Testing common gases

From ANIMAL PEOPLE, May 2001:

 

WASHINGTON D.C.–American Petroleum Institute chief
toxicologist Lorraine Twerdok doesn’t like to do animal testing, she
told ANIMAL PEOPLE on April 12. Twerdok said the Petroleum HPV
Testing Group headed by the American Petroleum Institute would do
animal testing to the extent required to satisfy concerns about
public health and safety, but stipulated that using animals was
never their first choice of methods if another approach could be used.

Readers of the April edition of the American Anti-Vivisection
Society newsletter Activate For Animals were given a different
impression, beneath a front-page headline asserting, “American
Petroleum Institute Plans Pointless Animal Tests.”

Twerdok and American Petroleum Institute spokesperson Susan
Hahn had not exactly expected praise from anti-vivisectionists for
the Petroleum HPV Group’s Petroleum Gases Test Plan, submitted to
the Environmental Protection Agency and posted to the American
Petroleum Institute web site back in August 2000. They expected
opposition to any use of animals in testing. They had already caught
flak from PETA.

Still, they admitted, they had hoped someone would
appreciate the American Petroleum Institute effort to keep animal
testing to a minimum, in a “voluntary” response to the EPA High
Production Volume Challenge.
Hahn put “voluntary” in quotes, she explained, because the
EPA put the HPV Challenge in terms that mean, “If you don’t do this
testing yourselves in a manner that we find acceptable, the
government is going to make you do it by regulation–and then you are
going to have to do it their way, even if you have a better way.”
“In 1998,” began Activate For Animals, “the EPA and
then-U.S. Vice President Al Gore announced a six-year program to test
2,800 major industrial chemicals to measure their toxicity and
analyze possible health risks to humans. In response to the public
outcry regarding the millions of animals who would be sacrificed,
the EPA implemented several positive changes to the HPV program.
Despite these revisions, which would save tens of thousands of
animals, few test plans submitted to the EPA reflect the changes.
“A primary example,” Activate For Animals charged, “is the
American Petroleum Institute’s plan to kill thousands of animals in a
series of unnecessary toxicity tests of butane, propane, and coal
dust…Needless animal suffering will take place because the American
Petroleum Institute insists on reproducing data that is already
available.”
Alarmed, Sylvia Bancroft of the Humane Education Network in
Palo Alto, California, asked ANIMAL PEOPLE to find out whether the
EPA had “disallowed the 1999 agreed-upon HPV testing requirements,”
or lacked the ability to enforce them.
But the “several positive changes to the HPV program,” which
Bancroft called “the 1999 agreed-upon HPV testing requirements,”
based on her understanding from American AV, turned out to be a
one-page list of suggestions distributed by the EPA in both October
1999 and October 2000.
HPV program participants were asked to “conduct a thoughtful,
qualitative analysis rather than use a rote checklist approach;
maximize the use of existing and scientifically adequate data;
maximize the use of existing and scientifically appropriate
categories of related chemicals and structure activity relationships;
and use in vitro genetic toxicity testing to generate any needed
genetic toxicity screening data,” rather than testing in live
animals, “unless known chemical properties preclude its use.”
The HPV program is one of three major chemical safety testing
programs now underway, in fulfillment of requirements of the 1996
Food Quality Protection Act and other legislation and lawsuits
pursued for more than 30 years by environmental, consumer
protection, public health, occupational safety, and child welfare
advocacy groups. The other testing programs are the Voluntary
Children’s Chemical Evaluation Program and the Endocrine Disrupter
Screening Program.
Taking the lead since 1967 in pursuing testing of all
chemicals in common use, the Environmental Defense Fund in January
1999 reached agreement with the Chemical Manu-facturers Association
on the HPV research protocal–and were immediately assailed in a PETA
mass mailing for allegedly proposing to kill “millions of animals” in
redundant tests using obsolete methods.
In fact, as EDF staff attorney Karen Florini explained to
ANIMAL PEOPLE (March 1999, page 10), the HPV protocol already
included statements of all the principles later touted by PETA et al
as the “several positive changes to the HPV program” to which
Activate For Animals and Sylvia Bancroft referred.

