Comprehensive

Review of
Patulin Control
Methods in
Foods
Matthew M. Moake, Olga I. Padilla-Zakour,

and Randy W. Worobo

ABSTRACT: The mycotoxin, patulin (4-hydroxy-4H-furo [3,2c] pyran-2[6H]-one), is produced by a number of fungi com-mon to fruitand vegetable-based products, most notably apples. Despite patulins original discovery as an antibiotic, it has come under heavy
scrutiny for its potential negative health effects. Studies investigating these health effects have proved inconclusive, but there is little
doubt as to the potential danger inherent in the contamination of food products by patulin. The danger posed by patulin necessitates its
control and removal from food products, creating a demand for handling and processing techniques capable of doing so, preferably at
low cost to industry. With this being the case, much research has been devoted to understanding the basic chemical and biological
nature of patulin, as well as its interaction within foods and food production. While past research has elucidated a great deal, patulin
contamination continues to be a challenge for the food industry. Here, we review in depth the past research on patulin with an emphasis
upon its influence within the food industry, including its regulation, health effects, biosynthesis, detection, quantification, distribution
within foods, and control, during the various stages of apple juice production. Finally, key areas where future patulin research should
focus to best control the patulin contamination problem within the food industry are addressed.

Introduction

Patulin is a mycotoxin produced by a number of fungi common to

fruit- and vegetable-based products, most notably apples. Ap-ples
are the 3rd most important fruit crop in the United States after citrus
fruits and grapes, with 40% of apples being used for juice and other
processed products (USDA 2002). Patulin contamina-tion within
apple products poses a serious health risk to consum-ers,
particularly children whom have been shown by a USDA sur-vey to
consume increased levels of apple products during the 1st y of life
(6.4 g/kg body weight/d), compared with adults (1 g/kg bw/d)
(Plunkett and others 1992), placing them at increased risk for
patulin toxicity. The health risks posed by patulin necessitate its
control and removal from apple products, creating a demand for
food-processing techniques capable of doing so, preferably at low
cost to industry. Here, we review past research devoted to the

understanding and control of patulin, with an emphasis upon patulins influence within the food industry.

History and Regulation

Patulin (4-hydroxy-4H-furo [3,2c] pyran-2[6H]-one), Figure 1, is

a water-soluble lactone 1st isolated as an antibiotic during the

MS 20040335 Submitted 5/21/04, Revised 8/17/04, Accepted 10/18/04.

Authors are with Dept. of Food Science and Technology, New York State
Agricultural Experiment Station, Cornell Univ., Geneva, NY 14456-0462.
Direct inquiries to author Worobo (E-mail: rww8@cornell.edu).

1940s (Stott and Bullerman 1975). Owing to co-discovery of the

compound by various groups, it has historically been known by
names such as clavacin (Anslow and others 1943), expansine
(Van Luijk 1938), claviformin (Chain and others 1942), clavatin
(Bergel and others 1943), gigantic acid (Philpot 1943), and
myo-cin C (DeRosnay and others 1952). Initially isolated as a
broad-spectrum antifungal antibiotic (Korzybski and others
1976), it was later found to inhibit more than 75 different
bacterial species in-cluding both Gram-positive and Gramnegative bacteria (Ciegler and others 1971). Continued studies
on the application of the compound (Raistrick and others 1943),
later found to be unsup-ported by clinical studies (Medical
Research Council 1944; Stans-field and others 1944),
suggested patulin to have applications in treatment of nasal
congestion and the common cold. Not long af-ter, various
studies suggested patulin to be not only toxic to fungi and
bacteria but also to animals (see below, Health Effects) and
higher plants, including cucumber, wheat, peas, corn, and flax
(Iy-engar and Starky 1953; Norstadt and McCalla 1963, 1968;
Berestetskyi and Synytskyi 1973)

As continued evidence for the negative health effects of patulin

surfaced, many regulatory agencies began placing caps on
patu-lin content within foods. European countries were among
the 1st to address the concern, and today many countries
across the world, particularly those within the EU, limit
allowable patulin content within foods at 50 g/L (Moller and
Josefsson 1980; van Egmond 1989; AIJN 1990; Stoloff and
others 1991; Rovira and others 1993; Forbito and Babsky 1996;
Gokmen and Akar 1998).

COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETYVol. 1, 2005

Technologists

2005 Institute of Food

Patulin control in foods . . .

Table 1The health effects of patulin

Acute symptom
Source

Agitation, convulsions, dysponea, pulmonary congestion,

Escoula and others 1977; Hayes and others 1979
edema, hyperemia, GI tract distension

Nausea
Walker and Wiesner 1944
Epithelial cell degeneration, intestinal hemorrhage
Mahfoud and others 2002
Intestinal inflammation
McKinley and Carlton 1980a, 1980b; McKinley and others

1982; Mahfoud and others 2002

Ulceration
Escoula and others 1977; Hayes and others 1979; McKinley and Carlton 1980a,

1980b; McKinley and others 1982; Mahfoud and others 2002

Chronic symptom
Source

Genotoxic
Mayer and Legaror 1969; Korte 1980; Thust and others 1982; Lee and Roschenthaler

1986; Roll and others 1990; Hopkins 1993; Pfeiffer and others 1998

Neurotoxic
Hopkins 1993
Immunotoxic
Hopkins 1993; Wichmann and others 2002
Immunosuppressive
Wichmann and others 2002
Teratogeneic
Ciegler and others 1976; Roll and others 1990
Carcinogenic
Dickens and Jones 1961; Oswald and others 1978
Cellular level effect
Source

Plasma membrane disruption

Riley and Showker 1991; Mahfoud and others 2002
Protein synthesis inhibition
Hatez and Gaye 1978; Miura and others 1993; Arafat and Musa 1995
Transcription disruption, translation disruption
Moule and Hatey 1977; Arafat and others 1985; Lee and Roschenthaler 1987
DNA synthesis inhibition
Cooray and others 1982
Na-coupled amino acid transport inhibition
Ueno and others 1976
Interferon- production inhibition
Wichmann and others 2002
RNA polymerase inhibition
Moule and Hatey 1977
Aminoacyl-tRNA synthetases inhibition
Arafat and others 1985
Na-K ATPase inhibition
Phillips and Hayes 1977, 1978; Riley and Showker 1991

Muscle aldolase inhibition

Ashoor and Chu 1973
Urease inhibition
Reiss 1977
Loss of free glutathione
Burghardt and others 1992; Barhoumi and Burghardt 1996
Protein crosslink formation
Fliege and Metzler 1999
Protein prenylation inhibition
Miura and others 1993

With-in Foods), apple juice and cider remain the major source of
hu-man patulin consumption.

Health Effects
While 50 g/L is now the norm for patulin regulation, several countries
have set even lower limits for patulin at 25 to 35 g/L (van Egmond
1989). In conjunction with these maximum content standards, a joint
Food and Agriculture Organization-World Health Organization
(WHO) expert committee established a provi-sional maximum daily
intake of 0.4 g/kg body weight for patulin (WHO 1995). The United
States has been much slower to set reg-ulation on patulin, but today
the U.S. Food and Drug Administra-tion limits patulin to 50 g/L in
single-strength and reconstituted apple juices (USFDA 2004). The
limitation of these regulations to apple juice and apple juice
concentrate was likely based upon the fact that, at the time, only
apple juice and cider had been

Figure 1The structure of patulin (4-hydroxy-4H-furo [3,2c] pyran2[6H]-one)

found to be naturally contaminated by patulin (WHO 1990).

While this fact has since been disproved (see below, Patulin

Assessment of the health risks posed by patulin to humans is based

upon a wide number of studies during the past 50-plus years that
implicate a number of acute, chronic, and cellular level health effects
as summarized in Table 1. Results of these studies are, as a whole,
inconclusive, but suggest that acute symptoms of patulin
consumption can include agitation, convulsions, dyspo-nea,
pulmonary congestion, edema, ulceration, hyperemia, GI tract
distension, intestinal hemorrhage, epithelial cell degenera-tion,
intestinal inflammation, vomiting, and other gastrointestinal and
kidney damage (Walker and Wiesner 1944; Escoula and oth-ers
1977; Hayes and others 1979; McKinley and Carlton 1980a, 1980b;
McKinley and others 1982; Mahfoud and others 2002). Chronic
health risks of patulin consumption can include neuro-toxic,
immunotoxic, immunosuppressive, genotoxic, teratogenic, and
carcinogenic effects (Dickens and Jones 1961; Mayer and Legaror
1969; Ciegler and others 1976; Oswald and others 1978; Korte
1980; Thust and others 1982; Lee and Rschenthaler 1986; Roll and
others 1990; Hopkins 1993; Pfeiffer and others 1998; Wichmann and
others 2002).

The basis for these various toxic effects appears to be mixed. On a

cellular level, patulin has been shown to have effects includ-ing
plasma membrane disruption (Riley and Showker 1991; Mah-foud
and others 2002), inhibition of protein synthesis (Hatez and Gaye
1978; Miura and others 1993; Arafat and Musa 1995), inhi-bition of
+

Na -coupled amino acid transport (Ueno and others

Vol. 1, 2005COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY 9

CRFSFS: Comprehensive Reviews in Food Science and Food Safety

1976), disruption of transcription and
translation (Moule and Hatey 1977;
Arafat and others 1985; Lee and
Roschenthaler 1987), inhibition of DNA
synthesis (Cooray and others 1982),
and inhibition of interferon- producing
T-helper type 1 cells (Wichmann and
others 2002). Patulin is believed to
cause cell damage by forming adducts
with thiol-containing cellular components such as glutathione and
cysteine-containing proteins (Har-wig
and others 1973a; Barhoumi and
Burghardt 1996). Indeed, many
enzymes with a sulfhydryl group in their
active site are sen-sitive to patulin.
+

Roschenthaler 1987). Thus, while

patulin toxicity may result from thiolrelated in-teraction in a number of
cases, there appear to be exceptions to
this rule.

Biosynthesis

Patulin is produced by 60-plus species

of mold encompassing over 30 genera
(Lai and others 2002). Included within
these are

Na -K dependent ATPase (Phillips

and Hayes 1977, 1978; Riley and
Showker 1991), RNA polymerase
(Moule and Hatey 1977), aminoacyltRNA synthetase (Arafat and others
1985), and muscle aldolase (Ashoor
and Chu 1973) have all been shown to
be inhibited by patulin. Furthermore,
loss of free glutathione in living cells is
associated with patulin exposure
(Burghardt and others 1992; Barhoumi
and Burghardt 1996), and treatment
with exogenous cysteine and
glutathione prevented pat-ulin toxicity
within intestinal epithelium (Mahfoud
and others 2002). Patulin has also
been shown to induce intra- and
intermo-lecular protein cross-links. This
reaction is preferential with the thiol
group of cysteine, but also occurs with
the side chains of lysine and histidine,
and -amino groups (Fliege and Metzler
1999). Other observations have also
noted patulins reactivity with NH2
groups (Lee and Roschenthaler 1986).
Similarly, patulin has been shown to
inhibit protein prenylation, a necessary
post-translational protein modification
involved in the activation of many
proteins, including numerous
oncogenes, such as Ras, that must be
prenylated for proper function (Miura
and others 1993). However, some
enzymes, such as urease, which lack a
sulfhydryl group in their active site, are
also sensitive to patulin (Reiss 1977).
Finally, patulins inhibition of
transcription and translation ap-pears
to be through direct interaction with
RNA and DNA (Moule and Hatey 1977;
Arafat and others 1985; Lee and

Penicillium expansum (P. leucopus), P.

patulum (P. urticae, P. griseofulvum), P.
crustosum, P. roqueforti, P. claviforme,
Paecilo-myces spp., Saccharomyces
vesicarium, Alternaria alternata, Byssochlamys nivea, B. fulva, Aspergillus
giganteus, A. terreus, and A. clavatus
(Lovett and others 1974; Rice and
others 1977; Harwig and others 1978;
Northolt and others 1978; Draughon
and Ayres 1980; Ough and Corison
1980; Roland and Beuchat 1984a; Aytac and Acar 1994; Laidou and others
2001; Moss and Long 2002). Patulin
production in culture has been shown
to occur when growth rate diminishes
because of limitations on cell growth
such as nitrogen consumption
(Grootwassink and Gauch-er 1980).

Patulin biosynthesis is well understood

and involves a series of condensation and
redox reactions, many, if not all, of which
are enzyme catalyzed. Studies based
primarily upon kinetic pulse-ra-diolabeling
and cell-free extract systems have
elucidated the patu-lin metabolic pathway
in great detail; however ongoing studies
on the subject continue to produce new
intermediaries in the path-way. Patulin is
a polyacetate-derived secondary
metabolite or polyketide (Turner 1976). Its
synthesis is initiated with acetyl coenzyme A (CoA) and 3 units of malonyl
CoA, making it a tetra-ketide (Ciegler and
others 1971; Turner 1976; Steyn 1992).
Acetyl CoA and 3 malonyl-CoA are
condensed into 6-methylsalicylic acid (6MSA) by a 760000-Dalton homotetramer
enzyme called 6-methylsalicylic acid
synthetase (6-MSA synthetase)(Gaucher

1975; Lynen and others 1978). The

gene encoding for 6-MSA has been
cloned and characterized from P.
patulum and P. urticae (Beck and
others 1990; Wang and others 1991).
Inactivation of 6-MSA synthetase has
been shown to be the 1st limitation on
patu-lin production (Neway and
Gaucher 1981). 6-MSA synthetase loss
is a selective process because the
highly similar fatty acid synthetase of P.
urticae (Lynen and others 1978) is
stable under the same reaction
conditions that inactivate 6-MSA
synthetase (Lam and others 1988).
This finding is further verified by
studies in which treatment of 6-MSA
synthetase reaction mixtures, containing Nicotanimide Adenine Dinucleotide
Phosphate (NADPH) co-factor, acetylCoA, and malonyl CoA, with the
reducing agent, dithiothreitol, and
proteinase inhibitor,
phenylmethylsulfonyl fluo-ride,
stabilized 6-MSA synthetase. This
suggests proteolysis and
conformational integrity play a role in
the regulation of 6-MSA synthetase
(Lam and others 1988).

