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OCR for page 39
39
NITRITE
Catherine S ~ . Hi faire
A. 8ACK&ROIJl~D AND CONTEXT
1. Describe the chemical and its uses.
Nitrogen exists in nature in various forms one of which is nitrate.
Nitrites are chemicals that form when living systems act upon nitrate
salts, which are widely distributed in soil, plant s, and cancer, or
upon n i trogen in o ther forms .
Nitrite inhibits the growth of various microorganisms found in
foods, including Clostridium botulinum. It also helps to maintain the
typical reddish color of cured meats, inhibits the development of
rancidity in meat and fish, and may contribute to the flavor of cured
products. lathe addition of nitrite to meres has been permitted in the
U. S. since 1925. It is currently added to meats and fish primarily as
an antimicrobial. Approximately 25Z of all meats consumed by the U.S.
population contain added nitrite.
2. Describe how the question of risk was elevated to the agency
level .
There are two aspects related to the risks of nitrite inge.s tion:
(a) The contribution of nitrite to the formation of nitro-
samines (a large group of chemicals over 90 percent of which
are care inogens in animal ~ ~ .
N_: This case study describes assessment procedures and summarizes
issues and interpretations raised by others, but it is not intended to
present independent positions or interpretations on either scientific
or policy matters. The case has been reviewed by individuals outside
the s tudy pro j ec t who are d i rec t ly f ami 1 far wi t h t he f ede ra 1 analyse s
and decisions described; however, responsibility for the paper rests
with the author, and it does not necessarily reflect the judgment of
the Committee on the Institutional Means for Assessment of Risks to
Public Realtl, or the National Research Council. It has not been sub-
jec ted to internal review procedures the t app ly to report s prepared by
NRC commi t tees .
OCR for page 40
40
(b) The carcinogen/city of nitrite per se.
Two agencies are involved in the regulation of the use of nitrite in
cured meats--USDA and F0A. Interest in risks associated with
nitro~amine formation stem from findings in the 1910s that vitro
gamines were found in a number of foods. Earlier findings had also
indicated that nitrosamines could form in the body fat lowing inges tion
of nitrite. In 1970, the US~OA and FDA formed a group to coordinate
research activities in tqnis area.
In 1972, ache t?Sl)A was petitioned to ban or greatly reduce the use
of nitrite. The petition was denied. Based on additional evidence of
the presence of nitrosamines in bacon, the Secretary of Agriculture
appointed an advisory Expert Panel on Nitrites ant Nitrosamines. In
September 1974, the Panel provided a prel imaginary report which prompted
USDA to propose several regulations that reduced the levels of nitrite
permitted in various meat products ~
In 197S, the Panel issued its final report recommending levels of
nitrite in a variety of products. USOA published a final regulation
on the use of nitrite in bacons Further action on the rules proposed
by USI)A in 1975 and the other reco~enda~cions of the Expert Panel were
halted in mid-1978 by a report that nitrite Per se was carcinogenic in
animal s.
3. under what statutes and agency jurisdiction does the chemical
fall' What statutory tes ts governed the decision?
lathe Federal Food, Drug, and Cosmetic Ace (2l U. S.C. 301 et
seq. ~ (FI)&C Act), as amended on September 6, 1958, by the Food
Additives Amendment (2l U.S.C. 348), requires FI)A to establish
regulations prescrib ing the coadi tions under which a food additive
may be safely used. The act defines a ''food additives as any
substance which becomes or may be expected to become a component
of foods either directly or indirectly or r.`hicl, may otherwise
affect the characteristics of the food. Before a regulation can
be established the additive must be shown to be safe and
functional for its intended uses (i.e., it must accomplish the
effect for which it is to be used--preser~ra~i~res must preserve).
The act states, however, that no food adtiti,Je shall be deemed
3a fe if it is found to be carcinogenic ~ induce cancer) when
ingested by man or animal or if it is found, after tests which
evaluate the safety of food additives, to induce cancer in man or
animal. Ibis provision is commonly known as the Delaney Clause.
