NAPHTHALENE
Ambient Water Quality Criteria
Criteria and Standards Division
Office of Water Planning and Standards
U.S. Environmental Protection Agency
Washington, D.C.
EPA LIBRARY SERVICES RTF NC
TECHNICAL DOCUMENT COLLECTION
-------
823R780O9
CRITERION DOCUMENT
NAPHTHALENE
CRITERIA
Aquatic Life
For freshwater aquatic life, no criterion for napthalene can
be derived using the Guidelines, and there are insufficient data-
to estimate a criterion using other procedures.
For saltwater aquatic life, no criterion for naphthalene can
be derived using the Guidelines, and there are insufficient data
to estimate a criterion using other procedures.
Human Health
For the protection of human health from the toxic properties
of naphthalene ingested through water and through contaminated
aquatic organisms, the ambient water criterion is determined to be
143 ug/1.
-------
NAPHTHALENE
Introduction /
Naphthalene is the most abundant single constituent
of coal tar (Schmeltz, et al. 1977). In 1974, 1.8 x 105
metric tons of naphthalene were produced from coal tar,
and 1.1 x 10 metric tons were produced from petroleum (Brown,
et al. 1975; U.S. EPA, 1976). This compound is used as
an intermediate in the production of dye compounds and the
formulation of solvents, lubricants, and motor fuels. One
of the principal uses of naphthalene as a feedstock in the
United States is for the synthesis of phthalic anhydride.
It has also been used directly as a moth repellant and insec-
ticide as well as an antihelminthic, vermicide, and an intes-
tinal antiseptic.
Napthalene is a bicyclic aromatic hydrocarbon with
the chemical formula C,,,Hg and a molecular weight of 128.16.
Pure naphthalene forms a white crystalline solid at room
temperature whereas the crude or technical grades may range
in color from brown to tan. Naphthalene vapor and dust
can form explosive mixtures with air (Windholz, 1976).
Pure naphthalene melts at 80.2°C; the less pure forms
of the compound will melt at temperatures ranging from 74
to 80°C. The boiling point of naphthalene is 217.96° at
atmospheric pressure (Manufacturing Chemists Assoc. 1956).
At 15.5°C, the density is 1.145 (Manufacturing Chemists
Assoc. 1956) and at 100°C the density is 0.9625 (Marti,
1930; Weast, 1975). At 19.8°C the vapor pressure of solid
naphthalene is 0.0492 mm Hg (Gil'denblat, et al. 1960).
A-l
-------
The solubility of naphthalene in water has been reported
to range between 30,000 ;ag/l (Mitchell, 1926) and 40,000
;ug/l (Josephy and Radt, 1948) at 25°C. The solubility of
naphthalene in seawater will vary according to the degree
of chlorosity; in seawater of average composition the solu-
bility of naphthalene is approximately 33,000jug/l (Gordon
and Thome, 1967) . Naphthalene has also been reported to
be soluble in organic solvents (Spector, 1956).
Naphthalene can oxidize in the presence of light and
air, and it was determined that 50 percent of the theoretical
CO2 was liberated after 14 days (Ludzack and Ettinger, 1963).
The process involves initial conversion to naphthaquinone
with subsequent rupture of one of the aromatic rings and
the release of CO2 (Kirk and Othmer, 1967). However, this
oxidation process occurs only at elevated temperatures (Josephy
and Radt, 1948).
When combined with alcohol and ozone, cyclic alkoxy-
hydroxyperoxides are formed. In an acidic medium, these
peroxides will be converted to methyl phthalaldehydate;
in a basic medium, they are converted to phthalaldehydic
acid (Bailey, et al. 1964). When combined with metal nitrate
within a temperature range of 55°C to 180°C, naphthalene
can be nitrated at the alpha position (Alama and Okon, 1964).
In the presence of oxygen, I^SO,, a vanadium oxide catalyst,
and Si04, naphthalene can be converted to phthalic anhydride
(Morotskii and Kharlampovich, 1968).
Microorganisms can degrade naphthalene to 1,2-dihydro-
1,2,-dihydroxynaphthalene and ultimately to carbon dioxide
A-2
-------
and water. Studies have indicated a degradation rate under
laboratory conditions of up to 3.3 ug/1 (Lee and Anderson,
1977).
Naphthalene has been shown to be toxic to microorganisms
and has been reported to reduce photosynthetic rates in algae.
It has also been reported to be acutely toxic to various
invertebrate and vertebrate species of aquatic organisms.
In laboratory mammals and humans, naphthalene has been linked
to blood disorders and is suspected of traversing the placental
membrane in humans following naphthalene ingestion by the
mother.
Naphthalene has a varied environmental distribution
and has been detected in ambient water (up to 2.0 ;ug/l) ,
sewage plant effluents (up to 22 ;ig/l) , and drinking water
supplies (up to 1.4 /ig/1) (U.S. EPA, 1971-1977). Recent
studies have determined that naphthalene will accumulate
in sediments by more than 100 times the concentration in
the overlying water (Cox, et al. 1975; Lee and Anderson,
1977).
Naphthalene has been shown to bioconcentrate in both
invertebrate and vertebrate species of aquatic organisms.
It has also been suggested that much of the naphthalene
taken up by aquatic organisms returns to the ecosystem in
fecal matter without being metabolized. In addition, iin
vitro studies have identified three naphthalene metabolites
derived from rat liver microsome preparations; these probably
resulted from hydroxylation and conjugation with water-soluble
moieties.
A-3
-------
REFERENCES
Alama, W., and K. Okon. 1964. Direct nitration of benzene,
naphthalene, and phenol by inorganic nitrates. Buil. Wojskowa
Akad. Tech. 13: 51.
Bailey, P.S., et al. 1964. Ozonolysis of naphthalenes;
the aromatic products. Jour. Org. Chem. 29: 697.
Brown, S.L., et al. 1975. Research program on hazard priority
ranking of manufactured chemicals. Phase II - Final Report,
A report prepared by Stanford Research Institute. National
Science Foundation, Washington, D.C. pp. 62-A-l.
Chemical Economics Handbook. 1976. Chem. Inf. Serv., Stanford
Res. Inst., Menlo Park, Calif.
Cox, B.A., et al. 1975. An experimental oil spill: The
distribution of aromatic hydrocarbons in the water, sediment,
and animal tissues within a shrimp pond. In Proc. Conf.
Prevent. Control Oil Pollut. San Francisco, March 25-27,
1975. Am. Petrol. Inst., Washington, D.C.
Gil'denblat, I.A., et al. 1960. Vapor pressure over crystal-
line naphthalene. Jour. Appl. Chem. USSR. 33: 245.
A-4
-------
Gordon, J.E., and R.L. Thorne. 1967. Salt effects on non-
electrolyte solutions. Geschim. Cosmochim. Acta. 31:
2433.
Josephy, E., and F. Radt, eds. 1948. Encyclopedia of organic
chemistry: Series III. Elsevier Publishing Co., Inc.,
New York.
Kirk, R.E., and D.F. Othraer. 1967. Encyclopedia of chemical
technology. 2nd ed. John Wiley and Sons, Inc, New York.
Lee, R.F., and J.W. Anderson. 1977. Fate and effect of
naphthalene: Controlled ecosystem pollution experiment.
Bull. Mar. Sci. 27: 127.
Ludzack, F.J., and M.B. Ettinger. 1963. Biodegradability
of organic chemicals isolated from rivers. Purdue Univ.
Eng. Bull. Ser. No. 115: 278.
Manufacturing Chemists Assoc. 1956. Chemical safety data
sheets SD-58: Naphthalene. Washington, D.C.
Marti, F.B. 1930. Methods and equipment used at the Bureau
of Physiochemical Standards. Bull. Soc. Chim. Bedgrad.
39: 590.
A-5
-------
Mitchell, S. 1926. A method for- determining the solubility
of sparingly soluble substances. Jour. Chem. Soc. 129:
1333.
Morotskii, O.A.f and G.D. Kharlampovich. 1968. Phthalic
anhydride. Izobret., Prom. Obraztsy, Tovarnye Znaki. 45:
22.
Schmeltz, I., et al. 1977. The role of naphthalenes as
carcinogens. A paper presented at the 16th Annu. Meet.
Soc. Toxicol. Toronto, Can. March 27-30, 1977.
Spector, W.S., ed. 1956. Handbook of toxicology. Saunders
Publishing Co., Philadelphia.
U.S. EPA. 1971-1977. Unpublished data from Region IV, Atlanta
Ga.
U.S. EPA. 1976. Organic chemical producer's data base program.
Chemical No. 2701. Radian Corporation.
Weast, R.C. 1975. Handbook of chemistry and physics. CRC
Press, Cleveland, Ohio.
Windholz, M., ed. 1976. The Merck Index. 9th ed. Merck
and Co., Rahway, N.J.
A-6
-------
AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
A limited variety of aquatic species has been exposed to
naphthalene and all tests were under static procedures with
unmeasured test concentrations. Fifty percent effect levels are
in the range of 5,600 to 82,000 ug/1. One embryo-larval test with
the fathead minnow demonstrated no adverse effects at the highest
test concentration of 440 ug/l«
Acute Toxicity
The adjusted 96-hour LC50 value for the mosquitofish (Wallen,
et al. 1957) is 82,000 ug/1 (Table 1) and after division by the
species sensitivity factor (3.9) results in a Final Fish Acute
Value of 21,000 ug/1.
Daphnia magna appears to be more sensitive with an adjusted
48-hour EC50 of 7,260 ug/1 (Table 2). Based on this single datum,
*The reader is referred to the Guidelines for Deriving Water
Quality Criteria for the Protection of Aquatic Life [43 FR 21506
(May 18, 1978) and 43 FR 29028 (July 5, 1978)] in order to better
understand the following discussion and recommendation. The
following tables contain the appropriate data that were found in
the literature, and at the bottom of each table are the calcula-
tions for deriving various measures of toxicity as described in
the Guidelines.
