Review

Received: 11 August 2016 Revised: 27 September 2016 Accepted article published: 4 October 2016 Published online in Wiley Online Library: 11 November 2016

(wileyonlinelibrary.com) DOI 10.1002/jsfa.8064

The new Israeli feed safety law: challenges in

relation to animal and public health
Shimon Barel,a Dani Elad,b Olga Cuneaha and Jakob A Shimshonia*

Abstract
The Israeli feed safety legislation, which came to prominence in the early 1970s, has undergone a major change from simple
feed safety and quality regulations to a more holistic concept of control of feed safety and quality throughout the whole
feed production chain, from farm to the end user table. In February 2014, a new law was approved by the Israeli parliament,
namely the Control of Animal Feed Law, which is expected to enter into effect in 2017. The law is intended to regulate the
production and marketing of animal feed, guaranteeing the safety and quality of animal products throughout the production
chain. The responsibility on the implementation of the new feed law was moved from the Plant Protection Inspection Service
to the Veterinary Services and Animal Health. In preparation for the law’s implementation, we have characterized the various
sources and production lines of feed for farm and domestic animals in Israel and assessed the current feed safety challenges in
terms of potential hazards or undesirable substances. Moreover, the basic requirements for feed safety laboratories, which are
mandatory for analyzing and testing for potential contaminants, are summarized for each of the contaminants discussed.
© 2016 Society of Chemical Industry

Keywords: food safety; feed safety; feed contaminants; public health; Israel

INTRODUCTION contaminants. The VSAH is presently responsible for the imple-

Feed manufacturing is a vital and active industry in Israel, pro-
viding feed for food-and non-food producing animals, including
household pets and zoo animals.1 Exercising adequate control
over the ingredients used in these feeds and the process of
their manufacture can have significant impact on the health and
well-being of food-producing animals and therefore on public
health.2
The Israeli feed safety legislation, which came to prominence in
the early 1970s, has undergone a major change from simple feed
safety and quality regulations to a more holistic concept of control
of food safety and quality throughout the whole food production
chain, from farm to the end user table. In February 2014, a new law
was approved by the Israeli Parliament, namely the Control of Ani-
mal Feed Law, which is expected to enter into effect in 2017.3 The
major changes implemented in the present feed safety law refer
to: (i) enhanced supervision and enforcement on improved animal
welfare; (ii) regular monitoring for various feed contaminates
based on a yearly performed risk assessments aimed at optimiz-
ing sample size and sampling periods; (iii) rigorous adaption of
European maximum residual level (MRL) and maximum level (ML)
values, as a result of the more stringent export conditions imposed
by the European market as compared to the US market; and (iv) a
shift of the responsibility on the implementation of the new feed
law and feed safety laboratory tests from the Plant Protection and
Inspection Services (PPIS) to the Veterinary Services and Animal
Health (VSAH). Furthermore, the law is intended to regulate the
production and marketing of animal feed, guaranteeing the safety
and quality of animal products throughout the production chain.
The new law specifically addresses the mandatory requirements
of the production, marketing and utilization of safe feed prod-
mentation of the new feed law, including the control of feed
quality and implementing MLs of potential feed toxicant/
contaminants.1
The most commonly utilized feeds and feed ingredients in Israel
constitute grains, oilseeds, fruit/vegetable by-products, forage
(e.g. grasses, hay and silage), directly dried products (e.g. bak-
ery by-products), biofuel by-products (e.g. distillers’ grains), food
processing by-products and co-products, minerals (e.g. trace ele-
ments and binders), animal by-products (e.g. meat and bone meal,
fats, poultry litter), aquatic products (e.g. fishmeal, shellfish, fish
by-products, seaweed and krill), fermentation/biomass products,
viable microbes and silage additives.1
Worldwide, routine feed analysis provides crucial information
for: (i) veterinary and public health inspection services, with
respect to evaluating the risk exposure to animals and humans;
(ii) farmers, with respect to optimizing nutrient utilization in ani-
mal feeds; (iii) feed compounders, with respect to preparing feed
mixtures suitable for different animal production systems; and (iv)
researchers, with respect to relating animal performance to feed
characteristics and the potential carryover of contaminants into
the food chain.2
To ensure feed safety, it is important to use analytical tech-
niques that have a high sensitivity (i.e. that can reliably detect
∗ Correspondence to: JA Shimshoni, Kimron Veterinary Insti-
tute, Department of Toxicology, 50250 Bet Dagan, Israel.
E-mail: jakobshimshoni@gmail.com
a Department of Toxicology, Kimron Veterinary Institute, Bet Dagan 50250, Israel
b Department of Bacteriology, Kimron Veterinary Institute, Bet Dagan 50250,
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ucts for farm and domestic animals, being free from hazardous Israel