The next stage of patulin biosynthesis

involves the conversion of 6-MSA into mcresol via the activity of 6-MSA
decarboxylase (Lam and others 1988).
M-cresol is then converted into m-hydroxybenzyl alcohol by m-cresol 2hydoxylase (Murphy and Lynen 1975).
The next step in patulins biosynthetic
pathway is debated among 2 main
mechanisms. Both agree that m-hydroxybenzyl alcohol is eventually converted to
gentisaldehyde (Forrest-er and Gaucher
1972; Zamir 1980), however the
intermediary be-tween these 2
compounds is believed to be either
gentisyl alcohol (Sekiguchi and others
1983; Iijima and others 1986) or mhydrox-ybenzaldehyde (Sekiguchi and
others 1983). Some studies have
suggested that both are possible, with mhydroxybenzaldehyde being favorable
(Gaucher 1975), whereas others believe
that m-hydroxybenzaldehyde is not
converted to gentisaldehyde but rather to
m-hydroxybenzoic acid (Murphy and
Lynen 1975). In the 2nd case, mhydroxybenzyl alcohol dehydrogenase
converts m-hydroxybenzyl alcohol into m-

hydroxybenzaldehyde (Gauch-er 1975;

Murphy and Lynen 1975). Both this
enzyme and m-cresol 2-hydroxylase have
been shown to require oxygen and
NADPH to function (Murphy and Lynen
1975).

Once gentisaldehyde has been formed, it

is then converted to isoepoxydon,
phyllostine, neopatulin, E-ascladiol, and
finally to patulin (Sekiguchi and Gaucher
1977, 1978; Sekiguchi and Gau-cher
1979; Sekiguchi and others 1979, 1983).
The conversion of isoepoxydon to
phyllostine is accomplished via an NADPdepen-dent isoepoxydon dehydrogenase
(Sekiguchi and Gaucher 1979).
Conversion of neopatulin to E-ascladiol is
accomplished through a reduction by
NADPH. The product of this reaction, Eascladiol, is then either oxidized to patulin
or nonenzymatically transformed to its
isomer Z-ascladiol (Sekiguchi and others
1983). The biosynthetic pathway of
patulin is summarized in Figure 2.

Detection and Quantification

The established limit of 50 g/L in the

United States as the maxi-mum patulin
level allowed in fruit products has
provided an in-centive for the
development of faster and more specific
analytical methods with lower detection
limits. A comprehensive review of the
development of thin-layer gas and liquid
chromatographic methods for the
detection and confirmation of identity of
patulin has been previously published by
Shephard and Leggott (2000).

The most common method currently used

to quantify patulin in fruit products is highperformance liquid chromatography
(HPLC) with ultraviolet (UV) detection.
This is the official method adopted by
AOAC Intl. for apple juice (method
995.10) with a detection limit of 5 g/L. The
juice is extracted 3 times with ethyl
acetate and cleaned up by liquid-liquid
extraction with a 1.5% sodium car-bonate
solution. The ethyl acetate extract is dried
with anhydrous sodium sulfate; the
solvent is then evaporated, normally
under ni-trogen, and the dried residue is
dissolved with acidified water (pH

10
2005

COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETYVol. 1,

Patulin control in foods . . .

4 by addition of
acetic acid).
This prepared
extract is ready
for HPLC
analysis. The
recommended
liquid
chromatograph
y (LC) systems
include
analytical
reversed-phase
LC columns
such as
octadecylsilane
fully endcapped with 5
m particle
stationary
phase, 12 to 25
nm pore size,
carbon loading
of 12% to 17%,
and a UV
detector set at
276 nm,
although a
photo diode
array detector
is preferred to
aid in the
presumptive
identification of
the patulin
peak. The
system can be
run isocratically
at 1 mL/min using 3% to 10%
acetonitrile in
acidified water
(0.095 parts
per vol-ume
perchloric acid
60%) as long
as patulin
separates from
5-hydroxymethylfurf
ural (HMF), a
common
compound
found in apple
juice that elutes
just before
patulin. For
cloudy apple

juice and apple puree, a

collaborative
study of 12
participants
from European
countries was
recently
conducted to
validate the
effectiveness of
this LC
procedure for
patulin
determination
with a slight
modifica-tion.
Prior to the
ethyl acetate
extraction, the
samples were
treated with
pectinase
enzymes and
held overnight
at room
temperature or
for 2 h at 40 C
and then
centrifuged at
4500 g for 5
min. Based on
the results, the
method is
recommended
for patulin at
greater than 50
g/L in cloudy
apple juice and
purees (MacDonald and
others 2000).

The
simultaneous
quantification of
patulin and HMF
in apple juice by
reversed-phase
HPLC has been
reported by
Gokmen and
Acar (1999).
The method
developed uses
a 5- m C18
analytical
column (150 4
mm), a
photodiode

array detector
operating at 250
to 300 nm, and
a mobile phase
of wateracetonitrile (99:1
v/ v) at 1.0
mL/min. Sample
preparation
followed the
official method
described
earlier.
Complete
separation of
HMF and patulin
was achieved in
less than 9 min
at detection
limits of less
than 0.01 g/L
and less than 5
g/L respectively.

The HPLC/UV
procedure is
routinely used
for quantitative
deter-mination
of patulin in
apple products,
but methods to
confirm the
presence of
patulin usually
include more
specific
detection techniques such as
mass
spectrometry
(MS) after LC or
gas chromatography (GC)
separations. For
GC-MS
analysis, patulin
is detect-

ed as its
trimethyl silyl
derivative
(TMS-patulin)
with electron
ion-ization
(Roach and
others 2002). In
addition, GCMS with negative ion
chemical
ionization

allows
detection of
underivatized
pat-ulin in
apple juice
extracts. A
variety of
capillary
columns in
qua-drupole,
ion trap, and
magnetic
sector
instruments
can be used for
patulin
confirmation
when present
in apple juice at
68 to 3700 g/L
(Roach and
others 2000).
Underivatized
patulin was
successfully
analyzed via
GC with
electronic
pressure
control, oncolumn
injection, and
selected ion
monitoring
allowing
detection limits
of 4 g/L
(Llovera and
others 1999). In
another study,
a combination
of diphasic
dialysis
extraction, insitu acylation,
and GC-MS
permitted the
quantification of
patulin from 10
g to 250 g/L
(Sheu and
Shyu 1999).

Rychlik and
Schieberle
(1999)
developed 2
methods to
quanti-tate
patulin by stable
isotope dilution

assays using
13

C-labeled
patulin as the
internal
standard. One
method used
LC/MS in negative
electrospray
ionization mode
without
derivatization,
while the 2nd
procedure
utilized high
resolution gas
chromatography
/ high resolution
mass
spectrometry
(HRGC/HRMS)
after trimethylsilylation of the
patulin
isotopomers.
The
HRGC/HRMS
method showed
better
repeatability,
higher recovery
rates, and 100
times lower
detection limit
(0.012 g/L)
compared with
the standard
HPLC/UV
procedure. This
highly sensitive
method might be
useful for
physiological
studies on
patulin
metabolism in
humans.

Sewram and
others (2000)
developed an
HPLC-MS-MS
method with

selective
reaction
monitoring to
achieve a
detection limit
of 4 g/L without
derivatization.
The MS
detection was
performed after
atmospheric
pressure
chemical
ionization in
negative ion
mode. This
procedure
correlated well
(R = 0.99) with
the standard
HPLC/ UV
method.

An improved
LC/MS patulin
determination
has been
reported by
Takino and
others (2003).
They compared
atmospheric
pres-sure
chemical
ionization
against
atmospheric
pressure
photoionization and
found that it
provided lower
chemical noise
and sig-nal
suppression,
thus allowing
higher
sensitivity.
Quantification
of

Figure 2Patulin bio-synthetic

pathway. Shown here are the
metabolic intermediar-ies and

relevant en-zymes involved in the

biosynthesis of patulin (Gaucher
1975; Murphy and Lynen 1975;
Sekiguchi and Gaucher 1979;
Sekiguchi and others 1983; Iijma
and others 1986; Priest and Light
1989).

Vol. 1, 2005COMPREHENSIVE

REVIEWS IN FOOD SCIENCE AND

FOOD SAFETY 11

CRFSFS: Comprehensive Reviews in Food Science and Food Safety

patulin was linear in the 0.2 to 100 g/L
range with detection lim-its of 1 g/L in
apple juice samples. Analysis time was
10 min us-ing an on-line extraction
method based on column switching
that eliminated the need for timeconsuming off-line sample preparation. Another technique to perform
rapid analysis of patulin with simpler
sample preparation using capillary
electrophoresis was reported by Tsao
and Zhou (2000). In this study, a
micellar elec-trokinetic capillary
chromatography mode was selected
with a photodiode array detector set at
273 nm. The procedure requires a
small sample volume (2 mL) and
minimal usage of solvents as the
separation is achieved by migration of
charged particles in the run buffer.
Detection limits were reported as 3.8
g/L.

Rapid clean-up and faster analytical

methods based on immu-nochemical
technology are currently being
investigated. The low molecular weight
of patulin presents a challenge for this
area of research and development
(McElroy and Weiss 1993).

In addition to traditional isolation

methods for potential patulin-producing
molds, numerous rapid methods
utilizing polymerase chain reaction
(PCR)based methodologies have
been developed. Marek and others
(2003) have developed a PCR-based
method using primers specific to the
polygalacturonase gene to identify
patulin-producing fungi (P. expansum)
in 4 to 5 h, a much faster time
compared with culture methods that
require 48 h. The lowest level of
detection with spore extracts was the
DNA equivalent from 25 spores of P.
expansum. Further work will be
required to apply this method to food
systems. A gene probe for the patulin
metabolic pathway has also been
described by Paterson and oth-ers
(2000). The probe for this PCR
detection method was based on the
unique iso-epoxy dehydrogenase gene
to allow testing for potential patulin

production directly from food and

environmen-tal samples without any
need for pre-enrichment of patulin-producing molds.

Patulin Within Foods

Patulin-producing strains have been

isolated from a variety of fruits and
vegetables including apples, grapes,
cherries, crabap-ples, pears, apricots,
persimmons, strawberries, nectarines,
rasp-berries, black mulberries, white
mulberries, lingon berries, peach-es,
plums, tomatoes, greengages,
bananas, blueberries, black cur-rants,
almonds, pecans, peanuts, and
hazelnuts (Pierson and oth-ers 1971;
Harvey and others 1972; Buchanan
and others 1974; Lovett and others
1974; Sommer and others 1974;
Akerstrand and others 1976;
Andersson and others 1977; Frank and
others 1977; Harwig and others 1978;
Brackett and Marth 1979a; Je-linek and
others 1989; Jiminez and others 1991;
Prieta and others 1994; Leggott and
Shephard 2001; Demirci and others
2003; Ri-tieni 2003).

The presence of patulin-producing

fungi does not necessarily guarantee
patulin production, however. Patulin
production is usu-ally, but not
exclusively, associated with apple soft
rot and blue mold rot, most commonly
caused by P. expansum (Brian and others 1956; Pierson and others 1971;
Harwig and others 1973b; Sommer and
others 1974). This fungi, which is the
most common cause of apple rot in the
apple industry (Rosenberger 2003),
has been shown to naturally cause
blue-rot in apples, cherries, plums,
apricots, peaches, nectarines, pears,
and quince (Pierson and oth-ers 1971;
Harvey and others 1972; Buchanan
and others 1974). Further, apples,
peaches, strawberries, bananas,
greengages, to-matoes, cherries, and
pears have all been shown
experimentally to support blue-rot
(Lovett and others 1974; Laidou and
others 2001).

Patulin-production within fruits,

vegetables, and their products has been
investigated and often appears to be
dependent on such factors as water
activity (aw), temperature, pH, and other
chemical characteristics intrinsic to fruits
(Sommer and others 1974;

Northolt and others 1978; McCallum and

others 2002). pH and patulin production
have been shown to be inversely related,
with patulin being unstable at high pH
(McCallum and others 2002).
Temperature has been shown to affect
pathogen growth and, to a greater extent,
the production of patulin (McCallum and
others 2002). Patulin production has
been observed at all temperatures
permitting P. expansum growth,
encompassing an approximate range of 0
to 30 C (Sommer and others 1974). B.
nivea has been shown to grow faster at
temperatures of 30 and 37 C while patulin production was highest at 21 C
(Roland and Beuchat 1984b). As
testament to the variability seen in patulin
production, even cultivar differences
among apples affect the patulin
production of P. expansum (McCallum
and others 2002), with Jonathan, Goudreinetter, Coxs Orange Pippin, and
Bramley being particularly susceptible,
whereas Golden Delicious appears to be
particularly resistant (Northolt and others
1978; Corbett 2003).

