Toxicity Profiles
Toxicity Summary for ACENAPHTHENE
NOTE:
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- EXECUTIVE SUMMARY
- 1. INTRODUCTION
- 2. METABOLISM AND DISPOSITION
- 2.1 ABSORPTION
2.2 DISTRIBUTION
2.3 METABOLISM
2.4 EXCRETION
- 3. NONCARCINOGENIC HEALTH EFFECTS
- 3.1 ORAL EXPOSURES
3.2 INHALATION EXPOSURES
3.3 OTHER ROUTES OF EXPOSURE
3.4 TARGET ORGANS/CRITICAL EFFECTS
- 4. CARCINOGENICITY
- 4.1 ORAL EXPOSURES
4.2 INHALATION EXPOSURES
4.3 OTHER ROUTES OF EXPOSURE
4.4 EPA WEIGHT-OF-EVIDENCE
4.5 CARCINOGENICITY SLOPE FACTORS
- 5. REFERENCES
January 1994
Prepared by Rosmarie A. Faust, Ph.D., Chemical Hazard Evaluation Group, Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, *, Oak Ridge, Tennessee.
Prepared for OAK RIDGE RESERVATION ENVIRONMENTAL RESTORATION PROGRAM
*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.
EXECUTIVE SUMMARY
Acenaphthene, also known as 1,2-dihydroacenaphthylene or 1,8-ethylenenaphthalene, is a
tricyclic aromatic hydrocarbon that occurs in coal tar. It is used as a dye intermediate, in the
manufacture of some plastics, and as an insecticide and fungicide (EPA, 1980). Acenaphthene has
been detected in cigarette smoke, automobile exhausts, and urban air; in effluents from
petrochemical, pesticide, and wood preservative industries (EPA, 1980); and in soils, groundwater,
and surface waters at hazardous waste sites (ATSDR, 1990).
No absorption data are available for acenaphthene; however, by analogy to structurally-related
polycyclic aromatic hydrocarbons (PAHs), it would be expected to be absorbed from the
gastrointestinal tract and lungs (EPA, 1988). The anhydride of naphthalic acid was identified as a
urinary metabolite in rats treated orally with acenaphthene (Chang and Young, 1943).
Although a large body of literature exists on the toxicity and carcinogenicity of PAHs,
primarily benzo[a]pyrene, toxicity data for acenaphthene are limited. Acenaphthene is irritating to
the skin and mucous membranes of humans and animals (Sandmeyer, 1981; Knobloch et al., 1969).
Acute toxicity data for animals include oral LD50s of 10 g/kg for rats and 2.1 g/kg for mice
(Knobloch et al., 1969) and an intraperitoneal LD50 of 600 mg/kg for rats (Reshetyuk et al., 1970).
Oral exposure of rats to daily 2-g doses of acenaphthene for 32 days produced peripheral blood
changes, mild liver and kidney damage, and pulmonary effects (Knobloch et al., 1969). Subchronic
oral exposure to acenaphthene at doses of 350 mg/kg for 90 days produced increased liver weights,
hepatocellular hypertrophy, and increased cholesterol levels in mice. Reproductive effects included
decreased ovary weights at doses of 350 mg/kg and decreased ovarian and uterine activity as well
as smaller and fewer corpora lutea at 700 mg/kg/day (EPA, 1989). Adverse effects on the blood,
lungs, and glandular tissues were reported in rats exposed daily to 12 mg/m3 of acenaphthene for 5
months (Reshetyuk et al., 1970).
A reference dose (RfD) of 6E-1 mg/kg/day for subchronic oral exposure (EPA, 1993a) and 6.E-2
mg/kg/day for chronic oral exposure to acenaphthene (EPA, 1993b) was calculated from a no-observed-adverse-effect level (NOAEL) of 175 mg/kg/day from a 90-day gavage study with mice.
The critical effect was hepatotoxicity. Data were insufficient to derive an inhalation reference
concentration (RfC) for acenaphthene (EPA, 1993a,b).
No oral bioassays were available to assess the carcinogenicity of acenaphthene. A limited
inhalation study in which rats were exposed to 12 mg/m3 acenaphthene for 5 months and observed
an additional 8 months provided no evidence of carcinogenicity (Reshetyuk et al., 1970). The EPA
has not assigned a weight-of-evidence classification for carcinogenicity to acenaphthene (EPA,
1993a,b).