B-l
-------
the Final Invertebrate Acute Value for naphthalene is 350 ug/1.
Since this concentration is lower than the equivalent value for
fish, 350 ug/1 is also the Final Acute Value.
Chronic Toxicity
Exposure concentrations as high as 440 ug/1 (Table 3) caused
no adverse effects on survival or growth during an embryo-larval
test with the fathead minnow (U.S. EPA, 1978). This datum results
in a Final Fish Chronic Value that is greater than 33 ug/1- No
chronic data for invertebrate species are available.
Plant Effects
A 50 percent reduction in the number of cells of the alga,
Chlorella vulgaris, occurred at a concentration of 33,000 ug/1
(Table 4). This concentration is the Final Plant Value.
Residues
No measured steady-state bioconcentration factor (BCF) is
available for naphthalene. A BCF can be estimated using the
octanol-water partition coefficient of 2,300. This coefficient is
used to derive an estimated BCF of 210 for aquatic organisms that
contain about 8 percent lipids. If it is known that the diet of
the wildlife of concern contains a significantly different lipid
content, an appropriate adjustment in the estimated BCF should be
made.
Miscellaneous
Soto, et al. (1975a) observed the death of 61 percent of the
cells of the alga, Chlamydomonas angulosa, at a concentration of
34,400 ug/1 (Table 5). There was a 50 percent mortality of coho
salmon after an exposure of less than six hours to 5,600 ug/1
(Holland, et al. 1960).
B-2
-------
CRITERION FORMULATION
Freshwater Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Final Fish Acute Value = 21,000 ug/1
Final Invertebrate Acute Value = 350 ug/1
Final Acute Value = 350 ug/1
Final Fish Chronic Value = greater than 33 ug/1
Final Invertebrate Chronic Value = not available
Final Plant Value = 33,000 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = greater than 33 ug/1
0.44 x Final Acute Value = 150 ug/1
No freshwater criterion can be derived for napthalene using
the Guidelines because no Final Chronic Value for either fish or
invertebrate species or a good substitute for either value is
available, and there are insufficient data to estimate a criterion
using other procedures.
B-3
-------
l.i •!(!'•• J ».! i .!• . . ; i•-.!'.. -.1 i-.'-i'- . • . i
Table I. Freshwater fish acute values for naphthalene (Wallen, et al. 1957)
Adjusted
Bioasaay Teat Time LC50 LC50
Cone ,** thra) jug/H
Mosqultofish. S U 96 150,000 82,000
Gambusla afflnls
* S » static
** U = unmeasured
A 9 AAA
Geometric mean of adjusted values - 82,000 vg/1; —^"Ip " 21.000 ng/l
CD
I
-------
CD
I
U1
Table 2. Freshwater Invertebrate acute values for naphthalene (U.S. EPA, 1978)
Adjusted
Oiodssay Test Time 1£$Q I.CbO
HfetliQU* Cone .** (tits} (ini/1)
Cladoceran, S U 48 8,570 7.260
Daplinla ma an a
* S = static
•** u = unmeasured
' Geometric mean of adjusted values •» 70260 ug/lj ^|^ " 35°
-------
03
I
Table 3. Freshwater fish chronic values for naphthalene (U.S. EPA, 1978)
Chronic
Limits Value
Organism yest*
Fathead minnow, E-L >440 >220
Pimcphales promelaa
* E-L - embryo-larva
Geometric mean of chronic values » >220 tig/1,' '^j " >33 V&/1
Lowest chronic value - >220 pg/1
-------
03
I
-4
tt ,,
Tdble A. Freshwater plane effects for naphthalene (Kauss & llutchlnson, 1975)
Concentration
Organism Etfect (ng/i) _
Alga. EC50 48-hr 33,000
Chlorclla viilgara cell numbers
Final plant value - 33,000 ug/l
-------
CD
I
00
.*.:.•<; _j.-":,I.'| I.. :... ,:. .lliik. J».J.i .
Table S. Other freshwater data for naphthalene
Organism
Test
Result
Alga, 24 hra
CliTamydomonaa anguloaa
Alga, 24 hra
Chlamydomonaa anguloaa
Cuho salmon,
Oncorhynchus ktautch
Death of 6U of cells 34,400 Soto. et al. 1975a
Lose of photosynthetlc 107. Soto, et al. 1975b
capacity saturation
<6 hra 50% mortality
5.600 Holland, et al. 1960
-------
NAPHTHALENE
Ambient Water Quality Criteria
Criteria and Standards Division
Office of Water Planning and Standards
U.S. Environmental Protection Agency
Washington, B.C.
-------
CRITERION DOCUMENT
NAPHTHALENE
CRITERIA
Aquatic Life
For freshwater aquatic life, no criterion for napthalene can
be derived using the Guidelines, and there are insufficient data
to estimate a criterion using other procedures.
For saltwater aquatic life, no criterion for naphthalene can
be derived using the Guidelines, and there are insufficient data
to estimate a criterion using other procedures.
Human Health
For the protection of human health from the toxic properties
of naphthalene ingested through water and through contaminated
aquatic organisms, the ambient water criterion is determined to be
143 ug/1.
-------
NAPHTHALENE
Introduction
Naphthalene is the most abundant single constituent
of coal tar (Schmeltz, et al. 1977). In 1974, 1.8 x 105
metric tons of naphthalene were produced from coal tar,
and 1.1 x 10 metric tons were produced from petroleum (Brown,
et al. 1975; U.S. EPA, 1976). This compound is used as
an intermediate in the production of dye compounds and the
formulation of solvents, lubricants, and motor fuels. One
of the principal uses of naphthalene as a feedstock in the
United States is for the synthesis of phthalic anhydride.
It has also been used directly as a moth repellant and insec-
ticide as well as an antihelminthic, vermicide, and an intes-
tinal antiseptic.
Napthalene is a bicyclic aromatic hydrocarbon with
the chemical formula C-^gHg and a molecular weight of 128.16.
Pure naphthalene forms a white crystalline solid at room
temperature whereas the crude or technical grades may range
in color from brown to tan. Naphthalene vapor and dust
can form explosive mixtures with air (Windholz, 1976).
Pure naphthalene melts at 80.2°C; the less pure forms
of the compound will melt at temperatures ranging from 74
to 80°C. The boiling point of naphthalene is 217.96° at
atmospheric pressure (Manufacturing Chemists Assoc. 1956)
At 15.5°C, the density is 1.145 (Manufacturing Chemists
Assoc. 1956) and at 100°C the density is 0.9625 (Marti,
1930; Weast, 1975). At 19.8°C the vapor pressure of solid
naphthalene is 0.0492 mm Hg (Gil'denblat, et al. 1960).
A.-1
-------
The solubility of naphthalene in water has been reported
to range between 30,000 jag/1 (Mitchell, 1926) and 40,000
jug/1 (Josephy and Radt, 1948) at 25°C. The solubility of
naphthalene in seawater will vary according to the degree
of chlorosity; in seawater of average composition the solu-
bility of naphthalene is approximately 33,000jug/l (Gordon
and Thome, 1967). Naphthalene has also been reported to
be soluble in organic solvents (Spector, 1956).
Naphthalene can oxidize in the presence of light and
air, and it was determined that 50 percent of the theoretical
CO2 was liberated after 14 days (Ludzack and Ettinger, 1963).
The process involves initial conversion to naphthaquinone
with subsequent rupture of one of the aromatic rings and
the release of C02 (Kirk and Othmer, 1967). However, this
oxidation process occurs only at elevated temperatures (Josephy
and Radt, 1948) .
When combined with alcohol and ozone, cyclic alkoxy-
hydroxyperoxides are formed. In an acidic medium, these
peroxides will be converted to methyl phthalaldehydate;
in a basic medium, they are converted to phthalaldehydic
acid (Bailey, et al. 1964). When combined with metal nitrate
within a temperature range of 55°C to 180°C, naphthalene
can be nitrated at the alpha position (Alama and Okon, 1964).
In the presence of oxygen, K2SO4, a vanadium oxide catalyst,
and Si04, naphthalene can be converted to phthalic anhydride
(Morotskii and Kharlampovich, 1968).
Microorganisms can degrade naphthalene to 1,2-dihydro-
1,2,-dihydroxynaphthalene and ultimately to carbon dioxide
A-2
-------
and water. Studies have indicated a degredation rate under
laboratory conditions of up to 3.3 ug/1 (Lee and Anderson,
1977).
Naphthalene has been shown to be toxic to microorganisms
and has been reported to reduce photosynthetic rates in algae.
It has also been reported to be acutely toxic to various
invertebrate and vertebrate species of aquatic organisms.
In laboratory mammals and humans, naphthalene has been linked
to blood disorders and is suspected of traversing the placental
membrane in humans following naphthalene ingestion by the
mother.
Naphthalene has a varied environmental distribution
and has been detected in ambient water (up to 2.0 jug/1) ,
sewage plant effluents (up to 22 jag/1) , and drinking water
supplies (up to 1.4 jug/1) (U.S. EPA, 1971-1977). Recent
studies have determined that naphthalene will accumulate
in sediments by more than 100 times the concentration in
the overlying water (Cox, et al. 1975; Lee and Anderson,
1977) .
Naphthalene has been shown to bioconcentrate in both
invertebrate and vertebrate species of aquatic organisms.
It has also been suggested that much of the naphthalene
taken up by aquatic organisms returns to the ecosystem in
fecal matter without being metabolized. In addition, in
vitro studies have identified three naphthalene metabolites
derived from rat liver microsome preparations; these probably
resulted from hydroxylation and conjugation with water-soluble
moieties.