Apple juice and cider were once

thought to be the only prod-ucts to
naturally contain patulin (WHO 1995).
However, compil-ing research has now
shown patulin to occur naturally in such
fruit and vegetable products as apple,
apple-acerola, grape, pear, sour cherry,
blackcurrant, orange, pineapple, and
passion fruit juices, pasteurized and
unpasteurized apple cider, apple
puree, corn, strawberry, blackcurrant,
and blueberry jams, and some types of
baby food (Lovett and others 1974;
Sommer and others 1974; Frank and
others 1977; Scott and others 1972;
Harwig and others 1978; Brackett and
Marth 1979a; Ehlers 1986; Wheeler
and others 1987; Jelinek and others
1989; Lin and others 1993; Prieta and
others 1994; Rychlik and Schieberle
1999; Ake and others 2001; Leggott
and Shephard 2001; Ritieni 2003).
Further-more, evidence suggests that

other juices, including blueberry, red

raspberry, boysenberry, pear,
cranberry, strawberry, black cherry, and
peach can support growth and
associated patulin production of B.
fulva and/or P. expansum (Rice and
others 1977; Larsen and others 1998).

Besides fruit and vegetable products,

patulin has also been iso-lated from
cheddar cheese (Bullerman and
Olivigni 1974) and grain products such
as barley and wheat malts, feed
silages, cere-al stubbles (Escoula
1974, 1977; Lopez-Diaz and Flannigan
1997; Pittet 1998), bread, and related
flour/dough products (Reiss 1972,
1976). In 1 study, 23 strains of
Aspergillus and Penicillium isolated
from moldy bread were tested for
patulin production. Twenty-one of 23
moldy bread samples were found
positive for 27 to 160 g patulin/kg
(Tyllinen and others 1977). Finally,
patu-lin has been attributed to the
death of 100 cows fed malt (Ciegler
1977) and to hemorrhagic syndrome
and death in silage-fed cat-tle (Syrett
1979).

Within the food industry, apples and

their respective products are of
greatest concern for patulin
contamination. While a variety of other
food sources and products have
demonstrated patulin and/or patulinproducer contamination, the frequency
of these events is much less than that
of the apple industry. Patulin has been
identified in apples from Canada
(Harwig and others 1973b; Sommer
and others 1974), England (Brian and
others 1956; Som-mer and others
1974), New Zealand (Walker 1969),
United States (Sommer and others
1974; Ware and others 1974), Australia
(Sommer and others 1974), and South
Africa (Leggott and Shep-hard 2001),
and has been found in apple juices
from Canada (Scott and others 1972),
United States (Ware and others 1974),
Sweden (Josefsson and Andersson
1976), South Africa (Brown and
Shephard 1999; Leggott and Shephard
2001), Turkey (Gok-men and Acar
1998), Brazil (de Sylos and RodriquezAmaya 1999), Austria (Steiner and
others 1999a), Italy (Ritieni 2003), Belgium (Tangi and others 2003), France,

and Australia (Sommer and others

1974).

12
2005

Numerous studies around the world

have examined the extent and degree
to which apple products have been
contaminated by

COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETYVol. 1,

Patulin control in foods . . .

patulin. In
Wisconsin, 23
of 40 roadside
apple juices
were found to
contain
between 10 to
350 g patulin/L
(Brackett and
Marth 1979a).
A 2nd study
showed that 8
of 13
commercial
apple juices
tested
contained
between 44
and 309 g
patulin/L juice
(Ware and
others 1974). A
Turkish study
showed 215 of
215 apple juice
concentrates
examined had
between 7 and
375 ppb patulin
with 43% being
above the 50ppb
international
standard
(Gokmen and
Acar 1998).
Finally, a 1996
to 1998 study
in South Africa
showed that 5
of 22 juices
sampled
contained
between 10
and 45 ppb
patulin, and
29% of infant
apple products
showed 5 to 20
ppb (Brown
and Shephard
1999). A
summary of
patulin contamination
within foods is
given in Table
2.

Control
During Apple
Harvest,
Processing,
and Storage

In North
America, apple
juice is typically
a byproduct
pro-duced from
culled apples
unfit for other,
higher quality
and higher
profit, purposes
(Rosenberger
2003). Apples
are typically
harvest-ed and
processed, and
those lower
quality apples
unfit for 1st
quality edible
retail apples
are stored in
controlled
atmosphere,
refrigerated
storage for
anywhere up to
around 12 mo
when the next
harvest comes
in.

Current
methods for
preventing
mycotoxin
contamination
of foods include
(1) strict
adherence to
moisture
control, (2)
implementation of
good
manufacturing
practices, (3)
good quality
as-surance

efforts, and (4)

adherence to
Hazard
Analysis
Critical Control
Points
principles
(Lopez-Garcia
and Park 1998;
Park and
others 1999).
Existing and
developmental
preventive
measures
during
preproduction
are based upon
fruit quality and
facility
sanitation
measures. The
quality of fruit
resulting from
harvesting is
the 1st step in
controlling
patulin levels.
With the
highest quality
hand-picked
fruit being used
for direct-forretail sale,
processed
apple products
usually are
produced from
mechani-cal
harvest,
windfalls,
insectdamaged, or
culled fruit.
Bruises, skin
breaks, and
other physical
damage within
these apples
pro-vide a
perfect entry for
P. expansum
and other
patulinproducing
species into the
fruit. Studies
have examined
the effect of
fruit quality and
harvest method
on the patulin
content of the

result-ant
juices. In 1
study, patulin
was
undetectable in
7 cultivars of
tree-picked
cider, whereas
it was detected
between 40.2
and 374 g/L in
4 cultivars of
ground-harvest
cider (Jackson
and others
2003). Many of
the patulin
control
measures
suggested by
the Joint
FAO/WHO
Food
Standards
Programme are
based upon the
careful
selection of
fruits as based
upon good
agricul-tural
practice
(CODEX 2002).
However, as
indicated by a
New York State
Hudson Valley
Lab study that
showed around
20% of bagged,
in-store, retail
apples to
contain
consumervisible blue-rot
(Rosenberger
2003), even the
highest level of
fruit selection
and good
agricultural
practices
cannot
eliminate
apple-rot and
associated
patulin
contamination.

Standard
postharvest

processing,
including
washing,
sorting, and
packaging,
poses a 2nd
means of both
fungal control
and
contamination
alike. Washing
with highpressure water
has been shown
to reduce patulin
levels within
apple juice by
21% to 54%
(Acar and others
1998). A 2nd
study showed
that washing of
groundharvested
apples resulted
in a 10% to
100% patulin reduction,
depending on
initial patulin
level and
washing
treatment
(Jackson and
others 2003).
However, these
same washes
can also serve
as a source of
contamination.
Contaminated
bins, storage
rooms, drencher
washes, drying
brushes after
apple wash, and
other steps
within the
processing cycle
can all provide a
source of fungal
inoculum cycling
in poorly
sanitized setups.
Prevention
methods aimed
at cleaning and
sterilizing
storage and
processing
facilities
routinely and in
between
seasons are
being mapped
out, but have not
yet been fully

developed. Plus,
the older,
complicat-ed
design of many
packing-house
and processing
equipment in-

hibits the ability

to effectively
sanitize. Even if
effective
strategies are
successfully
mapped out,
the inherent
variability in
apple han-dling
facilities will
require
customization
of sanitation
methods for
each operation
(Rosenberger
2003), posing a
considerable
cost to
producers.

Apple storage
poses yet a 3rd
means of
fungal control
and
contamination.
Conflicting
evidence exists
as to whether
stan-dard
controlledatmosphere,
refrigerated
storage is
sufficient to
prevent apple
soft rot
(Sommer and
others 1974;
Lovett and others 1975a;
Paster and
others 1995).
Classically
associated with
wounded fruit,
in the mid1990s,
nonwounded,

stem-end infected blue-rot

began to
appear with
increasing
frequency.
Long-term,
controlled
atmosphere
storage has
now been
shown to allow
the slow growth
and stembased invasion
of fungi into
apples
(Rosenberger
2003).
Furthermore,
these facilities
are not
available to all
producers,
forcing many to
use deckstorage, which
can drastically
increase patulin
production.
Alternatives to
room storage
are the use of
packaging
materials such
as polyethylene, which
through their
own
atmospheric
control, have
been shown to
reduce patulin
production in
apples
(Moodley and
others 2002). In
the same study
mentioned
previously
(Jack-son and
others 2003),
patulin was not
detected in
cider from
culled, treepicked apples
stored 4 to 6
wk at 0 to 2 C,
but was
detected at
levels between
0.97 and 64 g/L

in stored, treepicked,
unculled fruit.
Cider from
apples stored
in controlled atmosphere and
culled showed
0 to 15.1 g/L
patulin while
un-culled apple
fruit showed
59.9 to 120.5
g/L patulin.
Thus, stor-age
can exacerbate
any flaws in
prior handling
steps, such as
harvesting. The
longer the
storage of the
apples, the
greater the risk
of increased
patulin content.
This is
particularly
evident to juice
producers
within the U.K.
who see
dramatic rises
of patulin
content within
juice produced
in June, July,
and August
the months just
prior to the new
harvest season
where source
ap-ples have
been stored for
almost a year
(Corbett 2003).
Further-more,
even if apples
are perfectly
processed prior
to storage, addition of
diphenylamine,
which is used
to treat storage
scald in stored
apples, can
provide an
inoculum of
patulinproducing fungi
in the fruit

(Rosenberger
2003).

Various
treatments have
been
investigated for
the ability to reduce the apple
rot and patulin
production seen
within the harvest,
processing, and
storage steps.
Postharvest
treatment of apples with
benzimidazole
fungicides was
used from the
1970s through
the early 1990s
but has since
been largely
abandoned due
to fungal
resistance
(Rosenberger
2003).
Insecticide
treatment of
apples can
reduce growth of
patulinproducing molds
and thereby
patulin
production
between 85%
and 100%
(Draughon and
Ayres 1980), but
the treatment
raises questions
about the safety
of
organophosphat
e insecticides
and is thus
nonpreferen-tial.
Combinations of
heat treatment,
calcium
infiltration, and
bio-logical
control with an
antagonistic
bacteria,
Pseudomonas
syrin-gae, were
investigated
alone or in
combination to

reduce incidence of
postharvest
apple decay.
Apples
inoculated with
P. ex-pansum
and heated at
38 C for 4 d
showed no
decay lesions
af-ter storage at
1 C for 6 mo.
After heattreatment
inoculation with
P. expansum
followed by
infusion of 2%
calcium chloride
alone and Ps.
syringae
treatment alone
reduced decay
incidence by
25% each.
Calcium
treatment plus
Ps. syringae
treatment
without and with
subsequent heat
treatment
reduced decay
by 89% and
91%,
respectively
(Conway and
others 1999).
Finally, other
meth-ods used
for the control of
human
pathogens like
Escherichia coli,
such as washing
with solutions of
peroxyacetic
acid, chlo-rine
dioxide, and
chlorine (Sapers
and others
1999;
Wisniewsky and
others 2000;
Annous and
others 2001),
may also
provide some
benefit toward
preventing
postharvest
apple decay.
Howev-er, these
methods have
yet to be
analyzed for

their
effectiveness

against fungal
spores.

Vol. 1, 2005COMPREHENSIVE

REVIEWS IN FOOD SCIENCE AND

FOOD SAFETY 13

CRFSFS: Comprehensive Reviews in Food Science and Food Safety

Control during Production

For both removal of patulin during

production and postproduc-tion, effective
decontamination/detoxification
procedures must (1) inactivate, destroy,
or remove the toxin, (2) not produce or
leave

new toxic substances, (3) retain

nutritive value/acceptability of the
product, (4) not significantly alter the
technological processes as-sociated
with the product, and (5) if possible,
destroy fungal spores (Park and others
1988). Methods of patulin control within

Table 2Food industry distribution of patulin and patulin-producing fungi

Foods contaminated with

patulin-producing fungal strains

Source

Apples
Pierson and others 1971; Sommer and others 1974; Frank and others 1977; Brackett and
Marth

1979a; Prieta and others 1994; Leggott and Shephard 2001; Ritieni 2003
Grapes
Sommer and others 1974; Harwig and others 1978
Cherries
Harvey and others 1972; Buchanan and others 1974; Lovett and others 1974; Andersson
and others

1977; Arici and others 2002

Crabapples
Sommer and others 1974
Pears

Pierson and others 1971; Buchanan and others 1974; Sommer and others 1974
Apricots
Harvey and others 1972; Buchanan and others 1974; Sommer and others 1974
Persimmons
Sommer and others 1974
Strawberries
Andersson and others 1977; Frank and others 1977; Arici and others 2002
Nectarines
Harvey and others 1972
Raspberries
Andersson and others 1977; Arici and others 2002
Black mulberries
Arici and others 2002
White mulberries

Lingon berries
Andersson and others 1977
Peaches
Harvey and others 1972; Buchanan and others 1974; Andersson and others 1977; Frank
and others 1977
Plums
Harvey and others 1972; Buchanan and others 1974; Andersson and others 1977
Tomatoes

Greengages
Frank and others 1977
Bananas

Blueberries
Akerstrand and others 1976; Andersson and others 1977
Black currants
Andersson and others 1977
Almonds

Pecans
Jiminez and others 1991
Peanuts

Hazelnuts

Foods contaminated with patulin Source

Apple juice
Lovett and others 1974; Sommer and others 1974; Frank and others 1977; Scott and others
1977;

Brackett and Marth 1979a; Prieta and others 1994; Rychlik and Schieberle 1999;

Leggott and Shephard 2001; Ritieni 2003

Apple-acerola juice
Rychlik and Schieberle 1999
Pear juice
Ehlers 1986
Grape juice
Harwig and others 1978; Rychlik and Schieberle 1999
Sour cherry juice

