[Federal Register Volume 64, Number 43 (Friday, March 5, 1999)]
[Proposed Rules]
[Pages 10597-10604]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-5495]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 372

[OPPTS-400137; FRL-6054-2]
RIN 2070-AC00


Acetonitrile; Community Right-to-Know Toxic Chemical Release 
Reporting

AGENCY: Environmental Protection Agency (EPA).

ACTION: Denial of petition.

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SUMMARY: EPA is denying a petition to remove acetonitrile from the list 
of chemicals subject to the reporting requirements under section 313 of 
the Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA) 
and section 6607 of the Pollution Prevention Act of 1990 (PPA). EPA has 
reviewed the available data on this chemical and has determined that 
acetonitrile does not meet the deletion criterion of EPCRA section 
313(d)(3). Specifically, EPA is denying this petition because EPA's 
review of the petition and available information resulted in the 
conclusion that acetonitrile meets the listing criteria of EPCRA 
section 313(d)(2)(B) and (d)(2)(C) due to its potential to cause 
neurotoxicity and death in humans and its contribution to the formation 
of ozone in the environment, which causes adverse human health and 
environmental effects.

FOR FURTHER INFORMATION CONTACT: Daniel R. Bushman, Petitions 
Coordinator, 202-260-3882 or e-mail: [email protected], for 
specific information regarding this document or for further information 
on EPCRA section 313, contact the Emergency Planning and Community 
Right-to-Know Information Hotline, Environmental Protection Agency, 
Mail Code 5101, 401 M St., SW., Washington, DC 20460, Toll free: 1-800-
535-0202, in Virginia and Alaska: 703-412-9877, or Toll free TDD: 1-
800-553-7672.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does This Document Apply To Me?

    This document does not make any changes to existing regulations. 
However, you may be interested in this document if you manufacture, 
process, or otherwise use acetonitrile. Potentially interested 
categories and entities may include, but are not limited to the 
following:


[[Page 10598]]



------------------------------------------------------------------------
                                               Examples of Potentially
                 Category                        Interested Entities
------------------------------------------------------------------------
Chemical manufacturers                      Chemical manufacturers that
                                             manufacture acetonitrile,
                                             use acetonitrile as a
                                             chemical intermediate, or
                                             use acetonitrile in the
                                             manufacturing or processing
                                             of pharmaceuticals,
                                             agriculture chemicals,
                                             butadiene, isoprene and
                                             specialty chemicals and
                                             products (e.g., new high
                                             density batteries)
------------------------------------------------------------------------
Chemical processors and users               Facilities that use
                                             acetonitrile as a process
                                             or reaction solvent
------------------------------------------------------------------------

    This table is not intended to be exhaustive, but rather provides a 
guide for readers regarding entities likely to be interested in this 
document. Other types of entities not listed in this table may also be 
interested in this document. Additional businesses that may be 
interested in this document are those covered under 40 CFR part 372, 
subpart B. If you have any questions regarding whether a particular 
entity is covered by this section of the CFR, consult the technical 
person listed in the ``FOR FURTHER INFORMATION CONTACT'' section.

B. How Can I Get Additional Information or Copies of This Document or 
Other Support Documents?

    1. Electronically. You may obtain electronic copies of this 
document from the EPA Home Page at http://www.epa.gov/. On the Home 
Page select ``Laws and Regulations'' and then look up the entry for 
this document under the ``Federal Register - Environmental Documents.'' 
You can also go directly to the ``Federal Register'' listings at http:/
/www.epa.gov/fedrgstr/.
    2. In person or by phone. If you have any questions or need 
additional information about this action, please contact the technical 
person identified in the ``FOR FURTHER INFORMATION CONTACT'' section. 
In addition, the official record for this document, including the 
public version, has been established under docket control number OPPTS-
400137. This record includes not only the documents physically 
contained in the docket, but all of the documents included as 
references in those documents (including the references cited in Unit 
VII. of this preamble). A public version of this record, which does not 
include any information claimed as Confidential Business Information 
(CBI), is available for inspection from 12 noon to 4:00 p.m., Monday 
through Friday, excluding legal holidays. The official record is 
located in the TSCA Nonconfidential Information Center, Rm. NE-B607, 
401 M St., SW., Washington, DC. The TSCA Nonconfidential Information 
Center telephone number is 202-260-7099.

II. Introduction

A. Statutory Authority

    This action is taken under sections 313(d) and (e)(1) of EPCRA, 42 
U.S.C. 11023. EPCRA is also referred to as Title III of the Superfund 
Amendments and Reauthorization Act of 1986 (SARA) (Pub. L. 99-499).

B. Background

    Section 313 of EPCRA requires certain facilities manufacturing, 
processing, or otherwise using listed toxic chemicals in amounts above 
reporting threshold levels, to report their environmental releases of 
such chemicals annually. These facilities must also report pollution 
prevention and recycling data for such chemicals, pursuant to section 
6607 of the PPA, 42 U.S.C. 13106. EPCRA section 313 established an 
initial list of toxic chemicals that comprised more than 300 chemicals 
and 20 chemical categories. Acetonitrile was included on the initial 
list. Section 313(d) authorizes EPA to add or delete chemicals from the 
list and sets forth criteria for these actions. EPA has added and 
deleted chemicals from the original statutory list. Under section 
313(e)(1), any person may petition EPA to add chemicals to or delete 
chemicals from the list. Pursuant to EPCRA section 313(e)(1), EPA must 
respond to petitions within 180 days, either by initiating a rulemaking 
or by publishing an explanation of why the petition is denied.
    EPCRA section 313(d)(2) states that a chemical may be listed if any 
of the listing criteria are met. Therefore, in order to add a chemical, 
EPA must demonstrate that at least one criterion is met, but does not 
need to examine whether all other criteria are also met. Conversely, in 
order to remove a chemical from the list, EPA must demonstrate that 
none of the criteria are met.
    EPA issued a statement of petition policy and guidance in the 
Federal Register of February 4, 1987 (52 FR 3479) to provide guidance 
regarding the recommended content and format for submitting petitions. 
On May 23, 1991 (56 FR 23703), EPA issued guidance regarding the 
recommended content of petitions to delete individual members of the 
section 313 metal compounds categories. EPA has also published in the 
Federal Register of November 30, 1994 (59 FR 61432) (FRL-4922-2) a 
statement clarifying its interpretation of the section 313(d)(2) and 
(d)(3) criteria for modifying the section 313 list of toxic chemicals.

