107

In: Endocrine Disrupters

T. Grotmol, A. Bernhoft, G.S. Eriksen and T.P. Flaten, eds.
Oslo: The Norwegian Academy of Science and Letters, 2006.

Effects of synthetic disrupters in farm animals

Erik Ropstad
Department of Production Animal Sciences, Norwegian School of Veterinary
Science, P.O. Box 8146 Dep, NO-0033 Oslo, Norway
E-mail: erik.ropstad@veths.no Telephone: +47 22 59 74 69 Telefax: +47 22 59 70 81

Abstract
The sources and effects of Endocrine Disrupting Compounds (EDCs) are
reviewed and discussed with their potential effects on farm animal health.
Much of the available information pertaining to EDCs is derived from epi-
demiological studies of wildlife species and from laboratory animal studies.
While such studies have significant limitations, they are considered to be
valuable indicators of potential effects in farm animals. Generally the mea-
sured concentrations of EDCs are low in farm animals, although accidental
pollution of farm animal feeds has occurred with detrimental effects on
animal health. Little is known of the concentrations that are required to
perturb physiological functions in farm animals, the effects of prolonged
exposure to low doses and the effects of cocktails of EDCs. However, there
is increasing evidence of causal relationships between EDCs and the health
and reproductive function of farm animals. Although the evidence of
adverse effects of EDCs in farm animals is sparse often circumstantial, it is
concluded that it would be unwise to say that these compounds do not pose
some threat to animal health.

Background
Persistent organic pollutants (POPs) such as dioxins, polychlorinated biphenyls
(PCBs), organochlorine pesticides (OP), phtalates, polyaromatic hydrocarbons
(PAHs), alkyl phenols and brominated flame retardants (BFRs) are found in air,
water and sediments as well as in animal and human tissues. Concerns have
been raised among the scientific community, policy makers and general public
regarding the potential hazard to human and animal development and health.
Particular attention has been given to their potential for disrupting the endocrine
system (EDCs; Endocrine Disrupting Compounds) (1,2). Since PCBs demon-
strably disrupt normal development and function in fish, birds and mammals, the
production and use of PCBs have been restricted or banned since the 1970s and
environmental concentrations are now decreasing (3,4). Worryingly, environ-
mental concentrations of other POPs such as BFRs continue to increase due to
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their continued production and use, and there is growing concern regarding ani-
mal and human health risks posed by the environmental levels these substances
(5).
It is critically important that we determine whether environmental concentra-
tions of POPs, such as for example PCB and PBDE isomers, may elicit adverse
effects in fish, wildlife, farm animals (6) and ultimately humans, especially du-
ring sensitive life stages such as the fetus and developing newborn. Knowledge
about most of the EDCs, their sources, environmental behaviour and toxicity is
extremely limited, precluding the completion of comprehensive risk assessments
(5,7,8). Considerable uncertainty remains regarding the causes of reported
effects of exposure to POPs. The critical issue is whether the detected levels of
POPs in the environment exert adverse health effects and specifically which
chemical compounds are responsible for the toxic effects. Humans may be ex-
posed via drinking water or via consumption of contaminated fish or animals.
Mixtures of persistent organic chemicals (POPs) are composed of different
compounds and exist at different absolute and relative concentrations at loca-
tions and in different biological matrices. There are gaps in the knowledge on
which agents occur in a mixture and at which level they exert toxicity. More-
over, there is also considerable uncertainty about mechanisms of action. Assess-
ment of potential effects of EDCs on animal development and reproduction is
complicated due to life stage specific differences in the sensitivity to endocrine
action, the possible translation of subtle physiological alterations during deve-
lopment into irreversible reproductive effects of the adult organism, pleiotrophic
actions of hormones within the organism and the interference with non-EDC
effects by the same compounds (2).
Most studies of EDC have been focused on two categories of animals. One
category is wild animals which have exhibited signs of disruption of their repro-
ductive processes (9). The second category is laboratory rodents which have
been used to investigate mechanisms of EDC action. By contrast there are rela-
tively few reports of effects of EDC exposure on levels of tissue accumulation
or on the physiology of domestic animals and many of those involve high doses
of single EDC (10,11). EDC are generally present in the environment at ex-
tremely low concentrations, well below what would be considered sufficient to
induce changes in physiology in domestic species.
Some related arguments are presented, for example the argument that the pro-
duction of many relevant EDC has been banned for years so that levels have
declined. A further related argument is that effects on wildlife species have been
observed only when environmental levels of exposure have been abnormally
high. Furthermore, it is known that important potential EDCs are metabolized in
the gastrointestinal tract (12), and finally, many EDC have much lower affinity
for hormone receptors than the natural hormones (13).
Taken together, these arguments may have contributed to the view that EDC
are not a threat to farm animal health, even when they are exposed, potentially,
to elevated environmental concentrations following the application of sewage
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sludge to pasture (14). While tissue concentrations have been reported in various
animal species near the top for the food chain, including marine mammals, birds
of prey and alligators (15,16), there are relatively few reports of tissue levels in
primary producers such as domestic animals. However, they are generally pre-
sent at low concentrations, many orders of magnitude below concentrations that
would induce a conventional toxic effect (17).

What adverse effects are known?