Blackcurrant juice
Rychlik and Schieberle 1999
Orange juice

Pineapple juice
Ake and others 2001
Passion fruit juice

Apple cider
Brackett and Marth 1979; Wheeler and others 1987; Leggott and Shephard 2001
Apple puree
Leggott and Shephard 2001; Ritieni 2003
Corn
Lin and others 1993
Strawberry jam

Blackcurrant jam
Jelinek and others 1989
Blueberry jam

Baby food
Prieta and others 1994; Leggott and Shephard 2001; Ritieni 2003
Cheddar cheese
Bullerman and Olivigni 1974
Barley Malt
Lopez-Diaz and Flannigan 1997
Wheat Malt

Bread
Reiss 1972, 1976
Countries with apple and

juice contamination
Source

Canada
Scott and others 1972; Harwig and others 1973b; Sommer and others 1974
England

Brian and others 1956; Sommer and others 1974

New Zealand
Walker 1969
United States
Sommer and others 1974; Ware and others 1974
South Africa
Leggott and Shephard 2001
Sweden
Josefsson and Andersson 1976
Turkey
Gokmen and Acar 1998
Brazil
de Sylos and Rodriguez-Amaya 1999
Austria
Steiner and others 1999a
Belgium
Tangi and others 2003
Australia
Sommer and others 1974
France

14

COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD

SAFETYVol. 1, 2005

Patulin control in foods . . .

standard apple
juice production
steps are
centered on 3
areas. The 1st
of these
involves the
quality of the
fruit and
processing of
this fruit, prior
to pressing. As
previously
mentioned,
processed
apple products
often utilize
lower quality
fruit that is
unsuitable for
direct market
retail. Removal
of decayed/
damaged fruit
or trimming of
moldy portions
can
significantly
reduce patulin
levels in apple
products
(Lovett and
others 1975b;
Taniwaki and
others 1992;
Sydenham and
others 1995,
1997; Beretta
and others
2000).
Trimming of
rotten sections
of apple has
been shown to
re-move up to
99% of patulin
contamination
(Lovett and
others 1975b).
However, this
process is
expensive and
labor intensive.
Furthermore,
patulin can be
detected in
visibly sound
fruit (Jack-son

and others
2003) and can
spread from
rotten areas of
apples into
sound areas
(Beretta and
others 2000).
Two studies
showed that
patulin could
diffuse 1 to 2
cm from the
rotten core in
apples
(Taniwaki and
others 1992;
Rychlik and
Schieberle
2001), 0.6 cm
in pears
(Laidou and
others 2001),
and throughout
the entire fruit
in tomatoes
(Rychlik and
Schieberle
2001).
Producers
tests on apples
have shown
that patulin
level is often
not related to
the physical
quality of the
fruit, with both
high-rot fruit
and top-quali-ty
eating fruit
often having
high levels of
patulin in tests
(Corbett 2003),
as further
demonstrated
by the
previously
mentioned
Hud-son Valley
study on retail
apples. While
often beneficial,
the sort-ing of
decayed apples
to the level of
being effective
is difficult to
impossible,
often

necessitating
the need to
reject entire
juice loads of
apples. If
reliant on this
method, smallscale
producers who
cannot afford
these losses
will be forced to
sort by hand,
in-creasing
costs to the
point that many
may cease
operating
(Rosen-berger
2003).

The 2nd area of

standard juice
production
capable of
reducing patulin
levels involves
the juice
clarification
process. Results
from this
process have
been mixed, and
those methods
most success-ful
at removing
patulin often do
so at the
expense of juice
sensory and
authenticity
qualities. Some
sources suggest
that standard
fruit juice
production
processes
remove only
about 20% of
patu-lin (Stray
1978; Harrison
1989). One
study showed
that the traditional apple juice
production
processes of
depectinization,
clarifi-cation,
and filtration
through a rotary
vacuum precoat
filter could

reduce patulin
levels by 39%.
In the same
study, use of
depectini-zation,
clarification,
mixing with
gelatin/bentonite
, and ultrafiltration resulted in a
25% decrease in
patulin (Acar
and others
1998). A 2nd
study examined
the effects of
gelatin/bentonite
flocculation,
filtration,
activated
charcoal,
ultrafiltration,
polyvinylpolypyrr
oli-done, and
polystyreneDivinyl Benzene
(DVB)based
macro po-rous
resin on apple
juice color,
clarity, phenolic
content, organic
acid content,
and patulin
reduction.
Activated
charcoal
treatment had
the highest
patulin reduction
with 40.9% but
also significantly reduced color
and phenolic
content, 2
characteristics
associat-ed with
juice
authenticity.
PolystyreneDVBbased
macro porous
resin was the
2nd most
effective,
reducing patulin
by 11%. None of
the treatments
altered organic
acid content
significantly
(Artik and others
2001).
Centrifugation
and fining of
juice pulp have
been shown to

reduce patulin
levels by 89%
and 77%,
respec-tively.
However, these
methods make
the removed
cake and/or filter potentially
highly toxic and
unfit for any
further use, such
as often is done
with juice
sediments in
animal feed
(Bissessur and
others 2001).
This could
represent a loss
of income for
many juice
producers.
Batch
absorption with
synthetic
polymers has
also been
investigated
(Canas and
Aranda 1996),
as has enzyme
treat-ment with
pectinase
enzymes used
to break down
the pectin coat
surrounding
protein particles,
allowing
aggregation and
sedimen-tation
of protein
particles and, in
the case of
patulin
contamina-tion,
their associated
patulin adducts.
This method has
resulted in a
73% decrease in
patulin content
within juice
(Bissessur and
oth-ers 2002).

The 3rd juice

production
process
capable of
reducing
patulin

levels is the
pasteurization
process. Of the
3 processes
mentioned thus
far, this is by far
the least
effective.
Repeated
studies have
shown that,
while unstable at
high pH
(McCallum and
others 2002),
patulin is
relatively stable
to thermal
degradation in
the pH range of
3.5 to 5.5, with
lower pH leading
to greater
stability (Heatley
and Philpot
1947; Lovett and
Peeler 1973).
The half-life of
patulin held at
25 C at pH 6.0
and 8.0 has
been shown to
be 55 and 2.6 d,
respectively
(Brackett and
Marth 1979c). In
1 study, no
patulin reduction
occurred during
concentration
and pasteurization (Aytac
and Acar 1994),
while a 2nd
study did show a
50% reduction
of patulin in
apple juice
treated for 20
min at 80 C
(Scott and
Somers 1968)
a much longer
treatment than
used in standard
pasteurization
procedures. A
3rd study
showed pasteurization
treatments
between 60 and
90 C for 10 s
were only able

to reduce patulin
levels by 18.8%
(Wheeler and
others 1987).
Ev-idence also
shows that
patulin is
nonvolatile and,
upon distilla-tion
production of
apple aroma,
patulin remains
within juice concentrate (Kryger
2001). Finally,
not only is the
pasteurization
pro-cess unable
to significantly
reduce patulin
levels, it often
fails to fully
remove heat
resistant patulinproducing fungi,
such as B. nivea
and B. fulva
(Ough and
Corison 1980),
allowing for
poten-tial
continued
production of
patulin within the
finished juice.

As a final stage
of the production
process, studies
have exam-ined
the effects of
storage on
patulin content.
Mixed studies
show either a
decrease (Scott
and Somers
1968; Harwig
and others
1973a) or no
change
(Pohland and
Allen 1970;
Zegota and
others 1988) of
patulin levels in
apple juice with
refrigerated
storage. Similar
studies within
grape juice have
shown stability
(Ough and
Corison 1980) or

an approximate
50% decrease
(Scott and Somers 1968) of
spiked patulin
levels in grape
juice after 5 wk.

Control
Postproducti
on

Filtering and
adsorption

A number of
studies have
been devoted to
the removal of
patu-lin from
juice through the
use of
adsorption
filters, columns,
and agitation
treatments using
carbon-based
material.
Agitation with 20
mg/mL activated
charcoal
followed by
filtration through
a 40-or 60-mesh
charcoal column
reduced a 30g/mL patulin
solu-tion to
below
detectable
levels. Further,
use of 5 mg/mL
charcoal in
agitation was
able to reduce
patulin to below
detectable levels
in naturally
contaminated
cider. However,
color loss was
marked-ly
present in this
resulting juice
(Sands and
others 1976). In
a 2nd study, 0,
0.5, 1.0, 1.5,
2.0, 2.5, and 3
g/L activated

charcoal was
added to
naturally
contaminated
apple juice
containing 62.3
ppb patulin.
Samples were
mixed for 0, 5,
10, 20, and 30
min. Three
grams/liter
activated
charcoal was
found to be most
effective with a
time period of 5
min. Clearness
of juice
increased, color
of juice
decreased, and
small decreases
in fumaric acid,
pH, and Brix
were also seen
(Kadakal and
Nas 2002). In
another study,
ultrafine
activated carbon
was bound to
granular quartz
producing a
com-posite
carbon
adsorbent
(CCA). Columns
with varying
amounts of CCA
were prepared
and 10 g/mL
patulin were
filtered through
at 1 mL/min.
Fifty percent
breakthrough
values for
columns with
1.0, 0.5, and

0.25 g CCA
were 137.5,
38.5, and 19.9
g, respectively
(Huebner and
others 2000).

In a 4th study
designed to
compare the
effects of
different car-bon
activation
methods, steam
activated carbon
NORIT SA 4 and
NORIT SX 4
performed
equally,
removing 80%
and 70%,
respec-tively, of
an initial 1 g/L
patulin solution
in 12 Brix juice
at 55 C.
Chemically
activated carbon
NORIT CA 1
removed only
45% of the
same solution.
This study also
showed that
increased Brix
levels of juice
led to decreased
patulin removal
efficiency, with
NORIT SA 4
removing only
20% of patulin
from 20 Brix
juice. Within this
study, patulin
removal was
independent of
juice tem-

Vol. 1, 2005COMPREHENSIVE

REVIEWS IN FOOD SCIENCE AND

FOOD SAFETY 15

CRFSFS: Comprehensive Reviews in Food Science and Food Safety

perature between 30 and 65 C
(Leggott and others 2001), while in
another study, patulin binding to
activated carbon compounds was
shown to be endothermic, with
increased temperatures re-sulting in
improved patulin removal (Mutlu and
others 1997).

Despite these initial studies where

activated carbon was shown to reduce
patulin, little work has been done to
optimize carbon for this process.
Furthermore, the use of activated
carbon poses a substantial cost to the
juice industry (Leggott and others
2001), being both time consuming and
expensive (Bissessur and others
2001). Outside of the cost of carbon
material itself, activated char-coal
treatment creates excess waste that
must be dealt with eco-logically (Artik
and others 2001). Also, as mentioned
within sever-al of the studies, negative
affects on color, fumaric acid content,
pH, and Brix have been observed with
carbon adsorption. These and other
modifications made by carbon
absorption treatments can negatively
alter the taste perception and quality of
the juice (Huebner and others 2000).
Finally, the use of clays can pose a risk
due to removal of essential nutrients
from juice (Park and Troxell 2002).
Similar analysis with activated carbon
compounds has not been performed,
but could very likely have the same
neg-ative result.

Chemical modification

Chemical decontamination methods

have also been shown to be effective
and are likely the most easily suitable
for industry. Many of the chemicals
examined thus far are already
considered food grade
additives/treatments, and therefore,
their use would be preferential to many
other forms of treatment. Plus,
because addi-tion of chemical agents
to human foods solely for reducing
myc-otoxin levels is currently not

permitted in the U.S. (Park and Trox-ell

2002), treatments already accepted for
other purposes would allow more rapid
integration within industry. Furthermore,
many of these same treatments have
been shown to be effective in in-hibiting
patulin-producing molds (see below,
Patulin Production in the Final
Product), making them a double-edged
sword in patu-lin control.

Numerous chemical treatments have

been utilized to detoxify patulin.
Included within these treatments are
chemicals designed to oxidize and
reduce patulin to hopefully less toxic
compounds, as well as treatments to
bind up patulin in the form of less toxic
thiol-based adducts. Two of the most
potent means of chemical detoxification
of patulin are ammoniation and
potassium perman-ganate oxidation.
Treatment with ammonia has been
shown to re-duce patulin levels by up to
99.9% in laboratory waste (Fremy and
others 1995) and 99.8% in juice.
However, in the 2nd study, the resultant
product was unfit for consumption (Ellis
and others 1980). Oxidation by
potassium permanganate in acidic and
alkali conditions also resulted in better
than 99.99% patulin reduction in
laboratory waste (Fremy and others
1995).

Treatment with various sulfur-containing

compounds has been another area of
intense investigation. Studies involving
the use of sulfur dioxide have produced
mixed results. Most studies agree that
patulin is unstable in the presence of
sulfur dioxide (Pohland and Allen 1970),
but they vary on its degree of
effectiveness. One study showed that 100
ppm sulfur dioxide immediately reduced
patulin levels by 50% (Ough and Corison
1980). In a 2nd study, a 42% re-duction of
patulin was achieved with 100 mg sulfur
dioxide/kg ap-ple juice (Aytac and Acar
1994). However, in a 3rd study, 200 ppm
sulfur dioxide, the maximum allowable
within the food industry, caused only a
12% patulin decrease in 24 h. Sulfur
dioxide (2000 ppm) showed a 90%
decrease after 2 d and plateaued at that
level. Within this study, 2 reactions were
shown to be involved. The 1st, a
reversible reaction, occurred presumably

through the addition of sulfur dioxide to

the hemiacetal ring of patulin, forming a
carbonyl hydroxysulfonate. The 2nd
reaction is thought to be irreversible and
to occur due to an opening of the lactone
ring structure at one

of the double bonds (Burroughs 1977).