III. Description of Petition and Regulatory Status of Acetonitrile

    Acetonitrile is on the list of toxic chemicals subject to the 
annual release reporting requirements of EPCRA section 313 and PPA 
section 6607. Acetonitrile was among the list of chemicals placed on 
the EPCRA section 313 list by Congress. Acetonitrile is listed under 
the Clean Air Act (CAA) as a volatile organic compound (VOC) and a 
hazardous air pollutant. Acetonitrile is also on the Hazardous Waste 
Constituents List under the Resource Conservation and Recovery Act 
(RCRA).
    On February 4, 1998, EPA received a petition from BP Chemicals Inc. 
(BP) and GNI Chemicals Corporation (GNICC) to delete acetonitrile from 
the list of chemicals reportable under EPCRA section 313 and PPA 
section 6607. Specifically, BP and GNICC believe that acetonitrile 
meets all of the criteria for delisting under EPCRA section 313(d)(3) 
because: (1) ``acetonitrile is not known to cause and cannot be 
reasonably anticipated to cause significant adverse human health 
effects at concentrations that are reasonably likely to exist beyond 
facility boundaries as a result of continuous or frequently recurring 
releases''; (2) ``at exposures likely to be found at facility fence 
lines, acetonitrile is not known to cause and cannot be reasonably 
anticipated to cause cancer or teratogenic effects of serious 
irreversible reproductive dysfunction, neurological disorders, 
heritable genetic mutations, or other chronic health effects''; and (3) 
``acetonitrile is not known to cause or reasonably likely to cause 
significant adverse effects to the environment because it is not toxic 
or persistent and does not readily bioaccumulate.'' In addition, the 
petitioners believe that EPA's policy requiring that a chemical not be 
a VOC ``. . . is irrelevant and should not be considered for this 
delisting petition.'' The petitioners argue for a revised 
interpretation of the EPCRA section 313 VOC policy, contending that EPA 
does not have the statutory authority to list chemicals based upon 
their status as a VOC. EPA has stated in past Federal Register 
documents (54 FR 4072, January 27, 1989; 54 FR 10668, March 15, 1989; 
59 FR 49888, September 30, 1994; 60 FR 31643, FRL-4952-7, June 16, 
1995; and 63 FR 15195, FRL-5752-6, March 30, 1998) that VOCs meet the 
criteria for

[[Page 10599]]

listing under EPCRA section 313 due to the fact that VOCs contribute to 
tropospheric ozone. Notwithstanding the petitioners' belief that a 
chemical's VOC status is irrelevant to EPCRA section 313 listing, the 
petitioners have submitted a petition to EPA's Office of Air and 
Radiation (OAR) to add acetonitrile to the list of ``negligibly 
photoreactive chemicals'' under 40 CFR 51.100(s)(1).

IV. EPA's Technical Review of Acetonitrile

    The technical review of the petition to delete acetonitrile from 
TRI reporting requirements (Ref. 1) included an analysis of the 
chemistry (Ref. 2), toxicology (including metabolism and absorption, 
health effects, and ecological effects) (Ref. 3), environmental fate, 
and exposure (Ref. 4) data known for acetonitrile. A more detailed 
discussion for each related topic can be found in EPA's technical 
reports (Refs. 2, 3, 4, 5, and 6) and the studies contained and 
referenced in the docket.

A. Chemistry and Use

    Acetonitrile, also known as cyanomethane and methyl cyanide, is a 
colorless, volatile, flammable liquid (boiling point = 81.6  deg.C; 
flash point = 12.8  deg.C) with an ether-like odor. It is completely 
miscible with water and many organic solvents. Its high dielectric 
constant and dipole moment make it an excellent solvent for both 
inorganic and organic compounds, including polymers. Acetonitrile forms 
a low boiling azeotrope with other organic solvents. The impurities 
present in commercial grade acetonitrile are water, unsaturated 
nitriles, toluene, aldehydes, and amines. Acetonitrile is a relatively 
inert material but produces hydrogen cyanide when heated to 
decomposition or reacted with acids or oxidizing agents.
    Acetonitrile is produced commercially as a by-product during the 
manufacture of acrylonitrile by high temperature catalytic oxidation of 
propylene in the presence of ammonia (the Sohio process of propylene 
ammoxidation). Acetonitrile and hydrogen cyanide are principal by-
products of the process. The ratio of acetonitrile to acrylonitrile 
produced is typically 1:35 (Refs. 2, 6, and 7). Reported production of 
acetonitrile in the United States (US) in 1993 was 17,859,000 kilograms 
(kg) (Ref. 6).
    Acetonitrile is primarily used as: a reaction solvent in the 
production of pharmaceuticals; an analytical instrumentation/extraction 
solvent; an extraction solvent in extracting butadiene and isoprene 
from reaction steams; and a solvent for the manufacture and formulation 
of agricultural chemicals. Acetonitrile is also used for extracting 
fatty acids (e.g., from fish liver oils and other animal and vegetable 
oils) and in refining copper, dyeing textiles, recrystallizing 
steroids, and other extraction applications. Acetonitrile is also used 
as a chemical intermediate for many types of organic compounds (Refs. 
2, 6, and 7).

