They KNEW the "gun was loaded"!
Were
they blinded by the glitter of huge profits?
Why did they decide to
support this toxic soup?
********************* Lead-in to NSDA Protest *********************
Aspartame was never proven to be safe, nor effective as a diet aid.
Because aspartame changes brain chemistry and breaks down into a witches
brew of toxins and tumor agents there was great concern by the National
Soft Drink Association over putting this once-upon-a-time "ulcer drug"
turned "safe food additive"... into beverages.
There was also concern over how much a child could eventually consume.
Going from bad to worse... not mentioned in the NSDA document (although
admitted by an FDA Commissioner) is the fact that the allowable daily
dose was never set for humans to begin with... but for rats, because
they tolerate more of the wood alcohol (metanol). In l983 aspartame was
in only in a few hundred products, and yet, the NSDA and many others
were already very concerned. They could soon get this toxin in
beverages and in coffee, tea and other hot drinks. The secret trade
information (read into the congressional record and posted on DORway)
stated that aspartame could not be used for everything. It also
mentioned that considering the complete conversion to DKP (a brain tumor
agent), that if they told the FDA of this problem they would never get
aspartame approved.
The National Soft Drink Association, who protested so strongly, for some
reason ignored their own 30-page protest, and turned around and lobbied
for NutraSweet. What power these chemical and pharmaceutical companies
exhibit! Searle was the original manufacturer but was later acquired by
Monsanto Corporation, who created Nutrasweet and Equal.
As hundreds of complaints poured into the FDA the objections of the NSDA
came to be a reality. The CDC was asked to investigate: they did, and
indeed it was a most damning report that included memory loss, seizures,
liver problems, mood alteration, cardiac arrest and death - for
starters. However, the coverup continued because a summary was added to
this investigation that contradicted the report saying that the findings
were "mild". By virtue of this short one-paragraph summary (to a 146
page report) the term "mild death" is now a defacto part of CDC jargon.
Searle studies were the target of an indictment for fraud not carried
out when two U.S. Prosecutors went to work for the law firm defending
Searle. Senator Metzenbaum introduced a bill that never got out of
committee (in l985) because Monsanto lobbying power was too strong. On
the program "60 Minutes" Dr. Ralph Walton declared that 83 of 90
independent tests showed aspartame to have significant problems (Dec 29,
l996), but then the usually aggressive expose staff failed to name those
problems, or to confront the manufacture with this information.
The manufacturer and the FDA has succeeded in preventing any new
independent studies and the FDA has refused to answer 26 questions on
DORway, even down to why the studies that showed aspartame triggers
brain tumors were never replicated. In addition, the FDA refuses to
confirm or deny that they now allow aspartame in products without the
required warning label "PHENYLKETONURICS: Contains phenylalanine".
Dr. H. J. Roberts (at a press conference in the 80's) warned the world
by saying that something had to be done soon or we might have a plague
on our hands within 5 to 10 years. The FDA sent out a brochure
explaining the safety of aspartame full of propaganda that had nothing
to do with the truth (rebutted on DORway).
During 1996 the FDA decided to remove all restrictions on the use of
aspartame (ignoring the fact that aspartame breaks down faster when
heated above 86 degrees F). In order to do so the FDA had to show a
reduction in complaints (they admit to over 10,000 "official" complaints
on this "most complained about substance, ever") so they diverted new
complaints. One source indicated the FDA was referring complaints to
the "Aids Hotline". Then, in order to reduce the number of existing
complaints (to further show a reduction) they revised their book keeping
system in order to eliminate hundreds of once-valid reports.
During June of l996, Dr. David Kessler granted blanket approval (for
this neurotoxin, a dangerous drug that changes brain chemistry and
interacts with other drugs) to be used the same as sugar... in
everything. He did so without public notification, and shortly after
being requested by retired Senator Metzenbaum to initiate additional
safety testing.
Yes... the NSDA "knew the gun was loaded" but became a turncoat,
lobbying for industry, with full knowledge of what would happen to the
public. After 17 years on the market on-going "independent studies" are
still "in progress" because the rat test subjects have been replaced by
over 200 million human consumers, residing in 100 countries of the
world, who unknowingly ingest this toxic soup from over 5000 products
believing they are "safe" and a "diet aid". "Proof of the pudding" is
in the medical system that is at its breaking point from a need to
continually treat victims of aspartame disease... who cannot be cured by
medications. Complete removal of aspartame from the diet is the only
possible cure.
Perhaps the phrase that best applies is that "ASPARTAME is a Pandora's
box of chameleon-like toxins and tumor agents that have 92 FDA
acknowledged ways to ruin your life, death being one of them".
******************************************************
Pages S5507 through S5511 of the Congressional Record dated May 7, l985.
These pages contain six of the 30 pages of protest by the National
Soft Drink Association. For this reason the beginning of the page
starts in the middle of a sentence.
****************** NSDA Protest (summary) ********************
May 7 1985 CONGRESSIONAL RECORD -- SENATE S5507
headaches, mood alterations, and behavior changes."
The report language accompanying this bill directs the FDA to
ensure that these tests are undertaken.
At mark up, I proposed an amendment which would require the
manufacturers of diet soft drinks to include on their label how much
aspartame (NutraSweet) each serving contains.
I believe consumers have a right to this information given the
questions which have been raised about NutraSweet and the extraordinary
increase in consumption levels of this product since its introduction in
1981 (last year per capita consumption increased 66%).
The National Soft Drink Association has lobbied strongly against
this proposal. However, this is the same association which, in 1983,
prepared a draft legal document objecting to NutraSwseet's being allowed
on the market, citing serious and unresolved questions about the public
health. Though that document was not filed, it indicates the
organization had significant health concerns relating to the amount of
aspartame consumed before this product was approved for soft drinks.