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 www.soci.org
low levels of harmful material in diverse matrices).4 – 7 The VSAH
is presently faced with a demand for efficient enforcement tools,
for quick decisions or when confronted by large numbers of sam-
ples (e.g. at entry points of shipments, trading situations, on
contamination sites, or in case of feed safety crisis). In the last
decade, countless fatal intoxication events occurred in farm ani-
mals and household pets in Israel, as a result of the presence
of hazardous feed contaminants.8 – 21 In the present review, we
characterize the current status of the Israeli feed market, which
is followed by a discussion of the most common feed contam-
inants encountered in feeds in Israel. Towards the end of the
discussion, we elaborate on the needs of a future feed safety
laboratory.
CURRENT STATUS OF THE ISRAELI ANIMAL
FEED MARKET
Israel depends mostly on feed imports to meet its grain and feed
needs.22 – 26
Wheat and corn are the main ingredients of feedstuffs used
in the local poultry, dairy, cattle and aquaculture farms in Israel.
The Israeli feed milling industry shifts easily from corn, barley and
sorghum to feed wheat, depending on price.22 – 26
Local production
As a result of continued unfavorable rainfall in most parts of Israel,
it is estimated that domestic wheat production for 2016/17 will not
change compared to production levels of previous years, and will
total of approximately 100 000 tones.1
In the coming decades, experts predict difficulties in the ability
to produce feedstuffs as a result of world population growth
and climate change. Therefore, Israel must prepare for a possible
shortage of feed in the next two decades and consider more
efficient recycling of industry by-products into feed and replacing
current agricultural crops with wheat.
Local mixed grains market
Approximately 90% of the local feed milling industry is controlled
by seven feed millers. The total market of the Israeli feed milling
industry is estimated at 2.3–2.55 million tons of mixed grains per
year.1
Imported feed ingredients
Imported feed products to Israel are regulated today by the Min-
istry of Agriculture and are subject to inspection at the time
of entry to the ports. Total grain imports in 2016/17 are esti-
mated to decrease slightly to just above 3 million tons, mostly
wheat (approximately 1.5 million tons) and corn (approximately
1.25 million tons). The slight decrease is mainly a result of increased
local grains stocks combined with shortage of grains from Ukraine
and Russia.
Pet food
Israel imports approximately 50 000 tons pet foods every year.1 If
we add on that the local production of pet food, than we have
a local pet food market size of approximately 100 000 tons. The
inspection and acceptance of imported pet foods to Israel is mainly
based on certifications and microbiological tests of the imported
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Feed mill plants
The feed mills in Israel (24 feed mills) produce animal feed for
all kind of domestic animals in several sectors. Each feed mill
laboratory has basic equipment to meet the quality needs of the
product and the customer.
Feed centers
These manufacture and supply total mixed ration (TMR) for all
branches of ruminants: dairy cows, dry cows, beef cattle, heifers,
goats and sheep. Israel currently has 18 feed centers.
Poultry litter
Poultry litter is an important feed component in the Israeli beef
cattle, as well as a fertilizer in horticulture, providing a rich grow-
ing medium and a good source of nitrogen for plants, mainly
in organic agriculture.27 Approximately 65 000 tons are used as
feed ingredient for cattle and 105 000 tons are used as compost-
ing ingredients generated on the poultry farms or used directly,
without composting process, as a fertilizer in horticulture. Recy-
cled animal waste, such as processed chicken manure, has been
used in Israel as a feed ingredient for almost 40 years. This ani-
mal waste contains large amounts of protein, fiber and minerals,
and has been deliberately mixed into animal feed for these nutri-
ents. Although the practice of feeding animal waste to animals
appears to be unpleasant, the use of this product is safe as long
as it meets certain specifications required by the VSAH, such as
non-hazardous levels of antimicrobials and pathogenic clostrid-
ium and salmonella strains. The specifications set by the VSAH
require that processed animal waste products do not contain haz-
ardous materials such as metal, glass, nails or other harmful mat-
ter. They must be free of harmful pathogenic organisms, pesticide
residues, parasites or drug residues, below the levels permitted
by the VSAH. Nevertheless, every year dozens of fatal intoxication
events are diagnosed in cattle following ingestion of poultry litter
contaminated with coccidiostats and botulinum toxins.13 – 15,28,29
FEED SAFETY: MAJOR CONTAMINATION
SOURCES
Industrial areas such as the Haifa Bay and Ashdod include factories
that deal with chemicals, petrochemicals and traditional industry.
The area is an economic anchor for both the country and the most
important source of income for most residents in both areas. Con-
sequently, the Haifa Bay and Ashdod industrial zones are some of
the most sensitive areas in Israel in terms of air and water pol-
lution, releasing significant amounts of heavy metals, persistent
organic pollutants (POPs) such as dioxins, and aromatic hydrocar-
bons into the environment.30 Moreover, Jerusalem and Tel Aviv,
the major cities in Israel, face severe air-pollution problems, pri-
marily from automobile emissions.30 – 32 Some of Israel’s rivers are
heavily polluted, such as the Shorek, Besor, Jordan and the Kishon
rivers, mostly as a result of chemical industry and sewage dis-
charged directly into the river.34 – 38 The industrial and automo-
bile pollutants directly affect the feed and food quality, by emit-
ting pollutants that ultimately leak into our ground water and soil,
thereby contaminating our edible crops and drinking water. POPs
such as dioxins and certain heavy metals such cadmium, mer-
cury and arsenic tend to accumulate in animal tissues, exposing
humans to deleterious health effects over the long term. The wide
spread utilization of pesticides and herbicides in agricultural land
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has resulted in hazardous residues being reported for fruits and
vegetables in Israel.39
The most updated hazards related to feed and food safeties
in Israel are briefly discussed below. The following criteria were
selected for enlisting major feed contaminates affecting feed
safety: (i) relevance of the hazard to animal and public health;
(ii) extent of the occurrence of the hazard; and (iii) impact of the
hazard on international trade in food and feed.
MAJOR FEED CONTAMINANTS IN ISRAEL
Because it is impossible to eliminate most of the feed contami-