B. Metabolism and Absorption

    Absorption of acetonitrile occurs after oral, dermal, or inhalation 
exposure. Although no quantitative absorption data were found for oral 
exposure, signs of acute toxicity, observed after oral exposure, 
indicate that absorption occurs. In humans, 74 percent of acetonitrile 
was absorbed orally from cigarette smoke held in the mouth for 2 
seconds; when inhaled into the lungs, absorption increased to 91 
percent. Dogs exposed by inhalation to 16,000 parts per million (ppm) 
of acetonitrile for 4 hours appeared to reach steady-state blood 
concentrations within 3 to 4 hours (Ref. 3).
    Acetonitrile and its metabolites are transported throughout the 
body in the blood. After oral or inhalation exposures in experimental 
animals, acetonitrile or its metabolites were found in the brain, 
heart, liver, kidney, spleen, blood, stomach, and muscle. After a fatal 
human inhalation exposure, metabolites were found in the brain, heart, 
liver, kidney, spleen, blood, stomach, and muscle, as well as skin, 
lungs, intestine, testes, and urine (Ref. 3).
    Acetonitrile is metabolized to hydrogen cyanide and thiocyanate, 
which are responsible for the toxic effects of the chemical. Metabolism 
is mediated by the cytochrome P-450 system (Refs. 3 and 8).
    Acetonitrile is excreted as acetonitrile in expired air and as 
acetonitrile or its metabolite in urine. Urinary excretion of the 
thiocyanate metabolite following oral exposure in rats ranged from 11.8 
percent to 37 percent of the administered dose. Acetonitrile 
concentrations of 2.2 to 20 micrograms/100 milliliters (ml) of urine 
have been found in heavy smokers (Ref. 3).

C. Toxicity Evaluation

    1. Acute effects. The only available data regarding acute effects 
of acetonitrile in humans are from reports of accidental poisonings 
resulting from acute exposures. It is likely that these acute exposures 
were at concentrations in excess of 500 ppm (Refs. 3 and 8). At these 
concentrations, acetonitrile affects the central nervous system 
producing excess salivation, nausea, vomiting, anxiety, confusion, 
hyperpnea, dyspnea, rapid pulse, unconsciousness, and convulsions, 
followed by death from respiratory failure. These effects are 
consistent with those following inorganic cyanide exposure and with 
effects seen with other aliphatic nitriles, suggesting that the toxic 
effects of acetonitrile may be correlated with the metabolic release of 
cyanide. Acute effects of acetonitrile in humans at concentrations less 
than 500 ppm consist of irritation of the mucous membranes. No other 
human data were available that allow characterization of acute toxicity 
at lower concentrations (Ref. 3).
    In animal studies, acetonitrile induced acute toxicity at 
relatively high inhalation exposures. In acute exposure inhalation 
toxicity studies, the LC50 (i.e., the concentration of a 
chemical that is lethal to 50 percent of the test organisms) ranges 
from 2,300 to 5,700 ppm in mice and from 7,500 to 16,000 ppm in rats 
(Refs. 3 and 8). Mice and guinea pigs appear to be more sensitive than 
rats for acute toxicity by the oral route. The lowest LD50 
(i.e., the dose of a chemical that is lethal to 50 percent of the test 
organisms) values in older rats ranged from 1,300 to 6,700 milligrams 
per kilogram (mg/kg); young rats appeared to be more sensitive with a 
LD50 value of 157 mg/kg (Refs. 3 and 8). A LD50 
range of 390 to 3,900 mg/kg was reported by the dermal route in rabbits 
(Ref. 3). Non-lethal effects at 500 ppm in mice include respiratory 
effects, convulsions, and eye and lung irritation (Refs. 3 and 8).
    2. Chronic effects--i. Carcinogenicity. EPA has identified no human 
data in the literature on the cancer effects of acetonitrile. The 
carcinogenicity of acetonitrile has been studied in experimental 
animals by the National Toxicological Program (NTP) in F344/N rats and 
B6C3F1 mice in 2-year inhalation studies (Ref. 9). Under the conditions 
of the 2-year inhalation studies, there was equivocal evidence of 
carcinogenic activity of acetonitrile in male F344/N rats based on 
marginally increased incidences of hepatocellular adenoma and carcinoma 
in the high-dose (400 ppm) group. There was no evidence of carcinogenic 
activity of acetonitrile in female F344/N rats, or male and female 
B6C3F1 mice exposed to any concentration of acetonitrile (Refs. 3 and 
9).
    No evidence of carcinogenicity of structurally related chemicals 
has been identified. Acrylonitrile is carcinogenic but it is not a good 
analogue for acetonitrile because acrylonitrile contains a double bond 
and is

[[Page 10600]]