A 4th study found the sul-fur dioxide
inactivation of patulin to be reversible
or irreversible de-pending on pH
(Steiner and others 1999b).
Sulfur compounds common to
biological systems and fre-quently
associated with patulin toxicity, such as
glutathione, cys-teine, and
thioglycolate, are believed by many to
produce biologi-cally inactive products
when reacted with patulin (Cavallito
and Bailey 1944; Geiger and Conn
1945; Reinderknecht and others 1947;
Singh 1967; Hoffman and others 1971;
Ciegler and others 1976). In 1 study,
treatment with cysteine and glutathione
pre-vented the negative effects of
patulin infection on rumen fermentation, while non-sulfhydrylcontaining
ascorbic acid and ferulic acid did not
protect against patulin toxicity (Morgavi
and others 2003). Patulin has been
shown to form a number of adducts
with N-acetylcysteine, glutathione, and
cysteine (Fliege and Metzler 2000).
While patulin-cysteine adduct mixtures
are slightly bacteri-cidal to Grampositive and Gram-negative species
(Geiger and Conn 1945; Reinderknecht
and others 1947), they have been
shown to reduce the bactericidal
effects of patulin by more than 100 fold.
Furthermore, treatment of mice with a
cysteine-patulin adduct mix, 85 times
the equivalent lethal dose50
concentration of patulin alone, resulted
in no deaths or macroscopic pathological effects (Lindroth and von Wright
1990).

Another chemical method examined for

the decontamination of patulin has
been treatment with a variety of
organic acids and vitamins, many of
which are considered to be food-grade
addi-tives. In one study, addition of
ascorbate and ascorbic acid in-creased
the rate at which patulin was reduced
from solution in a concentrationdependent manner. These reduction

rates were found to be slower in juice,

but still present. A mechanism was
proposed in which a reaction of
ascorbate or ascorbic acid with metal
ions produced singlet oxygen
molecules that attacked and oxidized
patulin. However, no evidence for any
such reaction products was given
(Brackett and Marth 1979b). A 2nd
study uti-lizing ascorbic acid found that
treatment with 500 mg/kg juice could
produce a 50% reduction of patulin
(Aytac and Acar 1994). A 3rd study,
however, found that degradation by
ascorbic acid re-sulted in only 5%
degradation in 3 h and 36%
degradation after 44 h (Fremy and
others 1995). Besides ascorbic acid,
treatment of apple juice with the B
vitamins, thiamine hydrochloride,
pyridox-ine hydrochloride, and calciumd-pantothenate, caused statisti-cally
significant reductions in patulin content
over control juices (Yazici and Velioglu
2002).

Yet another chemical detoxification

method examined has been the use of
ozone, which has recently been
approved for use in the treatment and
processing of foods (FR 2003) and has
been shown as an effective alternative
to heat pasteurization of juice. In 1
study, treatment of a 32 M patulin
solution with 10% ozone for 15 s
reduced patulin to undetectable level
and produced no detectable reaction
products (McKenzie and others 1997).
Fur-ther, other mycotoxins such as
aflatoxins B1, G1, B2, and G2 (Maeba
1988) as well as zearalonone (Doyle
and others 1982) have been shown to
be effectively degraded by ozone.

In all of these cases, preliminary

evidence is promising. Howev-er,
inadequate research has been done to
examine the efficacy and full functional
range of applicability for the treatment.
Further-more, the reaction mechanisms
for few if any of the chemical
detoxification treatments are fully
understood, and both the reac-tion
products and their respective toxicities
are still unknown and must be
determined prior to use. The regulatory
approval for some of the proposed
chemical treatments such as
ammoniation and potassium

permanganate must be sought prior to

use in the food industry.

Biological control

Biological methods of patulin control

result largely from the ob-

16
2005

COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETYVol. 1,

Patulin control in foods . . .

servation that
patulin is almost
always
completely
degraded during yeast
fermentation.
Besides being
quite successful,
this meth-od is
much better
understood
compared with
other
decontamination methods.
Approximately
90% of patulin
can be removed
during yeast
fermentation
(Burroughs
1977). In 1
study, 6 of 8
yeast strains
reduced patulin
levels to below
detectable
levels, while all
8 strains
resulted in a
99% or better
decrease in total
pat-ulin content.
Control juice, on
the other hand,
stored for an
equal amount of
time (2 weeks),
had only a 10%
reduction
(Stinson and
others 1978). In
a 2nd study,
yeast
fermentation
reduced patulin
levels
completely after
2 wk. This same
study also
showed that
patulin levels
failed to
decrease
significantly in
juices that had
been yeast
fermented and
then filter
sterilized to
remove yeast,

suggesting that
active yeast,
and not their
byproducts,
were re-quired
for the reduction
(Harwig and
others 1973a).
Treatments of
patulin along
with
cyclohexamide,
a protein
synthesis
blocker of yeast,
completely
blocked protein
synthesis and
prevented the
detoxification of
patulin. Addition
of
cyclohexamide 3
h after pat-ulin
addition,
however,
resulted in a
reduced, but
continued, rate
of patulin
degradation,
suggesting that
the proteins
synthesized
within the 3-h
window were
catalytically
active against
patulin and did
not just bind it
up in adduct
formation
(Sumbu and
others 1983). A
later study
showed that 3
strains of
Saccharomyces
cere-visiae
reduced patulin
levels during
fermentive
growth but not
aerobic growth.
This reduction
resulted in the
production of 2
ma-jor products:
E-ascladiol,
patulins
immediate
biosynthetic
precur-sor, and
its isomer Z-

ascladiol. These
2 products were
also seen in the
treatment of
patulin with the
reducing agent
sodium borohydrate (Moss and
Long 2002). Eascladiol is itself
a mycotoxin
(Su-zuki and
others 1971),
which has
reduced toxicity
compared with
patulin and also
reacts with
sulfhydrylcontaining
compounds
(Sekiguchi and
others 1983).

While effective,
biological
control with
yeast is limited
to prod-ucts
that can be
fermented.
Furthermore,
yeast are
themselves
sensitive to
patulin, and at
concentrations
greater than
200 g/ mL,
yeast have
been shown to
be completely
inhibited,
prevent-ing
fermentive
detoxification
(Sumbu and
others 1983).
No re-search
has been done
to examine the
potential use of
other fermenting
microbes, such
as lactic acid
bacteria, in
decreasing patulin content
within juices.
Similar
reducing

enzymes and
environ-ments
produced by
these bacteria
may very well
be able to degrade patulin.
Finally, no
research has
investigated the
direct enzymatic
degradation of
patulin.
Reducing
enzymes such
as those
involved in
yeast
fermentation,
as well as
lactone
degrading enzymes such as
-lactamase,
may well be
able to degrade
patulin alone.

Electromagneti
c irradiation

Electromagnetic
radiation has
been shown in
preliminary studies to reduce the
content of
patulin and other
mycotoxins
within juice. In 1
study, treatment
of juice with
0.35-kGy
ionizing radiation caused a
50% reduction
of patulin with
no acceleration
of nonenzymatic
browning of the
juice (Zegota
and others
1988). The UV
light sensitivity
of aflatoxins has
been
demonstrated
on several
accounts, but no
studies have

been performed
specifically on
patulin (Doyle
and others
1982; Valletrisco
and others
1990).

Patulin
Production
in the Final
Product

Limited work
has been done
to examine the
potential growth
and production
of patulin by
fungi in stored,
finished product
juices. It is well
known that
many
Aspergillus and
Byssochlamys
spp. molds,
many of which
produce patulin,
are heat
resistant and
can survive the
pasteurization
processes used
in juice and cider production.
Furthermore,
many of the
same patulinproduc-ing
molds have also
been shown to
grow and
produce patulin
at

standard cold
storage
temperature
down to 0C
(Sommer and
others 1974).
Taken together,
these 2 facts
suggest that
finished apple
juice and cider
could very well
support the

continued production of
patulin by fungi.
If this is the
case, any
single
treatment
patulin control
method, such
as physical
adsorption,
would potentially be
moot due to
production of
patulin by
active fungi
postprocessing.
Studies must
be done to
examine this
potential within
juices, and, if
possible, to
provide
correlates
between mold
numbers and
patulin levels
within juice.

With the
possibility of
fungi actively
producing
patulin within
juice, control
measures
should aim not
only at the
reduction of
patulin itself,
but the
inhibition of
both fungal
growth and
patulin
production
within juice.
Some studies
have examined
the effects of
many patulinreducing
treatments on
live patulinproducing
fungi. Sulfur
dioxide, sodium
benzoate, and
potassium

sorbate have
been
investigated for
the affect on B.
nivea growth
and patu-lin
production
within juice.
Seventy-five
ppm sulfur
dioxide, 150
ppm potassium
sorbate, and
500 ppm
sodium
benzoate all
signif-icantly
retarded B.
nivea growth
and patulin
production
(Roland and
Beuchat
1984a). A 2nd
study showed
that treatment
of B. nivea with
50 g/mL
potassium
sorbate
completely
eliminated
patulin
production at
37 C.
However,
higher
concentrations
(75 and 100
g/mL) were
needed at
lower
temperatures
(21 C) to inhibit growth,
and even with
growth
inhibition, these
treatments
failed to inhibit
patulin
production
(Roland and
others 1984b).
A related study
showed that
0.1% of
potassium
sorbate
eliminated
patulin
production in P.
patulum, but

interestingly,
this same treatment elevated
patulin
production in P.
roqueforti
(Bullerman and
Olivigni 1974).
A 4th study
showed that
0.1 M
potassium
sorbate
reduced P.
expansum
growth by 83%
and patulin
production by
98%, while 0.1
M sodium
propionate
caused a 48%
reduction in
growth and
98% reduction
in patulin
production
(Lennox and
McElroy 1984).

A separate set
of studies
showed that
treatment with
0.2% lem-on oil
reduced patulin
production, and
a mix of 0.05%
lemon oil and
0.2% orange oil
resulted in a
90% reduction
of patulin production (Hasan
2000). Finally,
in a series of
unsuccessful
studies,
addition of
0.5% and
0.75% citric
and lactic acid
reduced production of
aflatoxins and
sterigmatocysti
n, but not
patulin. These
same
treatments also
failed to inhibit

P. expansum
growth (Reiss
1976).

an emphasis
upon the
following areas.

Conclusions

Patulin
detection

While studies
investigating the
health effects of
patulin have
proved
inconclusive,
there is little
doubt as to the
potential danger
inherent in the
contamination of
food products by
patulin. Past research has
elucidated a
great deal about
the chemical
and biolog-ical
nature of patulin,
has made
advances in
methods for
detect-ing
patulin, and has
revealed a
number of
potential control
mea-sures that
may provide a
basis for fully
effective control
measures within
the future. Still,
patulin
contamination
continues to be
present within
the food
industry. Thus,
future research
must con-tinue
to address the
threat of patulin
contamination
within food
products, with

While methods
for detecting
and quantifying
patulin have
great-ly
improved over
the years, the
sensitivity of
these methods
is still often a
limiting factor
for many
aspects of
patulin control
re-search.
Currently, no
rapid analytical
technique
exists for the
anal-ysis of
patulin, and the
standard
methodology
for patulin
quantifi-cation
requires
dedicated
instrumentation
and trained
operators. A
rapid detection
method that
can be used
in-house by
the food
industry without
any
complicated
equipment
would be extremely
beneficial.

Vol. 1, 2005COMPREHENSIVE

REVIEWS IN FOOD SCIENCE AND

FOOD SAFETY 17

CRFSFS: Comprehensive Reviews in Food Science and Food Safety

patulin control measures are applied to all
products where a threat exists.
Patulin control

References
Efficacy evaluation of food-processing
techniques for mycotox-in reduction must
consider (1) stability of mycotoxin, (2)
nature of process, (3) mycotoxin-food
interactions, and (4) mycotoxin-mycotoxin interactions (Park and Troxell
2002). Efforts to control the contamination
of apple products by patulin currently
focus on 3 areas: prevention of patulin
contamination in the harvesting, processing, and storage steps; removal of
patulin during processing; and
postproduction treatments to remove or
detoxify patulin. While many of the control
measures mentioned previously have
shown promise, none are yet at the point
of providing guaranteed patulin control
within food products. Also to be
considered is the increasing level of juice
imports into the United States. Imports
comprise 60% of the U.S. apple juice
market, with most being low acid juices
from China that are later blended with
higher acid U.S. juices for consumption.
Higher U.S. demand for apple products
will increase the levels of these often
quality-questioned imports (USDA 2002).
Domestic control measures based upon
prepro-duction and production-stage
treatment of patulin cannot be ex-pected
to be utilized by juice exporters, and thus
blending of im-ported juices could serve
as a source of patulin contamination capable of undermining any of the
aforementioned control mea-sures. With
this trend in mind, postproduction patulin
control measures must almost certainly
be included within any successful control
regime. Successful patulin control will
most likely result, not from a single
treatment, but from a combination of
control measures throughout the
production process.

Patulin prevalence

While most commonly associated with

apple juice and apple cider, patulin has
been detected as a natural contaminant
in a va-riety of other apple-based and
nonapple-based products. Stud-ies
should continue to investigate and
monitor other varieties of fruit and
vegetable products to guarantee that

Acar J, Gkmen V, Taydas EE. 1998. The effects of

processing technology on the

patulin content of juice during commercial apple

juice concentrate production.

Z Lebensm Unters Forsch A. 207:32831.

Ake M, Eba B, Malan AK, Atindehou E. 2001.