1. INTRODUCTION
Acenaphthene (CAS Reg. No. 83-32-9), also known as 1,2-dihydroacenaphthylene or
1,8-ethylenenaphthalene, is a tricyclic aromatic hydrocarbon with a chemical formula of C12H10 and
a molecular weight of 154.21 (Budavari et al., 1989). It is a crystalline solid with a boiling point of
279C, a melting point of 95C, and a density of 1.189 g/mL. Acenaphthene is insoluble in water
but is soluble in ethanol, methanol, propanol, chloroform, benzene, toluene, and glacial acetic acid
(Budavari et al., 1989). It has a vapor pressure of 4.47x10-3 mm Hg (ATSDR, 1990) and a log
octanol/water coefficient of 3.92-5.07 (Enzminger and Ahlert, 1987).
Acenaphthene occurs in coal tar produced during the high temperature carbonization or coking
of coal. It is used as a dye intermediate, in the manufacture of some plastics, and as an insecticide
and fungicide (EPA, 1980). Acenaphthene is an environmental pollutant and has been detected in
cigarette smoke, automobile exhausts, and urban air; in effluents from petrochemical, pesticide, and
wood preservative industries (EPA, 1980); and in soils, groundwater, and surface waters at
hazardous waste sites (ATSDR, 1990). The compound is one of a number of polycyclic aromatic
hydrocarbons (PAHs) on EPA's priority pollutant list (ATSDR, 1990).
2. METABOLISM AND DISPOSITION
2.1 ABSORPTION
Data regarding the gastrointestinal or pulmonary absorption of acenaphthene in humans or
animals were not available. However, data from structurally-related PAHs suggest that
acenaphthene would be absorbed readily from the gastrointestinal tract and lungs (EPA, 1988).
2.2 DISTRIBUTION
No human or animal data were available concerning the tissue distribution of acenaphthene.
2.3 METABOLISM
Chang and Young (1943) isolated the anhydride of naphthalic acid (naphthalene-1,8-dicarboxylic acid) from the urine of male white rats fed a diet containing 1% acenaphthene (total
dose 4.1 g) or dosed by gavage with a suspension of 0.1 g acenaphthene on alternate days (total dose
1.8 g), suggesting that the five-membered ring in acenaphthene undergoes cleavage.
2.4 EXCRETION
Chang and Young (1943) identified the anhydride of naphthalic acid in the urine of rats that had
been orally dosed with acenaphthene. The parent compound was not detected. No other data were
available on the excretion of acenaphthene.
3. NONCARCINOGENIC HEALTH EFFECTS
3.1 ORAL EXPOSURES
3.1.1 Acute Toxicity
3.1.1.1 Human
Information on the acute oral toxicity of acenaphthene in humans was not available. Lillard and
Powers (1975) investigated the reaction of humans to an odor from an aqueous solution of
acenaphthene that could result in rejection of contaminated water. The lowest levels eliciting human
responses ranged from 0.022 to 0.22 ppm.
3.1.1.2 Animal
Knobloch et al. (1969) determined oral LD50s of 10 g/kg and 2.1 g/kg for rats and mice,
respectively. Young rats given daily doses of 2 g/kg of acenaphthene in olive oil for 32 days
exhibited loss of body weight, peripheral blood changes (unspecified), increased aminotransferase
levels in blood serum, and mild morphological damage to the liver and kidneys. At the end of the
treatment period, mild bronchitis and localized inflammation of the bronchial tissue was observed
(Knobloch et al., 1969).
Gershbein (1975) examined the effect of acenaphthene on the extent of liver regeneration as an
indicator of the ability to induce a proliferative response in partially hepatectomized rats. Daily
administration of a diet containing 0.1% acenaphthene for 10 days produced a statistically significant
(p<0.01) increase in the extent of liver regeneration compared with controls. This effect was not
observed when rats were fed a diet containing 0.03% acenaphthene for 10 days.
3.1.2 Subchronic Toxicityg>
3.1.2.1 Human
Information on the subchronic oral toxicity of acenaphthene in humans was not available.
3.1.2.2 Animal
In a subchronic gavage study, male and female CD-1 mice were administered 0, 175, 350, or 700
mg/kg/day of acenaphthene for 90 days (EPA, 1989). There were no treatment-related effects on
survival, body weight, or total food intake. No clinical signs of toxicity or ophthalmologic
alterations were observed. Statistically significant (p0.05) increases in liver weights accompanied
by microscopic alteration (cellular hypertrophy) occurred in mid- and high-dosed rats (both sexes).
Additionally, high-dosed males and mid- and high-dosed females had significantly (p0.05)
increased cholesterol levels. In females, acenaphthene elicited adverse effects on the reproductive
system characterized by decreased ovary weights (mid- and high-dosed mice, p0.05) and decreased
activity of the ovaries and uterus, as well as fewer and smaller corpora lutea (high-dosed mice).