genotoxic. Acetonitrile is biotransformed via a cytochrome P450 
monoxygenated system to cyanohydrin, which then decomposes slowly to 
hydrogen cyanide and formaldehyde and subsequently is detoxified. Based 
on the results of the NTP studies, there is insufficient evidence to 
conclude that acetonitrile may or has the potential to cause cancer in 
humans (Refs. 3 and 9).
    ii. Mutagenicity. Positive results were obtained in some in vitro 
studies that would present a concern, albeit weak, for mutagenicity. 
However, due to the lack of evidence for effects in the mammalian gonad 
in vivo, either in mutagenicity studies or in reproductive/teratology 
studies, there is no basis for concern for potential heritable gene or 
chromosomal mutagenicity of acetonitrile (Ref. 3).
    iii. Developmental toxicity. Information in humans reviewed by the 
Agency regarding the developmental toxicity of acetonitrile is limited 
to a study of laboratory workers and pregnancy outcomes, in which a 
slightly elevated, although non-significant, odds ratio was reported 
for congenital malformations for women exposed to acetonitrile. Seven 
cases of spontaneous abortion were noted for women exposed to 
acetonitrile out of a total of 206 cases reported (535 women were 
involved in the study). This study was confounded by worker exposure to 
other chemicals (Refs. 3, 10, and 11).
    The developmental toxicity of acetonitrile has been evaluated in 
rats, rabbits, and hamsters. Overall, evidence for developmental 
toxicity is weak. Oral and inhalation studies in rats and rabbits have 
shown no signs of developmental toxicity at doses that did not produce 
excessive maternal mortality. The only data available on hamsters 
utilized short durations (60 minutes on day 8 of gestation) to high 
concentrations of acetonitrile vapor or by gavage on day 8 of 
gestation. There were some signs of developmental toxicity in hamsters 
by both routes at dose levels that did not produce overt maternal 
mortality; however, these studies are difficult to interpret for human 
risk assessment because: (1) Very high doses were used, and (2) no 
developmental effects have been observed in other species at doses 
below those which produced extreme maternal toxicity (10 percent 
mortality or greater).
    iv. Reproductive toxicity. Since no definitive two-generation 
reproductive toxicity or fertility studies with acetonitrile have been 
identified, information in animals is limited to developmental toxicity 
studies in which only some reproductive parameters were assessed. 
Moreover, the data appear to be equivocal. For example, there were no 
changes in pregnancy rates or resorptions in rats exposed to doses as 
high as 500 milligram/kilogram/day (mg/kg/day) (Ref. 14). However, in 
another study, significant increases in post-implantation losses and 
early resorptions in rats exposed to 275 mg/kg/day acetonitrile were 
observed (Ref. 15). In other studies, acetonitrile was not shown to 
produce any effects on: The testis, epididymis, and cauda epididymis 
weights; sperm motility, number, or morphology; or the average estrous 
cycle length, frequency of estrous stages, or terminal female body 
weight (Ref. 16). In conclusion, available animal studies do not fully 
characterize the reproductive toxicity of acetonitrile. Although some 
reproductive parameters appeared to be unaffected in some studies, none 
of the studies evaluated the reproductive performance or reproductive 
system effect of offspring exposed in utero. Therefore, there is not 
sufficient information to fully characterize the potential for 
reproductive toxicity of acetonitrile (Ref. 3).
    v. Neurotoxicity. In humans, the nervous system is a major target 
for acetonitrile toxicity. In reports of accidental poisonings in 
humans exposed to presumed high concentrations of acetonitrile, signs 
of salivation, nausea, vomiting, anxiety, confusion, hyperpnea, 
dyspnea, rapid pulse, unconsciousness, and convulsions followed by 
death from respiratory failure were observed (Refs. 3 and 8). No 
information was found on the adverse neurotoxic effects of long-term 
human exposure to acetonitrile. Brief references appear in the 
Hazardous Substances Data Bank (HSDB) (Ref. 17) suggesting that chronic 
exposure to acetonitrile may cause headache, anorexia, dizziness, and 
weakness, but no additional information on neurotoxicity was provided 
in support of these statements (Ref. 3).
    Neurotoxicity studies indicate that subchronic exposures 
(subchronic is defined by EPA's Integrated Risk Information System 
(IRIS) as multiple or continual exposures occurring usually over three 
months (Ref. 18)) to acetonitrile can cause serious and irreversible 
health effects in animals. Monkeys appeared to be more sensitive than 
rats to the neurotoxic effects of acetonitrile with signs of 
neurotoxicity, such as brain hemorrhages, hyper-excitability, and over-
extension reflexes, observed at or near 350 ppm. Subchronic inhalation 
studies have been conducted on rats, monkeys, and dogs (Ref. 19). 
Wistar rats (15 per sex per exposure level) were exposed to 0, 166, 
330, and 655 ppm of acetonitrile for 7 hours a day for 5 days a week 
for 90 days. One out of five rat brains examined in the 655 ppm 
exposure group had focal cerebral hemorrhage. This effect was similar 
to that reported in Rhesus monkeys that were exposed to acetonitrile at 
330, 660, and 2,510 ppm (approximately 28, 55, and 210 mg/kg/day) for 7 
hours a day for up to 99 days. The monkey exposed to 2,510 ppm died 
with severe pulmonary effects after the second day of exposure, and the 
two monkeys exposed to 660 ppm died after 23 and 51 days, with severe 
brain hemorrhage and pulmonary abnormalities. The monkey exposed to 330 
ppm acetonitrile exhibited unusual reflexes and excitability toward the 
end of the study. On gross examination, brain hemorrhage was also found 
in the monkey exposed to 330 ppm. Brain hemorrhages, hyper-
excitability, and over-extension reflexes were also observed in three 
monkeys exposed to 350 ppm (approximately 30 mg/kg/day) of acetonitrile 
(Ref. 3). There were no signs of neurotoxicity reported for dogs.
    In an embryo-fetal toxicity and teratogenicity study of 
acetonitrile, signs of neurotoxicity were found when acetonitrile was 
tested in the bred female New Zealand white rabbits receiving 2, 15, or 
30 mg/kg/day by oral gavage (Ref. 20). Observations of dams at the high 
dose level showed neurological signs of ataxia, decreased motor 
activity, bradypnea, dyspnea, and impaired or lost righting reflex 
(Refs. 3 and 8).
    Other laboratory studies also show that inhalation exposure to 
acetonitrile can adversely affect the nervous system of animals. In a 
report on acute exposure inhalation toxicity in rats submitted by E.I. 
du Pont de Nemours and Company (Refs. 3 and 21), toxicity was evaluated 
in groups of 10 male Sprague-Dawley rats exposed to acetonitrile for 4 
hour periods. Dose levels and number of mortalities were not reported. 
Mortality was observed up to 24 hours post-exposure and the 
LC50 was determined to be 17,100 ppm. Clinical signs of 
neurotoxicity during exposure included irregular respiration, hyperemia 
followed by pale ears, face-pawing, and lack of coordination in all 
animals and unreactivity in decedents (Ref. 3).
    In summary, subchronic exposures to acetonitrile can cause serious 
and irreversible health effects in animals at concentrations of 
acetonitrile at or near 350 ppm (approximately 30 mg/kg/day). 
Developmental studies in animals and acute inhalation studies in 
animals and exposures to humans provide additional support for the 
potential for acetonitrile