The following quotes are from a document entitled "Objections of the
National Soft Drink Association to a Final Rule Permitting the Use of
Aspartame in Carbonated Beverages and Carbonated Beverage Syrup Bases
and a Request for a Hearing on the Objections." The document is dated
August 8, 1983, and was prepared by Patton, Boggs and Blow and the
General Counsel for the National Soft Drink Association:
"G. D. Searle and Company has not demonstrated to a reasonable
certainty that the use of aspartame in soft drinks, without quantitative
limitations, will not adversely affect human health as a result of the
changes such use is likely to cause in brain chemistry and under certain
reasonably anticipated conditions of use."
"For these reasons, Searle has not met its burden of demonstrating
to a reasonable certainty that the unlimited use of aspartame,
especially in combination with carbohydrates, will not adversely affect
human health. The questions posed by Dr. Wurtman are significant because
of the seriousness of the potential effects (e.g., changes in blood
pressure) and because of aspartame's anticipated widespread use--use
that includes consumption by potentially vulnerable sub-groups, such as
children, pregnant women and hypertensives."
"Specifically, Searle has not met its burdens under section 409....
to demonstrate that aspartame is safe and functional for use in soft
drinks."
"Collectively, the extensive deficiencies in the stability studies
conducted by Searle to demonstrate that aspartame and its degradation
products are safe in soft drinks intended to be sold in the United
States, render those studies inadequate and unreliable."
There have been hundreds of reports from consumers around the
country suggesting a possible relationship between their consumption of
NutraSweet and subsequent symptoms including headaches, aberrational
behavior, slurred speech, etc.
During the Labor Committee hearing on saccharin, NutraSweet and
cyclamate held on April 2, Dr. Richard Wurtman of M.I.T., testified as
follows:
"The problem at present is that it is difficult if not impossible
for the patient or his physician to know how much aspartame it
contains....I believe it is essential that companies which include
aspartame in their products be required to indicate on the labels (in
readable print) how much of the sweetener is present in each can or
serving. This simple change in labeling practice would, I believe,
sharply reduce the number of consumers who believe without probable
foundation that they have suffered aspartame-related side-effects.
Perhaps more importantly, it would also enable physicians to identify
those patients who might really have had such responses, so that such
people might then undergo controlled clinical testing."
Since 1981 , the FDA has attached an ADI (acceptable maximum daily
intake) to NutraSweet. That ADI is currently 50 milligrams per kilogram
of body weight. While an adult weight in 154 pounds would not meet that
limit before he consumed 5 liters of diet soft drink, a four-year-old
weight in 25 pounds would hit that limit at three cans of diet soda.
Consumers have no way of knowing if they have reached the FDA limit
without knowing how much is in the can. Ideally, we should have the ADI
on the can as well, but it will take some time to figure out how that
could be done effectively. In the meantime we should ensure that the
quantity is on the label. We must start somewhere, and this is an
important first step.
Many questions must be resolved concerning aspartame. The FDA
should take an active role to ensure that tests are conducted to
determine whether individuals, particularly children, are likely to
experience side-effects from NutraSweet at current and projected
consumption levels. The FDA should also run tests on how NutraSweet
affects those who might be taking different types of medication.
Finally, given the serious questions which remain regarding the FDA
approval process for NutraSweet, the FDA should ensure that certain key
pivotal animal tests are repeated. Only when all of these questions are
resolved can consumers be certain that they are receiving the full
protection provided by our food and drug laws.
________________________
EXHIBIT 1
OBJECTIONS OF THE NATIONAL SOFT DRINK ASSOCIATION
TO A FINAL RULE PERMITTING THE USE OF ASPARTAME
IN CARBONATED BEVERAGES AND CARBONATED
BEVERAGE SYRUP BASES AND A REQUEST
FOR A HEARING ON THE OBJECTIONS.
(Docket No. 82F-0305)
DRAFT: JULY 28, 1983
Objection One: Searle has not demonstrated to a reasonable
certainty that aspartame and its degradation products are safe for use
in soft drinks. Without quantitative limitations, under temperature
conditions likely to prevail in the United States.
SUMMARY OF BASIS FOR OBJECTION
Aspartame is inherently, markedly and uniquely unstable in aqueous
media.
In a liquid, such as a soft drink, APM will degrade as a function of
temperature and pH. Higher temperatures and more acidic liquids
increase the rate of degradation. Higher temperatures may also affect
the degradation products which are formed. Given the circumstance of
APM's unusual instability, reliable and comprehensive analyses of APMs
degradation in soft drinks--both as to the rate of degradation (and the
subsequent loss of sweetness) and to the confirmed identification of the
major degradation products--is crucial to establish the safety of the
use of APM. Without adequate identification of AMP's significant
decomposition products, it is not possible to find, to a reasonable
certainty, that APM is safe. The data and information submitted by
Searle in support of its petition to amend 21 C.F.R. 172.804 to permit
APM use in soft drinks, however, do not demonstrate that APM is safe for
use in soft drinks. These data are insufficient to establish safety
because the petition lacks comprehensive, reliable and accurate
analytical data on APM and the products "adversely affected:" by the
issuance of the regulation authorizing the use of aspartame ("APM") in
soft drinks. As the national trade association representing the soft
drink industry in this country, NSDA's member soft drink manufacturers
and soft drink franchisers are directly and immediately affected by the
issuance of a regulation which authorizes the use of a new sweetener in
its products. Approximately seventy-six percent of the nations 1600
soft drink manufacturers are active members of the Association. These
members account for more than ninety percent of the soft drink
production in this country. In addition, the vast majority of soft
drink franchisers which manufacture the concentrates and syrups from
which soft drinks are made are associate members of the Association.
II. SUMMARY OF BASIS FOR THE OBJECTIONS
(To be added).
OBJECTIONS OF THE NATIONAL SOFT DRINK ASSOCIATION
TO THE ISSUANCE BY THE FOOD AND DRUG ADMINISTRATION
OF A REGULATION (21 C. F. R. 172.804) TO AUTHORIZE THE
USE OF ASPARTAME IN CARBONATED BEVERAGES
AND CARBONATED BEVERAGE BASES.