nants from feedstuffs and as measure of public and animal health
protection, contaminates were fixed at MLs, which should pre-
vent adverse effects on animal or consumer health based on risk
assessment estimations.40 – 42 Below, the currently most important
undesirable feed contaminants are described based on safety
assessment and prevalence.
Trace elements
The amount of trace elements in feed depends on the natural
content and on the conditions under which feed is produced and
processed.43 Some elements have nutritional functions and are
essential to health, such as copper, selenium, manganese and zinc,
whereas others, such as lead, cadmium, arsenic and mercury, have
no nutritional relevance and can cause serious illnesses.43
Mercury
Mercury exists in the environment as elemental mercury (metal-
lic), inorganic mercury and organic mercury (primarily methyl
mercury).44,45 Among the organic forms, the most toxic is
methylmercury.45 Methylmercury is able to cross blood–brain
and the placental barriers; hence, the nervous system is the pri-
mary site of toxicity in animals and humans.45 Methylmercury
bioaccumulates along the food chain, particularly in the aquatic
food chain, with long-lived carnivorous fish and marine mam-
mals exhibiting the highest content.46 In Israel, the ML value for
mercury in fish is 0.5 mg kg−1 .41 A survey conducted between
2010 to 2014 measuring total mercury levels in 223–367 fish
samples of nine to 13 different common edible species along the
Israeli Mediterranean coastline revealed that 4.9–7.9% of all fish
samples analyzed exceeded the ML value of 0.5 mg kg−1 mercury,
whereas, in the Haifa Bay area alone, the percentage of polluted
fish samples exceeding the ML value was significantly higher at
6.6–19.5%.34 – 37
Arsenic
Arsenic is found in both organic and inorganic form occurring
in different ores, minerals, rocks and ground water.47,48 Inorganic
arsenicals are more than ten times more toxic than the organic
form.47,48 Acute poisoning in animals and humans is characterized
by gastrointestinal adverse effects, neurological signs, collapse
and death. Subacute exposure is characterized by depression,
anorexia, incoordination and dark, haemorrhagic diarrhoea.49
In 2010–2014, 725 of the most common fish species were
analyzed for total arsenic levels, yielding levels ranging between
0.025 and 153 mg kg−1 , of which 26% were > 10 mg kg−1 wet
weight.34 – 37 According to the US Environmental Protection
Agency estimation, the maximal percentage of inorganic arsenic
of the total arsenic in fish is 10%; hence, approximately 26% of
the analyzed fish species are potentially above the ML levels of
1 mg kg−1 inorganic arsenic.50
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Cadmium
Cadmium is commonly found as a mineral forming cadmium
oxides, phosphates, chlorides and sulphates.51 Cadmium usu-
ally enters the environment from zinc refining, coal combus-
tion, mine wastes, steel production and the use of dicadmium
phosphate minerals as feed additive, as well as sewage sludge
as soil fertilizer.51 – 53 Chronic cadmium poisoning is associated
with osteoporosis, renal lesions, mineral imbalance and death.52
According to reports published in 2010–2013, a total of 705 liver
poultry samples in Israel were analyzed, of which 8.3% were found
to be above the ML value of 500 μg kg−1 .54 – 57 In 2010, of the
42 beef liver samples analyzed, 17% exceeded the ML value of
500 μg kg−1 . However, in subsequent years (2011–2013), no resid-
ual levels of cadmium in beef liver samples were reported.
Reports published by the PPIS indicated a low prevalence of cad-
mium in various imported grain commodities such as wheat, bar-
ley, soy and alfalfa, with 1.3% of 670 samples analyzed exceeding
the ML of 1 mg kg−1 .
Copper
Although copper does not belong to the heavy metals that are
generally known to pose the greatest risk of elements to animal
and human health, it is interesting that, in Israel, copper causes
more health problems than all the heavy metals combined.
Chronic copper toxicosis in sheep, mainly in East Friesan/Awassi
bread crosses, is frequently diagnosed in Israel every year. Between
2010 and 2013, 64 different sheep herds were chronically intoxi-
cated following ingestion of TMR containing toxic copper levels.
The most common causes of copper toxicosis in Israel comprise
excess copper in sheep concentrates or in poultry litter commonly
fed to ruminants. Recently, a major and rare copper toxicosis
occurred in dairy cows following exposure to TMR containing
toxic levels of copper sulphate (500 mg kg−1 ), as a result of dose
miscalculation by the grower.
Mycotoxins
The risk of contamination by mycotoxins is an important feed and
food safety concern for grains and other field crops. Mycotoxins
are toxic secondary metabolites of mold infestations, affecting as
much as one-quarter of global food and feed crop output.58,59
Mycotoxins are produced by fungi of various genera when they
grow on agricultural products before or after harvest or during
transportation or storage.58
Mycotoxins may be carcinogenic (e.g. aflatoxins, ochratoxins,
fumonisins), oestrogenic (zearalenone), neurotoxic (fumonisin
B1 ), nephrotoxic (ochratoxins, citrinin), dermanecrotic (tri-
chothecenes) or immunosuppressive (aflatoxin B1 , ochratoxin
A and trichothecenes).60 – 62 Mycotoxins are regularly found in
feed ingredients, such as maize, sorghum grain, barley, wheat, rice
meal, cottonseed meal, groundnuts and other legumes.59,60,63
To protect consumers from these health risks, many countries
have adopted regulations to limit exposure to mycotoxins.64 – 66
However, diverging perceptions of tolerable health risks, which are
associated mainly with the level of economic development and
the susceptibility of a nation’s crops to contamination, have led to
widely varying standards among different national or multilateral
agencies.65
Aflatoxins
Aflatoxins are hepatotoxic and carcinogenic secondary metabolic
products from fungi, in particular those belonging to the
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Aspergillus flavus and Aspergillus parasiticus species.67
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More than 20 aflatoxin-like secondary metabolites have been
identified and aflatoxin B1 (AFB1) was shown to possess the most
toxic and carcinogenic properties to humans and animals.67 Afla-
toxins are found as natural contaminants in many feedstuffs of
plant origin, not only especially in cereals, but also in fruits, hazel-
nuts and almonds.67 AFB1 can cause chronic diseases in humans
and animals and have different effects such as hepatotoxicity,
genotoxicity and immunotoxicity.67,68 The analysis of imported
grain samples in 2010 and 2011 revealed AFB1 levels above the
ML value of 20 μg kg−1 in 3% of all analyzed samples (n = 536) with
a maximum concentration of up to 149 μg kg−1 , possibly posing a
health risk to farm animals.