A-3
-------
REFERENCES
Alama, W., and K. Okon. 1964. Direct nitration of benzene,
naphthalene, and phenol by inorganic nitrates. Buil. Wojskowa
Akad. Tech. 13: 51.
Bailey, P.S., et al. 1964. Ozonolysis of naphthalenes;
the aromatic products. Jour. Org. Chem. 29: 697.
Brown, S.L., et al. 1975. Research program on hazard priority
ranking of manufactured chemicals. Phase II - Final Report,
A report prepared by Stanford Research Institute. National
Science Foundation, Washington, D.C. pp. 62-A-l.
Chemical Economics Handbook. 1976. Chem. Inf. Serv., Stanford
Res. Inst., Menlo Park, Calif.
Cox, B.A., et al. 1975. An experimental oil spill: The
distribution of aromatic hydrocarbons in the water, sediment,
and animal tissues within a shrimp pond. In Proc. Conf.
Prevent. Control Oil Pollut. San Francisco, March 25-27,
1975. Am. Petrol. Inst., Washington, D.C.
Gil'denblat, I.A., et al. 1960. Vapor pressure over crystal-
line naphthalene. Jour. Appl. Chem. USSR. 33: 245.
A-4
-------
Gordon, J.E., and R.L. Thome. 1967. Salt effects on non-
electrolyte solutions. Geschim. Cosmochim. Acta. 31:
2433.
Josephy, E., and F. Radt, eds. 1948. Encyclopedia of organic
chemistry: Series III. Elsevier Publishing Co., Inc.,
New York.
Kirk, R.E., and D.F. Othmer. 1967. Encyclopedia of chemical
technology. 2nd ed. John Wiley and Sons, Inc, New York.
Lee, R.F., and J.W. Anderson. 1977. Fate and effect of
naphthalene: Controlled ecosystem pollution experiment.
Bull. Mar. Sci. 27: 127.
Ludzack, F.J., and M.B. Ettinger. 1963. Biodegradability
of organic chemicals isolated from rivers. Purdue Univ.
Eng. Bull. Ser. No. 115: 278.
Manufacturing Chemists Assoc. 1956. Chemical safety data
sheets SD-58: Naphthalene. Washington, B.C.
Marti, F.B. 1930. Methods and equipment used at the Bureau
of Physiochemical Standards. Bull. Soc. Chim. Bedgrad.
39: 590.
A-5
-------
Mitchell, S. 1926. A method for determining the solubility
of sparingly soluble substances. Jour. Chem. Soc. 129:
1333.
Morotskii, O.A., and G.D. Kharlampovich. 1968. Phthalic
anhydride. Izobret., Prom. Obraztsy, Tovarnye Znaki. 45:
22.
Schmeltz, I., et al. 1977. The role of naphthalenes as
carcinogens. A paper presented at the 16th Annu. Meet.
Soc. Toxicol. Toronto, Can. March 27-30, 1977.
Spector, W.S., ed. 1956. Handbook of toxicology. Saunders
Publishing Co., Philadelphia.
U.S. EPA. 1971-1977. Unpublished data from Region IV, Atlanta
Ga.
U.S. EPA. 1976. Organic chemical producer's data base program.
Chemical No. 2701. Radian Corporation.
Weast, R.C. 1975. Handbook of chemistry and physics. CRC
Press, Cleveland, Ohio.
Windholz, M., ed,, 1976. The Merck Index. 9th ed. Merck
and Co., Rahway, N.J.
A-6
-------
AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
A limited variety of aquatic species has been exposed to
naphthalene and all tests were under static procedures with
unmeasured test concentrations. Fifty percent effect levels are
in the range of 5,600 to 82,000 ug/1. One embryo-larval test with
the fathead minnow demonstrated no adverse effects at the highest
test concentration of 440 ug/1.
Acute Toxicity
The adjusted 96-hour LC50 value for the mosquitofish (Wallen,
et al. 1957) is 82,000 ug/1 (Table 1) and after division by the
species sensitivity factor (3.9) results in a Final Fish Acute
Value of 21,000 ug/1.
Daphnia magna appears to be more sensitive with an adjusted
48-hour EC50 of 7,260 ug/1 (Table 2). Based on this single datum,
*The reader is referred to the Guidelines for Deriving Water
Quality Criteria for the Protection of Aquatic Life [43 FR 21506
(May 18, 1978) and 43 FR 29028 (July 5, 1978)] in order to better
understand the following discussion and recommendation. The
following tables contain the appropriate data that were found in
the literature, and at the bottom of each table are the calcula-
tions for deriving various measures of toxicity as described in
the Guidelines.
B-l
-------
the Final Invertebrate Acute Value for naphthalene is 350 ug/1.
Since this concentration is lower than the equivalent value for
fish, 350 ug/1 is also the Final Acute Value.
Chronic Toxicity
Exposure concentrations as high as 440 ug/1 (Table 3) caused
no adverse effects on survival or growth during an embryo-larval
test with the fathead minnow (U.S. EPA, 1978). This datum results
in a Final Fish Chronic Value that is greater than 33 ug/1. No
chronic data for invertebrate species are available.
Plant Effects
A 50 percent reduction in the number of cells of the alga,
Chlorella vulgaris, occurred at a concentration of 33,000 ug/1
(Table 4). This concentration is the Final Plant Value.
Residues
No measured steady-state bioconcentration factor (BCF) is
available for naphthalene. A BCF can be estimated using the
octanol-water partition coefficient of 2,300. This coefficient is
used to derive an estimated BCF of 210 for aquatic organisms that
contain about 8 percent lipids. If it is known that the diet of
the wildlife of concern contains a significantly different lipid
content, an appropriate adjustment in the estimated BCF should be
made.
Miscellaneous
Soto, et al. (1975a) observed the death of 61 percent of the
cells of the alga, Chlamydomonas angulosa, at a concentration of
34,400 ug/1 (Table 5). There was a 50 percent mortality of coho
salmon after an exposure of less than six hours to 5,600 ug/1
(Holland, et al. 1960).
B-2
-------
CRITERION FORMULATION
Freshwater Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Final Fish Acute Value = 21,000 ug/1
Final Invertebrate Acute Value = 350 U9/1
Final Acute Value = 350 ug/1
Final Fish Chronic Value = greater than 33 U9/1
Final Invertebrate Chronic Value = not available
Final Plant Value = 33,000 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = greater than 33 ug/1
0.44 x Final Acute Value = 150 ug/1
No freshwater criterion can be derived for napthalene using
the Guidelines because no Final Chronic Value for either fish or
invertebrate species or a good substitute for either value is
available, and there are insufficient data to estimate a criterion
using other procedures.
B-3
-------
03
I
! l.i -si'-' J . ••'. '. .r . ,; i ••.!'...••• i .-s:.i-: . .. i. • i'-i I •
Table 1. Freahwaccr fish acute values for naphthalene (Wallen, et al. 1957)
Adjusted
Bloaaoay Teat Time LC&O 1X50
Qtaanisa Mgtfrxi* cope.** n»raJ
Mosquitofish. S U 96 150,000 82,000
Gambuala affinls
* S » static
** U •» unmeasured
fl
Geometric mean of adjusted values - 82,000 ug/1* ^"5^ - 21.000 ug/1
-------
03
I
tn
,1 '...I.. .' , •„/ .
Table 2. Freshwater Invertebrate acute valuea for naphthalene (U.S. EPA, 1978)
Adjusted
Oiodssay Test Time I£50 -I.C!iO
tiEll!Si!i_ Cone .** ((as) (ni|/H
Cladoceran. S U 48 8,570 7,260
Daplinta magna
* S *> static
** u = unmeasured
Geometric mean of adjusted values •» 7.260 iig/lj ^2T^ = 35°
-------
03
I
a\
Table 3. Freshwater fish chronic values for naphthalene (U.S. EPA, 1978)
Chronic
Limits Value
Organism Test* fug/it (uo/l)
Fathead minnow. E-L >440 >220
Plmophales promelas
* E-L - embryo-larva
Geometric mean of <
Lowest chronic value - >220 pg/l
Geometric mean of chronic values •» >220 Mg/lJ >j~y » >33 ng/1
-------
03
I
-J
Table A. Freshwater plant effects for naphthalene (Kauss & llutchlnson, 1975)
Concentration
Organism Etiect (ug/i> _
Alga. EC50 48-hr 33,000
Chlorclla vulgaria cell numbers
Final plant value - 33.000 ng/l
-------
CO
I
CO
.>»:»...li -J'.-':,!'..! I.. :». .:. illi.k.'lVJ.i..
Table 5. Other freshwater data for naphthalene
Test
Organism
Result
Alga. 24 hrs
Chlainydomonaa anguloaa
Alga, 24 bra
Chlamydomonaa anguloaa
Cuho salmon,
Oncorhynchus ktsutch
Death of 61% of cells 34,400 Sato, et al. 197Sa
Loss of photosynthetlc 107. Soto, et al. 1975b
capacity saturation
<6 hrs 50% mortality
5,600 Holland, et al. 1960
-------
SALTWATER ORGANISMS
Introduction
As with freshwater organisms, the data base for napthalene
and saltwater organisms is limited to a few species for which
static test procedures were used with measured concentrations. A
variety of adverse effects were observed at concentrations of
1,000 to 2,600 ug/1.
Acute Toxicity
The adjusted 96-hour LC50 value for the sheepshead minnow was
1,125 ug/1 (Anderson, et al. 1974) and this result provides a
Final Fish Acute Value of 300 ug/1 (Table 6).
Anderson, et al. (1974) also exposed grass and brown shrimp
for 24 hours to napthalene and these data provide adjusted LC50
values of 744 and 715 ug/1, respectively (Table 7). Tatem (1976)
tested the grass shrimp (Palaemonetes pugio) and this result leads
to an adjusted LC50 of 2,585 ug/1. The geometric mean of these
data is 996 ug/1 and after division by the sensitivity factor
(49), a Final Invertebrate Acute Value of 20 ug/1 is derived.
