-744.
Bus, J.5., E.L. White, R.W. Tyl and C.S. Barren. 1979. Prenatal toxicity
i and metabolism of n-hexane in Fischer 344 rats after inhalation exposure
1 during gestation. Toxicol. Appl. Pharmacol. 51:295-302.
Bus, J.S., D. Deyo arid M. Cox. 1983. Disposition of radioactivity in rats
after acute inhalation exposure to c1^n-hexane. The Toxicologist. 3:135.
Cavender, F.L., H.W. Casey, H. Salem, D.G. Graham, J.A. Swenberg and E.G. Gralla.
1984. A 13-week vapor inhalation study of n-hexane in rats with emphasis
on neurotoxic effects. Fundam. Appl. Toxicol. 4:191-201.
CRC Handbook of Chemistry and Physics. 1979. R.C. Weast and M.G. Astle, eds.
CRC Press. West Palm Beach, Florida.
DiVincenzo, G.D., C.J. Kaplan and J. Dedinas. 1976. Characterization of
the metabolites of methyl n-butyl ketone, methyl i_sp-butyl ketone and
methyl ethyl ketone in guinea pig serum and their clearance. Toxicol.
Appl. Pharmacol. 36:511-522.
ESE. 1982. Environmental Science and Engineering. Treatment techniques
available for removal of n-hexane. ' In support of Office of Drinking
Water Health Advisory prepared for Science and Technology Branch, CSD,
ODW, U.S. EPA.
Herskowitz, A., N. Ishii and H. Schaumburg. 1971. N-hexane neuropathy—
A syndrome occurring as a result of industrial exposure. N. Engl. J. Med.
285:82-85.
Hewett, W.R., H. Miyajima, M.G. Cote and G.L. Plaa. 1980. Acute alteration
of chloroform-induced hepato- and nephrotoxicity by n-hexane, methyl-n-
butyl ketone and 2,5-hexanedione. Toxicol. Appl. Pharmacol. 53:230-248.
Howd, R.A., L.R. Bingham, T.M. Steeger, C.S. Rebert and G.T. Pryor. 1982.
Relation between schedules of exposure to hexane and plasma levels of
2,5-hexanedione. Neurobehav. Toxicol. Teratol. 4:87-91.
Jakobson, I., J.E. Wahlberg, B. Holmberg and G. Johansson. 1982. Uptake via thd
blood and elimination of 10 organic solvents following epicutaneous expo-
sure of anesthetized guinea pigs. Toxicol. Appl. Pharmacol. 63:181-187.
-------
n-Hexane ' March 31, 1987
-1 3-
Kimura, E.T., D.M. Ebert and P.W. Dodge. 1971. Acute toxicity and limits
. of solvent residue for sixteen organic solvents. Toxicol. Appl. Pharmacol.
19:699-704.
Kirk-Othmer. 1981. C-\ to Cg Alkanes. In Kirk-Othmer Encyclopedia of Chemical
Technology, 3rd ed. Wiley-Interscience. New York.
Krasavage, W.J., J.L. O'Donoghue, G.D. DiVincenzo and C.J. Terhaar. 1980.
The. relative neurotoxicity of methy1-n-butyl ketone, n-hexane and their
metabolites. Toxicol. Appl. Pharmacol. 52:433-441.
Marks, T.A., P.W. Fisher and E. Staples. 1980. Influence of n-hexane on
embryo and fetal development in mice. Drug and Chem. Toxicol. 3:393-406.
McCarty et al. 1979. Treatment for the control of trichloroethylene and
related industrial solvents in drinking water. U.S. Environmental.
Protection Agency, Drinking Water Research Division. Cincinnati, Ohio.
McGuire, M.J. and I.H. Suffet. 1980. Activated carbon adsorption of organics
from aqueous phase: Vol. 2. Ann Arbor Science Publishers, Inc. Ann
Arbor, Michigan.
Nomiyama, I., and J. Nomiyama. 1975. The effects of the cutaneous absorption
of n-hexane on humans. Jpn. J. Hyg. 30:140. (Cited in NIOSH, 1977)
NIOSH. 1977. National Institute for Occupational Safety and Health. Criteria
for a recommended standard...occupational exposure to alkanes (C5-C8).
Washington, DC. Publication No. 77-151.
NIOSH. 1978. National Institute for Occupational Safety and Health. Registry
of Toxic Effects of Chemical Substances (RTECS). 1978.
Perbellini, L., F. Brugnone and I. Pavan. 1980. Identification of the
metabolites of n-hexane, cyclohexane and their isomers in men's urine.
Toxicol. Appl. Pharmacol. 53:220-229.
Perry, R.H. and C.H. Chilton. 1973. Chemical Engineers' Handbook. 5th
Edition. McGraw-Hill Book Company, pp. 3-56.
Quentin, K.E., L. Weil and H. Berger. 1977. U.S. Patent 4,028,233, June 7,
1977, assigned to A.G. Hoechst, Germany Industrial Wastewater Cleanup,
Noyes Data Corporation, 1979.
Raye, R. 1983. In vitro toxicity of n-hexane and 2,5-hexanedione using
isolated perfused rabbit heart. J. Toxicol. Environ. Health. 11:879-884.
Singley, J.E., and L.J. Bilello. 1981. Advances in the development of design
criteria for packed column aeration. Submitted to Journal AWWA, 1981.
Takeuchi, Y., Y. Oho, N. Hisanaga, J. Kitoh and Y. Sugiura. 1980. A com-
parative study on the neurotoxicity of n-pentane, n-hexane and n-heptane
in"the rat. Brit. J. Ind. Med. 37:241-247.
-------
n-Hexane March 31, 1987
-14-
U.S. EPA. 1985. U.S. Environmental Protection Agency. Method 524.1.
Volatile organic compounds in water by purge and trap gas chromatography/
mass spectrometry. Environmental Monitoring and Support Laboratory,
Cincinnati, OH.,45268. June.
U.S. EPA. 1986. U.S. Environmental Protection Agency. Final guidelines for
carcinogen risk assessment. Federal Register. 51(185):33992-34003.
September 24.
Windholz, M. 1983. The Merck Index. 10th Edition. Merck and Co., Inc.,
Rahway, N.J. p. 678.
------- |