Under Chin provision if a substance is shown, based on scientific
analysis, to induce cancer when fed to test animals, FDA cannot
al low its uses
OCR for page 41
41
In addition, if after its approval, a substance is found, by
adequate scientific Stridence, to be carcinogenic, its '~se must be
banned. I f the evidence is not sufficient to prove that the
substance is carcinogenic out does raise substantial unresolved
ques tions about its safety, the general safety clause o f the act
(21 U.S.C. 348(c)~3~(A) ~ would require the banning of the
subs tance .
The requirements for revoking approval of a food additive are
not as demanding under the general safety clause as under the
Delaney Clause. Instead of proof that a substance causes cancer,
FDA is required only to present new evidence raising a substantial
unres o tved que s t ion about the s a fe ty ~ f an ap proved s ubs tance .
FDA does not have the burden of proving that a substance causes
cancer or that it is otherwise unsafe; FDA has only to present new
evidence that raises a subs tantial safety question. lithe burden
then is on the manufacturer to resolve the question by showing
that the subs Lance is safe.
The Food Additives Amendment exempts certain categories or'
food ingredients from the definition of "food additive . " One such
category includes those substances that have 'I prior sanctions. "
substance has a prior sanction if its use in food was sanctioned
or approved by FI)A or 'MISDO before September 6, t958, the effective
date of the amendment. Such approvals were granted under
provisions of the FDSC Act, the Poultry Products Inspection Act
(21 U.S.C. 451 et seq. ), and the Federal Meat Inspection Act (2l
U. S.C. Sol _ seq. ) .
Because prior sanctioned substances are not covered by the
definition of "food additive, " the provis ions of the Food
Additives Amendment, including the Delaney Clause, do not apply to
them. The three laws under which prior sanctions were granted
provide, however, that the public is to be protected from adul-
terated food products. They state that food is adulterated if "it
bears or contains any poisonous or deleterious subs tance which may
render it in jurious to health. " Thus, if competent scientif ic
evidence demonstrates a reasonable possibility that some Consumers
may be harmed by eating food containing a prior-sanctioned
substance, the food is adulterated and cannot be introduced into
the food supply.
USDA is responsible for assuring that the Nation's meat and
poultry supply is safe, wholesome, and properly labe led. While
FDA has primary responsibility for approving the use of substances
identified as food additives, US])A has the additional respon-
sibility to determine that an FDA-approved additive may be used in
meat and poultry products. This responsibility includes deter-
mining that the approved additive w~11 serve a useful purpose and
establishing a minimum amount of the additive necessary to achieve
that purpose. USDA also restricts and monitors the use of
approved additives to assure that requirements for safe use are
met .
OCR for page 42
42
40 Mat was the decision schedule?
May 2, 1978
May 16, 1978
July ~ 1978
Augus ~ 28, 1978
October 18, 1978
[larch 3D, 1979
March 30, 1979
Top FDA and USDA of ficials are
briefed on the s tudy showing
that nitrite is carcinoo
genie. (No written report
submitted. ~
Special At Hoc Working Group
begins review of s tudy and
development of regulatory
options .
USI)A and FI)A seek Attorney
General' s ruling on their plan
to phase out nitrite and
arrange for joint news con-
[erence announcing they r
decision concerning nitrite.
FDA t s '"50-page paper" outs
1 ining agency ~ s dec i s ion to
phase out nitrite is leaked.
FDA-USDA news confe renc e ~ s
cancel lied .
Interagency Woricing Group
(I.AWO) on nitrite meets.
2 pathologists on the IAW(;
reported that patllolog~cal
assessment of tumors in MIT
study may be faulty.
FDA contracted the UAREP, a
nonprofit Consortium repre-
senting pathology departments
of 15 universities to review
pathological s 1 ides of MIT
~ tuty .
The Attorney General found
that there was no legal basis
for a ohaseout and . i ~ nitri te
caus es cancer, the
were to assure its
removal from commerce
agenc He s
orderly
OCR for page 43
43
March 30, 1979
Spring 1979
August 15, 1980
Augus t 1980
September 1980
December 1981
B. CHARACTERIZATION OF RISK TO HUMANS
(Sections B & C were combined)
1 What health endpoints were evaluated?
.