This also becomes the Final Acute Value since 20 ug/1 is lower
than the Final Fish Acute Value of 300 ug/1.
Chronic Toxicity
No data are available on the chronic effects of naphthalene
on saltwater organisms.
B-9
-------
Residues
There is only one test result (Harris, et al. 1977b) that
determined an apparent equilibrium bioconcentration factor (BCF)
for napthalene. After nine days, the BCF for a copepod was 5,000
(Table 8). Data for other species for exposures of one hour to
one day are listed in Table 9. These BCF's range from 32 to 77
and indicate that equilibrium does not occur rapidly when those
results are compared to the BCF of 5,000 after nine days.
Miscellaneous
Berdugo, (1977) exposed the copepod (Eurytemora affinis) to a
concentration of 1,000 ug/1 and observed effects on egg production
and ingestion rate.
TV 10
-------
CRITERION FORMULATION
Saltwater Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Final Fish Acute Value = 300 ug/1
Final Invertebrate Acute Value = 20 ug/1
Final Acute Value = 20 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = not available
Residue Limited Toxicant Concentration = not available
Final Chronic Value = not available
0.44 x Final Acute Value = 8.8 ug/1
No saltwater criterion can be derived for napthalene using
the Guidelines because no Final Chronic Value for either fish or
invertebrate species or a good substitute for either value is
available, and there are insufficient data to estimate a criterion
using other procedures.
-------
Table 6. Marine flth acute values for naphthalene (Anderson, et al. 1974)
Adjusted
Bioaaaay Teat Time LCSO LC50
Q£
-------
Tublk 7. Marine invertebrate acute values for naphthalene
bioussay Teat Time
tf£tUQ«li_ Cone .**
LC50
Adjusted
LC'jO
Crass shrimp.
put$lo
Grass shrimp.
Palacmonetea pugio
Drown shrimp,
Penaeua aztecus
S
S
M
M
M
2A
96
24
2,600
744 Anderson, et al. 1974
2.350 2,585 Tatem. 1976
2,500 715 Anderson, et al. 1974
to
I
* S » static
** M " measured
Geometric mean of adjusted values - 996 ug/1 ! 996 - 20 pg/1
-------
...I
Table 8. Marine residues for napthalene (Harris, &t al. 1977b)
Time
Dioconcentr ation Factor * (days)
Copcpod, 5,000
Eurytemora af finis
00
* Dry weight to wet weight conversions.
-------
Table 9. Other marine data for napthalene
Test
03
I
Ul
Copepod.
Eurytemora afflnta
Copepod,
Eurytemora afftnls
0.16 days
1 day
Result
Jilil^U.
Reduction in Ingeatlon 1,000
rate of 102 (P - O.OS)
Copepod, 1 day
Calanus helgolandicua
Copepod, 1 day
Calanus helgolandtcus .
Blue mussel, 4 hrs
Mytilus eJulia
Sand goby, 1 hr
Clllichtus rolrabills
Sculpin, 3 hrs
OlJRocottus maculosua
Sand dab, 1 hr
Citharlchtya stlfemaeus
Reduction In
production by 83%
(P - 0.05)
Bloconcentration
factor « 50
Bloconcentratlon
factor *> 60
Bloconcentratlon
factor • 44
Bioconcentration
factor = 63
Bioconcentration
factor - 32
Bioconcentration
factor " 77
Berdugo. 1977
1,000 Berdugo, 1977
Harris, et al. 1977b
Harris, et al. 1977a
Lee, et al. 1972b
Lee. et al. 1972a
Lee, et al. 1972a
Lee, et al. 1972a
-------
REFERENCES
Anderson, J.W., et al. 1974. The effects of oil on estuarine
animals: toxicity, uptake and depuration, respiration.
In Pollution and physiology of marine organisms. Academic
Press, Inc. New York.
Berdugo, V. 1977. The effect of petroleum hydrocarbons
on reproduction of an estuarine planktohic copepod in labora-
tory cultures. Mar. Pollut. Bull. 8: 138.
Harris, R.P., et al. 1977a. Factors affecting the retention
of a petroleum hydrocarbon by marine planktonic copepods.
In Fate and effects of petroleum hydrocarbons in marine
ecosystems and organisms. Proc. Symp. 286.
Harris, R.P., et al. 1977b. Accumulation of carbon-14-
1-napthalene by an oceanic and an estuarine copepod during
long-term exposure to low-level concentrations. Mar. Biol.
42: 187.
Holland, G.A., et al. 1960. Toxic effects of organic and
inorganic pollutants on young salmon and trout. Wash.
Dep. Fish. Res. Bull. 5: 162.
B-16
-------
Kauss, P.B., and T.C. Hutchinson. 19J75. The effects of
\
water-soluble petroleum components on the growth of Chlorella
vulgaris Beijerinck. Environ. Pollut. 9: 157.
Lee, R.F., et al. 1972a. Uptake, metabolism and discharge
of polycyclic aromatic hydrocarbons by marine fish. Mar.
Biol. 17: 201.
Lee, R.F., et al. 1972b. Petroleum hydrocarbons: uptake
and discharge by the marine mussel Mytilus edulis. Science
177: 344.
Soto, C., et al. 1975a. Effect of naphthalene and aqueous
crude oil extracts on the green flagellate Chlamydomonas
angulosa. I. Growth. Can. Jour. Bot. 53: 109.
Soto, C., et al. 1975b. Effect of naphthalene and aqueous
crude oil extracts on the green flagellate Chlamydomonas
angulosa. II. Photosynthesis and uptake and release of
naphthalene. Can. Jour. Bot. 53: 118.
Tatem, H.E. 1976. Toxicity and physiological effects of
oil and petroleum hydrocarbons on estuarine grass shrimp
Palaemonetes pugio Holthuis. PhD dissertation. Texas A
& M University. 133 pp.
B-17
-------
U.S. EPA. 1978. In-depth studies on health and environmental
impacts of selected water pollutants. U.S. Environ. Prot.
Agency, Contract No. 68-01-4646.
Wallen, I.E., et al. 1957. Toxicity to Gambusia affinis
of certain pure chemicals in turbid waters. Sewage Ind.
Wastes 29: 695.
B-18
-------
\
Mammalian Toxicology and Human Health Effects
EXPOSURE
Introduction
Naphthalene, C10Hg, is an aromatic hydrocarbon with
two orthocondensed benzene rings. In 1965, 74.4 percent
of the napthalene produced in this country was used for
the manufacture of phthalic anhydride which, in turn, was
used in the manufacture of alkyd and polyester resins, dyes,
pigments, Pharmaceuticals and insecticides: 12.2 percent
was used in the manufacture of insecticides such as 1-naphthyl-
N-methylcarbamate (carbaryl)j 11 percent was used for the
production of 2-naphthol (used as a dyestuff, pigment and
pharmaceutical intermediate) and mothballs. The remainder
was used in the manufacture of alkyl-naphthalenesulfonates
(used in the manufacture of detergents and textile wetting
agents), alkylnaphthalenes (used in making textile spinning
lubricants), chlorinated naphthalenes and tetra and decahydro
naphthalenes (used in solvent mixtures). In 1965, the total
UoS. production of naphthalene was 373,000 metric tons while
in 1976 production of petroleum derived naphthalene was
48,720 metric tons.
In 1973„ 91 percent of the production was from petroleum
while the remainder originated from coal tar distillates.
In 1974, 35 percent was from petroleum while 58 percent
was from coal tar distallates originating from the high
temperature coking of bituminous coal (Brown, et al. 1975;
U.So EPA, 1976). This coal tar naphthalene in its crude
state contains impurities such as alkylnaphthalenes,
C-l
-------
alkylcoumarones and thianaphthene. This latter impurity
has been hypothesized as being the active ingredient in
moth balls (Thiessen, 1967).
Pure naphthalene melts at 80.29°C. and boils at 217.955°C.
It has a high vapor pressure (0.054 mmHg at 20°C.) and high
water solubility (19,000 jug/1 at 0°C and 30,000 jug/1 at
100°C.) compared to other polynuclear aromatic hydrocarbons.
02
-------
Ingestion from Food and Water
The two major sources of naphthalene in the aquatic
environment are from industrial effluents and from oil spills.
Industrial effluents have been found to have up to 32,000
jug/1 naphthalene. The final effluents of sewage treatment
plants receiving discharges from these facilities have been
noted to have up to 22 ug/1 naphthalene. Natural waters
have been noted to have up to 2.0 ug/1 of naphthalene while
drinking water supplies have been found to have up to 1.4
jig/1 naphthalene (U.S.EPA, Region IV, unpublished data).
A bioconcentration factor (BCF) relates the concentra-
tion of a chemical in water to the concentration in aquatic
organisms, but BCF's are not available for the edible por-
tions of all four major groups of aquatic organisms consumed
in the United States. Since data indicate that the BCF
for lipid-soluble compounds is proportional to percent lipids,
BCF's can be adjusted to edible portions using data on per-
cent lipids and the amounts of various species consumed
by Americans. A recent survey on fish and shellfish consump-
tion in the United States (Cordle, et al. 1978) found that
the per capita consumption is 18.7 g/day. From the data
on the nineteen major species identified in the survey and
data on the fat content of the edible portion of these spe-
cies (Sidwell, et al. 1974), the relative consumption of
the four major groups and the weighted average percent lipids
for each group can be calculated:
C-3
-------
Consumption Weighted Average
Group (Percent) Percent Lipids
Freshwater fishes 12 4.8
Saltwater fishes 61 2.3
Saltwater molluscs 9 1.2
Saltwater decapods 18 1.2
Using the percentages for consumption and lipids for each
of these groups, the weighted average percent lipids is
2.3 for consumed fish and shellfish.
