-------
DISCLAIMER
This report 1s an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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EXECUTIVE SUMMARY
AdlponHMle Is a colorless liquid at room temperature with no distinc-
tive odor (Smiley, 1981). It Is soluble In many organic solvents and Is
highly soluble 1n water (Smiley, 1981). It undergoes reactions typical of
nltrlles, e.g., hydrolysis to adlpamlde and adlplc add and alcoholysls to
substituted amides and esters (Smiley, 1981). AdlponltrUe can be produced
commercially either by ammonlatlon of adlplc add, dlmerlzatlon of acrylo-
nltrlle or hydrocyanatlon of butadiene (Smiley, 1981). Current domestic
manufacturers are E.I. Dupont In Orange, TX and Victoria, TX and Monsanto
Co. In Decatur, AL (SRI, 1986). As of January 1, 1986, the total adlpo-
nltrlle production capacity of these plants was estimated to be 929 million
pounds per year (SRI, 1986). The most Important use for this compound 1s as
an Intermediate In the manufacturer of hexamethylened1am1ne, a precursor of
Nylon 66 (Smiley, 1981). Ad1pon1tr1le may also be used In organic synthesis
and as a solvent (Kuney, 1985; Hawley, 1981; Smiley, 1981).
In the atmosphere, adlponltMle 1s expected to exist almost entirely In
the vapor phase. Reaction with photochemically generated hydroxyl radical
(estimated t./? -10 days) and physical removal by wet deposition are
predicted to be Important fate processes. Ad1pon1tr1le Is not susceptible
to reaction with ozone (U.S. EPA, 1987b). In water, aerobic blodegradatlon
1s the Important removal mechanism. Based on results of a blodegradatlon
study, It appears that the blodegradatlon half-life of adlponUrlle 1n
unaccllmated waters at 20°C Is -1 week (Ludzack et al., 1959a). Acclimation
of microorganisms should Increase the rate of blodegradatlon and lower
temperatures should decrease the rate of blodegradatlon (Ludzack et al.,
1959a). Adsorption to suspended solids and sediments, bloaccumulatlon 1n
1v
-------
aquatic organism and volatilization are not expected to be Important fate
processes In water. In soil, aerobic blodegradatlon 1s expected to be the
Important degradation mechanism. Adlponltrlle has the potential to undergo
extensive leaching; however, blodegradatlon of the compound would limit the
movement of this compound through soil. Volatilization 1s not expected to
be significant 1n soil.
Pertinent data regarding exposure to ad1pon1tr1le by Inhalation, dermal
contact or 1ngest1on of food could not be located In the available litera-
ture as cited 1n Appendix A. Adlponltrlle was tentatively Identified 1n the
drinking water obtained from New Orleans, LA, 1n January 1976 (Lucas, 1984).
Adlponltrlle was also detected 1n the effluent from a nylon manufacturing
plant (Shackelford and Keith, 1980).
There was little Information concerning toxldty of ad1pon1tr1le to
aquatic organisms. The lowest reported acutely toxic concentration for
freshwater fishes was 384 mg/i, an LC5Q for golden orfe (Knle et al.,
1983). The lowest reported acutely toxic concentration for freshwater
Invertebrates was 445 mg/i, an EC5Q for Immobilization of Daphnla magna
(BMngmann and Kuehn. 1982). Data for saltwater species could not be
located In the available literature as cited 1n Appendix A.
Studies of the metabolism of ad1pon1tr1le Indicate that 1t Is absorbed
by the gastrointestinal tract, metabolized to cyanide and excreted 1n the
urine as thlocyanate (Svlrbely and Floyd, 1964; Gh1r1nghell1, 1955a; Tan 11
and Hashimoto. 1985). Tanll and Hashimoto (1985) found that the metabolism
of adlponltrlle to cyanide In mice was greatly Inhibited by CC1. pretreat-
ment, which Inhibits certain drug metabolizing enzymes In the liver.
-------
Nylon workers exposed to adlponltrlle and hexamethylenedlamlne for 2-3
years showed a tendency for hyperchromlc anemia of the hemolytlc type and
slight leukopenla (Ceresa, 1948a). Ceresa (1948b) attributed these effects
to exposure to ad1pon1tr11e and hexamethylenedlamlne.
Dogs fed adlponltrlle 1n the diet at levels <500 ppm had normal blood
and urine values and tests for liver and kidney function (Svlrbely and
Floyd, 1964). During the first week of the study, dogs fed 1000 ppm were
not able to consume the entire dose. In a rat study (Svlrbely and Floyd,
1964), females treated with adlponltrlle 1n the drinking water at 0.5, 5.0
and 50 ppm and males at 50 ppm were found to have advanced adrenal degen-
eration.
Vomiting, tightness In the chest, headache, profound weakness with
difficulty standing, vertigo, respiratory difficulty, tachycardia and low
blood pressure were experienced by a human who consumed a few ml of adlpo-
nltrlle (GhlrlnghelH, 1955b). Zeller et al. (1969) reported seven cases of
skin Irritation 1n workers dermally exposed to adlponltrlle.
Adlponltrlle rubbed on the backs of guinea pigs for 1 month resulted In
weight loss, decreased calcium content of the blood, marked hyperchromlc
hemolytlc anemia with leukopenla and lymphomonocytosls. Hlstologlcal
examinations revealed swelling and congestion of nearly all Internal organs
(Ceresa, 1948b).
Rats exposed to adlponltrlle at 0.3 mg/8. for ten 6-hour exposures (5
days/week) showed Increases In blood glucose, urea nitrogen, creatlnlne and
urine glucose, and decreases In erythrocyte count, hemoglobin, leukocyte
count and urine osmolalHy. At 0.1 mg/l. Increases In urea nitrogen and
lymphocytes and decreases 1n the number of eoslnophlls and neutrophlls were
noted. No changes In clinical parameters were observed at 0.03 mg/8.
(Smith and Kennedy, 1982).
v1
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The oral ID™ In the rat was reported to be 960 mg/kg (Plokhova and
Rubaklna, 1965) and 300 mg/kg (NIOSH, 1978). Mice, with an oral LD5Q of
172 mg/kg, may be somewhat more sensitive to the acute oral toxldty of
adlponltrlle (Tan 11 and Hashimoto, 1985).
The carclnogenlcHy of adlponltrlle following Inhalation, oral or other
routes of exposure has not been studied. Ad1pon1tr1le tested negative for
reverse mutation In S. typhlmurlum at concentrations <10,000 yg/plate,
both with and without metabolic activation.
Johannsen et al. (1986) orally dosed pregnant rats with adlponltrlle at
0, 30, 50 or 80 mg/kg/day on gestation days 6-19. Two rats at 80 mg/kg/day
and one rat at 50 mg/kg/day died. Fetal body weights were significantly
reduced at 80 mg/kg/day, but this observation was not attributed to
treatment. No other changes were noted. No changes 1n fertility, gestation
or viability were noted In two litters from rats exposed to adlponltrlle In
the'r drinking water at 10, 100 or 500 ppm >jr 2 years (Svlrbely and Floyd,
1964).