Care inogenic i ty ~ as de tee ted in animal te s t s ~
Sec. of HEW and USDA hold
press conference to announce
intention to propose legis la-
tion to prohibit FDA and USDA
from banning before May 1,
1980 and to give F1)A and USDA
the author) ty to phase out
nitrite, if it is determined
. .
to Be carcinogenic ~ over a
period of years ~ dependent
upon the development 0 f
alternative means of food
preserve tion .
A number of bills are intro-
duced in Congress to prevent
the agencies from banning or
phasing out nitrite.
UAREP report fail s to confirm
carcinogenic) ty of ni tri te--
IAWG issues final report
stating nitrite is not a car-
c inogen .
F1)A and 13SI)A announc e the t no
ac ~ ion ski l l be ~ aken agai ns t
nitrite .
USDA - FDA under take jo int
contrac t we th the NAS for
review of health effects of
nitrate, nitrite, and
N-nitroso compounds.
NAS releases final report
confirming that nitrite per se
is not a carcinogen but that
it may contribute to formation
of carcinogenic nitrosamines.
.
OCR for page 44
44
2. What were the key data available for review'
study conducted for the FDA by Or. Paul Newberne, a senior
pathologic t at MIT, which showed that nitrite caused a
statistically significant increase in the number of lymphoid
tumors in rats.
In tale large lifetime s tudy conducted for the Food and Drug
Administration (FBA), sodium nitrite was administered to groups of
approximately 68 male and 68 female Sprague-0awley rats under a
variety of conditions. Groups ~ to 5 received 0, 250, 500, 1,000
or 2,000 mg/Icg sodium nitrite in the diet, and groups 6 and 7
received ~ ,000 or 2,000 mg/titer in drinking water. For these
groups, an agar-based semisynthetic diet was used. For groups 9
to Il. a commercial chow diet was substituted, and sodium nitrite
concentrations of 0, 1, 000 or 2, 000 mg/Icg diet were fed to the
animals. Groups 13 and 14 were given a refined casein diet
containing nitrite at O or 1,000 mg/Icg, while another two groups,
15 and 16, were fed the original semisynthet~c diet containing
nitrite at ~ or I, 000 mg/kg. Each of the latter two groups
contained only 34 animals -the dams that supplied the pups for
groups t and 4 0 Groups 17 and 18 were al so f ed the s emisynthe tic
diet containing nitrite at O or 1,000 mg/kg. Groups 1 through 16
were exposed prenatally, simile groups 17 and 18 were exposed at 21
days. Groups 3 and 12 served as positive controls and received
urethane (2,000 mg/liter) in drinking water or in the semi-
~ynthetic diet, respectively. The rats survived the sodium
nitrite regimens well, the only adverse effects being a loss of
weight in groups receiving 2,000 mg/kg in their died and, to a
lesser extent, in groups receiving 2,000 mg/liter in drinking
water.
Histopathologic assessment of the tissues indicated that by
considering all the groups receiving sodium nitrite together,
there was a statistically significant excess of lymphoid tumors
~ p ~ 0 . 01, based on ch i-s quare analys i s ~ . ~ is was re f lee ted
especially in the groups receiving sodium ni trite in drinking
water, where the excess of lymphoid tumo. s was statistically
significant, but the results were not significant in the other
groups treated with sodium nitrite.
In addition to malignant tumors of the lymphat ic system, an
alteration referred to as immunoblastic cell proliferation was
observed in the spleen and, occasionally, in the lymph nodes of
some members of all groups except the positive controls (groups of
8 and 12 ~ . The incidence of this abnormal i ty in nitrite-created
animals, however, was greater (11.2%) than in the untreated
animals (7%) . T.ne disease in humans, which is histologically
similar to that observed in rats, is cons ideret by some to develop
into tymphc'ma; others consider it not to be preneoplastic.
These results were taken as an indication that nitrite is
an enhancer or promoter of carc~nogenes is in rats.
OCR for page 45
45
3. To performed the initial analysis ?
'The FDA commissioner appointed a special ~ntra-agency Ad Hoc
Working Group to review the data and to make recormnendationse The
Chief Counsel was responsible for overall development of the
regulatory policy and the Acting Director, Bureau of Foods was
responsible for directing the scientific review of the study. The
other members of the Ad Hoc Working Group were the Commissioner,
Deputy Commi so loner, Execut ive Ass is tent to the Commiss toner,
Associate Director of Regulatory Affairs, Director of Health
Affairs, and two staff scientists from the Bureau of Foods .