No measured steady-state bioconcentration factor, (BCF)
is available for naphthalene, but the equation "Log BCF
= 0.76 Log P - 0.23" can be used (Veith, et al. Manuscript)
to estimate the BCF for aquatic organisms that contain about
eight percent lipids from the octanol-water partition coef-
ficient (P). Based on an octanol-water partition coefficient
of 2,300, the steady-state bioconcentration factor for naptha-
lene is estimated to be 210. An adjustment factor of 2.3/8.0
= 0.2875 can be used to adjust the estimated BCF from the
8.0 percent lipids on which the equation is based to the
2.3 percent lipids that is the weighted average for consumed
fish and shellfish. Thus, the weighted average bioconcentra-
tion factor for napthalene and the edible portion of all
aquatic orgnisms consumed by Americans is calculated to
be 210 x 0.2875 = 60.
Inhalation
Unusual exposure to naphthalene can occur to cigarette
smokers, naphthalene being identified as one of the polynu-
clear aromatic hydrocarbons found in cigarette smoke conden-
C-4
-------
sate (Akin, et al. 1976). Under industrial conditions indivi-
duals can be exposed to levels of naphthalene up to 1.1
63 '3
x 10 /ag/m (210 ppm) as vapor and up to 4.4 jug/m as particu-
lates (Table 1). Potential exposure categories in this
group are outlined in Table 2. Ambient air levels of naph-
thalene are negligible (Table 1), but the number of measure-
ments have been limited.
Dermal
Data on dermal exposure to naphthalene are very sparse.
See the "Effects" section for discussion of effects from
possible dermal exposure.
PHARMACOKINETICS
Absorption, Distribution and Excretion
Little detailed information is available on the absorp-
tion, distribution or excretion of naphthalene in man or
animals. Adequate amounts of naphthalene can be absorbed
when ingested as a solid to cause toxicity in man (Chusid
and Fried, 1955; Zuelzer and Apt, 1949; Nash, 1903; Gross,
et al. 1958; Haggerty, 1956). When taken as a solid, frag-
ments of naphthalene can appear in the stool (MacGregor,
1954). The toxicity appears to be increased if taken dissolv-
ed in oil (Solomon, 1957). The oral toxicity of a metabolite
of naphthalene, 1,4-naphtoquinone, is increased at least
fivefold when administered, dissolved in oil, to rabbits
as compared to an aqueous solution (Talakin, 1966). Sanborn
and Malins (1977) found a marked decrease in absorption
of naphthalene if bound to protein in shrimp. The authors
give this as evidence that naphthalene would be less likely
C-5
-------
TABLE 1
Air Levels of Naphthalene
o
Area Investigated
Industrial;
Naphthalene melt present
Coke Oven
Aluminum Reduction Plant
Ambient;
Providence, R.I.
Kingston, R.I.
Narragansett Bay, R.I.
Air Level Qug/m )
Vapor Particulate
Reference
1600 -
1.1 x 10*
11.35 -
1120
.72 -
311.3
,0001
,00003
,00005
0-4.40
.090-4.00
.00025
.00003
.000003
Robbins, 1951
Bj0rseth, et al. 1978a
Bj0rseth, et al. 1978b
Krstulovic, et al. 1977
Krstulovic, et al. 1977
Krstulovic, et al. 1977
-------
TABLE 2
Workers with Potential Naphthalene Exposure
(Tabershaw, et al. 1977)
Beta naphthol makers
Celluloid makers
Coal tar workers
Dye chemical makers
Fungicide makers
Hydronaphthalene makers
Lampblack makers
Moth repellant workers
Phthalic anhydride makers
Smokeless powder makers
Tannery workers
Textile chemical workers
Aluminum reduction plant workers
C-7
-------
to be absorbed when exposure was from food than when from
water.
When dissolved in a nonpolar solvent, absorption of
naphthalene by skin application caused less experimental
toxicity than when taken orally (Gaines, 1969). Dawson,
et al. (1958), however, found that two infants exposed to
naphthalene treated clothes developed toxic effects after
their skin was covered with baby oil. These authors suggest
that skin absorption might be significant under these circum-
stances.
Enough absorption can occur by inhalation of naphthalene
vapor to cause significant toxicity. Valaes, et al. (1963)
found toxicity in newborn infants when the only exposure
was to naphthalene vapor from clothes or blankets treated
with naphthalene stored in the infants' rooms or in an adja-
cent hall. One of these infants died.
Naphthalene distributes widely after absorption. Lawler,
et al. (1978) found that in mallards given naphthalene in
oil over a period of two weeks, naphthalene could be identi-
fied in all tissues examined. Its relative distribution
was as follows: skin >liver 7 brain = blood ?muscle >heart.
Naphthalene has not been identified in urine after absorption.
With sufficient absorption of naphthalene to result in toxi-
city to an 18 month old infant, Mackell, et al. (1951) noted
metabolites of naphthalene in the urine that were still
identifiable, two weeks after exposure but which had disappear-
ed 18 days after exposure.
C-8
-------
Metabolism
The metabolism of naphthalene has been extensively
studied in mammals. Naphthalene is first metabolized by
hepatic mixed function oxidases to the epoxide, naphthalene-
1,2-oxide (Figure 1). This epoxide has the distinction
of being the first arene oxide metabolite to have been isolat-
ed (Jerina, et al. 1970). Epoxide formation is an obligatory
step. The epoxide can be enzymatically converted into the
dihydrodiol, l,2-dihydroxy-l,2-dihydronaphthalene or conjugat-
ed with glutathione. The dihydrodiol can then be conjugated
to form a polar compound with glucuronic acid or sulfate
or be further dehydrogenated to form the highly reactive
1,2-dihydroxynaphthalene. This too can be enzymatically
conjugated to sulfate or glucuronic acid or spontaneously
oxidized to form another highly reactive compound, 1,2-naphtho-
quinone.
The epoxide can also be converted spontaneously to
1-naphthol or 2-naphthol by a keto tautomer intermediate
(Boyd, et al. 1972). 1-naphthol is the predominant spontan-
eous decomposition product of the epoxide/ being a more
stable resonant structure than 2-naphthol (Jerina, et al.
1970). 1-naphthol is excreted unchanged as well as conjugat-
ed with glucuronic acid or sulfate prior to excretion.
The finding of 1,4-naphthoquinone in the urine of a child
poisoned with naphthalene (Mackell, et al. 1951) suggests
that 1-naphthol can also be further oxidized in mammals
(Cerniglia and Gibson, 1977).
C-9
-------
"^
1-jloT
OH
, X
4r
1
OH
1.4 - AO0A
Figure 1: Pathways for the Metabolism of Naphthalene
(adapted from Bock, et al. 1976).
Enzymes: I- monooxygenase .
II- epoxide hydrase
III- UDP-gluconyltransferase
IV- glutathione-S-transferase
V- dihydrodiol dehydrogenase
VI- sulfotransferase
C-10
-------
A number of other metabolites have been found in liver
cells, liver microsomal preparations or bile as noted in
Table 3. The glutathione conjugate can be progressively
broken down to a cysteinylglycine compound and then a cys-
teine conjugate prior to acetylation to the mercapturic
acid, N acetyl-S-(l,2-dihydro-2-hydroxy-l-naphthyl)-L-cys-
teine either in the liver or kidney (Booth, et al. 1960).
A number of these metabolites have been identified in the
urine of mammals (Table 4). The presence of 1-naphthyl mercap-
turic acid may be explained by a spontaneous dehydrogenation
of the mercapturic acid of the dihydrodiol in acid urine
(Jerina, et al. 1968).
Naphthalene metabolites undergo further conversions
in the eye. The eye contains beta glucuronidase and sulfa-
tase which can hydrolyze the glucuronide and sulfate esters
of the dihydrodiol (Van Heyningen and Pirie, 1967). Catechol
reductase is also present in the eye. This enzyme can oxi-
dize the dihydrodiol to 1,2-dihydroxynaphthalene which in
turn can be spontaneously oxidized to 1,2-naphthaquinone
with the concomitant release of hydrogen peroxide. 1,2-
naphthaquinone can then oxidize ascorbic acid, which is
found in high concentration in the eye, to dihydroascorbic
acid with the release of more hydrogen peroxide. Dihydroas-
corbic acid can then be broken down to oxalate or diffuse
into the lens where it is reconverted to ascorbic acid with
the associated nonenzymatic oxidation of reduced glutathione
(Van Heyningen, 1970). As 1,2-naphthaquinone is reduced
by the reaction with ascorbic acid to 1,2-dihydroxynaphtha-
lene, it oxidizes NADPH. The dihydroxide will rapidly reduce
Oil
-------
TABLE 3
Naphthalene Metabolites: Liver/Bile
Metabolite
1-naphthol
2-naphthol
1-naphthyl glucosiduronic acid
1-naphthyl mercapturic acid
1,2-dihydro-l,2-dihydroxy napthalene
1,2-dihyro-2-hydroxy-l-naphthyl-
glucosiduronic acid
l,2-dihydro-l-hydroxy-2-naphthyl-
glucosiduronic acid
S-(1,2-dihydro-2-hydroxy-l-naphthyl)-L-
cysteine
N-acetyl-S-(l,2-dihydro-2-hydroxy-l-naphthyl)
1-cysteine
1,2-dihydroxy naphthalene
1,2-naphthoquinone
Naphthalene-l/2-oxide
S-(1,2-dihydro-2-hydroxy-l-naphthyl)-
glutathione
S-(1,2-dihydro-2-hydroxy-l-naphthul)-
L-cysteinyl glycine
(1,2-dihydro-2-hydroxy-l-naphthyl)-sulfate
2-hydroxy-l-naphthyl-glucosiduronic acid
Rabbit
2
2
2
2
Found in;
Rat
3,4
3
3,4
3
3,4
3,4
3
3
3
4
4
1,3
3
4
3
Fish
5
5
5
5
References;
1-Booth, et al. 1960
2-Jerina, et al. 1970
3-Bovland. et al. 1961
4-Bock, et al. 1976
5-ubal, et al. 1977
, et al. 1972b
-------
TABLE 4
Naphthalene Metabolites: Kidney/Urine
o
Metabolite
1-naphthol
2-naphthol
1-naphthyl sulfate
1-naphthyl glucosiduronic acid
S-(1-naphthyl)-L-cysteine
1-naphthyl mercapturic acid
l,2-dihydro-l,2-dihydroxy naphthalene
1,2-dihydro-2-hydroxy-l-naphthyl-
glucosiduronic acid
1,2-dihydro-l-hydroxy-2-naphthyl-
glucosiduronic acid
S-(1,2-dihydro-2-hydroxy-l-naphthyl)-L-
cysteine
N-acetyl-S-(l,2-dihydro-2-hydroxy-
1-napthyl)-L-cysteine
2-hydroxy-l-naphthyl sulfate
l-hydroxy-2~naphthyl sulfate
1,2-dihydroxynapthalene
1,2-naphthoquinone
1,4-naphthoquinone
Rabbit
1,2
1
1,7
1
1
1,5,7
1,2,6,7
2
1
1
2
Guinea Pig
7
7
7
Found in:
Mice
7
7
7
Rat
7
7
i
4,5,7
7
3
1,3
Man
9
9
9
9
References:
1- Boyland & Sims, 1958
2- Sims, 1959
3- Booth, et al. 1960
4- Young, 1947
5- Booth & Boyland, 1949
6- Corner, et al. 1954
7- Corner & Young, 1954
8- Bourne & Young, 1934
9- Mackell, et al. 1951
-------
cytochrome c (Van Heyningen and -Pirie, 1967). 1,2-naphthaqui-
none also binds irreversibly to lens protein and amino acids
(Van Heyningen and Pirie, 1966).