In the Federal Register of July 8, 1983 (48 Fed. Reg. 31376), the
Food and Drug Administration ("FDA") issued a regulation amending
section 172.804 of its regulations, 21 C. F. R. 172.804 to authorize the
use of aspartame in carbonated beverages and carbonated beverage bases
(collectively referred to as "soft drinks"). This action was taken in
response to a food additive petition (FAP 2A3661) filed on October 15,
1982 by the Searle Research and Development Division of the G. D. Searle
Co. ("Searle").
In these objections, NSDA demonstrates that there exist genuine and
substantial issues of fact material to FDA's amendment of its
regulations to permit aspartame use in soft drinks. Specifically,
Searle has not met its burdens under section 409 of the Federal Food,
Drug and Cosmetic Act, 21 U.S. C. 348 ("FDC Act") to demonstrate that
aspartame is safe and functional for use in soft drinks NSDA therefore
objects to the Commissioner's order amending 21 C. F. R. 172.804 and
requests that a hearing as provided under section 499 (f) of the FDC
Act, 21 U.S.C. 348 (f) be convened.
NSDA is a party that is, within the meaning of section 409(f)(l) of
the FDC Act. 21 U.S. C. 348 (f)(l). methyl ester (PM) and beta-aspartame
(beta-APM). (1) (Searle FAP at 13) Only in the cases of APM and DKP
did Searle use high pressure liquid chromatography (HPLC). For the other
four known principal breakdown products, Searle used thin-layer
chromatography (TLC).
HPLC is a far superior analytical method relative to TLC (cites)
and numerous SPLC methods exist for the detection and quantification of
amino acids (cites. Searle's choice of TLC over HPLC adversely affected
the quality and type of analytical data generated on APM and its
decomposition products in soft drinks The unfortunate and inexplicable
choice (2) of an inferior analytical technique, when superior and
recognized methods are available, has resulted in inadequate
characterization of APM's decomposition products.
********************** Begin Notes area **********************
(1) The importance of comprehensive and reliable analyses of APMs
decomposition products is demonstrated by the fact that based on the
chemical structure of APM, one would not expect PM or beta-APM to be
degradation products, indeed, initially Searle did not look for either
one. Other unexpected decomposition products of unproven safety could
of course, also be present when APM degrades.
********************** End Notes area **********************
May 7, 1985 CONGRESSIONAL RECORD -- SENATE S5508
HPLC is a practicable, well-accepted analytical method (3) which is
commonly-employed by FDA. When the safety and suitability for use of a
food additive such as APM with an acknowledged degradation problem (and
anticipated high consumption) is under evaluation, HPLC is clearly the
analytical method of choice.
TLC, on the other hand, produces good qualitative results, but is,
at best, only semi-quantitative, since the quantification used is based
on visual comparisons of spot sizes and intensities. (cite) Indeed,
Searle itself has acknowledged the inadequacy of the analytical method
that it chose when it described, in the petition, the quantity of
degradation products identified using TLC as "estimates." (cite)
The inappropriateness of using TLC as a principal analytical method
is compounded by the fact that the values of APM degradation products
being measured are close to the limits of detection of the method (cite
). (4) Thus, the values purportedly obtained by the TLC method cannot be
considered to be very precise. Finally, an important decomposition
product of APM, aspartic acid (AA) cannot be detected at all using TLC.
In short, for reasons which are not apparent, the petitioner chose
to use a semi-quantitative analytical method to analyze for numerous
major APM breakdown products close to the limits of detection, when that
method is not the best method available. The quality of the analytical
data presented are, therefore, substantially inferior to those which
could have reasonably been obtained.
(b) The Searle Analyses for APM Decomposition Products are
Deficient. Aside from its choice of TLC over HPLC, the analyses
conducted by the petitioner to identify and quantify the breakdown
products of APM in soft drinks are plagued by numerous significant
deficiencies which result in clear and unmistakable inadequacies in the
detection and quantification of the major decomposition products of APM
in soft drinks. In the face of these deficiencies, Searle has not
reasonably identified substances formed in soft drinks because of the
use of APM, as required under section 409 (c) (5) (A) of the FDC Act 21
U.S.C. 348 (c) (5) (A). The safety of this use of APM cannot be said to
have been shown to a reasonable certainty in the face of these
inadequacies.
There are at least six significant deficiencies in the HPLC
analyses undertaken by Searle to identify and quantify APM and DKP in
soft drinks:
(a) The standards for use of HPLC to detect APM and DKP were
prepared in buffered aqueous solutions. A far better technique would
have been to prepare the standards using beverage matrices. The use of
beverage matrices would have reduced the danger of interfering compounds
coeluting with the compounds of interest.
(b) Searle does not appear to have submitted to FDA to HPLC
chromatograms of the blanks (unsweetened beverages); without these
chromatograms, the results obtained in sweetened beverages cannot be
evaluated.
(c) The chromatograms of the beverages which were submitted by
Searle contain peaks which can cause difficulties with quantification.
For example, the DKP in the root beer chromatograms is badly overlapped
by another peak.
(d) No recovery data for DKP were presented and the precision of
the DKP concentrations was only determined for standard solutions.
(e) The purity of the initial APM was not established, although it
can contain at least five percent impurities, as calculated from the
zero time values in Searle's studies.
(f) Searle analyzed only single bottles at any given time and
temperature. This aspect of the study design fails to account for
anticipated bottle-to-bottle variations. Single bottle analytical data
cannot, under any circumstances, amount to a comprehensive and reliable
characterization of the decomposition products of an additive with a
well-known instability problem.
Likewise, the TLC analyses are deficient (these deficiencies are in
addition to the inherent limitations of the TLC method):
(a) Standards for the TLC analyses were prepared in distilled
water. As in the case of the HPLC analyses, the better technique would
have been to prepare them in beverage matrices.