4. To what extent were the resut ts presented quantitatively? What
factors influenced the degree of quantification?
The data from the MIT study were used to estimate leukemia-like
cancer risks to humans (Table I).
5. Row was uncertainty described in reaching the final inter-
pretations? Were crucial assumptions made explicit?
Assumptions that had to be made were listed:
(a) Cat humans consume t/4 of the amount of nitrite
initially added to cured products.
(b ~ Chat humans and rats are equally sens itive to the cancer-
causing effect of nitrite.
~ c ~ That there is a linear relationship between the incidence
of cancer resulting from the doses ingested by the rats and
that resulting froro the doses to which the average American is
exposed.
(d) That the risk of cancer from nitrite is evenly spread over
the American population.
6. How were qualitative factors dealt with?
A discussion of the validity of animal tests was included in a
document (the "50-page paper'') describing the basis for FDA's and
USDA's action regarding nitrite. This discussion did not empha-
size the uncertainty of extrapolating from animals to man but
instead served to refute arguments that have been made against
this use of animal tests.
OCR for page 46
46
TABI`E I: ESTIMATED LIFETIME CANCER RISK FROM NITRITE*
( From the "50-page paper" )
Based on I no idence In Tes t Ra ts o f
Dietary Source of Nitrite
All sourc es
Cured meats
(200 ppm nitrite)
o
LYmohomas
. .
1/ 3450-1/2040
(209 - 4O9)
Lymphomas +
I~unoblastic
Ce 11 prol if erat ion
1/1560-1/794
(6.4 - 12.6)
1.6 oz~day 1/16,7001/9090 1/7L40-1/3700
(0.6 - 10 t)
(lo4 - 247)
8 oz/day 1/3230~1/1890 (6.8 - 13.5)
(40 ppm nitrite)
1.6 oz/day 1/100,000-1/50,000 1/33, 300-1/20, 000
(0. 1 - 0.2)
(0.3 - 0.5)
oz/day 1/ 16, 700-1/943 I/ 7140-1/3700
(0.6 - 1006) (104 - 2.7)
*lathe two risk estimates in pacts case are based on: (1) the amount of nitrite
added to the rats' food or water; and (2) the average amount of nitrite to
which the rats were actually exposed at each dose level. The numbers in
parentheses are the estimated lifetime cancer risks per 10,000 population.
OCR for page 47
47
Other key qualitative factors were neglected, including the basis
for concluding that the tissue changes in the rat spleen were actually
related to leukemias. Ibis problem awaited scientific critique and
eventually led to the refutation of the FDA conclusion. Other factors
were the absence of a dose-response ant a charge that the different
groups o f tes ~ animals became mixed during the course of the
experiment .
7. Mat qualitative factors affected the weighting of data? Were
such criteria explicit and in accord with any general guide-
1 ines ?
-
The only qualitative factors discussed in this analysis were:
~ a) The acceptance of animal tee ts conducted at high doses
(this is consistent with [RLG guidelines.)
(b) The assumption that low dose effects are linearly related
to }ligh dose effects, i.e., effects are directly proportional
to dose even at lower doses. Allis is consistent with IRLO
guidel ines . ~
8. Describe any internal, internal advisory, and external
scientific review of the initial analysis. that, if any,
cri ticism was incurred?
Apparently, there was no internal or external peer review of
the ini tial analys is prior to ache Commiss loner informing the
Secretary of HEW of the plan to phase out nitrite.
In August 197S, an Interagency Working Group composed of
scientists from FDA, USDA, and NIH was convened to review the
scientific data of the MIT study. At the same time, the study
results were sent to outside reviewers.
The following criticisms were made:
(a) The method of showing statistical significance (combining
all treated animals in one group) was improper.
(b) The control groups had an unusually high incidence of
lyTephomas.
c ~ Dose-response was no t c [early demons tra ted .
(d) Additional studies in another strain of rat and another
species should be conducted before reaching a conclusion.
OCR for page 48
48
~ e) The possibility that the tumors were caused by nitro
samines could not be ruled out.