[[Page 10601]]

to cause severe neurological effects and even death in humans.
    vi. Other chronic effects. Subchronic exposures of acetonitrile at 
concentrations ranging from 100 to 2,510 ppm (in several species) 
resulted in lung congestion and edema; increases in liver and kidney 
weight with swelling of the proximal and convulated tubules; 
cytoplasmic vacuolation of hepatocytes; brain hemorrhages; decreases in 
hemoglobin and hematocrit; severe eye irritation; decreases in thymus 
weight, increases in heart weight; and forestomach hyperplasia (Ref. 
3). In addition, immunotoxic effects, such as a dose-dependent 
significant decrease in hematocrit, hemoglobin, red blood cells (RBC), 
white blood cells (WBC), and B-lymphocyte function, were observed in 
mice following inhalation exposure to acetonitrile (Refs. 3 and 22). 
There is uncertainty regarding the biological significance of the 
increases in relative liver weight, hepatic vacuolization, and some of 
the immunological changes observed after subchronic exposure since 
these effects were not seen following chronic dosing. It is possible 
that the lack of observed effects could be, however, the result of 
lower chronic exposure levels (Ref. 3). Chronic effects in rats and 
mice following chronic exposure to acetonitrile included increases in 
liver weights and forestomach lesions (Ref. 3). However, there is 
uncertainty regarding the biological significance of the forestomach 
lesions observed following inhalation exposure since oral exposure of 
acetonitrile as a result of the grooming of contaminated fur may also 
have been a contributing factor. Furthermore, it is difficult to assess 
the significance of the increases in liver weights without any 
information on the histopathological or functional changes (Ref. 3).
    vii. Toxicity related to ozone formation. Acetonitrile is currently 
considered a VOC and, as such, has the potential to contribute to the 
formation of ozone in the troposphere (i.e., the lower atmosphere). As 
EPA has previously stated, ozone can affect structure, function, 
metabolism, pulmonary defense against bacterial infection, and 
extrapulmonary effects (Ref. 23). Among these extrapulmonary effects 
are: (1) Cardiovascular effects; (2) reproductive and teratological 
effects; (3) central nervous system effects; (4) alterations in red 
blood cell morphology; (5) enzymatic activity; and (6) cytogenetic 
effects on circulating lymphocytes. Accordingly, EPA has concluded that 
acetonitrile, as a VOC, has the potential to cause these effects.
    3. Ecotoxicity. Acetonitrile is of low concern with respect to 
direct ecotoxicity based on measured data and Quantitative Structure 
Activity Relationship (QSAR) analysis. Acute acetonitrile toxicity for 
96-hour fish and 48-hour daphnid exposures were 1,100 to 1,640 
milligrams per liter (mg/L) (measured concentrations), and 4,900 mg/L, 
respectively (based on QSAR). Chronic acetonitrile toxicity for 21-day 
daphnid (reproduction) was greater than 200 mg/L (measured), and 470 
mg/L for fish (based on QSAR) (Refs. 3 and 24).
    Based on the limited number of laboratory studies conducted to 
date, the terrestrial toxicity of acetonitrile is low. No published 
experimental data are available for evaluating its bioaccummulation. 
Log bioconcentration factors for acetonitrile estimated using Lyman 
regression equations were -1.81 to 0.6 indicating no potential 
bioaccumulation (Refs. 3 and 25).
    As a VOC, acetonitrile contributes to the formation of ozone in the 
environment. As EPA has previously stated (Ref. 23), ozone's effects on 
green plants include injury to foliage, reductions in growth, losses in 
yield, alterations in reproductive capacity, and alterations in 
susceptibility to pests and pathogens. Based on known 
interrelationships of different components of ecosystems, such effects, 
if of sufficient magnitude, may potentially lead to irreversible 
changes of sweeping nature to ecosystems.

D. Acute Exposure Assessment

    Based on the results of animal studies, there are concerns for 
acute health effects associated with exposure to acetonitrile. Thus, 
pursuant to EPCRA section 313(d)(2)(A), EPA performed exposure 
assessments to determine whether acute health effects from acetonitrile 
would occur at concentrations reasonably likely to exist beyond the 
facility site boundaries as a result of continuous, or frequently 
recurring, releases. EPA's Toxic Release Inventory (TRI) release data 
were used to estimate acetonitrile exposures to the general population 
near the release sites. The fugitive emissions to air were the largest 
contributors to these exposures. Potential exposures due to water 
releases were also estimated.
    1. Ambient air exposure assessment. Acetonitrile releases reported 
to TRI for 1995 and 1996 were used for the exposure assessment. 
Significant changes occurred between 1995 and 1996 with a greater than 
50 percent increase in releases of acetonitrile occurring at the 
highest air releasing site. Short-term (acute exposure) air 
concentrations were estimated using the SCREEN3 and ISCST3 models. 
Among the ten top sites chosen for modeling, a plant in Memphis, 
Tennessee had the highest air releases for both 1995 and 1996, 
dominated by fugitive air releases. Using the SCREEN3 model, the 
estimated air concentrations of acetonitrile beyond facility site 
boundaries at sites with fugitive air emissions greater than 10,000 
kilograms per year (kg/year) for 1995 and 1996 ranged from 4 to 36 
milligrams per cubic meter (mg/m3) (2.4 to 22 ppm) for 1 
hour, and 1 to 14 mg/m3 (0.9 to 8 ppm) for 24 hours, 
respectively.
    Based on the 1995 data and the ISCST3 model, the 1 and 24 hours 
short-term (acute exposure) acetonitrile concentrations in air, at 100 
meters distance from the source center of highest release, in the 
direction of highest concentration, are 16 and 2.3 mg/m3 (or 
9.52 and 1.37 ppm), respectively. Under the same model scenario, the 
1996 data gave an estimated 23 and 3.3 mg/m3 (or 13.5 and 
2.0 ppm) of acetonitrile concentrations in air for the 1 and 24 hour 
short-term exposure, respectively. Other air concentrations of 
acetonitrile for ten top facilities were also modeled and the estimated 
data are summarized in the General Sciences Corporation (GSC) modeling 
support for exposure assessment of acetonitrile (Ref. 26). The highest 
estimates were at those facilities with boundaries of approximately \1/
4\ mile (400 meters) from the site center or less (Refs. 4 and 26).
    The short-term air modeling was intended to represent acute 
exposure scenarios for populations spending time in the surroundings of 
facilities, outside site boundaries, but not necessarily resident. 
However, the results should be considered ``what-if'' rather than 
established as high end, because of factors such as variability in 
meteorology, and uncertainties in release quantities and durations. It 
is important to recognize that the ambient air concentration estimates 
use the assumption that releases continue over 365 days per year, 24 
hours per day at a constant rate. If annual releases occurred over 
shorter time periods, the corresponding short-term concentrations would 
be higher than those presented in the exposure assessment report. For 
example, if a facility releases approximately 10,000 kilograms of 
fugitive air releases per year over 30 days per year rather than 365 
days per year, then the upper limit of the screening range would exceed 
40 mg/m3, exceeding the value (36 mg/m3) shown 
for the highest release of more than 200,000 pounds per year. The