Although increased liver weights without accompanying microscopic alterations or increased
cholesterol levels were also observed at the low dose, this change was considered to be adaptive
rather than adverse, providing a lowest-observed-adverse-effect level (LOAEL) of 350 mg/kg/day
and a no-observed-adverse-effect level (NOAEL) of 175 mg/kg/day.
3.1.3 Chronic Toxicity
Information on the chronic oral toxicity of acenaphthene in humans or animals was not available.
3.1.4 Developmental and Reproductive Toxicity
3.1.4.1 Human
Information on the developmental and reproductive toxicity of acenaphthene in humans
following oral exposure was not available.
3.1.4.2 Animal
Decreased ovary weights were seen in female CD-1 mice administered 350 or 700 mg/kg/day
of acenaphthene by gavage for 90 days (refer to Subsect. 3.1.2.2). In addition, mice exposed to 700
mg/kg/day exhibited decreased ovarian and uterine activity as well as smaller and fewer corpora
lutea (EPA, 1989).
3.1.5 Reference Dose
3.1.5.1 Subchronic
ORAL RfD: 6E-1 mg/kg/day (EPA, 1993a)
NOAEL: 175 mg/kg/day
LOAEL: 350 mg/kg/day
UNCERTAINTY FACTOR: 300
PRINCIPAL STUDY: EPA, 1989
COMMENTS: The same study, described in Subsect. 3.1.2.2, was used for the derivation
of the subchronic and chronic RfD. An uncertainty factor of 300 reflects 10 each for intra-
and interspecies variability and 3 for lack of adequate data in a second species and lack of
reproductive/developmental toxicity studies.
3.1.5.2 Chronic
ORAL RfD: 6E-2 mg/kg/day (EPA, 1993b)
NOAEL: 175 mg/kg/day
LOAEL: 350 mg/kg/day
UNCERTAINTY FACTOR: 3000
CONFIDENCE:
Study: Low
Data Base: Low
RfD: Low
VERIFICATION DATE: 11/15/89
PRINCIPAL STUDY: EPA, 1989
COMMENTS: The RfD is based on a 90-day gavage study with mice described in Subsect.
3.1.2.2, with hepatotoxicity as the critical effect. An uncertainty factor of 3000 reflects 10
each for intra- and interspecies variability, 10 for the use of a subchronic study for the
derivation of a chronic RfD, and 3 for lack of adequate data in a second species and lack of
reproductive/developmental toxicity studies.
3.2 INHALATION EXPOSURES
3.2.1 Acute Toxicity
Information on the acute toxicity of acenaphthene in humans or animals following inhalation
exposure was not available.
3.2.2 Subchronic Toxicity
3.2.2.1 Human
Information on the subchronic toxicity of acenaphthene in humans following inhalation exposure
was not available.
3.2.2.2 Animal
Adverse effects on the blood, glandular tissues (no details provided), and lungs were reported
in rats exposed by inhalation to 12 mg/m3 acenaphthene, 4 hours/day, 6 days/week for 5 months
(Reshetyuk et al., 1970). Effects on the lungs included hyperplasia and metaplasia of the bronchial
epithelium, which may have been the result of the pneumonia that killed many animals.
3.2.3 Chronic Toxicity
Information on the chronic toxicity of acenaphthene in humans or animals following inhalation
exposure was not available.
3.2.4 Developmental and Reproductive Toxicity
Information on the developmental and reproductive toxicity of acenaphthene in humans or
animals following inhalation exposure was not available.
3.2.5 Reference Concentration
Data were insufficient to derive a subchronic or chronic inhalation reference concentration
(RfC) for acenaphthene (EPA, 1993a,b).
3.3 OTHER ROUTES OF EXPOSURE
3.3.1 Acute Toxicity
3.3.1.1 Humans
Acenaphthene is irritating to the skin and mucous membranes (Sandmeyer, 1981).
3.3.1.2 Animals
Acenaphthene was irritating to the skin and conjunctiva of rabbits but was not sensitizing in
guinea pigs (Knobloch et al., 1969).
Reshetyuk et al. (1970) determined an intraperitoneal LD50 of 600 mg/kg for rats. Acenaphthene
in peanut oil injected subcutaneously into partially hepatectomized rats (total dose 5-20 mmol/kg)
daily for 10 days produced a statistically significant (p<0.01) increase in liver regeneration compared
with controls (Gershbein, 1975). An increase in the synthesis of liver protein was observed in rats
following an intraperitoneal injection of acenaphthene at a concentration equimolar to 1 mg of 20-methylcholanthrene (0.57 mg acenaphthene) (Arcos et al., 1961).