(f) The accuracy of the pathology diagnoses was questioned by
IAWG pa~hologis ts who reviewed some o f the tissue ~ rides .
9. How were the issues raised in the reviews ac~o~mnodated?
. . . ~
The ma jar issue was the ques tion of pathological diagnoses ~
Mile Interagency Working Group on Nitrite Research reviewed a
sample of histological slides and decided that there was
sufficient difference of opinion in the diagnoses to warrant a
further evaluation of the histopatl?ological findings. The
Uni~rersi ties Associated for Research and Education in Pathology
(UAREP), a nonprofit consortium of 15 universities organized ho
carry out education and research activities in pathology, was
selected by the FDA to review the slides. A Joint Committee of
Experts, which was established by the UAREP to perform this
review, diagnosed fewer Amphoras than had criminal ly been
reported . The dispari ty be tween the two series of diagnoses
involved the differentiation of lymphomas from extramedul lary
kematopoiesis, plasmacytosis, or histiocytic sarcoma. Further-
more, the committee was unable to confirm the diagnosis of
immunoblss~ic byperplasiaO
In i ts f inal report to the FOA, the Government Interagency
Working Group summarized its assessment of the 1JAREP committee 's
findings as follows:
I've major result of the histopathology review was that
most of the lymphoma diagnoses originally reported were
not confirmed A relatively high incidence of lymphomas
had been reported by Or. Newberne, [the scientist who
conducted the original study] with a significantly in-
creased incidence in the total combined treated groups
as compared to combined controls. Me UAREP pathologists,
on the other hand, diagnosed very few les ions as lympho~na,
with a resulting reduction of incidence to approximately
1: among treated and contra 1 group s . Thi s ra te 0 f 1yrephoma
incidence is similar to that usual ly seen spontaneous ly in
Sprague-Dawley rats.
UAREP pathologic ts did report a greater than 1: incidence
of other types of tumors, including his tiocytic sarcomas,
angiosarcomas, liver neoplasms, ear duct tumors, pancre-
atic tumors ~ pituitary tumor, and mammary tumors. However,
after statistical analysis and careful review by the IAWG,
no demonstration could be found that the increased incidences
of these tumors were induced by the inges tion of sodium
nitrite.
OCR for page 49
49
10. What other issues arose concerning scientif ic data and their
use? Briefly describe d issenting opinion.
See question ¢8
11. Is the substance subject to past or possible future
regulatory actions in other programs ? If so, did the program
office coordinate with other agencies or programs?
a_
The use of nitrite, especially in terms of the amounts
permitted in various products, has been regulated in the past (and
is subject to future regulation) by the USDA. In the case of the
planned phaseout of nitrite, FDA informed USDA of its activities--
the original announcement was to 'nave been made jointly by the
Secretaries o f HEW ant {JSDA.
C . INTO Rl?RETArl019
1. What role did risk assessment have in the f inal agency docu-
ment where standards were established ( proposed) to control
the che~nica 1?
(a) Risk assessment was used to show the reduction in risk
associated with a decrease in the amount of nitrite added to
bacon from 120 ppm to 40 ppm.
(b) Risk assessment was not used to compare risks from cancer
with risks from botulism ~ if nitrite were eliminated) . The
Ad Hoc Working Group felt the data were insufficient to
derive such an es timate .
It seems clear that the risk assessment was performed after
the decision to regulate had been made. Historically, both the
Commissioner of FDA and the Assistant Secretary of Agriculture at
that time believed that nitrite should be reduced based on the
nitrosamine potential. The latter individual had been frustrated
by the seeming requirement that nitrite itself be care, nogenic not
just a precursor to nitro~amines in order to remove it from the
food supply. Thus, when the tata apparent ly indicating a direct
carcinogenic effect emerged, the premise upon which nitrite could
be removed from food was obtained and led immediately to the
development o f regulatory strategies .
OCR for page 50
50
2. Were there variations in the assumptions used? Were these
Two risk assessments have been performed by FDA:
~ a) in the original Working Group Document (described in
preceding ques ~ ions ~ .
(b) in a subsequent report of the Nitrite Bask Force (formed
within the Bureau of Foods of F1)A).
ways .