Chronic oral exposure to adlponltrlle resulted 1n a LOAEL of 0.5 ppm
(0.07 mg/kg/day) that was associated with adrenal degeneration In the 2-year
rat study (Svlrbely and Floyd, 1964). This study was unavailable for review
and 1n addition appears to be an unpublished abstract. Data were considered
Inadequate for estimation of either an RfD or an RQ. It Is recommended that
comprehensive subchronlc oral testing be Initiated In the rat to determine a
NOAEL. Data were Insufficient for derivation of cancer-based risk
assessment values. Adlponltrlle was assigned to EPA Group 0, not
classifiable as to human carclnogenldty.
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TABLE OF CONTENTS
1. INTRODUCTION 1
1.1. STRUCTURE AND CAS NUMBER 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 1
1.3. PRODUCTION DATA 2
1.4. USE DATA 2
1.5. SUMMARY 2
2. ENVIRONMENTAL FATE AND TRANSPORT. . . 5
2.1. AIR 5
2.1.1. Reaction with Hydroxyl Radicals 5
2.1.2. Reaction with Ozone 5
2.1.3. Physical Removal Processes 5
2.2. WATER 5
2.2.1. Hydrolysis. . . 5
2.2.2. Mlcroblal Degradation 6
2.2.3. Bloconcentratlon 6
2.2.4. Adsorption 6
2.2.5. Volatilization 7
2.3. SOIL 7
2.3.1. Hyd-olysls 7
2.3.2. M1crob1al Degradation 7
2.3.3. Adsorption 7
2.3.4. Volatilization 7
2.4. SUMMARY 8
3. EXPOSURE 9
4. AQUATIC TOXICITY 10
4.1. ACUTE TOXICITY 10
4.2. CHRONIC EFFECTS 10
4.3. PLANT EFFECTS 10
4.4. SUMMARY 11
5. PHARMACOKINETCS 12
5.1. ABSORPTION 12
5.2. DISTRIBUTION 12
5.3. METABOLISM 12
5.4. EXCRETION 13
5.5. SUMMARY 13
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TABLE OF CONTENTS (cont.)
Page
6. EFFECTS 14
6.1. SYSTEMIC TOXICITY 14
6.1.1. Inhalation Exposures 14
6.1.2. Oral Exposures 14
6.1.3. Other Relevant Information 15
6.2. CARCINOGENICITY 18
6.2.1. Inhalation . 18
6.2.2. Oral 18
6.2.3. Other Relevant Information 18
6.3. MUTAGENICITY 18
6.4. TERATOGENICITY 18
6.5. OTHER REPRODUCTIVE EFFECTS 19
6.6. SUMMARY 19
7. EXISTING GUIDELINES AND STANDARDS 22
7.1. HUMAN 22
7.2. AQUATIC 22
8. RISK ASSESSMENT 23
8.1. CARCINOGENICITY 23
8.1.1. Weight of Evidence 23
8.1.2. Quantitative Risk Estimates 23
8.2. SYSTEMIC TOXICITY. . 23
8.2.1. Inhalation Exposure 23
8.2.2. Oral Exposure 24
9. REPORTABLE QUANTITIES 26
9.1. BASED ON SYSTEMIC TOXICITY 26
9.2. BASED ON CARCINOGENICITY 26
10. REFERENCES 29
APPENDIX A: LITERATURE SEARCHED 36
APPENDIX B: SUMMARY TABLE FOR ADIPONITRILE 39
1x
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LIST OF TABLES
No. TUIe Page
1-1 Current Domestic Manufacturers of AdiponHMle ........ 3
6-1 LD50 Values for Ad1pon1tr1le ................. 17
9-1 Oral Toxlclty Summary for AdlponHMTe Using Female
Wlstar Rats ......................... 27
9-2 Ad1pon1tr1le: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) ................... 28
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LIST OF ABBREVIATIONS
BCF B1oconcentrat1on factor
BOD Biological oxygen demand
CAS " Chemical Abstract Service
CS Composite score
EC5Q Concentration effective to 50% of recipients
(and all other subscripted concentration levels)
Koc Soil sorptlon coefficient standardized
with respect to organic carbon
Kow Octanol/uater partition coefficient
LC5Q Concentration lethal to 50% of recipients
(and all other subscripted dose levels)
Dose lethal to 50% of recipients
LOAEL Lowest-observed-adverse-effect level
MED Minimum effective dose
NOAEL No-observed-adverse-effect level
ppm Parts per million
RfD Reference dose
RQ Reportable quantity
RV,j Dose-rating value
RVe Effect-rating value
TWA Time-weighted average
x1
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1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
AdlponHMle 1s also known as hexanedlnHMle, adlplc add nHrlle,
tetramethyl cyanide and 1,4-d1cyanobutane (SANSS, 1987). The structure,
empirical formula, molecular weight and CAS Registry number are as follows:
N=C-CH2-CH2-CH2-CH2-CEN
Empirical formula: C,H0N.
o o e.
Molecular weight: 108.14
CAS Registry number: 111-69-3
1.2. PHYSICAL AND CHEMICAL PROPERTIES
Pure adlponltrlle Is a colorless liquid at room temperature with no
distinctive odor (Smiley, 1981). It undergoes reactions typical of
nltrlles, e.g., hydrolysis to adlpamlde and adlplc add and alcoholysls to
substituted amides and esters (Smiley, 1981). Adlponltrlle Is soluble In
methanol, ethanol, chloroalkane and aromatic solvents and has low solubility
1n carbon dlsulflde, ethyl ether and aliphatic hydrocarbons (Smiley, 1981).
Selected physical properties are given below:
Melting point, °C: 2.49 Smiley, 1981
Boiling point, °C: 295 Smiley, 1981
Vapor pressure at 20°C: 3.0xlO~3 mm Hg Neely and Blau, 1985
Water solubllHy, 20°C: 8xl04 mg/l Smiley, 1981
Log Kow: -0.32 Tanll and Hashimoto, 1985
-0.42 U.S. EPA, 1987a
Density, 20°C: 0.965 g/cm3 Smiley, 1981
Refractive Index, njj : 1.4343 Smiley, 1981
Flashpoint, °C: 159 (closed cup) Smiley, 1981
0071d -1- 06/25/87
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1.3. PRODUCTION DATA
Adlponltrlle can be prepared commercially using either adlplc acid,
acrylonltrlle or butadiene as feedstock (Smiley, 1981). In the adlplc add
process, the feedstock Is allowed to react with ammonia over a catalyst to
produce adiponltrlle. In one butadiene-based production process, butadiene
1s directly hydrocyanated 1n two successive steps to produce adiponltrlle.