Aflatoxin M1 (AFM1), a possible human carcinogen, is the major
oxidized metabolite of AFB1 and is excreted primarily in the urine
and less so in the milk.63,67 Israeli regulations concerning the dairy
industry are harmonized with European Union regulations; hence,
a ML of 0.05 μg kg−1 for AFM1 in milk is applied.69 Between 2010
and 2013, 3.5% of dairy milk samples exceeded the ML value of
0.05 μg kg−1 , clearly indicating an existing problem with AFB1
contaminated feed.
Household pets are occasionally affected by AFB1. For example,
in 2005/06, a major aflatoxicosis event occurred in dogs, following
ingestion of commercial pet diet containing corn contaminated
with 30–300 μg/kg−1 AFB1, resulting in high mortality rate and
severe clinical signs.70
Fumonisins
Fumonisins are mycotoxins produced mainly by Fusarium pro-
liferatum and Fusarium verticilloides, occurring mainly in maize,
wheat and other cereals.71 Fumonisin B1 is the most common and
economically important form, followed by B2 and B3.71 Fumon-
isins exposure in feed and food has been associated with the
occurrence of pulmonary edema in pigs, leukoencephaloma-
cia in horses, hepatic cancer in rats and esophageal cancer in
humans.59,71,72 Surprisingly, in Israel, the regulatory authorities do
not conduct a routine yearly analysis of feed and food products for
fumonisins, despite their widespread occurrence and their health
hazards for humans and animals.
Trichothecens
Trichothecens are produced on many different grains such as
wheat, oats or maize by various Fusarium species such as Fusar-
ium graminearum, Fusarium sporotrichioides, Fusarium poae and
Fusarium equiseti.73 Trichothecens are powerful toxic protein and
DNA synthesis inhibitors that are highly toxic to a wide range
of animal species.73 Chemically, trichothecenes can be classified
into four types of which type A and type B are the most preva-
lent types in agricultural commodities.73 Type A trichothecenes,
mainly diacetoxyscirpenol and T-2 toxin, are considered to be
more toxic than type B trichothecenes, the most common of
which is deoxynivalenol.73 Reports of the PPIS indicated that,
in 2010–2013, 1% of the imported grains contained T-2 levels
above the ML value, displaying a concentration in the range
0.1–514 μg kg−1 (PPIS, unpublished data). Numerous intoxication
events occurred during the late 1980s affecting poultry exposed to
toxic levels of trichothecenes in their feed.16 A flock of laying hens
exposed to T-2 and HT-2 toxin at 3.5 and 0.7 mg kg−1 , respectively,
for 5 consecutive days displayed severe clinical signs, including
depression, recumbency, feed refusal and cyanotic combs.16 Egg
production dropped by 96% after 5 days. In 1996 and 1999, T-2 and
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diacetoxyscripenol were found in feed of affected broiler and layer
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flocks at levels of 70–350 μg kg−1 , resulting in a high mortality rate
and severe oral lesions (Shlosberg A, unpublished case study).
Zearalenone
Zearalenone is an estrogenic compound produced by several
species of Fusarium fungi occurring on a wide range of substrates
such as wheat, maize, rice and sorghum.74 Zearalenone can cause
hyperestrogenism and impaired fertility and increased rate of
abortions.74,75 Zearalenone levels exceeding 1 mg kg−1 feed have
been shown to induce hazardous estrogenic effects over time in
various animal species.74,75 In 1986, an exceptionally high mortality
rate of 40% occurred in a flock of 24 000 broilers in Israel following
ingestion of feed contaminated with zearalenone at levels up to
5 mg kg−1 feed.76
Ochratoxins
Ochratoxins are a group of mycotoxins produced by several
Aspergillus and Penicillium species occurring most commonly on
a variety of cereal grains, grapes, dried fruits and coffee.77 Ochra-
toxin A is the most prevalent and relevant fungal toxin of this
group.78 In 1996, a major ochratoxicosis event occurred in Israel
affecting a flock of geese and broilers, resulting in a 30% mortal-
ity rate following ingestion of corn contaminated with ochratoxin
at concentrations up to 930 μg kg−1 .79 A mycotoxin survey (analyz-
ing only aflatoxins and ochratoxin A) conducted by the Israeli Min-
istry of Health between 2008 and 2012 in major food commodities,
revealed ochratoxin levels below the ML value of 50 μg kg−1 in all
of the samples analyzed.80
Pesticides and POPs
Pesticides and persistent organic environnmental pollutants (e.g,
organophosphates, organochlorides) may get into the feed as a
result of common agricultural practices with respect to spreading
pesticides.81 – 83
POPs
As a result of industrial activity, POPs are widely spread in the
environment and persist for many years after formation.84,85 POPs
are toxic chemicals consisting of highly diverse group of chemicals
that are currently (or were in the past) used as pesticides, solvents,
pharmaceuticals and industrial chemicals, such as organochlorine
insecticides (e.g. aldrin, dieldrin), brominated flame retardants,
dioxins and dioxin-like compounds (DLCs).84,85 POPs are known
to accumulate in the fatty tissue of living organisms (e.g. fish
meal and fish oil are well known to contain substantial levels of
POPs).83 – 85
In 2012, the Israeli Ministry of Health published the results
of a 5-year long survey (2006–2010) in which 5558 different
samples of fruits, vegetables, spices and grains for human con-
sumption were analyzed.86 The results of the survey revealed
pesticide levels above MRL values in 11.2% of all analyzed
samples, indicating a potentially hazardous chronic expo-
sure of the population to pesticides.86 Among the detected
pesticides exceeding their MRL values, the organochlorine
insecticide endosulfan was frequently detected in various food
commodities such as fruits and vegetables. Although endo-
sulfan has been banned in Israel subsequent to 2015, it is still
occasionally detected in fatal toxicosis events in wild animals
(Kimron Veterinary Institute, unpublished data).87
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Dioxins and DLCs
Dioxins and DLCs are by-products of various industrial processes,
commonly regarded as highly toxic compounds, including poly-
chlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans
and certain polychlorinated biphenyls (PCBs) bearing a coplanar
structure with affinity to the aryl hydrocarbon receptor, thereby
eliciting toxic effects common to dioxins (dioxin-like PCBs).88 – 90
Dioxins have been implicated in reproductive and developmental
toxicities, as well as in the compromised immune system.88 – 90
Dietary intake represents the most common route of human and
animal exposure to dioxins and PCBs.90 Foods of animal origin are
the greatest source of human exposure to these contaminants.91
Contaminated fats or oils added either intentionally or uninten-
tionally incorporated into manufactured feeds can be a major