[[Page 10602]]

concentrations estimated show a screening range (using SCREEN3 model at 
a distance of 100 meters from the source center) and provide key 
results for selected sites. The data also shows maximum results beyond 
facility boundaries, using distances from site centers indicated by 
site layouts in the industry report (Refs. 4 and 27). These estimated 
values of acetonitrile in air are well below those concentration levels 
that produced acute effects in animal studies.
    2. Drinking water exposure assessment. Both direct and indirect 
releases to water were modeled using river reach harmonic mean flows 
for long-term and low flow data for short term. The REACHSCAN model was 
used to estimate the contamination of acetonitrile at drinking water 
utility intakes downstream from facilities releasing to water or making 
offsite transfers to waste-water treatment facilities. While some 
locations have low to mid parts per billion (ppb) levels, few intake 
locations of drinking water utilities have levels above 1 ppb (1 
microgram per liter). Based on 1995 TRI water release data, the highest 
exposure potential with drinking water intakes downstream were found 
for an indirect discharger in Pennsylvania, with annual concentration 
of 100 ppb and the short-term concentration of 350 ppb. However, that 
facility changed reporting from ``transfers to publicly owned treatment 
works (POTWs)'' to ``other offsite transfers'' for 1996; several other 
facilities also reduced or ended water releases or transfers to POTWs 
for 1996. The highest drinking water utility intake level found using 
1996 TRI data was approximately 2 ppb for low flow conditions, and 0.7 
ppb for typical conditions (downstream from a facility in Rock Hill, 
South Carolina). Several fresh-water locations without verified 
drinking water intakes have mid ppb (e.g., 200 ppb) estimated levels 
(Ref. 4).
    Some potential drinking water situations have not been quantified 
due to lack of data. For example, offsite transfers to POTWs include 
several sites in Puerto Rico, for which surface water data have not 
been retrieved. Underground injection wells also may form sources of 
contamination to drinking water wells in ground water, in the event of 
containment failure (Ref. 4). Atmospheric deposition of acetonitrile 
can also contribute to surface water contamination near facilities 
releasing to air (Ref. 4).
    3. Exposure evaluation. EPA's exposure assessment attempted to 
determine whether, as a result of releases from EPCRA section 313 
covered facilities, acetonitrile is known to cause or can reasonably be 
anticipated to cause significant adverse acute human health effects at 
concentration levels that are reasonably likely to exist beyond 
facility site boundaries as a result of continuous or frequently 
recurring releases. The modeling used released data reported under 
EPCRA section 313 and included both conservative and non-conservative 
assumptions concerning releases and facility site information. Non-
conservative assumptions included the assumption that EPCRA section 313 
reported releases are spread over 365 days per year and 24 hours per 
day. Given a shorter release period, estimated exposures could be 
significantly higher. Under the conditions modeled here EPA believes it 
is unlikely that concentrations of acetonitrile sufficient to cause 
acute toxicity will exist beyond a facility's boundaries as a result of 
continuous, or frequently reoccurring, releases. This is because the 
exposure concentrations that resulted from the modeling (9.52 and 1.37 
ppm) are below the concentrations that have caused acute toxicity in 
laboratory animals (500 ppm).

V. Summary of Technical Review

    There is sufficient evidence to support a high level of concern for 
potential neurotoxicity and death following repeated exposure to 
acetonitrile. This comes from several lines of evidence. In repeated 
dose (subchronic) inhalation experiments in monkeys, neurological signs 
of toxicity (brain hemorrhages, hyper-excitability, and over-extension 
reflexes) and death were observed at concentrations of acetonitrile at 
or near 350 ppm (approximately 30 mg/kg/day). For effects seen in both 
the monkey and rabbit studies, the neurotoxicity risk assessment 
guidelines recommend that these endpoints be included as examples of 
possible indicators of an adverse neurotoxic effect (Ref. 28). 
Structural or neuropathological endpoints could include hemorrhage in 
nerve tissue. Neurological endpoints could include increases or 
decreases in motor activity and changes in motor coordination. When 
pregnant rabbits were exposed to the same amount of acetonitrile during 
gestation, signs of neurotoxicity (including ataxia (muscle 
incoordination), decreased motor activity, bradypnea (abnormally slow 
breathing), dyspnea (labored or difficult breathing), and impaired or 
lost righting reflex) and an increased incidence of maternal mortality 
were also observed. These effects are consistent with acute inhalation 
exposures to high concentrations of acetonitrile in humans in which the 
central nervous system is widely affected (exhibiting signs of 
salivation, nausea, vomiting, anxiety, confusion, hyperpnea, dyspnea, 
rapid pulse, unconsciousness, and convulsions followed by death from 
respiratory failure). The neurological effects seen in the 
developmental and acute studies provide supplemental support for the 
determination that acetonitrile can reasonably be anticipated to cause 
chronic neurotoxicity. These results are also consistent with those 
effects seen with inorganic cyanide and other aliphatic nitriles 
exposures, suggesting that the toxic effects of acetonitrile may be 
correlated with the metabolic release of cyanide.
    Acetonitrile is currently considered a VOC and, as such, it 
contributes to the formation of tropospheric ozone which, as EPA has 
previously determined, can cause significant adverse effects to human 
health and the environment (Ref. 23).
    The main effects of acetonitrile reported in humans (from 
accidental poisoning) are likely due to acute inhalation exposures to 
high concentrations. Based on the results of animal studies, there are 
concerns for acute health effects associated with exposure to 
acetonitrile. However, based on EPA's exposure assessment, it is 
unlikely that concentrations of acetonitrile, sufficient to cause acute 
toxicity, will exist beyond a facility's boundaries as a result of 
continuous, or frequently recurring, releases. There is not sufficient 
information to support a concern for carcinogenicity, mutagenicity, or 
reproductive toxicity. The case for developmental toxicity is weak. 
Some studies in rats produced no signs of developmental toxicity even 
in the presence of maternal toxicity. Other studies exhibited signs of 
developmental toxicity, however, in the presence of extreme maternal 
mortality. There is uncertainty regarding the biological significance 
of the increases in relative liver weight, hepatic vacuolization, and 
some of the immunological changes observed after subchronic exposure 
since these effects were not seen following chronic dosing. It is 
possible that the lack of observed effects could be, however, the 
result of lower chronic exposure levels. Acetonitrile is of low concern 
with respect to direct ecotoxicity based on measured data and QSAR 
analysis.