Aryl hydrocarbon hydroxylase, a mixed-function microso-
mal oxidase, is induced by many carcinogenic polycyclic
aromatic hydrocarbons. Alexandrov and Prayssinet (1973)
found that the intraperitoneal injection of 40 mg/kg of
naphthalene in corn oil into male Wistar rats daily for
a period of three days resulted in a 40 percent inhibition
of this enzyme's ability to hydroxylate benzo(a)pyrene.
Naphthalene also inhibited the inducability of this enzyme
by 3-methylcholanthrene. A number of other napthtalene
derivatives, including 1-naphthol and 2-naphthol, were tested
and were not found to depress the activity of this enzyme.
-------
EFFECTS
Lezenius (1902) described the case of a 36-year-old
pharmacist who, after taking 5 g of naphthalene in oil,
developed near blindness eight or nine hours later. An
examination a year later disclosed constricted visual fields
associated with optic atrophy and bilateral cataracts made
up of numerous whitish opacities. In 1906 Van der Hoeve
further described a case of a 44-year-man who worked with
powdered naphthalene and was found to have cataracts and a
retinal hemorrhage. A coworker was noted to have chorioretin-
itis in one eye. Ghetti and Mariani (1956) examined 21
workers in a plant producing a dye intermediate from naphtha-
lene and found cataracts in 8 of them with the following
age distribution:
t with cataracts
2
3
2
1
A model for the eye toxicity of naphthalene has been
developed in rabbits (Van Heyningen and Pirie, 1976) to
further investigate the disappearance of reduced glutathione
from the lens, first noted by Bourne (1937) , and its relation-
ship to the cataractogenicity of naphthalene. The authors
found that the metabolites of naphthalene released in the
eye were general metabolic and coenzyme inhibitors (Rees
and Pirie, 1967); that 1,2-dihydroxynaphthalene or 1,2-naphtha-
C-15
Age
20-30
30-40
40-50
50-60
£
4
5
8
4
-------
quinone combined with amino acids or irreversibly with the
thiol groups of lens protein to form a brown precipitate;
that the hydroperoxide formed in the oxidation of 1,2-dihydro—
xynaphthalene and ascorbic acid can act with the high levels
of glutathione peroxidase in the eye to oxidize glutathione;
that oxidized ascorbic acid easily enters the lens where
it readily oxidizes reduced glutathione nonenzymatically
(Van Heyningen, 1970); that the oxidized ascorbic acid also
oxidizes protein thiols, a mechanism that is normally prevent-
ed by reduced glutathione; that the oxidation of NADPH pre-
vents the reduction of oxidized glutathione by glutathione
reductase; that 1,2-naphtoquinone quickly combines irrevers-
ibly with lens and eye proteins thereby losing its ability
to oxidize ascorbic acid (Van Heyningen and Pirie, 1967);
that oxidized ascorbic acid breaks down to oxalate which
in turn precipitates as calcium oxalate crystals in the
vitreous humor and on the retina of the eye; and that lens
changes are preceded by evidence of injury to the epithelium
of the lens as well as retina (Pirie, 1968).
A hemolytic anemia with associated jaundice and occasion
ally renal disease from precipitated hemoglobin has been
described both in children and adults (Haggerty, 1956; Chusid
and Fried, 1955; Abelson and Henderson, 1951; Zuelzer and
Apt, 1949; Gidron and Leurer, 1956; Nash, 1903; Mackell,
et al. 1951) as well as in newborn infants (Cock, 1957;
Schafer, 1951) after exposure to naphthalene by ingestion,
inhalation or, possibly, by skin contact. Dawson, et al.
(1958) identified two newborn children who had both a naphtha
lene hemolytic anemia as well as a combined glucose-6-phosphate
C-16
-------
dehydrogenase deficiency and glutathione reductase deficiency.
The former defect was more prominent. Glucose-6-phosphate
dehydrogenase (G6PD) in the presence of glucose-6-phosphate
reduces NAPD to NADPH which in turn is required by glutathione
reductase to maintain glutathione in the reduced state.
In the absence of reduced glutathione there can be oxidative
denaturation of hemoglobin with precipitation of globin
as Heinz bodies and the associated stiffening of red blood
cell membranes. These abnormal red cells are then removed
from the circulation by the spleen and liver. NADPH is
also a cofactor for the reduction of methemoglobin (Kellermeyer,
et al. 1962). This can lead to the buildup of methemoglobin
or methemalbumin in the serum with excretion of these compounds
in the urine (Schafer, 1951). Both Valaes, et al. (1963)
and Naiman and Kosoy (1964) have noted that although most
infants with naphthalene-associated acute hemolytic anemia
have G6PD deficiency, there was a group of neonates that
had a milder form of hemolysis and did not have the enzyme
deficiency. Both groups noted high levels of bilirubin
in the serum of their cases with associated brain damage
(kernicterus) and even death in several infants. Gross,
et al.(1958) noted that red blood cells lose G6PD activity
with aging in G6PD deficient individuals such that older.--
populations of red blood cells are more susceptible to hemoly-
sis than young ones. In some forms of G6PD deficiency,
this can result in a self-limited form of hemolysis (Wintrobe,
et al. 1974).
C-17
-------
Hemolytic anemia has also been noted in individuals
exposed to a metabolite of naphthalene, 2-naphthol. Smillie
(1920) treated 79 Brazilians with 2-naphthol for hookworm
disease. Adults received a 6 g a day orally for three days
while children received a smaller dose. Four of those treated
were found to develop a hemolytic anemia, two associated
with splenomegaly. He identified three of those affected
as being black.
Acute, Sub-acute, and Chronic Toxicity
The acute lethality of naphthalene has been assessed
by several routes in several species as shown in Table 5.
The greater toxicity by an oral versus subcutaneous route
might be due to species variation in susceptibility but
might also indicate that naphthalene first has to be metabol-
ized by the liver to produce maximum toxicity.
Several other studies have been performed to assess
sublethal effects of naphthalene or its metabolites. Zuelzer
and Apt (1949) administered naphthalene in a solid form
to dogs by the oral route. One dog received 1800 mg/kg
in divided doses over a period of five days with resultant
lethargy, ataxia, a drop in hemoglobin by 83 percent and
a leukamoid reaction (white blood cell count of 119,000).
Two other dogs received 1530 mg/kg and 420 mg/kg in single
doses with a resultant drop in hemoglobin by 33 percent
and 29 percent respectively.
C-18
-------
TABLE 5
Tests of the Acute Toxicity of Naphthalene
Test Animal
Mice
Sherman rats
male
female
male
female
Rat
Rat
Rat
Route
Subcut.
40
40
10
10
Oral0
Oral2
Skinb
h
Skin0
Oral
Oral
Inhalation
LD50 (mg/kg)
5100
2200
2400
>2500
>2500
1780
9430
>100 ppm x
8 hr.
Reference
Irie, et al. 1973
Gaines, 1969
Gaines, 1969
Gaines, 1969
Gaines, 1969
NIOSH, 1977
Union Carbide Corp., 1968
Union Carbide Corp., 1966
Dissolved in peanut oil
Dissolved in xylene
C-19
-------
Mahvi, et al.(1977) administered naphthalene in corn
oil intraperitoneally to C57 B1/6J mice. Two groups of 63
mice received corn oil alone or remained untreated. Groups
of 21 mice each were given 67.4, 128, or 256 mg/kg. Three
animals from each dosage group were sacrificed at ten minutes,
1 hour, 6 hours, 12 hours, 24 hours, 48 hours, and 7 days
following treatment. Lung tissue was rapidly fixed and
examined by light, scanning electron microscopy, and transmis-
sion electron microscopy. No changes were noted in either
control group. Minor bronchiolar epithelial changes were
noted in the group receiving 6.4 mg/kg. Mice in the higher
dosage groups developed necrosis of secretory nonciliated
bronchiolar cells. Epithelial structure returned to normal
within seven days in all cases.