Another process Involves d1mer1zat1on of acrylonUrlle In an electrolyte
cell to produce adiponltrlle (Smiley, 1981). Table 1-1 lists production
Information concerning current domestic manufacturers of adiponltrlle.
Although closed since 1980, the Monsanto plant In Pensacola, PL, has a
yearly production capacity of 185 million pounds; this plant continues to
hydrogenate adiponltrlle produced at other Monsanto locations to make
hexamethylened1am1ne (SRI, 1986).
1.4. USE DATA
The most Important commercial use for adlponltrlle 1s as an Intermediate
In the manufacture of hexamethylenedlamlne, a p.^cursor of Nylon 66 (Smiley,
1981). Adiponltrlle may also be used In organic synthesis and as a solvent
(Kuney, 1985; Hawley, 1981; Smiley, 1981).
1.5. SUMMARY
Adiponltrlle 1s a colorless liquid at room temperature with no distinc-
tive odor (Smiley, 1981). It Is soluble In many organic solvents and Is
highly soluble In water (Smiley, 1981). It undergoes reactions typical of
nUMles, e.g.. hydrolysis to adlpamlde and adlplc acid, and alcoholysls to
substituted amides and esters (Smiley, 1981). Adiponltrlle can be produced
commercially either by ammonlatlon of adlplc add, dlmeMzatlon of acrylo-
nltrlle or hydrocyanatlon of butadiene (Smiley, 1981). Current domestic
manufacturers are E.I. Dupont In Orange, TX and Victoria, TX and Monsanto
0071d -2- 06/25/87
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TABLE 1-1
Current Domestic Manufacturers of Ad1pon1tr1lea
Company
Location
Annual Capacity0
(millions of pounds)
E.I. Dupont
E.I. Oupont
Monsanto Co.
Orange, TX
Victoria, TX
Decatur, AL
441
293
195
Total 929
aSource: SRI, 1986
^Estimates as of January 1, 1986
0071d
-3-
09/14/87
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Co. In Decatur, AL (SRI, 1986). As of January 1, 1986 the total adlpo-
nHMle production capacity of these plants was estimated to be 929 million
pounds per year (SRI, 1986). The most Important use for this compound Is as
an Intermediate 1n the manufacturer of hexamethylenedlamlne, a precursor of
Nylon 66 (Smiley, 1981). Adlponltrlle may also be used In organic synthesis
and as a solvent (Kuney, 1985; Hawley, 1981; Smiley, 1981).
0071d -4- 06/25/87
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2. ENVIRONMENTAL FATE AND TRANSPORT
Limited experimental data pertaining to the environmental fate and
transport of adlponltrlle could be located In the available literature as
cited 1n Appendix A. When possible, therefore, Information concerning the
fate and transport of this compound was derived from physical property data
or molecular structure.
2.1. AIR
Based on the estimated vapor pressure of 3.0xlO~3 mm Hg at 20°C,
adlponltrlle 1s expected to be present almost entirely 1n the vapor phase 1n
the atmosphere (E1senre1ch et al., 1981).
2.1.1. Reaction with Hydroxyl Radicals. The estimated rate constant for
the reaction of adlponltrlle with photochemically generated hydroxyl
radicals Is ~10~10 cmVmolecule-sec at 25°C using the method of Atkinson
(1985). Given the average hydroxyl radical concentration In air of 8xlOs
molecules/cm3 (U.S. EPA, 1987b), the estimated half-life for this reaction
Is -10 days (Atkinson, 1985).
2.1.2. Reaction with Ozone. Adlponltrlle 1s not susceptible to oxidation
by ozone 1n the atmosphere (U.S. EPA, 1987b).
2.1.3. Physical Removal Processes. Based on a water solubility of
8x10* mg/i at 20°C (Smiley, 1981), 1t appears that significant amounts
of adlponltrlle may be removed from the atmosphere by wet deposition.
2.2. HATER
2.2.1. Hydrolysis. In an abstract of a Russian study (Llnetskll and
Serebryakov, 1965), the first-order hydrolysis rate constant for adlpo-
n1tr1le 1n 2-5% NaOH solution at 100°C was reported as 1.18 mln'1. Under
environmental conditions, however, adlponltrlle 1s not likely to hydrolyze
significantly (U.S. EPA, 1986b).
OOTld -5- 09/14/87
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2.2.2. M1crob1al Degradation. Results of a blodegradatlon screening
study, which used a natural water sample as seed, Indicate that
blodegradatlon Is likely to be the most significant route of decomposition
for adlponUrlle under aerobic conditions In water (Ludzack et al., 1959a).
Incubation of 0.5-10 mg/i adiponltrlle In unaccllmated Ohio River water
resulted In BOO values equivalent to theoretical oxygen demands of 0, 40 and
>100X after 2, 5 and 12 days, respectively. Acclimation of microorganisms
was examined by redoslng, and degradation occurred twice as fast after
acclimation was achieved. The effect of temperature on blodegradatlon was
also studied; blodegradatlon at 5°C required -3.5 times longer than at
20°C. Ludzack et al. (1959b) studied the blodegradatlon of adiponltrlle by
activated sludge 1n a continuous feed test at 22-25°C; 93-98% BOD removal
was measured with a mean aerator detention time of 7-13 hours at an Influent
adiponltrlle concentration equivalent to a BOO of 275-350 mg/l.
Adiponltrlle at 500 mg/l Incubated for 72 hours In three different
activated sludge Inocula, was found to be resistant to biological oxidation
(Lutln, 1970). Ludzack et al. (1959a) found that nltrlle oxidation proceeds
by enzymatic hydrolysis leading to the formation of ammonia, followed by
nitrification.
2.2.3. Bloconcentratlon. A BCF of 1 was estimated for adlponUrlle using
a water solubility of 8.0x10* mg/l at 20°C (Smiley, 1981) and the
following linear regression equation (Lyman et al., 1982): log BCF = 2.791 -
0.564 log S. This BCF value suggests that adiponltrlle will not bloaccumu-
late significantly In aquatic organisms.
2.2.4. Adsorption. An estimated K value of 9 for adiponltrlle
(Section 2.3.3.) suggests that adsorption to sediments or suspended solids
In water would not be significant.
0071d -6- 09/14/87
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2.2.5. Volatilization. Henry's Law constant for adlponHMle was esti-
mated to be ~7xlO~9 atm-m3/mol at 25°C using a method of group contribu-
tions to Intrinsic hydrophlUc character (Hlne and Mookerjee, 1975). This
value of Henry's Law constant suggests that volatilization from water would
not be an Important removal mechanism (Lyman et al., 1982).
2.3. SOIL
2.3.1. Hydrolysis. Because of the lack of experimental data the signifi-
cance of this reaction cannot be determined.
2.3.2. H1crob1al Degradation. In the only study available regarding the
blodegradatlon of ad1pon1tr1le by soil microorganisms, Kuwahara et al.