Dtermination de la Patuline dans le Jus de Fruits
Commercialissen Cte dIvoire. Sci Aliment 21:199
206.

Akerstrand K, Molander A, Andersson A, Nilsson G.

1976. Occurrence of moulds and mycotoxins in frozen
blueberries. Vr Fda 28:197200.

Andersson AE, Josefsson G, Nilsson G, Akerstrand K.

1977. Mgelsvampar och Patulin I Frukt Och Br. Vr
Fda 8:2928.

Annous BA, Sapers GM, Mattrazzo AM, Riordan DC.

2001. Efficacy of washing with a commercial flatbed
brush washer, using conventional and experimental
washing agents, in reducing populations of
Escherichia coli on artificially inoculated apples. J
Food Prot 64:15963.

Anslow WK, Raistrick H, Smith G. 1943. Antifungal

substances from moulds. Part I. Patulin, a metabolic
product of Penicillium patulum Banier and Penicillium
expan-sum (Link). Thom Trans Soc Chem Ind 62:236.
Arafat W, Kern D, Dirheimer G. 1985. Inhibition of
aminoacyl-tRNA synthetases by the mycotoxin patulin.
Chem Biol Interact 56:33349.

Arafat W, Musa MN. 1995. Patulin-induced inhibition of

protein synthesis in hepatoma tissue culture. Res
Commun Mol Pathol Pharmacol 87(2):17786.

Arici, M, Demirici M, Gms T. 2002. Vorkommen von

Patulin in Fruchten und Fruchtsften in der Trkei.

Proceedings of the 24th Mycotoxin Workshop; 2002

Jun 3-6; Berlin, Germany.
Brackett RE, Marth EH. 1979b. Ascorbic acid and
ascorbate cause disappearance of patulin from buffer
solutions and apple juice. J Food Prot 42(11):8646.
Artik N, Acar J, Kabraman N, Poyrazoglu E. 2001.
Effects of various clarification treatments on patulin,
phenolic compound, and organic acid compositions of
apple juice. Eur Food Res Tech 213(3):1949.
Ashoor SH, Chu FS. 1973. Inhibition of muscle
aldolase by penicillic acid and patulin in vitro. Food
Cosmet Toxicol 11:9951000.

[AIJN] Assn. of the Industry of Juices and Nectars from

Fruits and Vegetables of the European Union. 1990.
Code of practice for the evaluation of fruit and
vegetable juices. 6.3:2. Brussels, Belgium. AIJN.

Aytac SA, Acar J. 1994. Einflub von L-Ascorbinsure

und Schwefeldioxidzusatz auf die Stabilitt von Patulin
in Apfelften und Pufferlsungen. Ernhrung. 1:157.

Brackett RE, Marth EH. 1979c. Stability of patulin at

pH 6.0-8.0 and 25 C. Z Leb-ensm Unters Forsch
169:924.

Brian PW, Elson GW, Lowe D. 1956. Production of

patulin in apple fruits by Peni-cillium expansum. Nature
178:2634.

Buchanan JR, Sommer NF, Fortlage RJ, Maxie EC,

Mitchell FG, Hseih DPH. 1974. Patulin from
Penicillium expansum in stone fruits and pears. J Amer
Soc Hort Sci 99(3):2625.
Bullerman LB, Olivigni FJ. 1974. Mycotoxin producing
potential of molds isolated from cheddar cheese. J
Food Sci 39:11668.

Barhoumi R, Burghardt RC. 1996. Kinetic analysis of

the chronology of patulin- and gossypol-induced
cytotoxicity in vitro. Fundam Appl Toxicol 30:2907.
Burghardt RC, Barhoumi R, Lewis EH, Bailey RH, Pyle
KA, Clement BA, Phillips TD. 1992. Patulin-induced
cellular toxicity: a vital fluorescence study. Toxicol Appl
Pharmacol 112:23544.
Beck J, Ripka S, Siegner A. Schiltz E, Schweizer E.
1990. The multifunctional 6-methylsalicylic acid
synthase gene of Penicillium patulum. Eur J Biochem
192:48798.
Burroughs LF. 1977. Stability of patulin to sulfur
dioxide and to yeast fermentation. J AOAC 60(1):100.

Berestetskyi OO, Synytskyi. 1973. Phytotoxic

activity in different strains of PenCanas P, Aranda M. 1996. Decontamination and
inhibition of patulin-induced cy-totoxicity. Environ
Toxicol Water Quality 11:24953.
icillium urticae banier. Mikrobiol Zh 35:349.

Cavallito CJ, Bailey JH. 1944. Preliminary note on the

inactivation of antibiotics. Science 100:390.
Beretta B, Gaiaschi A, Galli CL, Restani P. 2000.
Patulin in apple-based foods: occurrence and safety
evaluation. Food Addit Contam 17(5):399406.
Chain E, Florey HW, Jennings MA. 1942. An
antibacterial substance produced by Penicillium
claviforme. Brit J Exp Pathol 23:202.
Bergel F, Morrison AL, Klein R, Moss AR,
Rinderknecht J, Ward JL. 1943. An antibi-otic
substance from Aspergillus clavatus and Penicillium
claviforme and its prob-able identity with patulin.
Nature 152:750.

Ciegler A, Detroy RW, Lillehoj EB. 1971. Patulin,

penicillic acid, and other carci-nogenic lactones. In:
Ciegler A, Kadis S, Ajl SJ, editors. Microbial toxins. Vol
6. New York and London: Academic Press. p 409.

Bissessur J, Permaul K, Odhav B. 2001. Reduction of

patulin during apple juice clarification. J Food Prot
64(8):12169.

Ciegler A, Beckwith AC, Jackson LK. 1976.

Teratogenicity of patulin and patulin adducts formed
with cysteine. Appl Environ Microbiol 31:6647.

Brackett RE, Marth, EH. 1979a. Patulin in apple juice

from roadside stands in Wis-consin. J Food Prot
42(11):8623.

Ciegler A. 1977. Patulin. In: United States-Japan

natural resources program myc-otoxins in human and
animal health. Park Forest South, Ill.: Pathotox
Publishers. p 60924.

[CODEX] Committee on Food Additives and

Contaminants. 2002. Proposed draft code of practice
for the reduction of patulin contamination in apple juice
and apple juice ingredients in other beverages (at step
5 of procedure). Geneva, Switzerland. Joint FAO/WHO
Food Standards Programme. p 17.

Draughon FA, Ayres JC. 1980. Insecticide inhibition of

growth and patulin produc-tion in Penicillium
expansum, Penicillium urticae, Aspergillus clavatus,
Aspergil-lus terreus, and Byssochlamys nivea. J Agric
Food Chem 28:11157.

Ehlers D. 1986. HPLC-Bestimmung von Patulin in

Obstsften-Probenaufarbeitung Mit Einum
Modifizierten Extraktionsund Reinigungsverfahren.
Lebensm Cerich-tl Chem 40:15.
Conway WS, Janisiewicz WJ, Klein JD, Sams CE.
1999. Strategy for combining heat

Ellis JR, McCalla TM, Norstadt FA. 1980. Soil effects

on patulin disappearance and the effect of ammonia
on patulin phytotoxicity. Soil Sci 129:3715.

treatment, calcium infiltration, and biological control

to reduce postharvest deEscoula L. 1974. Toxinogenic moulds in ensilaged
forage. I. Presence of patulin in silage cutting fronts.
Ann Rech Vet 5:42332.
cay of Gala apples. Hort Sci 34(4):7004.

Cooray R, Kiessling K-H, Lindahl-Kiessling K. 1982.

The effects of patulin and pat-ulin-cysteine mixtures on
DNA synthesis and the frequency of sister-chromatid
exchanges in human lymphocytes. Food Chem Toxicol
20:8938.

Corbett D. 2003. PatulinU.K. producers perspective

In: Patulin technical sympo-sium. February 1819,
2003; Kissimmee, Fla. National Center for Food safety
adn Technology. Summit, Ill.
Demirci M, Arici M, Gumus T. 2003. Presence of
patulin in fruit and fruit juices produced in Turkey.
Ernaehrungs-Umschau 50(7):2623.

De Sylos CM, Rodriquez-Amaya DB. 1999. Incidence

of patulin in fruits and fruit juices marketed in
Campinas, Brazil. Food Addit Contam 16:714.

Escoula L. 1977. Moulds in silage and their toxic

effect. Fourrages 69:97114. Escoula L, Moore J,
Baradat C. 1977. The toxins of Byssochlamys nivea.
Part I.

Acute toxicity of patulin in adult rats and mice. Annal

Rech Vet 8:419. Federal Register. 2003. Secondary
direct food additives permitted in food for human

consumption, final rule 66(13): 33829. Available from:

frwebgate.access.gpo. gov/cgi-bin/getpage.cgi.
Accessed March 5, 2003.

Fliege R, Metzler M. 1999. The mycotoxin patulin

induces intra- and intermolecular protein crosslinks in vitro involving cysteine,
lysine, and histidine side

DeRosnay CD, Martin-Dupont, Jensen R. 1952. An

antibiotic, myocin. C. J. Med. Bordeaux et Sud-Ouest.
129:189.

chains, and -amino groups. Chemico-Biol Interact

123:85103.
Fliege R, Metzler M. 2000. Electrophilic properties
of patulin: N-Acetylcysteine

Dickens F, Jones HEH. 1961. Carcinogenic activity of

a series of reactive lactones and related substances.
Brit J Cancer 15:85100.

Dock LL. 1999. Development of thermal and nonthermal preservation methods for production of
microbiologically safe apple cider [Ph.D. thesis].
Lafayette, Ind.: Purdue Univ. 196 p.

Doyle MP, Applebaum RS, Brackett RE, Marth EH.

1982. Physical, chemical, and biological degradation
of mycotoxins in foods and agricultural commodities. J
Food Prot 45:96471.

and glutathione adducts. Chem Res Toxicol 13:373

81.

Forbito PR, Babsky NE. 1996. Rapid liquid

chromatographic determination of pat-ulin in apple
cider. J Chromatogr 730:538.

Forrester PI, Gaucher GM. 1972. Conversion of 6methyl salicylic acid into patulin by Penicillium urticae.
Biochem 11:110814.

18
2005

COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETYVol. 1,

Patulin control in foods . . .

Frank HK, Orth R,

Figge A. 1977.
Patulin in foods of
plant origin. II.
Several kinds of fruit
and vegetables and
fruit and vegetable
products. Z Lebensm
Unters For-sch
163:1114.

Grootwassink JWD,
Gaucher GM. 1980.
De novo biosynthesis
of secondary metabolism enzymes in
homogeneous
cultures of Penicillium
urticae. J
Bacteriology
141(2):44355.

Fremy JM,
Castegnaro MJ,
Gleizes E, De Meo M,
Laget M. 1995.
Procedures for
destruction of patulin
in laboratory wastes.
Food Addit Contam
12:8646.

Hasan HAH. 2000.

Patulin and aflatoxin
in brown rot lesion of
apple fruits and their
regulation. World J
Microbiol Biotechnol
16:60712.

Gaucher GM. 1975.

m-Hydroxybenzyl
alcohol
dehydrogenase.
Methods Enzymol
43:5408.

Gaucher GM. 1979.

MycotoxinsTheir
biosynthesis in fungi:
patulin and related
carcinogenic
lactones. J Food Prot
42:8104.

Geiger WB, Conn JE.

1945. The
mechanism of the
antibiotic action of
clavacin and penicillic
acid. J Am Chem Soc
67:1125.

Gokmen V, Akar J.
1998. Incidence of
patulin in apple juice
concentrates
produced in Turkey. J
Chromatogr 815:99
102.

Gokmen V, Acar J.
1999. Simultaneous
determination of 5hydroxymethylfurfural
and patulin in apple
juice by reversedphase liquid
chromatography. J
Chro-matogr A
847:6974.

Harrison
MA. 1989. Presence
and stability of patulin
in apple products: a
review.
J Food
Safety 9:14753.
Harvey JM, Smith Jr.
WL, Kaufman J.
1972. Market
diseases of stone
fruits: cherries,
peaches, nectarines,
apricots, and plums.
USDA Handbook
414:64.

Harwig J, Scott PM,

Kennedy BPC, Chen
YK. 1973a.
Disappearance of
patulin from apple
juice fermented by
Saccharomyces spp.
Can Inst Food Sci
Technol J 6(1):456.

Harwig J, Chen YK,

Kennedy BPC, Scott
PM. 1973b.
Occurrence of patulin
and patulin-producing
strains of Penicillium
expansum in natural
rots of apple in
Canada. Can. Inst.
Food Sci Technol J
6:225.
Harwig J, Blanchfield
BJ, Scott PM. 1978.
Patulin production by
Penicillium roque-forti
Thom from grape.
Can Inst Food Sci
Technol J 11(3):149
51.

Hatez F, Gaye F.
1978. Inhibition of
translation in
reticulocyte by the
mycotoxin patulin.
FEBS Lett 95:2526.

Hayes AW, Phillips

TD, Williams WL,
Ciegler A. 1979.
Acute toxicity of
patulin in mice and
rats. Toxicology
13:91100.

Heatley NG, Philpot

FJ. 1947. The routine
examination for
antibiotics produced
by molds. J Gen
Microbiol 1:2327.

conversion of gentisyl
alcohol into patulin by
microsomal
enzyme(s) and
retention of one of the
carbinol protons in
this reaction. Chem
Pharm Bull
34(8):35347.
Iyengar MRS, Starky
RL. 1953. Synergism
and antagonism of
auxin by antibiotics.
Science
118:357.