3.3.2 Subchronic Toxicity
Information on the subchronic toxicity of acenaphthene by other routes of exposure in humans
or animals was not available.
3.3.3 Chronic Toxicity
Information on the chronic toxicity of acenaphthene by other routes of exposure in humans or
animals was not available.
3.3.4 Developmental and Reproductive Toxicity
Information on the developmental or reproductive toxicity of acenaphthene by other routes of
exposure in humans or animals was not available.
3.4 TARGET ORGANS/CRITICAL EFFECTS
3.4.1 Oral Exposures
3.4.1.1 Primary Target Organs
1. Liver. Subchronic oral exposure of rats to acenaphthene produced increased liver
weights, hepatocellular hypertrophy, and increased cholesterol levels. Mild morphological
liver changes were seen in rats following subacute exposure.
2. Reproductive System. Subchronic oral exposure of rats to acenaphthene produced
decreased ovary weights, inactivity of the ovaries and uterus, and fewer and smaller corpora
lutea.
3.4.1.2 Other Target Organs
Information concerning other target organs following oral exposure to acenaphthene was not
available.
3.4.2 Inhalation Exposures
3.4.2.1 Primary Target Organs
The available data were inadequate to determine primary target organs for inhalation exposure
to acenaphthene.
3.4.2.2 Other Target Organs
1. Lungs. Pneumonia with hyperplasia and metaplasia of the bronchial epithelium was
reported in rats subchronically exposed to acenaphthene.
2. Blood. Subchronic exposure produced unspecified hematologic effects in rats.
3.4.3 Other Routes of Exposure
Skin. Acenaphthene is irritating to the skin and mucous membranes.
4. CARCINOGENICITY
4.1 ORAL EXPOSURES
Information on the carcinogenicity of acenaphthene in humans or animals following oral
exposure was not available.
4.2 INHALATION EXPOSURES
4.2.1 Human
Information on the carcinogenicity of acenaphthene in humans following inhalation exposure
was not available.
4.2.2 Animal
Reshetyuk et al. (1970) exposed rats by inhalation to 12 mg/m3 acenaphthene, 4 hours/day,
6 days/week for 5 months. Although the bronchial epithelium showed hyperplasia and metaplasia,
no signs of malignancy appeared during the 8-month observation period.
4.3 OTHER ROUTES OF EXPOSURE
4.3.1 Human
Information on the carcinogenicity of acenaphthene in humans by other routes of exposure was
not available.
4.3.2 Animal
Negative results were reported in a short-term predictive test for carcinogenicity in which newts
(Triturus cristatus) were injected subcutaneously with acenaphthene (dose not reported) (Neukomm,
1974).
Akin et al. (1976) isolated some PAH-rich fractions of cigarette smoke condensate and tested
them for tumor promotion on mouse skin. Female mice received an application of 125 g 7,12-dimethylbenz[a]anthracene (DMBA) as initiator; 3-4 weeks later the smoke condensate fraction
(containing acenaphthene and other PAHs) was applied 5 times weekly for 13 months. Compared
with controls treated with DMBA and acetone, the fraction containing acenaphthene elicited no
significant tumor-promoting activity.
To examine the effect of acenaphthene on a liver microsomal enzyme, dimethylnitrosamine
demethylase, the enzyme that demethylates the known carcinogen dimethylnitrosamine (DMN),
Arcos et al. (1976) injected male weanling rats intraperitoneally with acenaphthene at concentrations
equimolar to 40 mg of 20-methylcholanthrene (23 mg acenaphthene). After 24 hours, treated rats
showed a 5% decrease of enzyme activity compared with controls. The investigators noted that
demethylation is a requirement for carcinogenesis by DNM, and therefore it is possible that
acenaphthene may slightly inhibit DMN carcinogenesis.
4.4 EPA WEIGHT-OF-EVIDENCE
A weight-of-evidence classification for acenaphthene is not listed in HEAST (EPA, 1993a) or
IRIS (EPA, 1993b).
4.5 CARCINOGENICITY SLOPE FACTORS
No carcinogenicity slope factors were calculated.
5. REFERENCES
Akin, F.J., et al. 1976. "Identification of polynuclear aromatic hydrocarbons in cigarette smoke and
their importance as tumorigens." J. Natl. Cancer Inst. 57: 191. (Cited in EPA, 1980).
