Natural Resources Defense Council, Inc. et al v. United States Food and Drug Administration et al

Filing 33

DECLARATION of Jennifer A. Sorenson in Support re: 19 MOTION for Summary Judgment.. Document filed by Center For Science In The Public Interest, Food Animal Concerns Trust, Natural Resources Defense Council, Inc., Public Citizen, Inc., Union Of Concerned Scientists, Inc.. (Attachments: # 1 Exhibit A, # 2 Exhibit B, # 3 Exhibit C, # 4 Exhibit D, # 5 Exhibit E, # 6 Exhibit F, # 7 Exhibit G, # 8 Exhibit H, # 9 Exhibit I, # 10 Exhibit J, # 11 Exhibit K, # 12 Exhibit L, # 13 Exhibit M, # 14 Exhibit N, # 15 Exhibit O, # 16 Exhibit P, # 17 Exhibit Q, # 18 Exhibit R, # 19 Exhibit S, # 20 Exhibit T, # 21 Exhibit U, # 22 Exhibit V, # 23 Exhibit W, # 24 Exhibit X, # 25 Exhibit Y, # 26 Exhibit Z, # 27 Exhibit AA, # 28 Exhibit BB, # 29 Exhibit CC, # 30 Exhibit DD)(Sorenson, Jennifer)

EXHIBIT F
TO DECLARATION OF
JENNIFER A. SORENSON
Excerpt from National Academy of Sciences 1980 Report

The Effects on
Human Health of
Subtherapeutic Use
of Antimicrobials
in Animal Feeds
Committee to Study the Human Health Effects
of Subtherapeutic Antibiotic Use in Animal Feeds
Division of Medical Sciences
Assembly of Life Sciences
National Research Council

NATIONAL ACADEMY OF SCIENCES
WASHINGTON, D.C.

1980

CHAPTER 5

CONCLUSIONS AND RECOMMENDATIONS

CONCLUSIONS
A relatively small proportion of the research that has been
conducted on the subtherapeutic or therapeutic use of antimicrobials in animal feeds is truly epidemiological. Much of the
information on this subject has been generated by poorly controlled
studies of small numbers of subjects observed for brief periods.
An ideal study of the effects on human health resulting from
the subtherapeutic use of antimicrobials in animal feeds would be
able to relate, without conjecture or speculation, antimicrobials
in feed to changes in morbidity or mortality or to treatment complications caused by resistance to antimicrobials in humans who had
been exposed to animals or meat products during processing, handling,
or, especially, consumption. Changes in morbidity and mortality
could be used to quantitate the risk of the potential hazards posed
by increased prevalence of resistant bacteria, by the development
of plasmids conferring multiple resistance, or by the evolution of
especially efficient transfer mechanisms within the reservoir of
bacteria in animals.
Because the literature provides only isolated fragments of
information relating to various components of the meat production
system, it is insufficient for assessing the direct relationship
between the use of subtherapeutic levels of antimicrobials in
animal feeds and the health of humans. A major deficiency in
much of the literature is the lack of a clear differentiation between the consequences of subtherapeutic and therapeutic uses of
antimicrobials in animals. Moreover, data gathered in the United
Kingdom, the Federal Republic of Germany, and the Netherlands do
not indicate clearly whether restrictive regulations have actually
reduced or averted the postulated hazards to human health. Restrictions on the use of antimicrobials in the United Kingdom may