The second assessment differed from the first in the following
~ a) Newberne reprised his own data af ter the original risk
assessment was done, Cue second assessment uses the revised
data.
(b) Equal sensitivity to nitrite between rats and humans was
assumed on a mg/kg-body-we ight teas is rather than a
cone ent ra t ion-~n- theoso 1 id-die t teas is .
(c) In the earlier assessment, it was assumed that 1 ppm of
nitrite in water ~ 1 ppm nitrite in sol id diet . The second
assessment assumes 1 ppm in water = 2 ppm in dice.
(~) Di fferent estimates of daily nitrite intake for humans
were used.
The second estimate was approximately 9Z of the original
est imate.
(~e NAS also did a risk estimate for cancer risks from
nitride; however their estimate of carcinogenic risk was based on
ache con~cribution of nitrite to the formation of nitrosarQines--not
as a direct result of exposure to nitrite. ~
3. To the extent that there were issues/concerns about Questions
.
of science, would the outcome have been improved by coherent
federal guidelines on carcinogenic ri sk assessment?
Yes. Despite the fact that the major Elaw in the inter-
pretation of the study stemmed from differences in pathologic
diagnoses that cannot be addressed by inference guidelines, there
were many other scientific issues that were not appropriately
cons idered in the initial assessment of risks done by IDA.
Adherence to comprehensive guidelines would have required that
these issues by looked at more carefully and be addressed in the
risk assessment documents Such consideration may have led to a
more intense peer review of the study and its interpretation by
FDA .
OCR for page 51
51
In this case, peer review of agency decisions and the science
underlying the decisions Is probably more important than the use
of risk assessment guidelines. Vigorous peer review did not enter
into the process until the decision to regulate had already been
made. Normal methods of FDA review were not followed for reasons
that, at the time, appeared justifiable. In my opinion, it is
1 ilcely that the normal peer review procedure would have revealed
the fatal flaws in the MIT data since the normal procedure* would
have called for the formation of an IAWG and it was in the Working
Group that the questions about the strides pathology diagnoses
were first raised. In addition, more stringent agency oversight
of projects, such as the Newberne Study, 'which have major policy
implications, eight have arrested the situation even earlier in the
proces s .
PERFORMANCE CONST DERATIONS
1 Ability to obtain relevant scientific information
.
FDA contracted for this study. One way to approach this question
is to focus on the importance of quality control and peer review/
oversight of FI)A-sponsored research. A GAO report was highly
critical of FDA monitoring of the MIT study. Also, GAO recom-
mended that research guidelines should be developed for design,
data-recording and reporting, and statistical evaluation for
carcinogenicity assays. Thus, FDA's ability to get reliable
information in this case was dependent on its own foresight in
planning the study and its co~nit,nent to ensuring that the
experiment was conducted and interpreted properly. A major
consideration leadin. to inadequate oversight was the high regard
FDA scientists had for Dr. Newberne and his institution--MIT. As
it turns out, a major portion of his pathological diagnoses was
done by ~ tudents no t Dr . Newberne himsel f .
US])A and FDA do not have a formal written pa licy for evaluating
sc ientific information concerning the safety of food additives.
There is an informal review process that is supposed to identify
the strengths and weaknesses of the data and the possible regulatory
alternatives. Bureau of Foods is responsible for scientific evalua-
tion. If cancer is involved, the Division of Toxicology begins the
review. The study is then forwarded to the Cancer Assessment
Committee. If the Committee members feel that a substance has major
scientific, economic, and regulatory significance, they will recom-
mend formation of an interagency working group (IAWG) to evaluate
scientific meri t.
OCR for page 52
52
SO Credibility of assessments.
Assessments were done by four different groups: The Ad R.oc
Working Group, a Bureau of Foods Task Force, the Interagency
rWorlcing Group, and the NAS.
The credibility of the initial assessment was low. Scientists
within the agency who normally review such data and who were not
involved in the review of ni trite felt uncomfortable with the
caliber of individuals reviewing the study. Subsequent review of
the study revealed many flaws in tie data, casting further doubt
on the conclusions drawn in the original assessment.