source of dioxins and PCBs.91 In 2013, the Israeli Public Health
Services, together with the Ministry of Agriculture, conducted a
small survey on the presence of dioxins and DLCs in 120 samples
of animal-derived food products, such as milk, meat, eggs and
dairy products.92 According to the results published by the Public
Health Services, the eggs were the only animal-derived food
product with dioxins and DLCs levels above their MLs, with 24%
exceeding their ML value of 5 ng kg−1 .92
Organophosphorus pesticides
Organophosphorus pesticides are extensively used in Israel in
agriculture, public and veterinary health, as well as in home and
garden insecticides.93,94 Organophosphorus pesticides may cause
severe, sudden toxicosis, although there is evidence indicating
that non-lethal exposure may deleteriously affect behavior, the
immune system and reproduction, making a diagnosis of harm-
ful effects in populations difficult to perform.95 Many toxicosis in
animals diagnosed in Israel are a result of malicious poisonings in
farm, wild and particularly pet animals.20,54 – 57 Outbreaks of tox-
icosis in raptors caused by the illegal spraying of fodder crops
against rodents resulted in repeated large-scale toxicosis events
in Israel.20,96 The results of a survey conducted between 2006 and
2010, as well as the survey summary of 2011–2014 on the pres-
ence of pesticides in food commodities (mainly fruits and veg-
etables) by the Ministry of Health and Ministry of Agriculture,
might provide some indication regarding the burden of pesticide
residues in local fodder production, such as maize, wheat and
sorghum, in Israel.86,87 The survey results for between 2006 and
2010 revealed that 11.2% of the total samples analyzed exceeded
the regulated MRL values, potentially exposing the Israeli popula-
tion to hazardous health effects.86 Among the organophosphorus
pesticides found to exceed the recommended average daily intake
were dimethoate, fenamiphos, methamidophos, methidathion
and oxydemethon-methyl.86 Methamidophos was reported to be
implicated in numerous occasions in fatal wildlife intoxications,
affecting mainly raptors, waterfowls, jackals, foxes and boars.20,96
Between 4.2% and 15.6% of the food commodities (mainly
fruits and vegetables) tested in 2011–2014 exhibited pesticide
levels above their MRL values.87 The majority of the food sam-
ples exceeding the pesticides MRL values were vegetables (car-
rot, cucumber, fennel bulbs, radish), fruits (pumpkins, zucchini,
kiwifruit, pear, strawberry) and leaves (lettuce, beet leaves, gar-
den parsley, mint). The most common pesticides exceeding their
MRL values were metalaxyl, bifenthrin, dimethomorph, carbofu-
ran, chlorpyrifos, endosulfan, difenoconazole and methomyland
azoxystrobin.87 Recently, a study estimating the exposure of the
adult Israeli population to organophosphorus pesticides revealed
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that urinary organophosphorus pesticides levels in the Israeli pop-
ulation were higher compared to the general population in the
USA and Canada and also that fruit intake was a major source of
exposure.97
Carbamate pesticides
This smaller but very much used group of pesticides comple-
ments the organophosphorus pesticides and has similar toxico-
logical properties.95 Worldwide, they are extensively used in agri-
culture, in public and veterinary health, and as home and garden
insecticides.98,99 Some carbamates such as methomyl and dithio-
carbamates are extensively used in intensive agriculture systems,
such as in Israel.93,94 Most of the intoxication events diagnosed
in wildlife and household animals in Israel are the result of mali-
cious poisonings with aldicarb and methomyl, as well as a result
of the illegal usage of carbamate insecticides by farmers.20,54 – 57
According to the yearly reports of the Veterinary Services, between
2010 and 2013, approximately 180 fatal intoxication cases were
diagnosed in farm and household animals because of exposure to
methomyl and aldicarb.54 – 57
Coccidiostats
Coccidiostats are widely used in Israel mainly as poultry feed
additives for preventing or treating coccidiosis.9 It is generally
acknowledged that, under the practical conditions existing dur-
ing the production of mixed feeds, a certain percentage of a
feed batch remains in the production circuit and these resid-
ual amounts can contaminate subsequent feed batches.100 This
cross-contamination may result in the exposure of non-target
animal species and hence there are potential health risks for
non-target animal species, as well as potential residue deposition
in foods derived from these non-target species. In Israel, poultry
litter from broilers treated with coccidiostats is commonly used as
feed additive to livestock. Consequently, lethal cardiomyopathic
syndrome in beef cattle is frequently diagnosed in Israel every
year.13 – 15,54 – 57 Recently, a major fatal maduramicin intoxication
event occurred in a pig farm located in the southern part of Israel
affecting 22 gilts and two boars, resulting in a total mortality
of 65% within 2 days after the ingestion of feed contaminated
with lethal levels of maduramicin.9 It wasn’t only farm animals
that were reported to be fatally intoxicated with ionophors. In
2004, 17 dogs were intoxicated after the ingestion of commer-
cial dog food contaminated with toxic levels of lasalocid, result-
ing in 30% mortality rate.11 A survey of locally produced poultry
litter conducted in 2010–2013 by the PPIS revealed exception-
ally high levels of maduramicin (range 0.2–13 μg kg−1 ), lasalocid
(11–39 μg kg−1 ) and monensin (range 3.6–76.3 μg kg−1 ), exceed-
ing the MRL values in non-target animal feed (PPIS, unpublished
data).
A direct impact of the extensive usage of ionophors in ani-
mal feed is frequently observed by the carryover of ionophors
into animal-derived products such as eggs and poultry/turkey
meat.54 – 57,101 An alarmingly high prevalence rate of ionophors
(21.7%) was found in Israel in 2012 in eggs for human consump-
tion, whereas, in the subsequent year, the prevalence rate declined
to 4.8%.55,56 The analysis of poultry and turkey meat on the pres-
ence of ionophors in 2010–2013 yielded an average of 2.5% of all
meat products (n = 893) exceeding their MRL values.54 – 57 Clopi-
dol is frequently found in Israeli eggs for human consumption,
although it is not approved for usage for laying hens.54 – 57 Further-
1077
more, no MRL value for clopidol has been defined so far in eggs,
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 www.soci.org
despite its frequent prevalence in eggs. The high occurrence rate of
clopidol in eggs (12.8–34% in 2010–2013) is worrisome as a result
of the lack of toxicological data subsequent to long-term exposure
in humans.
Phytotoxins
Natural pastures in Israel contain few toxic plants, most of which
exhibit strongly aversive smell or taste toxins.102 Nevertheless,