- well - have altered the patterns dr -their use vithafr-sightficant
alteration in the total amounts used or their consequences. Therefore, it is not possible to conclude from the literature that restricting only the subtherapeutic use of p timicrobials will cause
a decrease in the overall prevalence of R organisms in humans or
animals. Furthermore, there is little information on qualitative
changes in resistance in the enteric bacteria of animals or humans.
For example, no data exist to indicate the extent to which new
resistance combinations or more efficient transfer mechanisms have
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been brought about by the subtherapeutic use of antimicrobials
in feeds.
After reviewing the evidence, the committee concluded that
the postulations concerning the hazards to human health that
might result from the addition of subtherapeutic anttnicrobials
to feeds have been neither proven nor disproven. The lack of data
linking human illness with subtherapeutic levels of antimicrobials
must not be equated with proof that the proposed hazards do not
exist. The research necessary to establish and measure a definite
risk has not been conducted and, indeed, may not be possible.
The committee gave considerable thought to the necessary
elements of the ideal study to measure accurately the effects on
human health resulting from the subtherapeutic use of antimicrobials in animal feeds and how such a study should be designed.
It concluded that a comprehensive, all-encompassing study
could not be realized or even approximated because of insurmountable technical difficulties. This decision reflected a number of
facts:
• There are marked differences in both the therapeutic and
subtherapeutic use of antimicrobials in the various major species
of animals raised for their meat and in the different regions of
the country.
• It is not clear how much the subtherapeutic use of antimicrobials, as compared to the therapeutic use, contributes to the
prevalence of resistant bacteria in animals.
• Animals with different histories of exposure to antimicrobials are known to exchange bacteria during normal rearing and
shipping prior to slaughter. Consequently, the types and amounts
of antimicrobials received by a particular slaughterbound animal
or its companions cannot be determined.
• Household members consume meats from animals that have
been exposed to different antimicrobial agents during the course
of different regimens, both subtherapeutic and therapeutic. Thus,
the
At ia-not practical to-determine original-eeleetive-preaaure
for resistant bacteria that may occur on a particular piece of
meat.
ributions• It is difficult to determine the relative-con
made by subtherapeutic and therapeutic levels of antimicrobials
in animals or in humans to the pool of resistant bacteria that
may affect human health.

54

The committee concluded that less comprehensive approaches,
although more feasible, could not provide direct evidence of a
consistent chain of events from animal production to meat consumption. However, it did outline a sequence of four possible studies
on individual aspects of the transmission chain. The results of
these studies, if interpreted with the recommended precautions,
would provide a useful scientific background for policymakers. At
best, however, the remaining gaps in our knowledge will still have
to be bridged by conjecture or speculation.
The committee also discussed some nonepidemiological aspects
of the subtherapeutic use of antimicrobials. A better understanding of the mechanisms through which subtherapeutic levels
of antimicrobials produce beneficial effects may lead to development of other substances or other treatments of equal or greater
effectiveness, thereby rendering this entire issue moot. For example, if the beneficial effect is caused primarily by controlling
infections, then other preventive techniques such as new vaccines
may yield equal benefit. If the mechanism is nutritional, i.e.,
nutrient sparing or an alteration of nutrient absorption, then new
nutritional supplements may yield the desired result.
Plasmids in isolates from animals and humans must be characterized to assess the possibility that subtherapeutic levels of
antimicrobials in animals produce qualitative changes in resistance
to antimicrobials in the enteric flora of animals, changes that
might subsequently affect human health.

RECOMMENDATIONS
The committee RECOMMENDS that future epidemiological studies,
whether the ones suggested here or others, be carefully planned to
fill gaps in our present knowledge and, especially, to avoid the
errors of ambiguous design and small sample size that have caused
such difficulties in interpretating the data. The proportionate
contributions to resistance made by subtherapeutic and therapeutic
uses of antimicrobials in animals and in humans urgently need resolution.
Thc commit-tee-RECOMMENDS increased and continued monitortN; -and surveillance of the occurrence of antimicrobial resistance in
bacteria in animals, in meat and meat products, and in humans,
especially in cases of human illness due to Salmonella and patho-genic E-corli-. If-restrictions on7antiMittObial use are adopted,
the committee RECOMMENDS that monitoring be continued in order to
determine the effect of such restrictions.

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The committee RECOMMENDS further research on:
• the mechanism of action of subtherapeutic levels of antimicrobials in feed (BARR, Appendix K) including characterization
of the composition and interactions of the gastrointestinal flora
(Savage, Appendix D),
• factors that inhibit the development and transfer of resistance in vivo (Jacoby and Low, Appendix C), and
• studies on the epidemiology of plasmid-mediated resistance
to antimicrobials in both animals and humans (O'Brien, Appendix I).