Reid, et al. (1973) gave naphthalene dissolved in sesame
oil to C57 B1/6J mice by the intraperitoneal route and found
coagulative necrosis of the bronchiolar and bronchial epithel
ium at a dose of 600 mg/kg. Controls received sesame oil
alone and no adverse effects were reported for this group.
The size of the treatment groups was not stated.
Pilotti, et al. (1975) treated ascites sarcoma BP8
cells ir\ vitro by incubating with naphthalene solutions
for 48 hours. The authors noted 100 percent growth inhibition
at a concentration of 128 mg/1 and 10 percent growth inhibi-
tion at a concentration of 12.8 mg/1.
C-20
-------
Several studies have also been done on the metabolites
of naphthalene. Van Heyningen and Pirie (1967) dosed one
rabbit with 300 mg of the dihydrodiol intravenously in divided
doses over three days and noted retinal lesions. They also
noted lens changes in four rabbits dosed externally with
one percent eye drops of the same compound (dissolved in
water) over a period of two to five, days for a total dose
of 40-70 mg per rabbit.
Mackellr et al. (1951) incubated blood from normal
human donors with naphthalene or its metabolites in various
concentrations. Hemolysis was noted as shown in Table 6.
These agents were also injected intravenously into white
male rabbits in concentrations of 0.25, 0.5, 1.0 and 1.25
mg/kg. Naphthalene, 2-naphthol,l,2-naphthaquinone and 1,4-
napthaquinone produced no hemolysis at 15 minutes after
the injection; 1-naphthol, however, produced six percent
and 9 percent hemolysis at the two higher dosages. Zinkham
and Childs (1958) performed similar in vitro experiments
with the same metabolites but measured drop in reduced gluta-
thione as an end point. They also investigated the effect
of these metabolites on blood from a patient who had hemoly-
ais after contact with naphthalene and who had red blood
cells sensitive to an oxidant (presumed G6PD) deficiency.
All four metabolites resulted in depression of reduced gluta-
thione levels. Naphthalene resulted in minor depression
of reduced glutathione levels at concentrations of 5000
mg/1 or greater.
C-21
-------
TABLE 6
In vitro Hemolysis of Red Blood Cells Exposed to Naphthalene and its Metabolites
(Mackell, et al. 1951)
Percent Hemolysis
o
i
to
K>
Compound
1-naphthol
2-naphthol
1,4-naphtha-
quinone
1,2-naphtha-
quinone
Naphthalene
Concentration (mg/1 blood)
10
<2
0
0
0
0
13.3
6
0
0
0
0
2£
14
3
0
0
0
40
46
11
0
0
0
100
53
32
0
0
0
200
65
48
4
<1
0
100U
74
60
18
12
0
-------
Several studies have been done on the subacute and
chronic toxicity of naphthalene, all involving a single
dose/day regime. Fitzhugh arid Buschke (1949) fed five wean-
ling rats two percent of naphthalene or 2-naphthol in their
diets for a period of at least 60 days and noted early catar-
acts in both groups.
Van Heyningen and Pirie (1976) dosed rabbits daily
by gavage with 1000 mg/kg of naphthalene for various periods
of time for a maximum of 28 days. They noted lens changes
developing after the first dose and retinal changes develop-
ing after the second dose.
Ghetti and Mariani (1956) fed five rabbits 1000 mg/kg/day
of naphthalene and noted the development of cataracts between
days 3 and 46. Topical application of a ten percent solution
in oil to the eyes of two rabbits did not produce cataracts
after a period of 50 days. Intraperitoneal injection of
500 mg/day of naphthalene in an oily solution to one rabbit
over a period of 50 days produced weight loss but no cataracts,
Synergism and Antagonism
There is little information on the synergistic or antago-
nistic effects of naphthalene. In a single case report Harden
and Baetjer (1978) described finding aplastic anemia in
%
a 68-year-old black female exposed to mothproofing compounds„
Yearly for a period of 39 years she had intermittently worked
in storing garments with mothproofing compounds, One month
prior to becoming ill she worked for a period of three weeks
in a hotr unventilated room mothproofing garments. She
handled a total of 7 kg of naphthalene and 5.5 kg of para-
023
-------
dichlorobenzene. It was estimated that she was exposed
to at or near 1400 ppm of paradichlorobenzene and 184 ppm
of napththalene.. The time of her exposure was consistent
with the onset of her bone marrow depression, estimat-
ed from her hematologic findings on admission two months
after first becoming ill. No other cases of aplastic anemia
have been described with either a naphthalene or paradichloro-
benzene exposure either alone or in combination with another
chemical.
Teratogenicity
Naphthalene or its metabolites can cross the placenta
in sufficient amounts to cause fetal toxicity. Both Zinkham
and Childs (1958) and Anziulewicz, et al. (1959) noted toxic
effects in infants where the only exposure was to the mother
during pregnancy. When a metabolite of naphthalene, 2-naph-
thol, was administered to pregnant rabbits, their offspring
were born with cataracts and evidence of retinal damage
(Van der Hoeve, 1913).
Mutagenicity
Naphthalene has been found to be nonmutagenic in several
microsomal/bacterial assay systems as outlined in Table 7.
Metabolites of naphthalene have not been tested.
'Carcinogenicity
Wolf (1976) reported six cases of malignant tumors
among 15 workers exposed to vapors of naphthalene and coal
tar for a period of up to 32 years at a coal tar naphthalene
production facility. Four workers contracted laryngeal
carcinoma and were all smokers. The other 2 workers devel-
oped neoplasms of the pylorus and cecum. There was no con-
-------
TABLE 7
Mutagenicity of Naphthalene in Various In Vitro Microsomal Assay Systems
o
i
N)
en
System
Rat microsomes/
Salmonella typhimurium
Mouse microsome/ .
Salmonella typhimurium
Mouse microsome/
E. coli
Strain
TA100
TA1535
TA1537
TA98
G46
K12
Result
Negative'
Negative*
Negative
Negative*
Neative
a
Reference
McCann, et al. 1975
McCann, et al. 1975
McCann, et al. 1975
McCann, et al. 1975
Kraemer, et al. 1974
Negative Kraemer, et al. 1974
Less than 0.09 revertants/nmol. Tested at 10, 100, 500 and 1000 ug/plate
Naphthalene-l,2-oxide used in the test system
-------
trol group.
Knake (1956) treated 40 white rats with 500 mg/kg of
coal tar naphthalene in sesame oil subcutaneously every
two weeks for a total of seven treatments; 34 rats survived
the treatment and five developed invasive or metastatic
lymphosarcoma prior to death. There was a two percent inci-
dence of malignancies in an untreated control group with
a similar incidence in a group treated with sesame oil alone.
His data are detailed in Table 8. The sites of the injections
of the naphthalene/sesame oil and sesame oil treated groups
were painted with carbolfuchsin (a known experimental carcin-
ogen) prior to each injection. The naphthalene contained
0.07 gram molecular weight impurities per 100 g (equivalent
to 10 percent methyl naphthalene).
In a second study, Knake (1956) painted a group of
mice with either benzene or a solution of coal tar naphtha-
lene in benzene and noted an excess of lymphatic leukemia
in the naphthalene/benzene group compared to the benzene
treated group or a group of untreated controls. His results
are detailed in Table 9.
Druckey and Schmahl (1955) used naphthalene as a vehicle
for testing the carcinogenic effects of anthracene. In
a preliminary study they looked at the potential carcinogenic
effects of naphthalene alone. BD I and BD III strain rats
Were used. One group of 28 rats was given 10 gm of naphtha-
lene orally per rat over a period of time and followed for
an excess of 1000 days. A second group of ten rats was
given a total dose c'f 0.82 gm of naphthalene per rat subcu-
taneously and followed for a similar period of time. No
C-26
-------
TABLE 8
Incidence of Tumors in White Rats Treated with 0.5 gm/kg Naphthalene Subcutaneous^y
(15% in sesame oil) Every Two Weeks for 14 Weeks and then Followed for 18 months
(Knake, 1956)
Treatment
Number of Animals
Total Survivors Lymphosarcoma
Fibroadenoma
0
1
M
Naphthalene
in sesame oil
Sesame oil
No treatment
40
40
101
0
4
0 (lifetime)
5
1
1
1
1
0
0
0
1
Other Malignant Tumor
34 naphthalene/sesame oil treated rats survived the initial treatment. 32 rats treated with
sesame oil alone survived the initial 14 weeks of treatment
}3.3 ml/kg/treatment
-------
TABLE 9
Incidence of Tumors in Inbred Black Mice Painted with 0.5% Naphthalene in Benzene
or Benzene Alone 5 days/week for Life (Knake, 1956)
Sarcoma Other
Treatment Number Leukemia Lymphosarcoma (other) Malignancy Lung Adenoma
Naphthalene in
Benzene 25 4a 1 013
Benzene 21 0 1 101
o No Treatment 1227 5 3 1 44 0
i
ro
00
All lymphocytic leukemia
-------
tumors were noted in either group.
Boyland, et al. (1964) found a four percent incidence
of bladder carcinoma in mice with naphthalene implaced in
their bladders. As seen in Table 10, there was a similar
or higher incidence of bladder carcinoma in mice treated
with various inert control substances including glass.
Kennaway (1930) and Kennaway and Hieger (1930) tested
the carcinogenicity of naphthalene in mice by a skin painting
experiment. They found that naphthalene was noncarcinogenic,
but did not give the details of their protocols.
Bogdat'eva and Bid (1955) painted naphthalene onto
the skin of rabbits at a dose sufficient to cause systemic
toxicity. No carcinomatous changes were noted after this
chronic study. Details of the protocol were not given.
Takizawa (1940) painted the skin of mice with a metabo-
lite of naphthalene, l,4-=naphthaquinone. They noted an
incidence of 15 to 20 percent skin papillomas with some
degenerating into malignant epithelomas in mice surviving
200 days. Further details of the protocol were not given.