VI. Rationale for Denial

    EPA is denying the petition submitted by BP and GNICC to delete 
acetonitrile from the EPCRA section 313 list of toxic

[[Page 10603]]

chemicals. This denial is based on EPA's conclusion that acetonitrile 
can reasonably be anticipated to cause serious or irreversible chronic 
health effects in humans, including neurotoxicity and death. Chronic 
health effects may result after acute, subchronic, or chronic 
exposures. EPA determines whether an effect is best considered to be 
chronic by looking at a number of factors, among which is the length of 
time it takes for the effect to manifest and the extent to which it 
persists after exposure to the toxicant ends. Acute or subchronic 
exposure to acetonitrile can produce serious and irreversible health 
effects, including brain hemorrhages and death. In addition, acute or 
subchronic exposure to acetonitrile produce the following serious 
health effects: Hyper-excitability, over-extension reflexes, ataxia 
(muscle incoordination), decreased motor activity, bradypnea 
(abnormally slow breathing), dyspnea (labored or difficult breathing), 
and impaired or lost righting reflex. Many of these effects (e.g., 
over-extension reflexes and hyper excitability) manifest toward the end 
of the exposure period and are thus considered chronic effects. Data 
from animal studies indicate that neurotoxicity and death can occur at 
the relatively low dose of approximately 30 mg/kg/day. Based on these 
data, EPA considers acetonitrile to have moderately high to high 
chronic toxicity. Therefore, EPA has concluded that acetonitrile meets 
the listing criteria of EPCRA section 313 (d)(2)(B).
    EPA has concluded that acetonitrile meets the listing criteria of 
EPCRA section 313(d)(2)(B) and (d)(2)(C) due to it contributing to the 
formation of ozone. EPA has concluded that VOCs, such as acetonitrile, 
contribute to the formation of tropospheric ozone which is known to 
cause significant adverse effects to human health and the environment. 
EPA has previously stated that ozone meets the listing criteria of 
EPCRA section 313(d)(2)(B) and (d)(2)(C) (59 FR 61432, November 30, 
1994). EPA has stated in prior Federal Register notices (54 FR 4072, 
January 27, 1989; 54 FR 10668, March 15, 1989; 59 FR 49888, September 
30, 1994; 60 FR 31643, June 16, 1995; and 63 FR 15195, March 30, 1998) 
that, because VOCs contribute to the formation of tropospheric ozone, 
they meet the criteria for listing under EPCRA section 313. EPA has 
also stated (54 FR 4072, January 27, 1989 and 54 FR 10668, March 15, 
1989) that while it is not EPA's intention to include all VOC chemicals 
on the EPCRA section 313 list, those VOCs whose volume of use or 
emissions are large enough to raise substantial VOC concerns would be 
retained on the EPCRA section 313 list. Acetonitrile is a VOC with a 
high production volume, and therefore, EPA has determined that 
acetonitrile should remain on the EPCRA section 313 list of toxic 
chemicals. In EPA's most recent petition denial based on VOC concerns 
(63 FR 15195, March 30, 1998), the Agency provided further explanation 
concerning its rationale for determining that indirect effects, such as 
those caused by VOCs, meet the EPCRA section 313 listing criteria.
    Because EPA believes that acetonitrile has moderately high to high 
chronic toxicity, EPA does not believe that an exposure assessment is 
appropriate for determining whether acetonitrile meets the criteria of 
EPCRA section 313(d)(2)(B). This determination is consistent with EPA's 
published statement clarifying its interpretation of the section 
313(d)(2) and (d)(3) criteria for modifying the section 313 list of 
toxic chemicals (59 FR 61432, November 30, 1994).
    As mentioned under Unit III. of this preamble, the petitioner's 
have submitted a petition to EPA's OAR to add acetonitrile to the list 
of negligibly photoreactive chemicals under 40 CFR 51.100(s)(1). 
Chemicals that appear on this list are excluded from EPA's definition 
of a VOC, since they have been determined to have a negligible 
contribution to tropospheric ozone formation. OAR's initial review of 
the petition indicates that acetonitrile may be a negligibly 
photoreactive chemical (Ref. 29). If OAR's initial assessment is 
confirmed and a rule is issued that adds acetonitrile to the list of 
negligibly photoreactive chemicals under 40 CFR 51.100(s)(1), then any 
concerns based solely on acetonitrile being listed as a VOC would no 
longer be a basis for listing acetonitrile under EPCRA section 313. 
However, since EPA has also concluded that acetonitrile meets the EPCRA 
section 313 criteria for listing based on concerns for chronic 
neurotoxicity, EPA's decision to deny the petition to delete 
acetonitrile from the EPCRA section 313 list of toxic chemicals would 
not be affected by a change in acetonitrile's status as a VOC.