HPV Testing Group

The American Petroleum Institute agreed to administrate the
Petroleum HPV Testing Group, described at the institute web site,
<www.api.org/hpv>, as “a consortium made up of 70 member companies”
belonging either to the American Petroleum Institute itself, the
National Petrochemical & Refiners Association, the Gas Producers
Association, and/or the Asphalt Institute.
“These companies represent 92% of U.S. refinery capacity,”
the web site explains.
Reviewing the Petroleum Gases Test Plan at the web site,
ANIMAL PEOPLE noted passage after passage describing efforts to avoid
animal testing.
For instance, the plan states that “Green coke [a refinery
byproduct] will be tested using a daphnid and alga species…The
aquatic invertebrate is generally considered more sensitive to
chemical toxicity than fish. If no effects are demonstrated in
Daphnica, the results will be used as evidence that these materials
would not be expected to produce acute effects in fish.”
Therefore ANIMAL PEOPLE asked American AV executive director
Tina Nelson, “On what basis does American AV contend that the
American Petroleum Institute ‘insists on reproducing data that is
already readily available?'”
Responded Nelson, “As you know, Activate For Animals is an
action alert type publication and reports on many different animal
protection issues that various organizations bring to our attention.
The American Petroleum Institute story was based on a critique of
their test plan by several different animal protection
organizations,” posted at
<www.epa./gov/chemrtk/ptrlgas/ptrlgpcr.htm>.
At that site were comments on the Petroleum Gases Test Plan
which were submitted to the EPA in November 2000 by Physicians
Committee for Responsible Medicine research coordinator Nicole
Cardello, on behalf of PCRM, PETA, the Humane Society of the U.S.,
the Doris Day Animal League, and Earth Island Institute.
American AV apparently amplified the Cardello comments
without doing independent evaluation for accuracy.

GRAS

“This test plan epitomizes the flaws and failures of the HPV
chemical-testing program,” Cardello charged. “It is a poorly
thought-out plan that calls for unnecessary and uninformative tests
on chemicals whose behaviors are already well-understood. It is an
exercise in testing for testing’s sake, with no concern for the
impact and cost of the tests. Illustrative of the benign chemical
nature of these compounds is the fact that propane, normal-butane,
and isobutane are all classified as Generally Recognized as Safe
(GRAS) compounds by the Food and Drug Administration (FDA).
Unfortunately, the API fails to recognize this simple fact and does
not cite any data used to make this GRAS determination.”
Yet the HPV program exists precisely because no data
supported the GRAS determination–ever. GRAS determinations were
made in an almost total absence of data. Most of the existing data
on GRAS substances was developed later, after previously unsuspected
possible toxic effects were discovered as result of people or animals
becoming injured or ill from routine and supposedly “safe” exposure.
Explained the Environmental Defense Fund and Robert H. Boyle
in their 1979 joint expose Malignant Neglect, “The Food Additives
Amendment of 1958 defined ‘food additive’ as a substance ‘not
generally recognized among experts…to be safe.’ For a substance to
win approval for use in food, the manufacturer had to demonstrate
that it was safe. The FDA skirted this regulatory responsibility by
creating a new classification of chemicals called Generally
Recognized As Safe, or GRAS. Such chemicals by definition did not
require testing for safety.