(b) Searle did not submit (and apparently did not attempt) any
recovery or precision data for its TLC analyses.
(c) In the TLC analyses, only single aliquots of single bottles
were analyzed at any given time and temperature, thus rendering the
putative quantitative results inherently unreliable.
(d) Measurable levels of beta-APM and PM may have existed in the
starting material, but were not quantified at the beginning of the
analyses (presumably because they were unexpected decomposition
products). Moreover, it is unclear from Searle's data how the spots on
the TLC plates were identified. If, as appears to be the case,
identification was based solely on the comparison of R values, the
identification can only be called tentative. Confirmation of the
identifications by spectroscopic methods should have been undertaken.
The failure to confirm these identifications undermines many of the
major assumptions made by Searle throughout its analytical studies.
Collectively, the extensive deficiencies in the stability studies
conducted by Searle to demonstrate that APM and its degradation products
are safe in soft drinks intended to be sold in the United States, render
those studies inadequate and unreliable. It is not possible on the
basis of these studies to conclude that the petitioner has demonstrated
that, notwithstanding its inherent instability, APM is safe for use in
soft drinks. The failure of proof by Searle is even more evident, as is
shown in the following section of these objections, when one considers
the extent to which the decomposition products of APM in soft drinks are
not known or identified.
(c) APM Decomposes Extensively in Soft Drinks Under Moderate
Conditions. But Searle's Data Fail to Identify Adequately the
Decomposition Products.
Notwithstanding the multiple and serious deficiencies in the
stability studies conducted on the APM in soft drinks, one conclusion
does emerge: under moderate conditions, extensive decomposition of APM
may occur in soft drinks. Moreover, a substantial portion of the
decomposition products are not known. APM cannot be considered to be
shown to be safe for use in soft drinks when the results of its known
decomposition phenomenon--marked breakdown in liquid beverages--are not
well identified.
For example, in Searle studies, a cola beverage was kept at 10
degrees C (86 degrees F) for 40 weeks. (cite) In analyses conducted at
that time, only fifty (50) percent (weight basis) of the original
starting material was found. (5) Even if one accepts one of Searle's
main assumptions about APM decomposition in soft drinks -- that is, that
aspartic acid (AA) is formed in amounts equal to the PHE and PM (mole
basis) (cite) -- the percent recovery to sixty-four (64) percent. (6)
Thus, even when viewed most favorably, the analyses fail to account for
over one-third of the original material.
This startling deficiency in the stability studies is further
demonstrated by this table, also drawing from Searle data of beverages
stored at 30 degrees C (86 degrees F), which illustrates the material
balances obtained: (7)
The inability to account for as much as thirty-nine (39) percent of
APM's decomposition products is significant. With such a high unknown
factor, judgements about the safety of APM in soft drinks cannot be made
confidently.
Possible explanations for, and speculation about, the material balance
discrepancies abound: secondary reactions may be occurring (possibly
with the flavor components in the beverages): additional, but
unidentified decomposition products may exist, (as occurred in the case
of PM and beta-APM): or the inaccuracy and inadequacies of the
analytical methods may account for the gaps in the data. No explanation
for the discrepancies in material balances--that is, for the high
percentage of unknown material--can, however, be supported on the basis
of the data submitted by Searle. The significance of the unknown
decomposition products simply cannot be determined in the absence of
complete, careful and reliable analyses--analyses which are not
currently available because the petitioner failed to conduct or submit
them. (8)
2. Searle Has Not Characterized The Decomposition Products of APM
in Soft Drinks Under Temperature Conditions To Which the Beverages Are
Likely To Be Exposed In the United States.
********************** Begin Notes area **********************
(2) The availability of HPLC to detect and quantify APM's decomposition
products is demonstrated by, among other things, a paper presented by
three representatives of Searle, (LeVon, Mazur and Ripper "Aspartame
(APM) as a Sweetener in Carbonated Soft Drinks") (Appendix). In that
paper, Searle stated that HPLC was currently used to detect APM. DKP and
AP and PHE. Nevertheless, the petition does not contain HPLC generated
data for AP or PHE.
(3) Section 171.1 (c) of the agency's regulations. 21 C.F.R. 171.1 (c),
required that an analytical method for detection of a food additive and
substances formed in or on food because of its use be practicable and
one which "can be applied with consistent results by any property
equipped and trained laboratory personnel." HPLC is clearly such a
method.
(4) FN w examples.
(5) This figure is derived as follows from Searle data: 13 percent APM,
21 percent DKP, 3 percent AP, 8 percent PHE, and 5 percent PM.
(6) The increase comes from 10 percent AA and 4 percent methanol.
(7) A material balance accounts for the quality of the starting
material, the quantity of identified decomposition products (or by-
products, reaction products, etc.) and the quantity of unknown material.
Because of the inadequacies in the analyses documented in section ---
above, the figures in this table may be inaccurate. Nevertheless, the
discrepancies in the material balance raise the possibility of
significant unknown decomposition products.
(8) A tempting, but unsatisfactory, resolution of the material balance
discrepancy is to assume that the safety of the decomposition products
were determined in the chronic studies in laboratory animals which
Searle conducted. This putative resolution does not hold, however,
because these degradation products would not have undergone testing,
since the APM in the feeding regimen was in freshly prepared doses.
********************** End Notes area **********************
May 7, 1985 CONGRESSIONAL RECORD -- SENATE S 5509
A suitable assessment of the stability of APM in soft drinks can be
conducted. Such an assessment would necessarily involve the use of
sample beverages in a variety of flavors and varying pH, and, most
importantly, involve exposure of the beverages to temperature conditions
which approximate those which are reasonably expected to occur in
practice (or under conditions which permit reasonable projections to be
made to actual conditions). (9) Unless the sample APM-sweetened
beverages are exposed to realistic temperature conditions, the
temperature-sensitive degradation characteristics of APM, and in
particular its potentially significant decomposition products, cannot be
known. The data submitted by Searle are not derived from appropriate
test conditions. Judgements about the extent of APM instability and its
degradation products in soft drinks under actual conditions of use
cannot, therefore, be inferred from the limited laboratory data.