(1980) found that Aeromonas sp. BN 7013 Isolated from soil 1s capable of
using ad1pon1tr1le as Us sole source of nitrogen. Relatively rapid
blodegradatlon of adlponUrlle 1n natural water samples and activated sludge
Inocula suggests that blodegradatlon may also be the most Important removal
mechanism 1n soil.
2.3.3. Adsorption. A K of 9 was estimated using a water solubility
of 8.0x10* mg/l at 20°C (Smiley, 1981) and the following linear regres-
sion equation (Lyman et al., 1982): log K = -0.55 log S * 3.64. This
K value Indicates that adlponltrlle should be highly mobile In soil and
susceptible to significant leaching (Swann et al., 1983).
2.3.4. Volatilization. Based on a vapor pressure of 3.0xlO~9 mm Hg at
20°C and a Henry's Law constant of 7xlO"9 atm-mVmol at 25°C, volatili-
zation of ad1pon1tr1le from moist and dry soil surfaces 1s not expected to
be a significant fate process.
007 Id -7- 09/14/87
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2.4. SUMMARY
In the atmosphere, adlponltrlle 1s expected to exist almost entirely In
the vapor phase. Reaction with photochemically generated hydroxyl radical
(estimated t,/2 -10 days) and physical removal by wet deposition are
predicted to be Important fate processes. Ad1pon1tr1le Is not susceptible
to reaction with ozone (U.S. EPA, 1987b). In water, aerobic blodegradatlon
1s the Important removal mechanism. Based on results of a blodegradatlon
study, 1t appears that the blodegradatlon half-life of adlponltrlle In
unaccllmated waters at 20°C 1s ~1 week (Ludzack et al., 1959a). Acclimation
of microorganisms should Increase the rate of blodegradatlon and lower
temperatures should decrease the rate of blodegradatlon (Ludzack et al.,
1959a). Adsorption to suspended solids and sediments, bloaccumulatlon 1n
aquatic organism and volatilization are not expected to be Important fate
processes In water. In soil, aerobic blodegradatlon 1s expected to be the
Important degradation mechanism. Adlponltrlle has the potential to undergo
extensive leaching; however, blodegradatlon of the compound would limit the
movement of this compound through soil. Volatilization Is not expected to
be significant In soil.
0071d -8- 06/25/87
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3. EXPOSURE
Pertinent data regarding exposure to ad1pon1tr1le by Inhalation, dermal
contact or Ingestlon of food could not be located 1n the available litera-
ture as cited In Appendix A. Adlponltrlle was tentatively Identified In the
drinking water obtained from New Orleans, LA, 1n January 1976 (Lucas, 1984).
Adlponltrlle was also detected In the effluent from a nylon manufacturing
plant (Shackelford and Keith, 1976).
0071d -9- 09/14/87
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4. AQUATIC TOXICITY
4.1. ACUTE TOXICITY
Two available studies reported acute toxldty data for fish or aquatic
Invertebrates exposed to adiponltrlle. Henderson et al. (1961) reported
96-hour LC5Q values of 820 and 1250 mg/l for fathead minnows, Plmephales
promelas. 1n hard and soft water, respectively. These authors also reported
96-hour LC5_ values of 720 mg/l for bluegllls, Lepomls macrochlrus. and
775 mg/l for gupples, Leblstes retlculatus. both 1n soft water. Hardness
1n these studies was 20 mg/l for soft water and 380 mg/l for hard water.
An LC,Q of 384 mg/l was reported for the golden orfe, Leudscus 1dus
(Kn1e et al., 1983).
The only Invertebrate species for which there was Information about
adiponltrlle toxlclty was the cladoceran, Daphnla magna. Brlngmann and
Kuehn (1982) reported a 24-hour EC,, for Immobilization of 445 mg/l,
while Knle et al. (1983) reported an EC5Q of 1250 mg/l.
4.2. CHRONIC EFFECTS
Pertinent data regarding chronic toxlclty of ad1pon1tr1le to aquatic
organisms could not be located In the available literature as cited 1n
Appendix A.
4.3. PLANT EFFECTS
Knle et al. (1983) reported that 408 mg/l was a 30-mlnute EC... for
Inhibition of culture growth of the bacterium Pseudomonas put Ida. Other
data for aquatic plants or bacteria could not be located 1n the available
literature as cited In Appendix A.
0071d -10- 09/14/87
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4.4. SUMMARY
There was little Information concerning toxldty of adlponltrUe to
aquatic organisms. The lowest reported acutely toxic concentration for
freshwater fishes was 384 mg/i, an LC5Q for the golden orfe (Knle et
al., 1983). The lowest reported acutely toxic concentration for freshwater
Invertebrates was 445 mg/l, an EC— for Immobilization of Daphnla magna
(Brlngmann and Kuehn, 1982). Data for saltwater species could not be
located 1n the available literature as cited 1n Appendix A.
0071d -11- 09/14/87
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5. PHARHACOKINETICS
5.1. ABSORPTION
Approximately 50% of the adlponltrlle consumed In the diet by mongrel
female dogs was recovered 1n the urine as thlocyanate (Svlrbely and Floyd,
1964). Dietary concentrations ranged from 10-1000 ppm.
5.2. DISTRIBUTION
Cyanide, an Important metabolite of ad1pon1tr1le, has been shown to
cross the blood-brain barrier and locate 1n the brain. Tan 11 and Hashimoto
(1985) measured cyanide at -0.71 wg/g of wet tissue In the brains of male
ddY mice given an oral 4.8 mmol/kg (519 mg/kg) dose of adlponltrlle. The
brains were harvested at the time of death, -83 minutes after treatment. In
mice pretreated with CC1. to Inhibit the hepatic mixed function oxldase
system (and presumably prevent degradation of adlponltrlle to cyanide), a
519 mg/kg dose of adlponltrlle did not cause death and cyanide was not found
1n the brain 83 ml.utes after treatment.
5.3. METABOLISM
A number of studies Indicate that adlponltrlle Is metabolized to
cyanide. Svlrbely and Floyd (1964) found that dogs fed adlponltrlle In the
diet at 10-1000 ppm showed a dose-related Increase In thlocyanate excreted
In the urine, which Is equivalent to -50% of the dose of adlponltrlle. The
amount of thlocyanate In the bloodstream of guinea pigs Injected
subcutaneously with adlponltrlle at 3-30 mg/kg was proportional to the
administered dose (Gh1r1nghell1, 1955a). Tan11 and Hashimoto (1985)
<•
Identified cyanide In the brains of mice orally dosed with adlponltrlle.
The metabolism of ad1pon1tr1le to cyanide was greatly Inhibited In mice
pretreated with CC1., as evidenced by the fact that cyanide was not found
1n the brains of pretreated mice.