Pirie (1968) treated Dutch and albino rabbits with
IgAg/day of naphthalene by gavage. After three doses they
noted mitotic arrest of the epithelial cells of the lens.
The arrest persisted for 15 days when replication of the
epithelial cells was first noted. .At 16 days numerous abnor-
mal mitotic figures in metaphase were noted in the epithelial
layer in association with cell overgrowth. This work is
significant in that one of the effects of 2 metabolites of
naphthalene, 1-naphthol and 2-naphthol, is to interfere
with the mitotic spindle function, as seen in root tips
C-29
-------
TABLE 10
Bladder Tumors in Mice with Naphthalene Bladder Implants
(Boyland, et al. 1964)
o
u>
o
Substance
Naphthalene
Inert Controls
Magnesium stearate
n-Hexadecanol
n-Octadecanol
Smooth glass
Roughened glass
Mice Surviving
to 30 weeks
Carcinoma
Adenoma/Papilloma
23
41
69
50
67
63
1
1
6
6
3
18
0
1
2
7
__-.
-------
of Vicia faba (Dean, 1978). Both metabolites cause a chromo-
somal lagging in anaphase and 1-naphthol results in a colchi-
cine-like accumulation of chromosomes in metaphase.
Naphthalene has also been tested for carcinogenic
activity in in vitro test systems using rodent embryo cells
pretreated with Rauscher leukemia virus. No effects were
seen at doses up to 100,000 jig/1 (Table 11).
C-31
-------
TABLE 11
Carcinogenic Activity of Naphthalene with In Vitro Test Systems
o
i
u>
NJ
Test System
Rat embryo cells/
Rauscher leukemia virus*
Dose (ug/1) —
Result
Reference
Mouse embryo cells/.
AKR leukemia virus1
50
1,000
5,000
10,000
50,000
100,000 >
100
500
1,000
5,000
Negative
Negative
Negative
Negative
Negative
Negative
r -
Negative
Negative
Negative
Negative
Freeman,
Freeman,
Freeman,
Freeman,
Freeman,
Freeman,
Rhim, et
Rhim, et
Rhim, et
Rhim, et
et
et
et
et
et
et
al.
al.
al.
al.
al. 1973
al. 1973
al. 1973
al. 1973
al. 1973
al. 1973
1974
1974
1974
1974
In addition to transforming ability, treated cells injected into newborn rats or mice,
respectively, without any evidence of tumorigenicity
Dissolved in acetone
-------
CRITERIA FORMULATION
Existing Guidelines and Standards
The only existing U.S. standard for naphthalene is
the Occupational Safety and Health Administration standard
of 10 ppm (50 mg/m ) of vapor exposure for a time-weighted
industrial exposure (39FR23540). This standard was adopted
from the American Confererice of Governmental Industrial
Hygienists1 Threshold Limit Value which in turn was based
on an irritant threshold for naphthalene of 15 ppm (ACGIH,
1971). At present the ACGIH also suggests a maximum 15 minute
exposure value of 15 ppm (75 mg/m ) (ACGIH, 1978) .
The maximum permissible concentration of naphthalene
in fishery water bodies of the USSR is 4 jag/1 (Mosevich,
et al. 1976).
Current Levels of Exposure
Natural waters have been found to contain up to 2 jug/1
of naphthalene while drinking water supplies have been found
to contain up to 1.4 /ig/1 of naphthalene (U.S.EPA, Region
IV, unpublished data). Ambient air levels have been measured
at .00035 jug/m in an urban area and .00006 /ag/m" in a small
town (Krstulovic, et al. 1977) «, Industrial exposures can
range as high as 1.1 x 10 /ig/m for naphthalene-using indust-
ries (Robbins, 1951) with exposures up to 1120 /ig/m for
coke oven workers (Bjorseth, et al. 1978a) and 310 ;ig/m
for aluminum reduction plant workers (Bjorseth, et al. 1978b) ,
No measurements of naphthalene have been reported for market
basket foods.
C-33
-------
Special Groups at Risk
Approximately 100 million people worldwide have G6PD
deficiency which would make them more susceptible to hemoly-
tic anemia on exposure to naphthalene. At present more than
80 variants of this enzyme deficiency have been identified
(Wintrobe, et al. 1974). The incidence of this deficiency
is 0.1 percent in American and European Caucasians but can
range as high as 20 percent in American blacks and greater
than 50 percent in certain Jewish groups (Table 12).
Newborn infants have a similar sensitivity to the hemoly-
tic effects of naphthalene, even without G6PD deficiency.
Zinkham and Childs (1957) surveyed 26 normal white and black
newborn infants and found that their blood reduced gluta-
thione levels dropped moderately to severely in all of the
samples tested when incubated with acetylphenylhydrazine,
suggestive of a glutathione reductase deficiency. Brown
and Burnett (1957) also noted that newborn infants have
a decreased capacity to conjugate chemical metabolites with
glucuronide secondary to an absolute decrease in the activity
of UDP-glucuronyl dehydrogenase and transferase. Such a
lack in glucuronidation can allow the build-up of toxic
amounts of 1,2-dihydroxynaphthalene and 1,2-naphthaquinone.
A small percentage of the population might have an
allergic hypersensitivity to naphthalene. Panburg (1940)
described a 43-year-old physician with a generalized exfolia-
tive dermatitis who was found to be allergic to naphthalene.
Both the clinical and histologic picture resembled a malig-
nancy, mycosis fungoides. A patch test with naphthalene
C-34
-------
TABLE 12
Frequency of G6PD Deficiency in Populations
(Wintrobe, et al. 1974)
Population G6PD Deficiency (%)
Northern European 0.1
American black male 13
American black female 20
Brazilian black male 8.2
Bantu male 37
Sardinian 14.35
Maltese 2.7
Italian 0.4
Greek 9.5
Sephardic, Oriental or Kurdish Jews .2.50
C-35
-------
was positive, resulting in urticaria. When all expoauce
to naphthalene was discontinued, the skin condition cleared
rapidly and did not recur over a three year period of followup.
Basis and Derivation of Criterion
All chronic toxicity studies using naphthalene have
failed to demonstrate any carcinogenic activity except for
those performed by Knake (1956). This author found an excess
occurrence of lymphosarcoma when naphthalene was given by
the subcutaneous route to rats, and of lymphocytic leukemia
when naphthalene was chronically painted on the skin of
mice using benzene as a solvent. However, the naphthalene
used in this study was derived from coal tar and contained
ten percent or more unidentified impurities. Furthermore,
a known experimental carcinogen, carbolfuchsin, was applied
prior to each injection of naphthalene in the former study.
In light of these defects, carcinogenicity data derived
from this study cannot be used as a basis for a naphthalene
water criterion.
No other chronic toxicity studies are available that
can be used as an adequate basis for a naphthalene criterion.
Furthermore, there are no adequate epidemiologic studies
that can be used as a basis.
The ACGIH (1971) has recommended a time-weighted thres-
hold limit value for an industrially exposed population
of 50 mg/m (50 ug/1) of naphthalene vapor in air. This
value was set to prevent workers with exposure to naphthalene
vapors from getting eye irritation. It is unclear, however,
whether exposures to water containing naphthalene in excess
of this level (50 ug/1) might also result in mucous membrane
C-36
-------
irritation. Until further information is available on the
direct irritant properties of naphthalene in water, the
ACGIH threshold limit value cannot be used as a basis for
a naphthalene water criterion.
Mahvif et al. (1977) noted a dose related response
by C57 B1/6J mice given intraperitoneal injections of naphtha-
lene in sesame oil. No bronchiolar epithelial changes were
noted in two control groups. The authors noted minimal
bronchiolar epithelial changes in the treated group receiving
6.4 mg/kg of naphthalene. Severe, reversible damage to bron-
chiolar epithelial cells was noted among two higher dosage
groups. The results of this study can be used as the basis
for the criterion. The minimal effect level of 6.4 mg/kg
is equivalent to a 448 mg dose for a 70 kg man and can reason-
ably be used as a basis for calculating an acceptable daily
dosage if it is reduced by a factor of 1000, which equals
448 ug, to protect sensitive individuals (Natl. Acad. Sci.,
1977).
No pharmacokinetic data are available on the absorption
of naphthalene by the oral route. Because of its high octanol:
water partition coefficient. (Krishnamurthy and Wasik, 1978),
it is reasonable to expect that naphthalene in water should
be nearly completely absorbed and an absorption efficiency
of 100 percent can be assumed.
For the purposes of establishing a water quality criter-
ion, human exposure to napthalene is considered to be based on
ingestion of 2 liters of water and 18.7 g of fish. Fish
bioaccumulate naphthalene from water by a factor of 60.
C-37
-------
With these considerations in mind, the following equa-
tion can be used to calculate a criterion value:
2 L * X + (0.0187 X 60) ' X = 448 ug
Where:
448 ug = limit on daily exposure for a 70 kg person
(ADI)
2 L = amount of drinking water consumed
0.0187 kg = amount of fish consumed
60 = bioaccumulation factor
Solving for X:
X = 143 ug/1
Thus, the recommended ambient water quality criterion
is 143 ug/1.
This calculation assumes that 100 percent of man's
exposure is assigned to the ambient water pathway. Although
it is desirable to arrive at a criterion level for water
based on contribution to total exposure, data on other routes
of exposure is not sufficient to support a factoring of
the criterion level.
In summary, based on the use of toxicologic data for
mice, the criterion level corresponding to an acceptable
daily intake of 448 ug/day, is 143 mg/1. Drinking water
contributes 64 percent of the assumed exposure while eating
contaminated fish products accounts for 36 percent. The
criterion can alternatively be expressed as 400 ug/1 if
exposure is assumed to be from the consumption of fish and
shellfish alone.
C-38
-------
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