VII. References

    1. British Petroleum, Inc. (BP) and GNI Chemicals Corporation 
(GNICC), 1998. Petition to Delist Acetonitrile from the List of Toxic 
Chemicals under the Authority of Section 313 of the Emergency Planning 
and Community Right-to-Know Act (EPCRA) of 1986. BP Chemicals Inc. and 
GNI Chemicals Corp. (February 1998).
    2. United States Environmental Protection Agency (U.S. EPA), Office 
of Pollution Prevention and Toxics (OPPT), Tou, Jenny, 1998. Chemistry 
Report for Acetonitrile in Response to EPCRA Section 313 Delisting 
Petition. (June 1998).
    3. USEPA, OPPT, Anitole, Katherine, 1998. Hazard Assessment for 
Acetonitrile in Response to Section 313 Delisting Petition of BP 
Chemicals Inc. and GNI Chemicals Corporation. (June 1998).
    4. USEPA, OPPT, Nold, Annett, 1998. Exposure Assessment for 
Acetonitrile in Response to Delisting Petition. (July 1998).
    5. USEPA, OPPT, Miller, Jim, 1998. Economic Analysis of the 
Proposed Deletion of Acetonitrile from the EPCRA Section 313 List of 
Toxic Chemicals. (March 1998).
    6. USEPA, OPPT, Blouin, John, 1998. Engineering Analysis of the 
Proposed Deletion of Acetonitrile from the EPCRA Section 313 List of 
Toxic Chemicals. (April 1998).
    7. The Merck Index. An Encyclopedia of Chemicals, Drugs, and 
Biologicals, 11th Edition, p.63, 1989, Merck Co., Inc.
    8. World Health Organization (WHO), 1993. International Program on 
Chemical Safety (IPCS), Environmental Health Criteria 154 - 
Acetonitrile, World Health Organization.
    9. National Cancer Institute (NCI)/National Toxicological Program 
(NTP), 1996. NTP Technical Report of the Toxicology and Carcinogenesis 
of Acetonitrile (CAS No. 75-05-8) in F344/N Rats and B6C3F1 Mice 
(inhalation studies). Carcinogenesis Technical Report Series; National 
Cancer Institute/National Toxicology Program; U.S. Department of Health 
and Human Services (U.S. HHS).
    10. Taskinen, H., Kyyronen, P., Hemminki, K., Hoikkala, M., 
Lajunen, K., and Lindbohm, M., 1994. Laboratory Work and Pregnancy 
Outcome. JOM 36:311-319.
    11. USEPA, OPPT, 1998. Hazard Assessment Emphasizing 
Epidemiological Data for the Acetonitrile Delisting Petition. 
Memorandum dated March 13, 1998, from Andrea Pfahles-Hutchens, Existing 
Chemicals Assessment Branch, to Katherine Anitole, Existing Chemicals 
Assessment Branch, RAD. Washington, DC: USEPA.
    12. USEPA, OPPT, 1998, Health Effects Test Guidelines OPPTS 
870.3700: Prenatal Development Toxicity Study, (EPA 712-C-98-207, 
August 1998).
    13. Willhite, C. 1983. Developmental Toxicity of Acetonitrile in 
the Syrian

[[Page 10604]]

Golden Hamster. Teratology 27, 313-325.
    14. Smith, M.K., George, E.L., Zenick, H., Manson, J.M., and 
Stober, J.A. 1987. Developmental Toxicity of Halogenated Acetonitriles: 
Drinking Water By-Products of Chlorine Disinfection. Toxicol. 46, 83-
93.
    15. Johannsen, F.R., G.L., Levinskas, P.E., Berteau and D.E. 
Rodwell. 1986. Evaluation of the Teratogenic Potential of Three 
Aliphatic Nitriles in the Rat. Fund. Appl. Toxicol. 7, 33-40.
    16. Morrissey, R.E., Schwetz, B.A., Lamb, J.C., Ross, M.Dd., 
Teague, J.L. and Morris, R.W. 1988. Evaluation of Rodent Sperm, Vaginal 
Cytology, and Reproductive Organ Weight Data from National Toxicology 
Program 13-Week Studies. Fund. Appl. Toxicol. 11, 343-358.
    17. Hazardous Substances Data Bank (HSDB), 1994. MEDLARS Online 
Information Retrieval System, National Library of Medicine. (Retrieved 
August, 1994).
    18. IRIS. U.S. Environmental Protection Agency's Integrated Risk 
Information System (IRIS).
    19. Pozzani, U.C., Carpenter, C.P., Palm. P.E., Weil, C.S. and 
Nair, J.H. 1959. An Investigation of the Mammalian Toxicity of 
Acetonitrile. J. Occup. Med. 12, 634-642.
    20. Argus Research Laboratories, Inc., 1984. Embryo-fetal Toxicity 
and Teratogenicity Study of Acetonitrile in New Zealand White Rabbits 
(Segment II Evaluation). Argus Research Laboratories, Inc. Project No. 
419-001, Final Report. EPA Document No. 40-8446070, Fiche No. 
OTS0507279.
    21. E.I. du Pont de Nemours Company, 1968. Acute Inhalation 
Toxicity in Rats with Cover Letter, Haskell Laboratory for Toxicology 
and Industrial Medicine. EPA Document No. 878220234, Fiche No. 
OTS0215023.
    22. Immunquest (1984). EPA Docket Office: FYI-OTS-0284-0292.
    23. USEPA. ``Addition of Certain Chemicals.'' Proposed rule, (59 FR 
1788, January 12, 1994).
    24. USEPA, OPPT, 1994. Estimating Toxicity of Industrial Chemicals 
to Aquatic Organisms using Structure-Activity Relationships. (May 1994)
    25. Screening Information Data Set (SIDS)/Organization for Economic 
Cooperation and Development (OECD), 1997. SIDS Initial Assessment 
Profile (Draft) on Acetonitrile. (March 1997).
    26. General Sciences Corporation (GSC), 1998. ``Modeling Support 
for Exposure Assessment of Acetonitrile,'' prepared for Exposure 
Assessment Branch, OPPT. EPA Contract No. 68-W7-0030, Work Assignment 
No. II-1. (Final Report for Acetonitrile, July 1998).
    27. Trinity Consultants (Dallas, Texas), 1998. ``Refined Modeling 
for Ten Acetonitrile Emitting Facilities,'' prepared for BP Chemicals 
and GNI Group, Inc., (January 20, 1998), Project 97440.0200.
    28. USEPA. ``Proposed Guidelines for Neurotoxicity Risk 
Assessment.'' Notice, (60 FR 192, October 4, 1995).
    29. USEPA. ``Photochemical Reactivity of Acetonitrile.'' Memorandum 
from G. T. Helms to Maria Doa, (October 1, 1998).

List of Subjects in 40 CFR Part 372

    Environmental protection, Chemicals, Community right-to-know, 
Hazardous substances, Intergovernmental relations, Reporting and 
recordkeeping requirements, Superfund, Toxic chemicals.

    Dated: February 24, 1999.

Susan H. Wayland,

Acting Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.

[FR Doc. 99-5495 Filed 3-4-99; 8:45 am]
BILLING CODE 6560-50-F