Jackson LS,
Beacham-Bowden T,
Keller SE, Adhikari C,
Taylor KT, Chirtel SJ,
Merker
RI. 2003. Apple
quality,

Hoffman H, Mintzlaff
HJ, Alperden I,
Leistner L. 1971.
Untersuchung uber
die In-aktiviering des
Mykotoxins Patulin
durch
Suofydrylgruppen.
Die Fleischwirtschaft.
51:15346, 1539.

Hopkins J. 1993. The

toxicological hazards
of patulin. Br Ind Biol
Res Assoc Bull 32:3
4.

Huebner HJ,
Mayura K, Pallaroni
L, Ake CL, Lemke
SL, Herrera P,
Phillips TD.

2000. Development
and characterization
of a carbon-based
composite material

for reducing patulin

levels in apple juice. J
Food Prot 63(1):106
10.

Iijimia H, Ebizuka Y,
Sankawa U. 1986.
Biosynthesis of
patulin, in vitro

storage, and washing

treatments affect
patulin levels
in
apple
cider. J Food Prot
66(4):61824.
Jelinek FF, Pohland
AE, Wood GE. 1989.
Review of mycotoxin
contamination.
worldwide occurrence
of mycotoxins in
foods and feeds. an
update. J AOAC
72:22330.

Jiminez M, Mateo R,
Querol A, Huerta T,
Hernandez E. 1991.
Mycotoxins and mycotoxigenic moulds in
nuts and sunflower
seeds for human
consumption. Mycopathologia 115:121
7.
Josefson E,
Andersson A. 1976.
Analysis of patulin in
apple beverages sold
in Sweden. Vr Foda
28:18996.

Kadakal C, Nas S.
2002. Effect of
activated charcoal on
patulin, fumaric acid,
and some other
properties of apple

juice. Nahrung/Food
46(1):313.

Korte A. 1980.
Chromosomal
analysis in bone
marrow cells of
Chinese hamsters
after treatment with
mycotoxins. Mutat
Res 78:419.

Korzybski T,
Kowszyk-Gindifier Z,
Kurylowicz S. 1967.
Antibiotics origin,
nature, and
properties Vol. II.
New York: Pergamon
Press. p 122330.

Kryger RA. 2001.

Volatility of patulin in
apple juice. J Agric
Food Chem 49:4141
3. Lai CL, Fuh Y-M,
Shih DY-C. 2000.
Detection of
mycotoxin patulin in
apple juice.

J Food Drug Anal

2:8596.

Laidou IA,
Thanassoulpopoulos
CC, LiakopoulouKyriakides M. 2001.
Diffusion of patulin in
the flesh of pears
inoculated with four
post-harvest
pathogens. J Phytopathol

34:307.
Larsen TO, Frisvad
JC, Ravn G,
Skaaning T. 1998.
Mycotoxin production
by Penicil-lium
expansum on
blackcurrant and
cherry juice. Food
Addit Contam
15(6):6715.

Lee K-S,
Rschenthaler RJ.
1986. DNA-damaging
activity of patulin in
Escherichia coli. Appl
Environ Microbiol
52(5):104654.

Lee K-S,
Rschenthaler R.
1987. Strand
scissions of DNA by
patulin in the presence of reducing
agents and cupric
ions. J Antibiot
40:6926.

Leggott NL,
Shephard GS. 2001.
Patulin in South
African commercial
apple prod-ucts. Food
Control 12:736.

Leggott NL,
Shephard GS,
Stockenstrm S,
Staal E, van
Schalkwyk DJ. 2001.
The reduction of
patulin in apple juice
by three different
types of activated
carbon. Food Addit
Contam 18(9):8259.

149:45761.

Lam KS, Neway JO,

Gaucher MG. 1988.
In vitro
stabilization
of 6-methylsalicylic acid
synthetase from
Penicillium urticae.
Can
J Microbiol

Lennox JE, McElroy

LJ. 1984. Inhibition of
growth and patulin
synthesis in Penicillium expansum by
potassium sorbate
and sodium
propionate in culture.
Appl Environ
Microbiol 48(2):1031
3.
Lin LM, Zhang J, Sui
K, Sung WB. 1993.
Simultaneous thin
layer
chromatographic

determination of
zearalenone and
patulin in maize. J
Planar
ChromatographyModern TLC 6:2747.

stored in a controlled
atmosphere. J AOAC
58(5):9124.

Lindroth S, von
Wright A. 1990.
Detoxification of
patulin by adduct
formation with
cysteine. J Environ
Pathol Toxicol Oncol
10(45):2549.

Lovett J, Thompson
RG, Boutin BK.
1975b. Trimming as a
means of removing
patu-lin from fungus
rotten apples. J
AOAC 58:90911.

Llovera M, Viladrich
R, Torres M, Canela
R. 1999. Analysis of
underivatized patulin
by a GC-MS
technique. J Food
Prot 62(2):2025.

Lopez-Diaz TM,
Flannigan B. 1997.
Production of patulin
and cytochalasin E by
Aspergillus clavatus
during malting of
barley and wheat. Int
J Food Microbiol
35:12936.

Lopez-Garcia R, Park
DL. 1998.
Effectiveness of postharvest procedures in
manage-ment of
mycotoxin hazards.
In: Bhatnagar D, Siha
S, editors.
Mycotoxins in agriculture and food
safety. New York:
Marcel Dekker. p
40733.

Lovett J, Peeler JT.

1973. Effect of pH on
the thermal
destruction kinetics of
patu-lin in aqueous
solution. J Food Sci
38:10945.

Lynen FH, Engeser J,

Freidrich W,
Schindlbeck R,
Seyffert J, Wieland F.
1978. Fatty acid
synthetase of yeast
and 6Methylsalicylate
synthetase of
Penicillium patu-lum
Two multi-enzyme
complexes. In: Srere
PA, Estabrook RW,
editors. Microenvironments and
metabolic
compartmentalization
. New York: Academic
Press. p 283303.

MacDonald S, Long
M, Gilbert J. 2000.
Liquid
chromatographic
method for determination of patulin in
clear and cloudy
apple juices and
apple puree:
collabora-tive study. J
AOAC Int
83(6):138794.

Maeba H, Takamoto
Y, Kamimura M,
Miura T. 1988.
Destruction and
detoxification of
aflatoxins with ozone.
J Food Sci 53: 6678.

Lovett J, Boutin B,
Thompson RG. 1974.
Patulin production in
cherry by Penicillium
and Aspergillus
species. J Milk Food
Technol 37:530.

Mahfoud R, Maresca
M, Garmy N, Fantini
J. 2002. The
mycotoxin patulin
alters the barrier
function of the
intestinal epithelium:
mechanism of action
of the toxin and
protective effects of
glutathione. Toxicol
Appl Pharmacol
18:120918.

Lovett J, Thompson
RG, Boutin BK.
1975a. Patulin
production in apples

Marek P, Annamalai
T, Venkitanarayanan
K. 2003. Detection of
Penicillium expan-

sum by polymerase
chain reaction. Int J
Food Microbiol
89:13944.

Mayer VW, Legaror

MS. 1969. Production
of petite mutants of
Saccharomyces cerevisiae by patulin. J
Agric Food Chem
17:4546.

McCallum JL, Tsao R,

Zhou T. 2002. Factors
affecting patulin
production by Penicillium expansum. J
Food Prot
65(12):193742.

McElroy LJ, Weiss

CM. 1993. The
production of
polyclonal antibodies
against the mycotoxin
derivative patulin
hemiglutarate. Can J
Microbiol 39:8613.

McKenzie KS, Sarr

AB, Mayura K, Bailey
RH, Miller DR,
Rogers TD, Norred
WP, Voss KA,
Plattner RD, Kubena
LF, Phillips TD. 1997.
Oxidative degradation
and detox-ification of
mycotoxins using a
novel source of
ozone. Food Chem
Toxicol 35:80720.

McKinley ER, Carlton

WW. 1980a. Patulin
mycotoxicosis in the
Swiss ICR mice.
Food Cosmet Toxicol
18:1817.

McKinley ER, Carlton

WW. 1980b. Patulin
mycotoxicosis in the
Syrian hamster. Food
Cosmet Toxicol
18:1739.

McKinley ER, Carlton

WW, Boon GD. 1982.
Patulin mycotoxicosis
in the rat: tox-icology,
pathology, and
clinical pathology.

Food Chem Toxicol

20:289300.

Medical Research
Council. 1944.
Clinical trial of patulin
in the common cold.
Lan-cet ii:373.

Miura S, Hasumi K,
Endo A. 1993.
Inhibition of protein
prenylation by patulin.
Fed Eur Biochem Soc
318(1):8890.

Moller TE, Josefsson

E. 1980. Rapid highpressure liquid
chromatography of
patulin in apple cider.
J AOAC 63:10556.

Moodley RS,
Govinden R, Odhav
B. 2002. The effect of
modified
atmospheres and
packaging on patulin
production in apples.
J Food Prot
65(5):86771.

Moss MO, Long MT.

2002. Fate of patulin
in the presence of the
yeast Saccharomyces cerevisiae.
Food Addit Contam
19(4):38799.

Moule Y, Hatey F.
1977. Mechanism of
the in vitro inhibition
of transcription by
patulin, a mycotoxin
from Byssochlamys
nivea. FEBS Lett
74:1215.

Morgavi DP, Boudra

H, Jouany J-P,
Graviou D. 2003.
Prevention of patulin
toxicity on rumen
microbial
fermentation by shcontaining reducing
agents. J Agric Food
Chem 51:690610.

Murphy G, Lynen F.
1975. Patulin
biosynthesis: The
metabolism of mhydroxyben-zyl
alcohol and mhydroxybenzaldehyde
by particulate
preparations from
Peni-cillium patulum.
Eur J Biochem
58:46775.
Mutlu M, Hizarcioglu
N, Gokmen V. 1997.
Patulin adsorption
kinetics on activated
carbon, activation
energy, and heat of
adsorption. J Food
Sci 62:12830.

Neway J, Gaucher
GM. 1981. Intrinsic
limitations on the
continued production
of the antibiotic
patulin by Penicillium
urticae. Can J
Microbiol 27:20615.

Norstadt FA, McCalla

TM. 1963. Phytotoxic
substance from a
species of Penicillium. Science
140:4101.

Norstadt FA, McCalla

TM. 1968.
Microbiological
population in
stubblefield mulched
soil. Soil Sci 107:188.

Northolt MD, Van

Egmond HP, Paulsch
WE. 1979. Patulin
production by some
fun-gal species in
relation to water
activity and

temperature. J Food
Prot 41(11):885 90.

Ough CS, Corison

CA. 1980.
Measurement of
patulin in grapes and
wines. J Food Sci
45:4768.

Oswald H, Frank HK,

Komitowski D, Winter
H. 1978. Long-term
testing of patulin
administered orally to
Sprague-Dawley rats
and Swiss mice.
Food Cosmet Toxi-col
16:2437.
Park DL, Lee LS,
Price RL, Pohland
AE. 1988. Review of
decontamination of
afla-toxin by
ammoniation: current
status and regulation.
J AOAC 71:685.

Park DL, Njapau H,

Bontrif E. 1999.
Minimizing risks
posed by mycotoxins
utilizing the HAACP
concept: food,
nutrition, and
agriculture. 23:49.

Park DL, Troxell TC.

2002. U.S.
perspectives on
mycotoxin regulatory
issues. Adv Exp Med
Biol 504:27785.

Paster N, Huppert
D, Barkai-Golan R.
1995. Production of
patulin by different

Vol. 1, 2005COMPREHENSIVE

REVIEWS IN FOOD SCIENCE AND

FOOD SAFETY 19

CRFSFS: Comprehensive Reviews in Food Science and Food Safety

R. 1970. Stability studies with

strains of Penicillium expansum in pear and apple

cultivars stored at different temperatures and modified
atmospheres. Food Addit Contam 12(1):518.
Paterson RRM, Archer S, Kozakiewicz Z, Lea A, Locke
T, OGrady E. 2000. A gene probe for the patulin
metabolic pathway with potential for use in patulin and
novel disease control. Biocontrol Sci Technol 10:509
12.
Pfeiffer E, Gross K, Metzler M. 1998. Aneuploidogenic
and clastogenic potential of the mycotoxins citrinin and
patulin. Carcinogenesis 19:13138.

Phillips TD, Hayes W. 1977. Effects of patulin on

adenosine triphosphatase activ-ities in the mouse.
Toxicol Appl Pharmacol 42:17587.

Phillips TD, Hayes W. 1978. Effects of patulin on the

kinetics of substrate and cationic ligand activation of
adenosine triphosphatase in mouse brain. J Pharmacol Exp Ther 205:60616.

patulin. J AOAC 53:688.

Priest JW, Light RL. 1989. Patulin biosynthesis:
epoxidation of toluquinol and gen-tisyl alcohol by
particulate preparations from Penicillium patulum.
Biochemistry 28:9192-200.

Prieta J, Moreno MA, Diaz S, Suarez G, Dominguez L.

1994. Survey of patulin in apple juice and childrens
apple food by diphasic dialysis membrane procedure.
J Agric Food Chem 42:17013.
Raistrick J, Birkinshaw JH, Bracken A, Michael SE,
Hopkins WA, Gye WE. 1943. Patulin in the common
cold. collaborative research on a derivative of
Penicillium patulum Banier. Lancet 245:625.

Reinderknecht H, Ward JL, Bergel F, Morrison AL.

1947. Studies on antibiotics. 2. Bacteriological activity
and possible mode of action of certain non-nitrogenous
natural and synthetic antibiotics. Biochem J 41:4639.
Reiss J. 1972. Nachweis von Patulin in Spontan
Vershimmeltem Brot und Gebck.
Naturwissenschaften 59:37.