OOTld -12- 11/17/87
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In an hi vitro study using mouse liver mlcrosomes, 6.23 ng cyan1de/mg
protein/minute were formed from an ad1pon1tr1le concentration of 3.1 mM
(Tan11 and Hashimoto, 1985). When mice were treated with CC1. before
mlcrosomes were harvested, cyanide was not detected after adiponltrlle was
added to the cultures. Tanll and Hashimoto (1985) stated that ad1pon1tr1le
1s probably hydroxylated at the a-carbon to form cyanohydMn, which
degrades spontaneously 1n alkaline medium to form hydrogen cyanide.
5.4. EXCRETION
Approximately 79% of the adiponltrlle (3-30 mg/kg) Injected subcuta-
neously Into guinea pigs was accounted for as thlocyanate excreted 1n the
urine (Gh1r1nghel11, 1955a). Dogs excreted -50% of an oral dose of adipo-
nltrlle as urinary thlocyanate; negligible amounts of thlocyanate were found
1n the feces (Svlrbely and Floyd, 1964).
5.5. SUMMARY
Studies of the metabolism of adiponltrlle Indicate that 1t 1s absorbed
by the gastrointestinal tract, metabolized to cyanide and excreted 1n the
urine as thlocyanate (Svlrbely and Floyd, 1964; Gh1r1nghell1, 1955a; Tanll
and Hashimoto, 1985). Tan11 and Hashimoto (1985) found that the metabolism
of adiponltrlle to cyanide In mice was greatly Inhibited by CC1. pretreat-
ment, which Inhibits certain drug metabolizing enzymes 1n the liver.
0071d -13- 11/17/87
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6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. Inhalation Exposures.
6.1.1.1. SUBCHRONIC — Pertinent data regarding the toxldty of
ad1pon1tr1le following subchronlc Inhalation exposure could not be located
1n the available literature as cited In Appendix A.
6.1.1.2. CHRONIC — Ceresa (1948a) reported that 27 Individuals who
had worked In the nylon Industry, handling adiponltrlle and hexamethylene-
dlamlne for 2-3 years, showed a definite tendency for hyperchromlc anemia of
the hemolytlc type and slight leukopenla or lymphomonocytosls.
6.1.2. Oral Exposures.
6.1.2.1. SUBCHRONIC ~ Pertinent data regarding the toxldty of
adiponltrlle following subchronlc oral exposure could not be located In the
available literature as dted In Appendix A.
6.1.2.2. CHRONIC — NIOSH (1978) reviewed chronic oral studies of
adiponltrlle In dogs and rats completed by Svlrbely and Floyd (1964). The
original study report could not be obtained. However, the original report
from the fourth portion of this series (SvUbely, n.d.) was located.
Apparently each of the segments were only reported Vn abstract form. In the
dog study, an unspecified number of female mongrel dogs were fed
adiponltrlle In the diet at "the equivalent of" 10, 100, 500 and 1000 ppm
for an unspecified period of time. Blood and urine values and tests for
liver and kidney function were normal In dogs fed adiponltrlle at <500 ppm.
During the first week, dogs fed 1000 ppm were not able to consume the entire
dose; the dogs vomited or failed to eat a portion of H.
In the rat study, an unspecified number of male and female Wlstar rats
were provided with 0.5, 5.0 or 50 ppm adiponltrlle In their drinking water
0071d -14- 11/17/87
-------
for 2 years. Throughout the study, body weights remained normal and no
hematologlc abnormalities were observed. At the end of the study, advanced
adrenal degeneration was found In female rats at all three ad1pon1tr1le
concentrations and 1n male rats exposed to 50 ppm. Degeneration of other
organs was also noted, but was not considered to be compound-related.
Determination of organ (spleen, liver, kidney) to body weight ratios
revealed no significant differences. No effect on survival was reported.
6.1.3. Other Relevant Information. NIOSH (1978) summarized a report by
GhlMnghelH (1955b) concerning a case of acute poisoning In which an
18-year-old man consumed a few ml of ad1pon1tr1le. The man experienced
vomiting, tightness 1n the chest, headache, profound weakness with diffi-
culty standing, vertigo, respiratory difficulty, tachycardia and low blood
pressure. The man recovered after being treated with sodium thlosulfate.
As reviewed by NIOSH (1978), Zeller et al. (1969) reported seven cases
of dermal exposure to adlponUrlle. Mild skin Irritation and Inflammation
developed 1n six of the workers within 5-15 r.inutes of exposure. The
seventh worker, whose shoe had been drenched with ad1pon1tr1le, had exten-
sive destruction of the skin of the foot. The Injury required surgical
treatment and the worker was Incapacitated for 117 days.
To determine 1f the effects observed 1n humans occupatlonally exposed to
ad1pon1tr1le and hexamethylenedlamlne (see Section 6.1.1.2.) could be
attributed to ad1pon1tr1le, Ceresa (1948b) and Ceresa and De Blaslls (1950)
examined the toxlclty of adlponUrlle and hexamethylenedlamlne 1n guinea
pigs. An unspecified dose of ad1pon1tr1le was rubbed on the backs of guinea
pigs dally for 1 month (Ceresa, 1948b). This treatment resulted In weight
loss, decreased calcium content of the blood, marked hyperchromlc hemolytlc
anemia with leukopenia and lymphomonocytosU. Hlstologlcal examinations
revealed swelling and congestion of nearly all Internal organs. Because
0071d -15- 11/17/87
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hemolytlc anemia with leukopenla and degenerative changes In the liver and
kidney were also noted 1n guinea pigs treated with subcutaneous Injections
of hexamethylenedlamlne, Ceresa and De Blas11s (1950) concluded that both
adlponltMle and hexamethylenedlamlne may contribute to the effects observed
1n humans.
Smith and Kennedy (1982) exposed groups of 10 male Charles River CD rats
to ad1pon1tr1le vapor at 0, 0.03, 0.1 or 0.3 mg/l (0, 30, 100 or 300
mg/m3) for ten 6-hour periods (5 days/week). After the ninth exposure,
blood and urine analyses were completed. Following the tenth exposure, 5
rats/exposure group were sacrificed and comprehensive hlstologlcal examina-
tions were conducted. The remaining rats were allowed to recover for 14
days when they were sacrificed for hlstologlcal examinations.
During the exposures, the signs of toxlclty observed In all exposed
groups Included Irregular breathing and mild salivation. Rats exposed at
0.3 mg/l showed weight loss during the first 5 exposures, and af.er 10
exposures had changes 1n clinical pa-ho-logy parameters Including. Increases
1n blood glucose, urea nitrogen, creatlnlne and urine glucose, and decreases
1n erythrocyte count, hemoglobin, leukocyte count and urine osmolalHy. At
0.1 mg/l, rats showed Increased blood urea nitrogen and lymphocytes and
decreased numbers of eoslnophlls and neutrophlls. No changes 1n clinical
chemistry parameters were observed at 0.03 mg/l. No hlstologlcal changes
were noted at any exposure concentration. Fourteen days postexposure,
clinical pathology parameters of all groups were normal and microscopic
changes 1n the organs were not observed.