reports of plant toxicosis in Israel have been made over the years
in various animals species.102 By far the most common fatal toxi-
cosis, including abortions, is that caused by plants of high nitrate
levels (>10 g kg−1 dry weight).102 Following ingestion, nitrate is
reduced by rumen microorganisms to the much more toxic nitrite,
which is subsequently absorbed into the bloodstream, leading
to the formation of methemoglobin and hypoxia.103 The most
important nitrate-containing plants in Israel frequently associ-
ated with abortions and intoxication events are the winter annual
weeds Malva nicaeensis and Silybum marianum, as well as the sum-
mer annual weeds of the Amaranthus species.102 These weeds
contaminate fields of fodder grown for hay and are often har-
vested together with the good feed. A survey of cattle feed in 50
Israeli farms revealed a wide range of nitrate levels in the hay.102
Toxic nitrate levels (> 15g kg−1 dry weight) were most frequently
determined in corn and Setaria straw (> 50%), followed by clover,
oat and vetch samples (25%).102 None of the corn, wheat and
sorghum silages displayed nitrate levels > 15 g kg−1 .102 In recent
years, several cases of fatal intoxication events in beef herds were
recorded following ingestion of Xanthium strumarium, an intro-
duced summer annual weed.102 There have been three recorded
mass pyrrolizidine-toxicosis events in beef cattle as a result of the
ingestion of hay contaminated with Heliotropium europeum.8,17,102
Heliotropium species are pyrrolizidine alkaloid (PAs) producing
weeds widely distributed in the Mediterranean region, often impli-
cated with lethal pyrrolizidine alkaloid intoxications in both live-
stock and humans.104,105
PAs are carcinogenic and hepatotoxic phytotoxins prevalent in
the Borginaceae, Asteraceae and Fabaceae families.105 PAs enter
the food and feeds chain by the co-harvesting of crops intended
for human and animal consumption, as well as by carryover into
animal-based products such as milk, eggs and honey.105
Although the health hazards associated with exposure to PAs are
well known, no regulations have been established in the European
Union, the USA or in Israel imposing limits for PAs in food and
beverages for human consumption. As a result of the potential
health-threatening effects potentially caused by PAs ingestion,
the Codex Committee on Contaminants in Foods proposed a
code of practice for weed control to prevent and reduce PA
contamination in food and feed.106 The main plant toxicosis in
sheep and goats is caused by an endemic plant, Ferula communis,
a winter perennial plant dominating pastures in the Jerusalem
foothills and in the Golan Heights.102 The plant contains natural
anticoagulants, namely 4-hydroxy-coumarin derivatives, causing
reduced blood coagulation with extensive hemorrhages leading
to fatal anemia.107
Veterinary drugs
Veterinary drugs are currently used for therapeutic indications,
disease prevention or as growth promotors.108 Hazardous expo-
sure may result from improper usage for non-target animals,
accidental overdose, or be a result of carryover in feed during
1078
feed production.2,108 This section focuses on antimicrobial drugs
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S Barel et al.
and their high prevalence as drug residues in animal-derived
food products, as well as their direct involvement in drug-related
intoxication events in farm animals. The antimicrobial drugs
presently approved for usage in farm animals include 𝛽-lactams,
sulfonamides, tetracyclines, aminoglycosides, chloramphenicol
analogues, fluoroquinolones, macrolides, nitrofuranes, baci-
tracin and polymyxin antibiotics.108,109 The antibiotics most
commonly detected in animal-derived products such as eggs,
beef and poultry liver belong to the sulfonamide, tetracycline and
fluoroquinolone classes.54 – 57
Although sulfonamides and fluoroquinolones are totally forbid-
den for use in treatment, prevention or growth promotion in lay-
ing hens, the drugs are occasionally found at levels exceeding
their MRL values in eggs, with a prevalence of up to 1% and 1.2%,
respectively.54 – 57 Tetracyclines are also frequently reported to
exceed their MRL value in eggs of 400 μg kg−1 , with an occurrence
rate of up to 2.9% reported in 2012.55 Consequently, the occur-
rence rate of up to 2.9% reported in 2012 resulted in 54 million
eggs being contaminated with tetracyclines and entering the local
Israeli market. Poultry, turkey and beef liver analysis in 2010–2013
revealed sulfonamide, fluoroquinolones and macrolides residues
exceeding their corresponding MRL values in up to 1.9% of all sam-
ples analyzed.54 – 57 Recently, a mass intoxication event in preg-
nant sheep occurred in Israel, following exposure to lethal dose
of oxytetracycline resulting in a high mortality rate (Shimshoni
JA et al., unpublished case study). A dose of 1 kg of oxytetracy-
cline was mixed with 250 kg of TMR and administered to a herd
of 280 pregnant sheep for the prevention of abortions. The dose
was approximately eight times the recommended maximal dose
of 10 mg kg−1 body weight for sheep, subsequently leading to the
high mortality rate.
Botulism
Botulism is a deadly motor paralysis caused by exposure to
botulinum neurotoxin (BoNT) produced primarily by Clostridium
botulinum types A-G.110 The spore-forming anaerobic organism
is frequently encountered in untreated poultry litter, as well as
in animal feed such as hay, silages and other bulky forages con-
taminated with decomposing animal tissue.111 Among the seven
immunologically distinct BoNT serotypes, the serotype BoNT-D
is most commonly associated with livestock poisoning in Israel,
whereas serotype BoNT-C1 is frequently encountered in poultry
poisoning, mostly water fowls.110 – 112 Clinically, botulism is char-
acterized as a lower motorneuron disease often resulting in deadly
respiratory muscle paralysis.110
In September 2013, an unusual mass botulinum toxicosis
outbreak occurred in 91 beef cattle and dairy farms resulting
in the death of 528 dead beef and dairy cows over approxi-
mately 42 days.113 The source of the botulinum toxicosis was
untreated poultry litter highly contaminated with BoNT-D pro-
ducing C. botulinum. In the subsequent year, two major botulinum
intoxication events occurred in January and October 2014 as a
result of the consumption of poultry litter contaminated with
BoNT-D producing C. botulinum, resulting altogether in 27 and
14 fatally intoxicated calves, respectively.114,115 In both cases,
decreased morbidity and mortality were observed in animals
vaccinated by the above-mentioned protocol.
Throughout 2015, numerous large scale botulinum toxicosis
events occurred in various animal species, including cattle, goats,
sheep, horses and reindeer (Kimron Veterinary Institute, unpub-
lished data). Reindeer bred in a local zoo located in the northern
J Sci Food Agric 2017; 97: 1073–1083
The new Israeli feed safety law www.soci.org