Philpot FJ. 1943. A penicillin-like substance from

Aspergillus giganteus Wehm. Nature 152:725.

Pierson CF, Ceponis MJ, McColloch LP. 1971. Market

diseases of apples, pears, and quinces. Agric
Handbook 376:146.

Reiss J. 1976. Prevention of the formation of

mycotoxins in whole wheat bread by citric acid and
lactic acid (mycotoxins in foodstuffs IX). Experientia
32(2):1689.

Reiss J. 1977. Inhibition of urease by the mycotoxin

patulin. Naturwissenschaften 64:97.
Pittet A. 1998. Natural occurrence of mycotoxins in
foods and feedsan updated review. In: Bars JL,
Galtier P, editors. Mycotox 98. Mycotoxin in Food
Chain. Processing and Toxicological Aspects.
Toulouse, France: Revue de Medecine Veterinaire. p
47992.

Plunkett LM, Turnbull D, Rudricks JV. 1992.

Differences between adults and chil-dren affecting
exposure assessment. In: Guelian PS, Henry CJ, Olin
SS, editors.

Rice SL, Beuchat LR, Worthington RE. 1977. Patulin

production by Byssochlamys spp. in fruit juices. App
Environ Microbiol 34(6):7916.

Riley RT, Showker JL. 1991. The mechanism of

patulins cytotoxicity and the anti-oxidant activity of
indole tetramic acids. Toxicol Appl Pharmacol
109:10826.

Similarities
and
differences between children

Ritieni A. 2003. Patulin in Italian commercial apple

products. J Agric Food Chem 51:608690.

and adults. Washington: ILSI

Press. p 7994.

Roach JAG, White KD, Trucksess MW, Thomas FS.

2000. Capillary gas chromatog-raphy/mass
spectrometry with chemical ionization and negative ion
detection for confirmation of identity of patulin in apple
juice. J AOAC Int 83(1):10412.

Pohland AE,
Allen

Roach JAG, Brause AR, Eisele TA, Rupp HS. 2002.

HPLC determination of patulin in apple juice with

GC/MS confirmation of patulin identity. In: Trucksess

and others, editors. Mycotoxins and food safety. New
York: Kluwer Academic/Plenum Pub-lishers. p 13540.

Roland JO, Beuchat LR. 1984a. Biomass and patulin

production by Byssochlamys nivea in apple juice as
affected by sorbate, benzoate, SO2, and temperature.
J Food Sci 49:4026.

Scott
PM, Miles WF, Toft
P, Dube JG. 1972. Occurrence of patulin

Roland JO, Beuchat LR. 1984b. Influence of

temperature and water activity on growth and patulin
production by Byssochlamys nivea in apple juice. Appl
Envi-ron Microbiol 47(1):2057.

in
apple
juice.
J Agric Food Chem 20:450.

Roll R, Matthiaschk G, Korte A. 1990. Embryotoxicity

and mutagenicity of mycotox-ins. J Envir Pathol
Toxicol Oncol 10:17.
Sekiguchi J, Gaucher GM. 1977. Conidiogenesis and
secondary metabolism in Penicillium urticae. Appl
Envir Microbiol 33:14758.
Rosenberger DA. 2003. Control of Penicillium
expansum during apple harvest and storage. In:
Patulin technical symposium. Feb 1819, 2003;
Kissimmee, Fla.; National Center for Food safety and
Technology; Summit, Ill.
Rovira R, Ribera F, Sanchis V, Canela R. 1993.
Improvements in the quantitation of patulin in apple
cider by high-performance liquid chromatography. J
Agric Food Chem 42:2146.

Sekiguchi J, Gaucher GM. 1978. Identification of

phyllostine as an intermediate of the patulin pathway in
Penicillium urticae. Biochem J 17:178591.

Sekiguchi J, Gaucher GM. 1979. Isoepoxydon, a new

metabolite of the patulin pathway in Penicillium urticae.
Biochem J 182:44553.
Rychlik M, Schieberle P. 1999. Quantification of the
mycotoxin patulin by a stable isotope dilution assay. J
Agric Food Chem 47:374955.

Rychlik M, Schieberle P. 2001. Model studies on the

diffusion behavior of the mycotoxin patulin in apples,
tomatoes, and wheat bread. Eur Food Res Technol
212:2748.

Sekiguchi J, Gaucher GM, Yamada Y. 1979.

Biosynthesis of patulin in Penicillium urticae:
identification of isopatulin as a new intermediate.
Tetrahedron Lett 1:412.

Sekiguchi J, Shimamoto T, Yamada Y, Gaucher GM.

1983. Patulin biosynthesis: en-

Sands DC, McIntyre JL, Walton GS. 1976. Use of

activated charcoal for the re-moval of patulin from
cider. Appl Envir Microbiol 32:38891.

Sapers GM, Miller RL, Mattrazzo AM. 1999.

Effectiveness of sanitizing agents in inactivating
Escherichia coli in golden delicious apples. J Food Sci
64:7347.
Scott
PM, Somers E. 1968. Stability of patulin and
penicillic acid

zymatic and nonenzymatic transformations of the

mycotoxin (E)-ascladiol. Appl Envir Microbiol
45(6):193942.
Sewram V, Nair JJ, Nieuwoudt TW, Leggott NL,
Shephard GS. 2000. Determination of patulin in apple
juice by high-performance liquid chromatographyatmospheric pressure chemical ionization mass
spectrometry. J Chromatogr A 897:36574.
Shephard GS, Leggott NL. 2000. Chromatographic
determination of the mycotoxin patulin in fruit juices. J
Chromatogr A 882:1722.

in
fruit
juices
and flour. J Agric Food
Chem 16:4835.

Sheu F, Shyu YT. 1999. Analysis of patulin in apple

juice by diphasic dialysis ex-traction with in situ
acylation and mass spectrometric determination. J
Agric Food
Chem 47:27114.

Singh J. 1967. Patulin. In: Gottlieb D,

Sydenham EW, Vismer HF, Marasas WFO, Brown N,

Schlecter M, van Der Weshui-zen L, Rheeder JP.
1995. Reduction of patulin in apple juice samples
influence of initial processing. Food Control 6:195
200.

Shaw PD, editors. Antibiotics I: mechanics

of action. Berlin: Springer-Verlag. p
62130.

Sydenham EW, Vismer HF, Marasas WFO, Brown NL,

Schlecter M, Rheeder JP. 1997. The influence of deck
storage and initial processing on patulin levels in apple
juice. Food Addit Contam 14:42934.

Sommer NF, Buchanan JR, Fortlage RJ.

1974. Production of patulin by Penicillium
expansum. Appl Microbiol 28:58993.

Stansfield JM, Francis AE, Stuart-Harris CH. 1944.

Laboratory and clinical trials of patulin. Lancet ii:370.

Steiner I, Werner D, Washttl J. 1999a. Patulin in fruit

juices. Part 1. analysis and control in Austrian apple
and pear juices. Ernhrung Nutr 23:2028.

Steiner I, Werner D, Washttl J. 1999b. Patulin in

obstsften. I. degradation of patulin. Ernhrung Nutr.
6:2515.

Steyn P. 1992. The biosynthesis of polyketide-derived

mycotoxins. J Envir Pathol Toxicol Oncol 11(1):4759.

Stinson EE, Osman SF, Huhtanen CN, Bills DD. 1978.

Disappearance of patulin during alcoholic fermentation
of apple juice. Appl Environ Microbiol 36(4):6202.

Stoloff L, van Egmond HP, Parks DL. 1991. Rationales

for the establishment of limits and regulations for
mycotoxins. Food Addit Contam 8:21322.

Stott WT, Bullerman LB. 1975. Patulin: a mycotoxin of

potential concern in foods. J Milk Food Technol
38(11):695705.

Stray H. 1978. High pressure liquid chromatographic

determination of patulin in apple juice. J AOAC
61:135962.

Syrett R. 1979. Moulds and mycotoxins in animal

foodstuffsReports of ADAS microbiologists. In:
Proceedings of a Third Meeting on Mycotoxins in
Animal Disease. Pinner, U.K.: Ministry of Agriculture,
Fisheries, and Food. Agricultural Development and
Advisory Service; 1978 April 17-18; Weybridge, U.K. p
47.

Takino M, Daishima S, Nakahara T. 2003. Liquid

chromatography/mass spectromet-ric determination of
patulin in apple juice using atmospheric pressure
photoion-ization. Rapid Comm Mass Spec 17:1695
972.
Tangi EK, Theys R, Mignolet E, Madoux M, Michelet
JY, Larondelle Y. 2003. Patulin in domestic and
imported apple-based drinks in Belgium: occurrence
and expo-sure assessment. Food Addit Contam
20(5):4829.

Taniwaki MH, Hoenderboom CJM, De Almeida Vitali A,

Eiroa MNU. 1992. Migra-tion of patulin in apples. J
Food Prot. 55:9024.

Thust R, Kneist S, Mendel J. 1982. Patulin, a further

clastogenic mycotoxin, is neg-ative in the SCE Assay
in Chinese hamster V79-E cells in vitro. Mutat Res
10:917.

Tsao R, Zhou T. 2000. Micellar electrokinetic capillary

electrophoresis for rapid analysis of patulin in apple
cider. J Agric Food Chem 48:52315.

Turner WB. 1976. Polyketides and related metabolites.

In: Smith JE, Berry DR, ed-itors. The filamentous fungi,
vol. 2. London: Edward Arnold, Ltd.

Ueno T, Matsumoto H, Ishii K, Kukita K-I. 1976.

Inhibitory effects of mycotoxins on Na+-dependent
transport of glycine in rabbit reticulocytes. Biochem
Pharmacol 25:20915.

Sumbu ZL, Thonart P, Bechet J. 1983. Action of

patulin on a yeast. Appl Environ Microbiol 45(1):1105.

Suzuki T, Takeda M, Tanabe H. 1971. A new mycotoxin

produced by Aspergillus clavatus. Chem Pharm Bull
19:17868.

[USDA] U.S. Dept. of Agriculture. 2003. Statistics of

fruits, tree nuts, and horticul-tural specialties. Natl.
Agricultural Statistics Service. Washington, D.C.,
U.S.A.

Available

from:

http://www.usda.gov/nass/pubs/agr02/02_ch5.pdf.

Van Luijk A. 1938. Antagonism of Penicillium spp.

versus Pythium debaryanum. Chron Bot 4:210.

Accessed

March 5, 2003.

Walker JRL. 1969. Inhibition of the apple phenolase

system through infection by Penicillium expansum.
Phytochemistry 8:5616.

[USFDA] U.S. Food and Drug Administration. 2004.

Compliance policy guide. Com-pliance policy guidance
for FDA staff. Sec. 510.150. Apple juice, apple juice
concentrates,

Walker K, Wiesner BP. 1944. Patulin and clavicin.

Lancet 246:294.

and apple juice productsAdulteration with patulin.

Available
from:
http://www.fda.gov/ora/compliance_ref/cpg/cpgfod/cpg
510-150.htm.
Ac-

Wang IK, Reeves C, Gaucher GM. 1991. Isolation and

sequencing of a genomic DNA clone containing the 3
terminus of the 6-methysalicylic acid polyketide
synthetase gene of Penicillium urticae. Can J Microbiol
37:8695.
Ware GM, Thorpe CW, Pohland AE. 1974. Liquid
chromatographic method for deter-mination of patulin
in apple juice. J AOAC 57:1113.

cessed
March
2, 2004.

Wheeler JL, Harrison MA, Koehler PE. 1987. Presence

of patulin in pasteurized apple cider. J Food Sci
52:47980.
Valletrisco MS, Casadio S, Stefanelli C. 1990. Use of
ultraviolet radiation to break down mycotoxins.
Industrie Alimentari 29(288):11112.
Wichmann G, Herbarth O, Lehmann I. 2002. The
mycotoxins citrinin, gliotoxin, and patulin affect
interferon- rather than interleukin-4 production in
human blood cells. Environ Toxicol 17(3):2118.
van Egmond HP. 1989. Current situation on
regulations for mycotoxins. Overview of tolerances
and status of standard methods of sampling and
analysis. Food Addit Contam 6:13888.
Wisniewsky MA, Glatz BA, Gleason ML, Reitmeier CA.
2000. Reduction of Escher-ichia coli O157:H7 counts
on whole fresh apples by treatment with sanitizers. J

20
2005

COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETYVol. 1,

Patulin control in foods . . .

hydrochloride,
pyridoxine hydroFood Prot 63:7038.

[WHO] World Health

Organization. 1990.
Evaluation of certain
food additives and
contaminants. WHO
thirty-fifth report of
the joint FAO/WHO
expert committee on
food additives.
Geneva: Technical
Report Services 789.
p 2930.

[WHO] World Health

Organization. 1995.
Evaluation of certain
food additives and
contaminants. WHO.
Forty-fourth report of
the joint FAO/WHO
expert committee on
food additives.
Geneva: Technical
Report Series 859. p
368.
Yazici S, Velioglu
YS. 2002. Effect of
thiamine

chloride, and
calcium-Dpantothenate on the
patulin content of
apple juice concentrate.
Nahrung/Food.
43(4):2567.
Zamir LO. 1980.
The biosynthesis of
patulin and penicillic
acid. In: Steyn PS,
ed-itor. The
biosynthesis of
mycotoxins. New
York: Academic
Press, Inc. p 224
68.

Zegota H, Zegota A,
Bachmann S. 1988.
Effect of irradiation
and storage on
patulin
disappearance and
some chemical
constituents of apple
juice. Z Lebensm
Unters Forsch
187:3214.

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