BACKGROUND PAPER IN SUPPORT OF FUMONISIN LEVELS IN ANIMAL FEED: EXECUTIVE
SUMMARY OF THIS SCIENTIFIC SUPPORT DOCUMENT
November 9, 2001
FDA Center for Veterinary Medicine
The complete document of the following can be downloaded from:
http://www.cfsan.fda.gov/~dms/fumonbg4.html
SUMMARY:
The purpose of this document is to provide the scientific support behind our
(CVM's) recommended maximum levels for fumonisins in animal feed (Table I).
Fumonisins are environmental toxins produced by molds and found primarily in
corn. The major types of fumonisins are B1 (FB1), B2 (FB2) and B3 (FB3).
Our goal was to identify fumonisin levels in feed that are adequate to
protect animal and human health and that are achievable with the use of good
agricultural and good manufacturing practices. We wish to emphasize that the
recommended levels are intended to provide guidance that may change
following public input and are not to be considered tolerances. Future
research and/or different interpretations of existing research could change
the recommended values.
These recommendations are the result of reviewing the published literature
to determine the effects of fumonisins when fed to various animals,
including horses, rabbits, catfish, ruminants, poultry and mink. There were
many gaps in the literature regarding the feeding of low levels of
fumonisins to animals. Although this compelled some extrapolation of the
data to establish draft guidance levels for fumonisins in the diets of
various species, all calculations are derived from factors found in the
literature.
In six instances, we grouped species together because the animals seemed to
have a similar sensitivity to fumonisins. This is an attempt to avoid a
multitude of guidance levels and does not necessarily imply that the species
are biologically similar.
Horses and rabbits were grouped together as the most sensitive species. Corn
and corn by-products used in rations of horses and rabbits should contain
less than 5 ppm of FB1 + FB2 + FB3 and comprise no more than 20% of the dry
weight of the total ration
(Table I). The total ration should contain less than 1 ppm of FB1 + FB2 +
FB3 (0.2 x 5 ppm FB1 + FB2 + FB3 = 1 ppm of FB1 + FB2 + FB3).
Catfish and swine were grouped together as intermediate in sensitivity to
fumonisins. Corn and corn by-products used in rations of catfish and swine
should contain less than 20 ppm of FB1 + FB2 + FB3 and comprise no more than
50% of the dry weight of the total ration (Table I). The total ration should
contain less than 10 ppm of FB1 + FB2 + FB3 (0.5 x 20 ppm of FB1 + FB2 + FB3
= 10 ppm of FB1 + FB2 + FB3).
Ruminants, mink and poultry were considered more resistant than horses,
rabbits, catfish and swine to fumonisin; however, there was no data found in
ruminants and mink at total dietary levels between 25 and 100 ppm of total
fumonisins, while the data in poultry at these levels was more robust. Due
to this data gap, we were more conservative in our recommendations for
ruminants and mink than in poultry.
Corn and corn by-products used in rations of ruminants that are at least 3
months old and fed for slaughter and in rations of mink fed for pelt
production should contain less than 60 ppm of FB1 + FB2 + FB3 and comprise
no more than 50% of the dry weight of the total ration (Table I). The total
ration should contain less than 30 ppm of FB1 + FB2 + FB3 (0.5 x 60 ppm of
FB1 + FB2 + FB3 = 30 ppm of FB1 + FB2 + FB3).
Corn and corn by-products used in rations of poultry fed for slaughter
should contain less than 100 ppm of FB1 + FB2 + FB3 and comprise no more
than 50% of the dry weight of the total ration (Table I). The total ration
should contain less than 50 ppm of FB1 + FB2 + FB3 (0.5 x 100 ppm of FB1 +
FB2 + FB3 = 50 ppm of FB1 + FB2 + FB3).
The National Center for Toxicological Research (NCTR in Jefferson, AR)
recently completed a chronic dietary bioassay with purified FB1. This study
showed clear evidence of kidney tumors in male rats and of liver tumors in
female mice at dietary levels of 50 ppm and above.
We believe 15 ppm of FB1 + FB2 + FB3 in the total ration of mink, ruminant
and poultry breeding stock should provide adequate protection against any
potential carcinogenic effects in these animals. This recommendation is
based upon the NCTR chronic study
where 15 ppm FB1 produced the same or fewer kidney and liver tumors compared
to the controls. Corn and corn by-products used in the rations of mink,
ruminant and poultry breeding stock should contain less than 30 ppm of FB1 +
FB2 + FB3 and comprise no more than 50% of the dry weight of the total
ration (Table I). If the recommended total fumonisin level in the total
ration for a species was less than 15 ppm, we did not believe that the
breeding stock of the species needed additional protection from possible
carcinogenic effects.
The last grouping was of animal species/classes not mentioned above (e.g.
dogs, cats). Often there was no published dietary study with fumonisins in
these animals and no historical indication/association of problems from
feeding corn. We believe 5 ppm of FB1 + FB2 + FB3 in the total ration should
provide adequate protection against any potential acute and/or carcinogenic
effects in these animals. This recommendation is based largely upon the NCTR
chronic study where 5 ppm FB1 appeared to be the
no-observed-adverse-effect level. Corn and corn by-products used in the
rations of these animals should contain less than 10 ppm of FB1 + FB2 + FB3
and comprise no more than 50% of the dry weight of the total ration (Table
I).
We acknowledge that extensively validated "quick" or confirmation tests are
not commercially available for total rations. However, the Association of
Official Analytical Chemists International has established an official
method (995.15) for determining fumonisins B1, B2 and B3 in corn. In
addition, the United States Department of Agriculture's Grain Inspection,
Packers and Stockyards Administration (GIPSA) announced on June 5, 2001,
that two test kits have been approved for official testing of fumonisins in
the national grain inspection system. GIPSA authorized the use of the
Veratox Quantitative Fumonisin Test kit, manufactured by Neogen Corporation,
to determine fumonisins in corn, corn meal, popcorn, rough rice, corn/soy
blend, and wheat; and RIDASCREEN® FAST Fumonisin test kit, manufactured by
r-Biopharm Inc., for fumonisins in corn, corn meal, sorghum, corn gluten
meal, corn germ meal,
and corn/soy blend. We believe that the recommended fumonisin levels will
stimulate additional interest in developing and certifying/validating
confirmatory tests and "quick tests" for determining fumonisins in corn,
corn by-products, and complete animal feed rations.
The following is a summary of pivotal studies that were crucial in our
decision making. While we reviewed each publication listed in the reference
section, no attempt was made to summarize each article.