Arcos, J.C., A.H. Conney, and N.P. Buu-Hoi. 1961. "Induction of microsomal enzyme synthesis
by polycyclic aromatic hydrocarbons of different molecular sizes." J. Biol. Chem. 236:
1291-1296.
Arcos, J.C., et al. 1976. "Dimethylnitrosamine-demethylase: Molecular size-dependence of
repression by polynuclear hydrocarbons. Nonhydrocarbon repressors." J. Toxicol. Environ.
Health 1: 395. (Cited in U.S. EPA, 1980).
ATSDR (Agency for Toxic Substances and Disease Registry). 1990. Toxicological Profile for
Polycyclic Aromatic Hydrocarbons. Acenaphthene, Acenaphthylene, Anthracene,
Benzo(a)anthracene, Benzo(a)pyrene, Benzo(b)fluoranthene, Benzo(g,i,h)perylene,
Benzo(k)fluoranthene, Chrysene, Dibenzo(a,h)anthracene, Fluoranthene, Fluorene,
Indeno(1,2,3-c,d)pyrene, Phenanthrene, Pyrene. Prepared by Clement International
Corporation, under Contract No. 205-88-0608. ATSDR/TP-90-20.
Budavari, S., M.J. O'Neil, and A. Smith (Eds.) 1989. The Merck Index. Merck & Co., Inc.,
Rahway, NJ, pp. 5-6.
Chang, Z.H. and Z. Young. 1943. "The metabolism of acenaphthene in the rat." J. Biol. Chem. 151:
87.
Enzminger, J.D. and R.C. Ahlert. 1987. "Environmental fate of polynuclear aromatic hydrocarbons
in coal tar." Environ. Technol. Letters 8: 269-278.
Gershbein, L.L. 1975. "Liver regeneration as influenced by the structure of aromatic and
heterocyclic compounds." Res. Commun. Chem. Pathol. Pharmacol. 11: 445-466.
Knobloch, K., S. Szedzikowski, and A. Slusarcyk-Zablobona. 1969. "Acute and subacute toxicity
of acenaphthene and acenaphthylene." Med. Pracy 20: 210-222. (Polish, Engl. Summary).
Lillard, D.A. and J.J. Powers. 1975. Aqueous odor thresholds of organic pollutants in industrial
effluents. EPA 660/4-75-002. U.S. Environmental Protection Agency, National Environmental
Research Center, Corvallis, OR. (Cited in U.S. EPA, 1980).
Neukomm, S. 1974. "The newt test for studying certain categories of carcinogenic substances." In:
Proc. Eur. Soc. for the Study of Drug Toxicity, Zurich, Switzerland, June 1973. Excerpta
Medica, Amsterdam. W.A.M. Duncan, Ed., Excerpta Medica Int. Congr., Series No. 311. (Cited
in U.S. EPA, 1980).
Reshetyuk, A.l., E.I. Talakina, and P.A. En'yakova. 1970. "Toxicological evaluation of
acenaphthene and acenaphthylene." Gig. Tr. Prof. Zabol. 14: 46-47.
Sandmeyer, E.E. 1981. "Aromatic hydrocarbons." In: Patty's Industrial Hygiene and Toxicology,
3rd. rev. ed., Vol. 2B. G.D. Clayton and F.E. Clayton, Eds., pp. 3346, 3351-3353.
U.S. EPA (U.S. Environmental Protection Agency). 1980. Ambient Water Quality Criteria for
Acenaphthene. EPA-440/5-80-015. Office of Water Regulations and Standards, Criteria and
Standards Division, Washington, DC.
U.S. EPA (U.S. Environmental Protection Agency). 1988. Drinking Water Criteria Document for
Polycyclic Aromatic Hydrocarbons (PAH). ECAO-CINDO10. Prepared by the Environmental
Criteria and Assessment Office, Office of Health and Environmental Assessment, U.S.
Environmental Protection Agency, Cincinnati, OH, for the Office of Drinking Water.
U.S. EPA (U.S. Environmental Protection Agency). 1989. Mouse Oral Subchronic Study with
Acenaphthene. Prepared by Hazelton Laboratories, Inc., for the Office of Solid Waste,
Washington, DC.
U.S. EPA (U.S. Environmental Protection Agency). 1993a. Health Assessment Summary Tables.
Annual FY-93. 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 (U.S. Environmental Protection Agency). 1993b. Integrated Risk Information System
(IRIS). Environmental Criteria and Assessment Office, Office of Health and Environmental
Assessment, Cincinnati, OH.
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