In a study of dairy cattle, Meijer et al. (18) showed that exposure to multiple
pollutants present in sewage that contaminated their drinking water supply
resulted in small reductions in milk production and increased age at first calving.
However, while these effects were induced in adult animals, additional, more
subtle effects of exposure to EDCs may affect the development of oocytes,
embryos, fetuses of neonates which are generally more sensitive to the effects of
EDCs (19-22). Direct evidence of effects of environmental concentration of
EDCs on physiological systems remains sparse but recent studies of effects of
exposure of sheep to environmental levels of a cocktail of EDCs and other
pollutants, through exposure to pastures fertilized with sewage sludge can
disrupt fetal testis development, resulting in reduced fetal testis weights, reduced
Leydig and Sertoli cell numbers and altered hormone profiles (17). Similarly,
fetal ovaries derived from sludge-exposed ewes exhibited increased expression
of the pro-apoptotic Bax protein suggesting that fetal ovarian development was
perturbed by exposure to pollutants.
In a two-generation study in goats where pregnant does were given environ-
mentally relevant doses of single PCB congeners (PCB 126 and PCB 153)
during gestation, adverse effects of gestational and lactational exposure to PCBs
were studied (13,24-28). The experimental protocols addressed long-term
exposure, low level exposure and exposure to single PCB congeners during the
periods of fetal and neo-natal development (goats). They were designed to
identify key substances to which humans and ecosystems are typically exposed
chronically.
The prepubertal LH concentration in the goat study was significantly lower,
the puberty was delayed and the progesterone level during the luteal phase of an
estrous cycle was higher in the group exposed to environmental relevant doses
of PCB 153 during gestation and lactation. PCB153-treated males showed a
significant smaller testis diameter in comparison to control. Neither of the trea-
ted groups showed differences in plasma FSH levels. PCB153-treated animals
differed significantly from control with respect to plasma LH and testosterone
levels. Sperm from PCB153-treated animals showed a significantly higher per-
cent of damaged DNA.
Although reported levels of pollutants in farm animals are generally very low,
and the reported consequences generally minor, it should be mentioned that
accidental pollution of animal feeds occurred in Belgium recently and had
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serious consequences, not only for farm animal health, but also for humans (29).
Approximately 20 companies collect animal fat from slaughterhouses and melt it
into a homogenous substance, which is sold to animal feed producers. It is a
common practice to include household waste fat collected at community waste
recycling centres in this product. In January 1999 mineral oil containing
polychlorinated biphenyls (PCBs; most likely oil from discarded transformers
originating from a waste recycling centre) was admixed to the fat delivered to 10
animal-feed producers. Between 15 and 31 January, the resulting 500 tons of
contaminated animal feed, containing approximately 60–80 tons of fat contami-
nated with 40–50 kg of PCBs and almost 1 g of dioxins, were distributed to
poultry farms and to a lesser extent also to rabbit, calf, cow, and pig breeding
and raising farms, mostly in Belgium. Small quantities were exported to the
Netherlands, France, and Germany. In Belgium, 445 poultry farms, 393 bovine
farms, 746 pig farms (or a quarter of this type of farm in Belgium) and 237 dairy
farms (representing 1.5% of the total number of dairy farms in Belgium) used
animal feed from the 10 contaminated animal-feed producers.
Pathologic conditions were first recorded on 4 February on Belgian chicken
farms. They included a decrease in egg production and hatching and an epide-
mic of chicken edema disease. Dioxin measurements showed a clear predomi-
nance of polychlorinated dibenzofuran over polychlorinated dibenzodioxin
congeners, a dioxin/PCB ratio of approximately 1:50,000 and a PCB fingerprint
resembling that of an Aroclor mixture, thus confirming contamination by
transformer oil rather than by other environmental sources. In this case the PCBs
contributed significantly more to total toxic equivalents (TEQ) than dioxins.
Assuming that as a consequence of this incident between 10 and 15 kg PCBs
and from 200 to 300 mg dioxins were ingested by 10 million Belgians, the mean
intake per kilogram of body weight is calculated to maximally 25,000 ng TEQ.
PCBs and 500 pg international TEQ dioxins. Estimates of the total number of
cancers resulting from this incident range between 40 and 8,000. Neurotoxic and
behavioural effects in neonates are also to be expected but cannot be quantified.

Implications
As empirical evidence of physiological effects of environmental levels of EDCs
on farm animal physiology emerges, perceptions of the risk to reproductive
function and health associated with exposure to these compounds may change.
To date, there have been few concerns about the risks associated with exposure
to EDCs with respect to farm animal health. In contrast to this, there are
numerous studies of patterns of change in human male fertility and associated
developmental abnormalities and, while the results are highly controversial,
there are indications of a long-term decline in sperm count and increased inci-
dences for testicular cancer and hypospadias (30-32). The biological signifi-
cance of these trends and the underlying causes remain the subject of debate, but
environmental pollutants are considered to be one possible causal factor. At this
 111

time there does not appear to be a clearly defined risk to farm animal fertility as
a result of exposure to EDCs. However, the preliminary observation that dis-
ruption of specific components of the physiology of the developing fetal gonads
can be induced by exposure to environmental levels of pollutants, including
EDCs, suggest that risks may yet become apparent.
Concerns about EDCs extend beyond effects on farm animals to humans who
consume meat and dairy products. This highlights the need for further assess-
ment of the effects of patterns of exposure to EDCs on physiological consequen-
ces so that the potential health risk can be assessed more rationally. EDCs are
ubiquitous. Thus, human and animal exposure can occur through multiple
routes. The observation of effects of exposure on physiological systems in farm
animals is merely indicative of the potential effects of slightly elevated envi-
ronmental concentrations of EDCs. Exposure to these compounds may occur
through many routes, including air, water and food. The risk of such exposure
needs to be addressed.
In conclusion, the evidence of adverse effects of EDCs in farm animals is
sparse and, with respect to other species, is often circumstantial. However, there
is increasing evidence of causal relationships between EDCs and the health and
reproductive function of farm animals. It would be unwise to conclude that these
compounds do not pose some threat to farm animals.

Acknowledgements
I wish to thank S. Rhind for his contribution to this manuscript.

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