“Initially,” EDF and Boyle wrote, “the FDA compiled a
tentative list of 198 substances that might be considered GRAS. At
best the list was based on educated hunches. The agency conducted
neither laboratory tests nor searches of the scientific literature,
and it made no explicit estimates of consumer exposure to each of the
198 substances. The FDA sent the list to 900 scientists, asking if
the substances were safe. Only 324 scientists responded. Of these,
only 69 commented on specific substances.”
Once the GRAS category was created, regulators stretched the
definition to include many substances which would normally never be
in food.
Meanwhile, as research methods advanced beyond the even then
obsolescent LD-50 and Draize tests, many GRAS chemicals were found
to have previously unsuspected longterm toxic effects.
EDF was founded in large part to seek actual investigation of
the potential risks from GRAS chemicals. Then-U.S. president Richard
Nixon endorsed the effort in 1969, asking Congress to order a review
of the GRAS list. Thirty-two years later the work is still just
beginning. It was delayed in part because of lawsuits in which the
petrochemical industry contended that the extensive testing now
required by the HPV Challenge was redundant, unnecesssary, unduly
costly, and excessively burdening to the manufacturers.
The HPV list, including the most commonly enountered GRAS
chemicals, was compiled in 1990 in an attempt to reduce the amount
of testing that might have to be done in order to determine safe
exposure limits. This in turn was a key part of a negotiated
settlement of the major legal issues.
The EPA and chemical industry representatives agreed then,
over opposition from EDF and other environmental groups, that
testing chemicals which were not commonly manufactured could be
dispensed with.

Industry vs. testing

The American Petroleum Institute in August 2000 submitted to
the EPA a Petroleum Gases Test Plan covering 153 of the HPV
substances identified in 1990, plus eight others omitted from that
list but believed to qualify for inclusion.
As the Petroleum Gases Test Plan outlined, “These substances
come from natural gas processing and petroleum refining. Most are
by-products from different processes in the refinery. Many are
combined and undergo further processing to remove unwanted impurities
before being sold. Others are burned as fuel to operate refinery
equipment. In either case, most of these petroleum gases are
intermediate process streams that do not leave the refinery. Only a
few of the 161 gases in the test plan are sold as finished products.”
Continued Cardello of PCRM, “By the API ‘s own admission,
extensive human and animal data already indicate that these compounds
are relatively non-toxic, and that people are generally exposed to
very low doses. There is absolutely no need to repeat these tests,
yet again, on animals. In fact, the toxicity of these compounds is
so low that the American Gas Association specifically requested that
these compounds be exempt from the HPV program in a recent letter.”
Indeed, the petrochemical industry has tried since the
beginning of federal regulation of chemical substances in 1906 to
hold testing requirements to a minimum. Testing costs money–and in
some instances, the findings from animal testing can retroactively
create liability for allegedly causing health risks to workers or the
public, if a court can be persuaded that the findings are applicable
and should have been foreseen. Removing petrochemical products such
as the once widely used preservative ethelyne dibromide (EDB) from
all use in food has cost the petrochemical industry millions of
dollars. In some cases, including the EDB scare of the early 1980s,
the animal testing data that caused the costly action later was found
to be probably inapplicable to human exposure.
According to Cardello of PCRM, “The available data also
indicate that environmental and occupational exposures occur at very
low levels-orders of magnitude less than the concentrations used in
both past and proposed toxicity studies. This fact underscores a
major flaw in the underlying assumption of the HPV program: high
volume production does not necessarily translate to high volume
exposure. With the petroleum gases, the existing literature
provides detailed information demonstrating that occupational and
environmental exposures are generally very low. The American
Petroleum Institute has ignored existing human exposure data…
Although much information exists,” Cardello reasserted, “the
American Petroleum Institute failed to report many toxicological,
occupational and environmental peer-reviewed studies. As we have
repeatedly pointed out in comments on previous test plans,
industries commonly ignore readily available toxicity information.”
Yet the American Petroleum Insti-tute has argued all along
that as Cardello pointed out, exposure to the chemicals in question
usually occurs at much lower levels than have previously been
studied. This is why the EPA wants low-level exposure to be studied
now. And far from ignoring the human exposure data, the Petroleum
Gases Test Plan explained, months before Cardello, that much data
already exists which can can be used. Where existing human exposure
data was not cited, American Petroleum Institute chief toxicologist
Lorraine Twerdok told ANIMAL PEOPLE, the data was “not robust enough
to extract valid conclusions.”
This may have occurred, Twerdok explained, because of a
small sample size or because a complication in the testing procedure
might have compromised the findings.
A cynical investigative reporter could also suggest based on
legal history going back to the days of first U.S. petroleum tycoon
John D. Rockefeller that the petrochemical industry might not be
particularly eager to use human exposure data which points toward
harmful effects from certain products: accepting it as valid could
be construed in a product liability or occupational injury lawsuit as
an admission of guilt.