Pesticide Application Pesticide QC

Pest & Disease Diagnosis

Environmental Pollutants Pesticide Residue
Analysis

Plant Protection Inspection Service (PPIS)

The Ministry of Agriculture

Imported Feed Agriculture Commodities

Ingredients

Various Environmental Contaminants

Feed Safety Laboratory (Trace elements, mycotoxins, phytotoxins,
persistent organic pollutants, pesticides and
bacterial contamination)

Veterinary Medical Products

Water
Supply

Animal Husbandry

Imported
Food Safety Laboratory Products of
(Commodities from animal origin) Animal Origin

Veterinary Services and Animal Health (VSAH)

Ministry of Health – The National Food Service

Information exchange between regulatory agencies

Responsibilities of the agency/laboratory
Irrigation/ drinking water might contain contaminates
Contamination source

Figure 1. Suggested framework for future term coordinated governmental laboratory activities (Ministry of Agriculture and Ministry of Health) for ensuring
feed and food safety.

part of Israel were fed alfalfa contaminated with animal carcass har-
boring BoNT-D producing C. botulinum. Within 2 weeks, 30 rein-
deer were fatally poisoned resulting in almost a complete wipeout
of the entire reindeer population. Animal carcasses in forages were
also the source of BoNT-D producing C. botulinum in other fatal
poisoning events in horses, goats and sheep resulting in the death
of 20, 17 and 68 animals, respectively (Kimron Veterinary Institute,
unpublished data). Moreover, dozens of calves were fatally poi-
soned in 2015 after exposure to an unknown source of BoNT-D
producing C. botulinum in their feed. Taken together, it appears
that, according to our records, botulism in recent years constitutes
the most common cause of death in livestock compared to other
feed contaminates described in the present review.
FEED SAFETY LABORATORY: ANALYSIS OF
UNDESIRABLE SUBSTANCES IN ANIMAL FEED
In the present section, we define the responsibilities and activities
of a feed safety laboratory that are required when facing the new
Law. Figure 1 depicts a framework for future term coordinated
governmental laboratory activities with respect to ensuring feed
and food safety. In general, a feed safety laboratory is required
to provide scientific and technical assistance to VSAH activities in
routine feed surveys and in the identification of feed contaminants
with respect to feed and food safety problems or emergency
situations, as well as to establish a pool of knowledge and facilities
for research projects and for supporting regulatory authorities
when handling various emerging issues.
Feed surveys
Feed surveys are crucial for gathering information on feed and
safety as a means of preventing feed and foodborne illness, as
well as maintaining animal health and food safety. Assessing the
survey data allows the VSAH to identify key feed safety issues
and to develop systems and processes for managing these issues
effectively.
Factors that are taken into consideration when deciding on a
survey include: the analyte in question, sample size and the cor-
responding MLs. The number of samples is the most controversial
1079

feed safety challenges in Israel as defined by the Feed Safety parameter that needs to be address in a survey plan.