LD-Q values for ad1pon1tr1le are presented 1n Table 6-1. Plokhova and
Rubaklna (1965) reported effects of acute lethal oral doses of ad1pon1tr1le
as excitation, convulsions, dyspnea, coma with death 1n 2-6 hours. H1sto-
pathologlc changes Included hyperemla and dystrophlc changes In brain,
0071d -16- 11/17/87
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TABLE 6-1
Values for AdlponHMle
Species
Route of
Administration
1050 Value
Reference
Rat
Rat
Rat
Mouse3
House5
Guinea pig
Rat
House
Inhalation
oral
oral
oral
oral
subcutaneous
subcutaneous
Intraperltoneal
1.71 mg/l
{1710 mg/m3)
(4-hour LC5o)
960 mg/kg
300 mg/kg
1.59 mmol
(-172 mg/kg)
2.65 mmol
(-287 mg/kg)
50 mg/kg
200 mg/kg
40 mg/kg
Smith and
Kennedy. 1982
Plokhova and
Rubaklna, 1965
NIOSH, 1978
Tan 11 and
Hashimoto, 1985
Tan 11 and
Hashimoto, 1985
Gh1r1nghell1,
1955b
NIOSH, 1978
Plzak and
Doull, 1969
aH1ce pretreated with an Intraperltoneal Injection of olive oil served as
controls 1n an experiment with mice pretreated with CC14 (see Section
5.2).
bH1ce were pretreated with an Intraperltoneal Injection of CC14. Mice
appear to be somewhat more sensitive than rats to the acute oral tox1c1ty
of adlponltrlle.
007 Id
-17-
06/25/87
-------
liver, kidney and myocardium. Mice appear to be somewhat more sensitive
than rats to the acute oral toxldty of ad1pon1tr1le.
6.2. CARCINOGENICITY
6.2.1. Inhalation. Pertinent data regarding the cardnogenlcHy of
adiponltrlle following Inhalation exposure could not be located In the
available literature as cited 1n Appendix A.
6.2.2. Oral. A NIOSH (1978) summary of a 2-year drinking water study of
adiponltrlle 1n VHstar rats did not report carcinogenic effects. Additional
Information concerning the cardnogenlcHy of adiponltrlle following oral
exposure could not be located In the available literature as dted 1n
Appendix A. The chemical 1s not currently scheduled for cancer testing by
the NTP (1987).
6.2.3. Other Relevant Information. Pertinent data regarding the carclno-
genldty of adiponltrlle by other routes of exposure could not be located In
the available literature as cited In Appendix A.
6.3. MUTAGENICITY
NIOSH (1978) reported that adiponltrlle was negative for reverse
mutation 1n Salmonella typhlmurlum strains TA1536, TA1537, TA1538 and TA98
.at concentrations <10,000 yg/plate, both with and without metabolic
activation.
6.4. TERATOGENICITY
Johannsen et al. (1986) dosed groups of 25 mated Charles River, COBD CD
rats by gavage with ad1pon1tr1le at 0, 30, 50 or 80 mg/kg/day on gestation
days 6-19. The dams were sacrificed on gestation day 20 and the number and
location of viable and nonvlable fetuses, early and late resorptlons, and
the total number of Implants and corpora lutea were determined. The fetuses
were examined for gross malformations and half were examined for visceral
malformations while the remaining were examined for skeletal anomalies.
0071d -18- 11/17/87
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During the study, two 80 mg/kg/day rats and one 50 mg/kg/day rat died.
No differences were found In uterine and fetal parameters measured at
sacrifice. Fetal body weights were reduced significantly (p<0.05) at 80
mg/kg/day but not at 30 mg/kg/day, although the fetal body weights were
essentially the same at these two dose levels. Because a dose-related
change In fetal body weight was not observed, the Investigators concluded
that there was no treatment-related effect on fetal body weight. Fetal
examinations revealed no treatment-related malformations.
6.5. OTHER REPRODUCTIVE EFFECTS
Svlrbely (n.d) reported In an unpublished abstract that exposure of
Holtzman rats (number unspecified) to 10, 100 or 500 ppm ad1pon1tr1le for
three generations (2 Utters/generation) did not result 1n any adverse
effects. Endpolnts monitored Included fertility, gestation (NOS) and
viability.
6.6. SUMMARY
Nylon workers exposed to adlponUrlle and hexamethylened1am1ne for 2-3
years showed a tendency for hyperchromlc anemia of the hemolytlc type and
slight leukopenla (Ceresa, 1948a). Ceresa (1948b) attributed these effects
to exposure to ad1pon1tr1le and hexamethylenedlamlne.
Dogs fed adlponUrlle In the diet at levels <500 ppm had normal blood
and urine values and tests for liver and kidney function (Svlrbely and
Floyd, 1964). During the first week of the study, dogs fed 1000 ppm were
not able to consume the entire dose. In a rat study (Svlrbely and Floyd,
1964), females treated with ad1pon1tr1le In the drinking water at 0.5, 5.0
and 50 ppm and males at 50 ppm were found to have advanced adrenal degen-
eration.
Vomiting, tightness In the chest, headache, profound weakness with
difficulty standing, vertigo, respiratory difficulty, tachycardia and low
0071d -19- 11/17/87
-------
blood pressure were experienced by a human who consumed a few ml of adlpo-
nHMle (Gh1r1nghell1, 1955b). Zeller et al. (1969) reported seven cases of
skin Irritation In workers dermally exposed to adlponltrlle.
Adlponltrlle rubbed on the backs of guinea pigs for 1 month resulted 1n
weight loss, decreased calcium content of the blood, marked hyperchromlc
hemolytlc anemia with leukopenla and lymphomonocytosls. Hlstologlcal
examinations revealed swelling and congestion of nearly all Internal organs
(Ceresa, 1948b).
Rats exposed to adlponUMle at 0.3 mg/j. for ten 6-hour exposures (5
days/week) showed Increases 1n blood glucose, urea nitrogen, creatlnlne and
urine glucose, and decreases 1n erythrocyte count, hemoglobin, leukocyte
count and urine osmolalHy. At 0.1 mg/i, Increases 1n urea nitrogen and
lymphocytes and decreases In the number of eoslnophlls and neutrophlls were
noted. No changes In clinical parameters were observed at 0.03 mg/i.
(Smith and Kennedy, 1982).
The oral LD.Q 1n the rat was reported to be 960 mg/kg (Plokhova and
Rubaklna, 1965) and 300 mg/kg (NIOSH, 1978). Mice, with an oral LD5Q of
172 mg/kg, may be somewhat more sensitive to the acute oral toxldty of
adlponltrlle (Tan11 and Hashimoto, 1985).
The carclnogenlcHy of adlponltrlle following Inhalation, oral or other
routes of exposure has not been studied. Adlponltrlle tested negative for
reverse mutation 1n S. typhlmurlum at concentrations <10,000 yg/plate,
both with and without metabolic activation.