To assess APM's instability in soft drinks, Searle exposed bottles
of ready-to-drink beverages in four flavors (cola, root beer, lemon-lime
and orange) to consistent temperatures of 55, 40, 50, 20 and 5 degrees
C. (10) According to Searle's petition, "(I)n each flavor a loss of APM
occurred with the rate of degradation directly related to the storage
temperature for the carbonated beverages. The rate of APM loss from
beverages was pH dependent." Moreover, Searle noted that "as the
temperature increases, the rate of degradation becomes more pronounced."
(11) Some of the effects on APM degradation in soft drinks are
illustrated in a table in the Searle petition. (12) In that table, for
example, after 20 weeks at 30 degrees C (86 degrees F), a beverage with
a pH between 2.5 and 3.0 contained less than 40 percent of the original
amount of APM. For beverages with similar pH, but kept at 40 degrees C
(104 degrees F) for 20 weeks, less than ten percent of the original APM
remained. Less pronounced degradation is seen at higher pH and/or at
lower temperatures.
Although these stability tests shown signification degradation of
APM at consistent temperatures over relatively short time periods, they
shed virtually no light on the probably degradation rate and products
for soft drinks exposed to a variety of temperatures--including
temperatures higher than any used in Searle's studies--during storage,
handing, sale and use, temperatures which are known to occur and to
which soft drinks are known to be exposed. Without stability studies
conducted under such conditions, APM cannot be said to be appropriately
stable in soft drinks, nor can its degradation products be considered to
be adequately identified (assuming that analytical techniques were used
which would yield complete and reliable results) nor can it be
considered to have been shown to be safe.
The range of temperature conditions to which soft drinks are
exposed during the summer months in the southern United States (13) is
illustrated by a study conducted by the Coca-Cola Company's Corporate
Packaging Department in 1976 and submitted to the Consumer Product
Safety Commission. (14) That study shows that during the summer
months, soft drinks are often exposed to relatively high temperatures
for certain time periods in the course of distribution from the bottling
plant to the consumer. High temperatures do, of course, routinely occur
in much of the United States, including the southern regions; conditions
of storage and distribution for soft drinks can elevate these
temperatures significantly.
In summary, the study assessed: (1) warehouse temperatures in
Marietta, Georgia and Wichita Falls, Texas: (2) route truck temperatures
in Wichita Falls; (3) full sun and outside ambient temperatures in
Wichita Falls; (15) and (4) parked car temperatures in Atlanta, Georgia
and Wichita Falls. Each of these test environments is known to occur in
practice and the tests were performed under actual, as opposed to
laboratory conditions.
Several significant conclusions can be drawn from this study.
First, in those situations where the bottled beverage is heated only by
conduction from the surrounding air (shaded location in a warehouse or
in the automobile trunk parked indoors) the ratio of product temperature
to the temperature of the surrounding air would be 0.92 to 0.94. In
enclosed environments exposed to sunlight, however, ratios much greater
than one would be expected. For example, a ratio of product temperature
to air temperature of 1.45 was found for a test car parked in full
sunlight. In other situations where sunlight was a direct heating factor
(e.g., open air service station promotions or open bay delivery trucks)
typical ratios were 1.10 to 1.15.
The effects of these ratios on product temperature are demonstrated
by using summer temperatures for Phoenix, Arizona, where the average
daily high in July is 40 degrees C (104 degrees F). During July in
Phoenix, a soft drink in full sunlight could reach a temperature of 49
degrees C (120 degrees F) (104 degrees x 1.15). The same product in a
car parked in full sunlight could reach 66 degrees C (151 degrees F)
(104 degrees F x 1.45) (16); soft drinks in a warehouse with an ambient
temperature of 110 degrees could reach temperatures of 38 degrees C (101
degrees F) to 39 degrees C (103 degrees F) (0.92-0.94 x 110 degrees F).
Overall, the study, considered together with representative
historical temperature data (Appendix ___) show that soft drinks will
frequently be exposed to temperatures of 32 degrees C (90 degrees F) to
49 degrees C (120 degrees F). In some cases product temperatures as
high as 66 degrees C (151 degrees F) (especially in the southwestern
United States) can be reached.
The effects of these high product temperatures on APM degradation
and the formation of degradation products, and the effects of
temperature variation (for example, soft drinks displayed at a service
station may reach temperatures of 49 degrees C (120 degrees F) for most
of the afternoon, drop in temperature overnight, and heat up again
during the following day) cannot be determined from the data submitted
by Searle to the FDA.
What those data do suggest, however, is that significant APM
degradation at high temperatures occurs within a short period of time.
For example, in Searle's stability tests, an orange beverage held at 40
degrees C (104 degrees F) average daily high for Phoenix during July)
for eight weeks, contained only fifty (50) percent of the original
amount of APM. A cola beverage held under the same conditions contained
only forty (40) percent of the original APM amount. And beverages
exposed to higher temperatures degrade even more rapidly. And, or
course, because of the temperature elevation ratios, product
temperatures could easily be much higher during actual conditions than
the stable temperatures used in the Searle laboratory studies.
Thus, it is known that APM will degrade rapidly at high
temperatures, including temperatures to which soft drinks are known to
be exposed intermittently during the summer. What is now known,
although the FDC Act requires the proponent of use to demonstrate it, is
what effects of degradation occur by virtue of exposure to these
temperatures.
More specifically, to demonstrate that APM is safe for use in soft
drinks, the petitioner must reasonably identify what degradation
products are formed under those conditions. Ultimately, of course, the
safety of the major degradation products must be determined. Under the
FDC Act, the data needed to make that determination--reliable and
competent data--must be provided by the petitioner.