J Sci Food Agric 2017; 97: 1073–1083 © 2016 Society of Chemical Industry wileyonlinelibrary.com/jsfa
 www.soci.org S Barel et al.

and/or ultraviolet (UV) light are not applicable for a single run anal-
Table 1. Number of samples required to detect at least one
non-compliant result with pre-defined probabilities (90%, 95% and ysis and require a substantial amount of time for sample prepa-
99%) in a population having known non-compliance prevalence116 ration, as well as analyte derivatization, to achieve the desirable
sensitivity. Immunochemical test kits based on ELISA detection
Minimum number of samples Confidence level of mycotoxins have a poorer performance compared to LC-MS/MS
required to detect a non-compliant non-compliant prevalence in terms of sensitivity, accuracy and reproducibility and are not
result with a confidence level of: (% in a population) applicable as a single analytical run for a wide range of mycotoxins.
99% 95% 90%
11 7 6 35 Trace elements
13 9 7 30 For lead, cadmium, arsenic and mercury, atomic absorption spec-
17 11 9 25 trometry techniques and ICP-MS are most frequently applied for
21 14 11 20 trace element speciation analysis.120 The ICP-MS allows determi-
29 19 15 15 nation of elements with an atomic mass ranging from 7 to 250 Da.
44 29 22 10 A typical ICP-MS will be able to detect in the region of ng/L to
90 59 45 5 10–100 mg L−1 .120 Unlike atomic absorption spectroscopy, which
459 299 230 1 can only measure a single element at a time, ICP-MS has the capa-
919 598 460 0.5 bility of scanning for all elements simultaneously. This allows rapid
4603 2995 2302 0.1 sample processing and analysis.

Veterinary drugs and coccidiostats

Table 1 depicts the minimum number of samples required to
detect a non-compliant result with a relevant confidence level.116
Methods of analysis
The methods of analysis that are in use for quality control, reg-
ulatory control and facilitating trade, range from easy-to-use
dipstick-type tests or plate-count methods to the use of sophis-
ticated equipment: high-performance liquid chromatography
(HPLC) tandem mass spectrometry (LC-MS/MS), gas chromatog-
raphy mass spectrometry (GC-MS) and inductively coupled
plasma-mass spectrometry (ICP-MS) that requires a high level
of technical expertise. Fast and inexpensive screening methods
such as enzyme-linked imunosorbent assay (ELISA) kits allow a
large number of samples in the field to be tested rapidly. Further
analysis with confirmatory methods is needed only for suspect
samples. Feed comprises a large variety of products differing
in their composition and may consist of complex matrices that
can negatively impact analyte recovery. This may mean that, for
each specific analyte, the technical procedure must be adjusted,
optimized and validated for different types of feeds (matrices) to
obtain reliable results.
Dioxins and DLCs
The method of choice for the combined confirmation of dioxins
and dioxin-like PCBs is gas chromatography-high resolution mass
spectrometry after an extensive sample clean-up procedure.117
Dioxin-like compounds such as PCBs can also be determined by
GC with other low resolution mass spectrometry instruments such
as GC-MS.
Mycotoxins and pyrrolizidine alkaloids
The method of choice for the determination and quantification of
a wide range of mycotoxins or pyrrolizidine alkaloids in a single
analytical run is LC-MS/MS or liquid chromatography coupled
with quadrupole-time of flight mass spectrometry.118,119 Both
instruments enable hundreds of various classes of mycotoxins to
be determined in a single run with high precision, accuracy and
sensitivity within 1 h of sample preparation. Other methods such
1080
Antimicrobials are by far the most important veterinary drugs cur-
rently used for the production of medicated feed. The most com-
monly used antimicrobials are coccidiostats, tetracyclines, peni-
cillines and sulfonamides, as reported from four feed premixes
manufacturers in Israel. To check for carryover of antibiotic veteri-
nary drugs in subsequent animal feed batches, methods such as
LC-MS/MS and HPLC-UV/FLD are frequently applied, depending on
the analyte of interest. For ionophoric coccidiostats a multi-analyte
LC-MS/MS is commonly applied as a result of their lack of chro-
matophor and poor volatility.121
Pesticides
Gas chromatography-mass spectrometry provides the analyst with
an excellent tool for analyzing many volatile and semi-volatile
substances in contaminated feedstuffs, such as organochlorine
pesticides, organophosphate and carbamates.
Full-scan GC-MS provides a complete recorded analysis of all
significant components in very complex mixtures of contaminated
feedstuffs. It is a great advantage to have a large database of
analytes and commercial MS libraries for GC-MS.
CONCLUSIONS
There are many pathways by which a contaminant can enter the
food chain. This includes feed processing that may induce chem-
ical changes, raw materials that may contain naturally occurring
toxicants, cross contamination of subsequent feed batches and
packaging material that may leach into the feed. A feed safety lab-
oratory needs to deal with many challenges such as determination
of analyte at trace levels in food and feed in complex matrices,
conducting surveys, supporting the legislative arm by setting up
MLs for newly discovered contaminants and conducting health
risk assessments.
The big question is should the laboratory testing facilities be a
service that the government has to provide or is it the responsi-
bility of the retailers/ producers of the raw materials or the end
product producers? The VSAH laboratories are at the front line
of public health on a very broad scale. Because of their availabil-
ity to decision makers to react, they are typically the front line
in a food and feed crisis or major animal and public health issue.

as thin-layer chromatography, GC-MS and HPLC with fluorimetric Furthermore, the feed safety laboratory should be equipped with

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The new Israeli feed safety law
state-of-the-art analytical instruments to enable rapid method
development for detecting chemical contamination in feed stuffs
and to be able to respond quickly to feed and food threats. Enforc-
ing the new feed safety law is of the utmost importance for ensur-
ing public health because feed contaminants might easily enter
animal-derived products such as meat, milk and eggs, thereby
directly endangering the end consumer.
ACKNOWLEDGEMENTS
We thank the Plant Protection Inspection Services (PPIS) of the
Ministry of Agriculture, for providing crude data of contaminants
in imported feed and food ingredients.
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