Johannsen et al. (1986) orally dosed pregnant rats with adlponltrUe at
0, 30, 50 or 80 mg/kg/day on gestation days 6-19. Two rats at 80 mg/kg/day
and one rat at 50 mg/kg/day died. Fetal body weights were significantly
0071d -20- 09/14/87
-------
reduced at 80 mg/kg/day, but this observation was not attributed to treat-
ment. No other changes were noted. No changes In fertility, gestation or
viability were noted 1n two litters from rats exposed to adlponltrlle In
their drinking water at 10, 100 or 500 ppm for 2 years (Svlrbely and Floyd,
1964).
0071d -21- 06/25/87
-------
7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
NIOSH (1978) recommended that employee exposure to adlponltrlle not
exceed 4 ppm (18 mg/m3) as a TWA for up to a 10-hour work shift 1n a
40-hour workweek. This recommendation Is based on the comparative acute
toxlclty of IsobutyronHrlle and adlponUrlle Injected subcutaneously 1n
female rats. Other guidelines or standards could not be located In the
available literature as dted In Appendix A.
7.2. AQUATIC
Guidelines and standards for the protection of aquatic organisms from
the effects of adlponltrlle could not be located In the available literature
as cited In Appendix A.
0071d -22- 06/25/87
-------
8. RISK ASSESSMENT
8.1. CARCINOGENICITY
Pertinent data regarding the cardnogenlcHy of adlponltrlle by any
route of exposure could not be located In the available literature as cited
1n Appendix A.
8.1.1. Weight of Evidence. Data were not located regarding the cardno-
genldty of adlponltrlle 1n humans or experimental animals; therefore,
ad1pon1tr1le 1s placed 1n EPA Group D (U.S. EPA, 1986c), not classifiable as
to human carclnogenlclty.
8.1.2. Quantitative Risk Estimates. The lack of data concerning the
carclnogenlclty of ad1pon1tr1le precludes the derivation of risk assessment
values based on carclnogenlclty.
8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposure.
8.2.1.1. LESS THAN LIFETIME EXPOSURES (SUBCHRONIC) '— The lack of
data concerning the toxlclty of adlponltrlle following subchronlc Inhalation
exposure precludes the derivation of a subchronlc Inhalation RfD.
8.2.1.2. CHRONIC EXPOSURES -- Nylon workers exposed to adlponltrlle
and hexamethylenedlamlne for 2-3 years showed a definite tendency for hyper-
chromic anemia of the hemolytlc type and slight leukopenla (Ceresa, 1948a).
The study 1s Inadequate for the derivation of an Inhalation RfD because
exposure was to a mixture of chemicals and because of the lack of quantita-
tive exposure data. The recommended occupational standard of 4 ppm (18
mg/m3) (NIOSH, 1978) based on acute subcutaneous toxlclty of ad1pon1tr1le
compared with 1sobutyron1tr1le In female rats 1s not adequate for determina-
tion of an RfD for Inhalation exposure.
0071d -23- 09/14/87
-------
8.2.2. Oral Exposure.
8.2.2.1. LESS THAN LIFETIME EXPOSURES (SUBCHRONIC) — The toxUHy of
adlponHMle following subchronlc oral exposure has not been studied.
8.2.2.2. CHRONIC EXPOSURES — In a study by Svlrbely and Floyd
(1964), blood and urine values and tests for liver and kidney function were
normal In dogs fed adlponltrlle at <500 ppm for an unspecified length of
time. During the first week of the study, dogs fed 1000 ppm were not able
to consume the entire dose.
Female rats provided with adlponltrlle 1n their drinking water at 0.5,
5.0 or 50 ppm and males at 50 ppm for 2 years were found to have advanced
adrenal degeneration (Svlrbely and Floyd, 1964). No changes In body weight,
organ weights or hematologlcal values were noted and no Increase 1n
mortality was reported. Advanced adrenal degeneration was observed 1n all
treated groups of females, but 1n males only at 50 ppm. These observations
suggest that 0.5 ppm may be near the threshold for adrenal effects In
females. Increased mortality was not reported 1n any treatment group, which
suggests that the effects on the adrenal were not life threatening. The
drinking water concentration of 0.5 ppm, therefore, constitutes a NOAEL 1n
male rats and may be considered a LOAEL In female rats. The fact that this
study was not available for review and that 1t appears from the evaluation
of other reports from this series that the report only existed as an
unpublished abstract precludes use of these data for RfO development.
It 1s known that adlponltrlle 1s metabolized to cyanide. Therefore, the
possibility that an RfD for adlponltrlle could be derived by analogy to
cyanide was Investigated. However, the effects on the adrenal gland
reported by Svlrbely and Floyd (1964) are Inconsistent with the reported
critical effects of cyanide which are predominately CNS lesions. In
addition the dose of adlponltrlle causing these adrenal lesions Is much
0071d -24- , 11/17/87
-------
lower than reported effect levels for cyanide (ATSDR, 1988). As a result of
discrepancy 1n both critical effects and effective doses for adlponltrlle
compared with cyanide, an RfO based on analogy 1s not derived. Adlponltrlle
has not been examined for carclnogenldty, and the one teratogenlclty study
(Johannsen et a!., 1986) located did not find fetal effects at doses below
those that caused maternal toxldty.
0071d -25- 11/17/87
-------
9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The toxldty of adlponltrUe was discussed 1n Chapter 6. The only data
potentially suitable for the derivation of an RQ are summarized In Table
9-1. In the 2-year rat study (Svlrbely and Floyd, 1964), advanced adrenal
degeneration was observed In female rats provided with ad1pon1tr1le In the
drinking water at 0.5 ppm. Due to reporting deficiencies as discussed 1n
Sections 6.1.2. and 8.2.2., these data are not used to estimate an RQ
(Table 9-2).
9.2. BASED ON CARCINOGENICITY
Data were not located regarding the carclnogenldty of ad1pon1tr1le 1n
humans or animals and the compound was assigned to EPA Group D, not classi-
fiable as to human carclnogenldty. Hazard ranking based on carclnogen-
Iclty, therefore. Is not possible.
OOVld -26- 11/17/87
-------
TABLE 9-1
Oral Toxldty Summary for AdlponHrlle Using Female Wlstar Ratsa»b
Average Vehicle/ Transformed Equivalent
Weight Physical Exposure Animal Dosec Human Dose^
(kg) State (mg/kg/day) (mg/kg/day)
Response
0..356
drinking
water
0.5 ppm In 0.07
the drinking
water for
2 years
0.01 advanced
adrenal
degeneration
aSo.urce: Svlrbely and Floyd, 1964; NIOSH, 1978
^Number of animals at start of experiment and purity of compound were not
reported.^
cCalculated by multiplying the 0.5 ppm drinking water level by 0.049
I/day, the reference water Intake for a 0.35 kg rat (U.S. EPA, 1985) and
by dividing by the rat body weight.