The credibility of the second review was not a major issue as
this was an internal document looking at the broader issues of
nitrosamine formation as well as nitrite carcinogenicity.
The final results of the TANG deliberations were released two
years after its review began. These results were supported by an
independent pathology review. Thus, it had more credibility than
the first assessment.
The findings of the NAS Committee on Nitrite have been largely
accepted.
3. What was the extent of diversity of policy orientations within
the assessment group? Outside pressures? Impact of pressures ?
Since the Ad Hoc Working Group was composed entirely of FDA staff
chosen by the Commissioner, it seems reasonable to assume that
similar "pot icy orientation" was shared 'oy the members of this
group. The Working Group ~ s deliberations were not conducted in an
open, public manner. Instead, their proceedings were kept secret,
even from other FDA personnel, because of the importance of the
issue and the fear of premature release of information. Thus,
outside input into the process was minimal and specie 1 interest
pressures would not blare come into p lay. FIowever9 the Working
Group was very much aware of the iTnplications of their decision
which would affect a $12-bilLion/yr industry and this fact, along
with the knowledge that nitrite protects against another risk--
botulism, most certainly affected the final approach suggested by
the Task Force.
4. What were the time and resources necessary to complete the
risk assessment?
The fire t assessment took two months .
Me second assessment by the IAWG took from Angus t 1978 to
March 1979 to comple te initial review and arrange for outside
pathology review. The results of that review were available in
August t980 and a final report of IAWG was issued August 15 $
1980. Cost of this review was approximately $900,000. The total
time required for the second assessment was two years.
OCR for page 53
53
lithe NAS report took IB months to complete and cos t approxi
mately $500, 000.
;. Responsiveness of the assessment agenda to public concerns,
interest group concerns, professional concerns, and emergence
of new ~ c ientific info. ma tion.
The decision to form an Ad Hoc Forking Group actually stemmed from
the Commissioner' s prey: ous experience with the proposed saccharin
ban, i. e., it reflected an agency awareness o f public concerns and
the importance to consider alternative regulatory actions. The
subsequent appointment of an Interagency Working Group resulted
from questions raised by F1)A scien~is ts concerning the carcino-
genicity data used to support the agency's regulatory position.
6. Ability of the risk assessment to identify research needs.
Although the director of the Bureau of Foods presented recommenda-
tions for additional research to clarify some o f the uncer~cainties
in Newberne's data, the FDA commissioner's judgment was that no
additional research was necessary. 'Thus, the first assessment
does not identify areas where further research might clarify the
issue. Later assessments did addres s Allis issue to varying
degrees; for example, the assessment done by the NAS does address
this issue rather extensively.
7. Extent to which risk assessment impeded or fac ilitated
regulation.
This is ~ confusing question because regulation was inappropriate
in this cane. So, if the question is reworded to "impeded or
facilitated making the most correct (or defensible) policy
decision'' I would answer that the assessment done by the Ad Hoc
Working Group did not result in the appropriate policy decision
while the assessment done by the IAWG did. The recently released
NAS review of nitrite would concur wi th this cone fusion.
S. Were related risk assessments consistent?
.,
No. (This question was addressed earlier. ~ AsseserQents done by
different groups led to different qualitative and quantitative
conclusions. That is, the Ad Hoc Working Group concluded that
nitrite was a carcinogen, as did the Bureau of Foods Task Force;
however, the risk estimates o f these two groups differed by
tenfold. she IAN concluded that nitrite was not carcinogenic, as
did the NAS Committee on Nitrites.
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9. tfas there a distinction between the weights given to science
and policy considerations?
Some observers of the nitri te decision would sugges t that policy
considerations were weighted more heavily than scientific con:
siderations in the initial as se~sment done by the Ad Hoc Forking
Group. Certainly, the makeup of the Group would indicate that the
"policy-~ypes" out numbered (and outranked) the scientists
inc. luded i n the group .
100 Mode and frequency of commun~cat ion between assessors and
regulators.
In the At bloc Working Group, the assessors and the regulators were
separated into two subgroups. The working group met frequently
during the two-mon~h period. In addition, the chief counsel did
review and convent on the scientific report, suggesting that there
was some interplay between two subgroups.
Representative terms from entire chapter:
food additives