Depressant effect

Nonetheless, the Petroleum Gases Test Plan began by
explaining that, “Much is already known about how simple petroleum
gases affect the body. The lighter gases (methane and ethane) are
considered simple asphyxiants,” it said, “which means that at low
concentrations they do not cause harmful effects. At very high
concentrations, however, they displace oxygen in the air and reduce
the amount available for breathing. Prolonged exposure can cause
asphyxiation. The heavier gases (propane and butanes) can also act
as asphyxiants but also have a mild depressant effect. Symptoms of
overexposure can include shortness of breath, drowsiness, headaches,
confusion, and decreased coordination.”
These symptoms tend to contribute to workplace accidents.
Accidents in which inhalation of petroleum gases contribute to human
errors leading to other kinds of injury are actually far more common
than incidents in which the gases themselves are known to have done
physical harm. Unfortunately, the threshholds for dangerous
exposure, both short-term and chronic, may be lower than the
threshholds of human perception.
“These symptoms [of overexposure] are reversible if exposure
is stopped,” the Petroleum Gases Test Plan continued. “At the
concentrations required to cause effects [noticed by the victim],
these gases also present an explosive hazard, so exposure to these
levels is rare. [However] Because these gases can affect the nervous
system, the simple gases (methane, propane, butane, and
isobutane) will be tested to determine what concentrations do have an
effect. This will be done in animal studies using high
concentrations for short durations. Because of the flammability
hazard, the concentrations used will be limited to one-half the
lower explosive limit of the gas. All the gases except methane will
also be tested in studies lasting 28 days to determine whether
prolonged exposures can affect any of the body’s organ systems.

Methane

“Methane is not being tested,” the Petroleum Gases Test Plan
stipulated, “as it is known to be present at high concentrations in
intestinal gases.
“In addition, longer-term (90-day) studies will be done with
liquified petroleum gas, using more specialized techniques to detect
possible nervous system harm.
“Many of the individual gases have already been tested in
studies using bacteria for their ability to alter DNA, and were
found to be negative,” the plan adds. But bacteria testing alone
may not produce useful data about DNA effects, because bacteria are
very simple organisms, many of which live by digesting gases, and
do not have the complex genetic structures that might be most
susceptible to DNA damage.
“No studies have been done to look for DNA alterations in
animals exposed to the gases,” the Petroleum Gases Test Plan
continues, “so these studies will be done using the individual gases
as well as the LPG sample.
“Animal studies will also be done on the individual gases to
determine their ability to cause adverse reproductive effects and
effects on the developing fetus,” the plan adds. “The liqified
petroleum gas sample will be evaluated to detect the possibility of
birth defects.
“Because these materials are gases, they will disperse to
the atmosphere if released into the environment; they would not be
expected to contaminate water, accumulate in the soil, or adversely
affect plant life,” the plan preface concludes. “For that reason,
no aquatic or other environmental effects studies are planned.
Information on their environmental fate may be developed if
appropriate.”
Responded Cardello, “If there ever was a situation in which
structure activity relationships [i.e., molecular-level chemical
interaction] were applicable to evaluate compounds’ toxicity, this
set of compounds provides the simplest, most straightforward
opportunity. Yet the API has chosen to waste the opportunity to make
use of existing data that would reduce both animal suffering and
overall cost.”
But as the detailed part of the Petroleum Gases Test Plan
reiterates, “Fish, aquatic invertebrate, and algal toxicity
studies will not be conducted. Instead, a technical discussion will
be developed that addresses the physical nature of these substances.”
It goes on to provide further particulars about how analysis
of chemical interaction will be used to avoid doing further testing.
(continued)