^Calculated by multiplying the animal transformed dose by the cube root of
the ratio' of" the animal body weight to the reference human body weight
(70 kg).
Reference rat body weight (U.S. EPA, 1985)
0071d
-27-
06/25/87
-------
TABLE 9-2
AdlponHMle
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route:
Dose*:
Effect:
Reference:
Data are Insufficient to evaluate an RQ.
RVd:
RVe:
Composite Score:
RQ:
'Equivalent human dose
0071d -28- 11/17/87
-------
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Bureau of State Services, Robert A. Taft Sanitary Engineering Center.
p. 100. (Cited 1n NIOSH, 1978)
Swann, R.L., D.A. Laskowskl, P.J. McCall, K. Vander Kuy and H.J. Dlshburger.
1983. A rapid method for the estimation of the environmental parameters
octanol/water partition coefficient, soil sorptlon constant, water to air
ratlio and water solubility. Res. Rev. 85: 17-28.
Tan1i1, H. and K. Hashimoto. 1985. Structure-acute toxlclty relationship of
dlnUrlles 1n mice. Arch. Toxlcol. 57(2): 88-93.
Tullar, P.E. 1947. Final report on the pharmacology and toxicology of
acrylonltrlle and acrylon. Kalusowskl Memorial Research Laboratories,
George Washington University.
0071d -33- 11/18/87
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U.S. EPA. 1980. Guidelines and Methodology Used In the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Criteria
Documents. Federal Register. 45(231): 49347-49357.
U.S. EPA. 1984. Methodology and Guidelines for Reportable Quantity
Determinations Based on Chronic Toxlclty Data. Prepared by the Office of
Health and Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response,
Washington, DC.
U.S. EPA. 1985. Reference Values for Risk Assessment. Prepared by the
Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH for the Office of Solid Waste, Washington,
DC.
U.S. EPA. 1986a. Methodology for Evaluating Potential Cardnogenlclty In
Support of Reportable Quantity Adjustments Pursuant to CERCLA Section 102.
Prepared by the Office of Health and Environmental Assessment, Cancer
Assessment Group for the Office of Solid Waste and Emergency Response,
Washington, DC.
U.S. EPA. 1986b. OHMTADS (Oil and Hazardous Materials Technical Assistance
Data Systems). On-Hne: February, 1987.
U.S. EPA. 1986c. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
0071d -34- 11/17/87
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U.S. EPA. 1987a. Graphical Exposure Modeling System (GEMS). CLOGP
computer program. Office of Toxic Substances, U.S. EPA, Washington, DC.
U.S. EPA. 19875. Graphical Exposure Modeling System (GEMS). Fate of Atmo-
spheric Pollutants (FAP). Office of Toxic Substances, U.S. EPA, Washington,
DC.
Zeller, H.V., H.T. Hofmann, A.M. Thless and W. Hey. 1969. Toxlclty of
nUMles. Zentralbl. ArbeHsmed. ArbeUsschutz. 19: 225-238. (CUed 1n
NIOSH, 1978)
0071d -35- 11/17/87
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APPENDIX A
LITERATURE SEARCHED
This HEED 1s based on data Identified by computerized literature
searches of the following:
TSCATS
CASR online (U.S. EPA Chemical Activities Status Report)
TOXLINE
TOXBACK 76
TOXBACK 65
RTECS
OHM TADS
STORET
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
These searches were conducted In February, 1987. In addition, hand searches
were made of Chemical Abstracts (Collective Indices J5-9), and the following
secondary sources should be reviewed:
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986. Documentation of the Threshold L1mVt Values and Biological
Exposure Indices, 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986-1987. TLVs: Threshold Limit Values for Chemical Substances In
the Work Environment adopted by ACGIH with Intended Changes for
1986-1987. Cincinnati, OH. Ill p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2A. John Wiley and
Sons, NY. 2878 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 28. John Wiley and
Sons, NY. p. 2879-3816.
Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John Wiley and
Sons, NY. p. 3817-5112.
007 Id
-36-
09/14/87
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Grayson, H. and D. Eckroth, Ed. 1978-1984. Klrk-Othmer Encyclo-
pedia of Chemical Technology, 3rd ed. John WHey and Sons, NY. 23
Volumes. ^
Hamilton, A. and H.L.'. Hardy. 1974. Industrial Toxicology, 3rd ed.
Publishing Sciences Group, Inc., Littleton, MA. 575 p.
IARC (International Agency for Research on Cancer). IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to
Humans. WHO, IARC, Lyons, France.
Jaber, H.M., W.R. Mabey, A.T. Lieu, T.W. Chou and H.L. Johnson.
1984. Data acquisition for environmental transport and fate
screening for compounds of Interest to the Office of Solid Waste.
SRI International, Menlo Park, CA. EPA 600/6-84-010. NTIS
PB84-243906.
NTP (National Toxicology Program). 1986. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
Status.
Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th
ed. Van Nostrand Relnhold Co., NY.
SRI (Stanford Research Institute). 1986. Directory of Chemical
Producers. Menlo Park, CA.
U.S. EPA. 1986. Report on Status Report 1n the Special Review
Program, Registration Standards Program and the Data Call In
Programs. Registration Standards and the Data Call 1n Programs.
Office of Pesticide Programs, Washington, DC.
U.S. EPA. 1985. CSB Existing Chemical Assessment Tracking System.
Name and CAS Number Ordered Indexes. Office of Toxic Substances,
Washington. DC.
USITC (U.S. International Trade Commission). 1985. Synthetic
Organic Chemicals. U.S. Production and Sales, 1984, USITC Publ.
1422, Washington. DC.
Verschueren, K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Relnhold Co., NY.
Wlndholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co.,
Inc., Rahway, NJ.
Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
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In addition, approximately 30 compendia of aquatic toxiclty data were
reviewed, Including the following:
Battelle's Columbus Laboratories. 1971. Water Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data from the Literature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Oohnson, W.H. and H.T. Flnley. 1980. Handbook of Acute Toxldty
of Chemicals to Fish and Aquatic Invertebrates. Summaries of
Toxldty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, Fish and Wildlife
Serv. Res. Publ. 137, Washington, DC.
HcKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency of California, State Water
Quality Control Board. Publ. No. 3-A.
Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington, DC. PB-269605.
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
EPA, Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876.
0071d -38- 09/14/87
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o
o
APPENDIX B
Summary Table for Adlponltrlle
Species
Exposure
Effect
RfD or qj*
Reference
I
01
Inhalation Exposure
Subchrontc
Chronic
Carclnogentclty
Oral Exposure
Subchronlc
ID
ID
ID
ID
Chronic
ID
Carctnogenlclty
ID
REPORTABLE QUANTITIES
Based on Chronic Toxlctty:
Based on Carclnogenlclty:
ID
ID
oo
ID = Insufficient Data
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