Objection Two: Searle has not demonstrated that APM use in soft
drinks will not adulterate the beverages under Section 402 (a)(3) of the
FDC Act.
SUMMARY OF BASIS FOR OBJECTION
As discussed above, it is well established that the petitioner for
issuance of a regulation authorizing the use of a food additive bears
the burden of proving, through reliable and competent data, each element
of the criteria set forth in section 409 of the FDC Act, 21 U.S.C. 348.
for issuance of a food additive regulation. The present record does not
contain data which demonstrate that the use of APM in soft drinks will
not result in the adulteration of the beverages under section 402 (a)(3)
of the FDC Act. 21 U.S.C. 342 (a) (3), which provides that a food is
adulterated if it contains, in whole or in part, "...a decomposed
substance or if it is otherwise unfit for food." Indeed, the present
record strongly suggests that the rapid degradation of APM in soft
drinks and the consequent loss of sweetness may well result, under
certain actual time and temperature conditions, in products which would
be adulterated under section 402. Without data which demonstrate that
APM-sweetened beverages will not be adulterated under section 402 (a)(3
). Searle has not met its burden of proof under section 409 (c) (3) (B)
of the FDC Act. 21 U.S.C. 348 (c) (3) (B).
FACTUAL BASIS FOR OBJECTION TWO
The marked and rapid decomposition of APM in soft drinks under
temperatures known to prevail is apparent from data in the present
record and discussed above in these objections. Those data show that it
is reasonable to expect APM to decompose in soft drinks sufficiently
rapidly under current handling and distribution procedures to adversely
affect product quality and taste. (17)
S 5510 CONGRESSIONAL RECORD -- SENATE May 7, 1985
It is well-established under section 402 (a) (3), that a food which
contains a decomposed substance (i.e., the decomposition products of APM
which, Searle's data show, can readily exceed the quantity of APM itself
in a short time)--especially where the decomposition has adversely
affected product quality or made the product unpalatable--is adulterated
and subject to seizure. FDA would consider beverages which had lost
substantial sweetness because of APM decomposition and which were
therefore not palatable, to be adulterated under section 402 (ax3). The
record is devoid, however, of evidence which demonstrate that APM used
to sweeten soft drinks will not, under reasonably anticipated conditions
of use, in fact cause the products to be adulterated. Without such
evidence Searle has not met the burden imposed under section 409 (c) (3)
(B).
(This objection will be expanded.)
Objection three: Searle has not demonstrated that APM is
functional for use in soft drinks under temperature conditions likely to
prevail in the United States.
SUMMARY OF BASIS FOR OBJECTION
In addition to data intended to assess the stability of APM in soft
drinks, Searle's petition for use of APM in soft drinks contains data
intended to show that APM is functional in the beverages, i.e., that it
achieves and retains the intended technical effect (sweetening) under
the conditions of use reasonably anticipated to occur. Searle has not
demonstrated that APM is functional in soft drinks because its data show
a significant loss of sweetness at temperatures to which soft drinks are
known to be exposed and within the range of time periods between
bottling and projected consumption. The functionality of an additive
cannot be considered to have been demonstrated if significant loss of
its intended technical effect because of temperature and pH dependent
degradation may occur under reasonably anticipated conditions of
handling, storage and use.
FACTUAL BASIS FOR OBJECTION THREE
To evaluate the functionality of APM, Searle conducted "sensory
evaluation" tests which used consumer taste panels to assess "perceived
sweetness" (cola, beverages only) and "overall liking" (or "acceptance")
(all flavors) over time periods up to 52 weeks and at three
temperatures: 5 degrees C (41 degrees F), 20 degrees C (66 degrees F)
and 30 degrees C (86 degrees F) Beverages sweetened with APM only (5, 20
and 30 degrees C) and APM with saccharin (20 degrees C) were tested;
beverages sweetened with sucrose (______ C) and saccharin (_______C)
were used as references. The beverages were rated at different time
periods by the panelists. (18)
Although no temperature used in Searle's sensory evaluation tests
approached the actual product temperatures which soft drinks will reach
(see section ____ above), significant loss of sweetening and overall
liking occurred for beverages sweetened with APM only within
extraordinarily short time periods. For example, APM-sweetened cola
beverages stored at 30 degrees C 86 degrees F) received on overall
liking score of less than 20 on a 0-100 scale after only 290 weeks
(after 20 weeks the product was apparently unpalatable, since Searle did
not present sensory evaluation data beyond this time). For an orange
beverage, overall likeness after 20 weeks at 30 degrees C 86 degrees F)
approached 5 ( on a nine point hedonic scale), the "neither like nor
dislike" or mean rating. Again, sensory evaluations were apparently not
conducted beyond 20 weeks.
Searle's characterization of the results of the sensory evaluation
tests avoid the clear implication of those tests: That APM has not
been shown to retain sufficient sweetness at temperatures which are
known to occur for APM-sweetened beverages to retain an acceptable
"overall liking" rating. Instead, Searle emphasizes an interesting, but
legally irrelevant finding: That APM sweetened beverages tested after
holding at relatively low temperatures were preferred to beverages
sweetened with alternative sweeteners. This characterization misses the
statutory purpose for which the studies were undertaken, that is, to
demonstrate that APM is a functional sweeteners in soft drinks.
Of particular importance is the fact that Searle's sensory
evaluation tests do not explore the effects on either sweetness or
overall likeness of APM-sweetened beverages exposed, either consistently
or intermittently, to the higher temperatures which prevail in much of
the United States. What is the effect on these two measures, for
example, of product temperatures of 100 to 120 degrees F? Is the
degradation greatly accelerated and the overall liking therefore
diminished in even shorter time periods? Will APM-sweetened beverages
stored in warehouses and carried on open route trucks or stored in
warehouses and displayed in open air service station promotions in the
southern states be acceptable when the consumer attempts to consume them
several weeks later? Is APM a functional sweetener for soft drinks if
APM-sweetened beverages in certain parts of the country would, during
the summer months, have to be treated as if they were perishable
commodities?19
(To be expanded with age distribution data.)
Objection No. Four: G. D. Searle and Company Has Not Demonstrated
To A Reasonable Certainty That The Use of Aspartame In Soft Drinks.
Without Quantitative Limitation. Will Not Adversely Affect Human Health
As a Result Of The Changes Such Use Is Likely To Cause In Brain
Chemistry And Function Under Certain Reasonably Anticipated Conditions
of Use.
SUMMARY OF BASIS FOR OBJECTION
In its July 8 Federal Register notice, FDA acknowledged receiving a
comment expressing concern about the effect on plasma and brain
phenylalanine PHE) and tyrosine (TYR) levels when aspartame is fed in
combination with a carbohydrate. 498 Fed. Reg. at 31379. The comment
included data demonstrating that in both rats and humans the feeding of
a carbohydrate with aspartame significantly enhances aspartame's
positive effect on the ratio of PHE and TYR to other large neutral amino
acids (LNAA) in the blood. The data submitted with the comment also
demonstrate that brain PHE and TYR levels in the rat are significantly
increased by the aspartame/carbohydrate combination.
The concern of the commentator, Dr. Richard J. Wurtman, Professor
of Neuroendocrine Regulation at the Massachusetts Institute of
Technology, was that, increased brain levels of PHE and TYR are likely
to affect the synthesis of certain neurotransmitters--substances vital
to the regulation of brain function--and that changes in the levels of
neurotransmitters could in turn cause adverse physiological effects (by,
for example, modifying the function of the autonomic nervous system)
and/or behavioral effects.
FDA response to Dr. Wurtman's comments by stating that it "..
. believes that the comment's conclusion regarding potential
phenylalanine induced changes in neurotransmitter function appear to be
unwarranted extrapolations..." (48 Fed. Reg. at 31379; emphasis added)
and by concluding that "... the data supplied with this comment do not
provide support for its hypothesis that the ingestion of aspartame and
carbohydrate will alter the brain levels of neurotransmitters and
thereby produce behavioral modifications." 48 Fed. Reg. at 31380, FDA
cites as support for its conclusion several studies submitted by Searle:
FDA did not discuss, however, much of the data submitted by Dr. Wurtman
(including those demonstrating significantly elevated brain levels of
PHE and TYR), and it apparently overlooked the significance of
aspartame's demonstrated blocking effect on glucose-induced elevation of
brain serotonin levels.
In light of the allocation of the burden of proof and the nature of
the safety standard in food additive proceedings (discussed above).
FDA's handling of Dr. Wurtman's concerns was unusual. The tone of the
July 8 notice suggested that the burden was on Dr. Wurtman to
demonstrate that aspartame is harmful and that, absent affirmative
demonstration of harm (which obviously is lacking at this point),
aspartame must be approved. To the contrary, however the burden is on
Searle to prove to a reasonable certainty that no harm to human health
will result from aspartame. Thus, the question for FDA in evaluating Dr.
Wurtman's concern is whether, in the minds of competent scientists, the
questions posed by Dr. Wurtman, and his data are sufficiently
significant from a safety standpoint that they should be more thoroughly
addressed by Searle in order to provide the statutorily required
"reasonable certainty" that no harm will result from aspartame's use.
********************** Begin Notes area **********************
17) FDA acknowledges this distinct possibility when it states its
"belief" that changes in these procedures will avoid the problem.
Section 409 cb3 B does not contemplate that a "belief" in unspecified,
but fundamental changes in industry practice are adequate to assure that
widespread use of a food additive will not adulterate the food.
18) Fn stating rating periods
19) In the preamble to the APM regulation, FDA dismissed summarily the
concern about the functionality of APM in soft drinks at temperatures
above 30 degrees C (86 degrees F): "The agency believes, however, that
storage at these times and temperatures can be avoided by attention to
handling and distribution." (48 Fed. Reg. at 31377). This summary
resolution of the functionality issued is inconsistent with the FDC Act
for two reasons. First, it is based on the agency's "belief" and not on
any objective evidence. The Act requires the agency to resolve material
issues based on facts, not on beliefs. Moreover, the facts--actual
temperature conditions to which the beverages are exposed and actual
beverage temperatures--suggest that degradation and consequent loss of
sweetness and overall liking (and hence functionality) may occur within
even shorter periods than the agency appeared to find acceptable.
Secondly, the purported resolution of the functionality issue by
assuming that significant loss of sweetness "can be avoided by attention
to handling and distribution" is an assumption unsupported by any
evidence in the present record (none is cited by the agency). In all
likelihood, the agency's "resolution" is entirely impracticable. To
assume that fundamental changes in handling and distribution will occur
to avoid an acknowledged functionality problem turns the FDC Act on its
head.
********************** End Notes area **********************
May 7, 1985 CONGRESSIONAL RECORD -- SENATE S5511
We object to the approval of aspartame for unrestricted use in soft
drinks (which could be as high as 550 mg/liter, or higher) on the ground
that Searle has not made the required showing. This objection is
supported by (1.e following points, which are discussed farther below
and supported by the accompanying affidavits:
(1) available evidence
demonstrates that the consumption of aspartame/carbohydrate combinations
by rats in amounts comparable to those likely to be encountered by
humans under certain reasonable anticipated conditions of use elevates
plasma ratios of PHE and TYR significantly and brain PHE and TYR levels
by factors of 3.0 and 3.5, respectively;
(2) available evidence from
human studies demonstrates that consumption of aspartame/carbohydrate
combinations in amounts likely to be to be encountered under certain
reasonable anticipated conditions of use elevates human plasma levels of
PHE significantly beyond the normal range:
(3) there are sound
scientific reasons to believe that human brain levels of PHE and TYR
will respond to aspartame consumption in a manner similar to rats:
(4)
there are sound scientific reasons to believe that increased brain
levels of PHE and TYR could affect the synthesis of neurotransmitters
and in turn various physiological functions and/or behavior: for
example. TYR is a known precursor of the catecholamine
neurotransmitters, and tyrosine levels have been shown to affect several
bodily functions controlled by the autonomic nervous system (including
regulation of blood pressure):
<5) the demonstrated ability of
aspartame to inhibit the glucose induced release of serotonin has the
potential to affect important serotonin-mediated behaviors, such as
satiety, food choice and sleep.
Despite the potential effects of aspartame/carbohydrate
combinations, the present record is devoid of readily obtainable
evidence that could resolve whether the effects are in fact likely to
occur. As will be demonstrated the data cited by FDA in its July 8
notice are not sufficient to resolve the issue. It would be possible,
however, to perform within approximately six months studies in rats that
would resolve conclusively whether levels of aspartame and carbohydrates
corresponding to those likely to be consumed by humans would affect the
synthesis of neurotransmitters and in turn cause detectable
physiological and behavioral effects. It also would be possible to
perform additional short-term studies in humans to determine whether
aspartame/carbohydrate combinations have observable effects on
physiological parameters (such as blood pressure) or behavior.
For these reasons, Searle has not met its burden of demonstrating
to a reasonable certainty that the unlimited use of aspartame,
especially in combination with carbohydrates, will not adversely affect
human health. The questions posed by Dr. Wurtman are significant
because of the seriousness of the potential effects (e.g., changes in
blood pressure) and because of aspartame's anticipated widespread use--
use that includes consumption by potentially vulnerable sub-groups, such
as children, pregnant women, and hypertensives. Dr. Wurtman's concerns
are shared by other distinguished scientists expert in this field
(affidavits attached). It is Searle's legal burden to submit data
sufficient to resolve the concerns.
FACTUAL INFORMATION SUPPORTING OBJECTION FOUR
1. FDA has underestimated the amount of aspartame that can be
consumed through its use in soft drinks because the agency has focused
on adult users assumed to average 60 kilograms in weight). FDA relied
upon an intake value of 34 mg/kg/day in assessing the possible risks of
aspartame, describing that level as the "...highest obtained from any
estimate of potential consumption and exceeding) the 99th percentile
consumption (25 mg/kg) for all age groups..." 48 Fed. Reg. at 31377.
For a 30 kg child, however, it would not be unusual for that level to be
achieved or, in terms of the effect on plasma PHE levels, even exceeded.
For example, if a 30 kg child consumed on a warm day after exercise
approximately two-thirds of a two-liter bottle of soft drink sweetened
solely with aspartame, that child would be consuming approximately 700
mg. of aspartame, or approximately 23 mg/kg. This alone roughly equals
what FDA considered the 99th percentile consumption level. If during
the day this child consumed other aspartame sweetened products, the
exposure level could quickly approximately FDA's so called "loading
dose" of 34 mg./kg. 18 Fed Reg. at 31377. In addition, however, data
derived from rats and humans demonstrate that concurrent consumption of
a modest amount of carbohydrate (approximately 3 grams per kg. or, for a
30 kg child perhaps several cookies) approximately doubles the effect of
the aspartame on the ratio of plasma PHE to other large neutral amino
acids (LNAA) (Wurtman affidavit). Thus, in terms of effect on the PHE/
LNAA ratio in the blood, the above described concurrent consumption of
aspartame and a carbohydrate is equivalent to an aspartame dose of as
much as 50 to 60 mg./kg.
2. Aspartame has been tested in rats to determine the effect of
aspartame and aspartame/carbohydrate combinations on the plasma ratios
and brain levels of various amino acids (Wurtman affidavit). In rats fed
200 mg/kg aspartame, the plasma PHE/LNAA ratio increased to 0.185 from
0.110 in the controls, and the brain PHE level increased from 52 n-
moles/g in the controls to 110 in the treated animals. When the same
amount of aspartame was fed with 3 g/kg glucose, however, the plasma
PHE/LNAA ratio increased sharply again to 0.240, while the brain PHE
level increased to 143 n-moles/g. In addition, there was a 3.5 fold
increase in brain TYR levels.
3. Aspartame and aspartame/carbohydrate combinations have also
been tested in humans by Searle and Dr. Wurtman (cite to Searle petition
and Wurtman affidavit). An aspartame dose of 34 mg/kg significantly
elevated the plasma PHE/LNAA ratio, an effect that is almost doubled by
the addition of 30 g of carbohydrate (equivalent to 4 or 5 cookies).
4. It is not possible to measure in vivo human brain levels of amino
acids resulting from consumption of aspartame or subsequent effects on
neurotransmitter synthesis. There are sound theoretical reasons,
however, far considering the rat to be an appropriate model for
assessing possible human effects (Wurtman affidavit). Moreover, there is
empirical evidence to support the use of the rat as a model for
evaluating possible effects of aspartame on human brain chemistry
(Wurtman affidavit).
5. There is scientific evidence suggesting that increases in brain
PHE and TYR levels of the order seen in the rat studies can effect
synthesis of neurotransmitters, which themselves can effect important
physiological functions and potentially behavior. (Wurtman affidavit
should catalogue this evidence.) Readily available tests could
determine whether aspartame has such neurotansmitter effects in rats or
effects the rat's physiological functions or behavior. (Wurtman
affidavit should describe tests.)
6. Aspartame has been demonstrated to inhibit the carbohydrate-
induced-synthesis of the neurotransmitter serotonin (Wurtman affidavit).
Serotonin blunts the sensation of craving carbohydrates and thus is
part of the body's feedback system that helps limit consumption of
carbohydrate to appropriate levels. Its inhibition by aspartame could
lead to the anomalous result of a diet product causing increased
consumption of carbohydrates.
***************** (separate footnote) ******************
Also it should be noted that this was written in l983 and put in the
Congressional Record in l985. After protesting the NSDA turned around
and lobbied for NutraSweet.