Persistent organic pollutants are carbon-containing chemicals that are resistant to chemical and biological degradation. The persistent halogenated pollutants (PHPs) contain halogen atoms (chlorine, fluorine, or bromine). Important groups of PHPs include polybrominated diphenyl ethers (PBDEs), polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), the polyfluoroalkyl substances (PFAS), and some of the organophosphorus flame retardants (OPFRs).
Persistent halogenated pollutants have worldwide dispersion, and atmospheric PHPs are deposited on soil and forages. Persistent halogenated pollutants include human-made chemicals, products of incomplete combustion (PCDD/Fs), and substances formed by biological synthesis (bromophenols) in aquatic systems. Persistent halogenated pollutants have multiple uses. They have been added to consumer products to provide unique properties such as fire retardation for reduction of the flash point of synthetic materials, and they also have been used as pesticides, dielectrics, disinfection agents, antisticking agents, oil- and water-resistant fabric coatings, and firefighting foams.
Environmental PHPs are a complex mixture of chemicals. Some PHPs biomagnify (bioconcentrate): PHPs in the diet are concentrated in the body at a factor higher than dietary amounts. Depots for PHPs are body lipids (fat and brain) and liver, and the PHPs in these depots generally have long half-lives. Bioconcentrated PHPs are important contaminants in animal-source human foodstuff, and animal-source ingredients are used in companion-animal and food-animal feed. Animal-derived foodstuff and feed include meats, dairy products, eggs, aquatic-source products, and products from the rendering industry. Rendered products include meat, bone- and fish meals, and recycled animal fats, including fish oil.
There are incidents of animal feed being directly contaminated with specific groups of PHPs. Examples are an incident in the US of polybrominated biphenyls (PBBs) contaminating dairy and other animal feeds, along with an incident in Europe in which PCBs (themselves contaminated with polychlorinated PCDD/Fs) contaminated recycled animal fats that were added to animal feed. Both incidents resulted in large-scale human exposure from animal-derived foodstuff, demonstrating the importance of a one-medicine approach to health and feed vigilance.
Triclosan, a chemical with antibacterial properties, is an emerging PHP of concern for bioconcentration in aquatic systems and endocrine disruption from both direct and indirect exposure. A polychlorinated hydroxydiphenyl ether, triclosan is widely used as a broad-spectrum antimicrobial and is an ingredient in hand sanitizers, many cleaning agents, and hygiene products. Surfaces of products such as cutting boards, food wrappers, refrigerator linings, and cat litter can be impregnated with triclosan for bactericidal action and to reduce odors.
Routes of Exposure of PHP Poisoning
The primary routes of exposure to PHPs are oral, dermal, inhalation, and translocation during fetal development. Most PHPs are ubiquitous environmental contaminants, and many bioconcentrate in body fat. A lifetime of exposure starts at embryogenesis. Feed, foodstuffs, and the indoor environment are the most important pathways by which PHPs contaminate domestic animals and humans.
Spreading sewage sludge on agricultural lands is a source of PFAS and other PHPs in milk from ruminants. Ungulates are exposed to PHPs during foraging; and cattle, sheep, and horses can consume from 1% to 30% of the dry-matter intake as soil. Birds and other animals consume contaminated soil by geophagy. Contaminated soil is present in harvested forages. Grass silages generally contain more PCDD/Fs than does corn (maize) silage. Consumption of forages and soil contaminated with PHPs by ruminants is an important source of PHPs in ruminant-derived foodstuff. Animal-derived by-products, especially fats, can be an important source of PHPs in the diet of food-producing animals, including poultry.
Human dietary exposure to PHPs is the highest from ingestion of ruminant-derived products and aquatic-source foodstuff. Rendered animal fats added to ruminant, swine, poultry, and fish feed is an important source of PHPs in the diet of humans consuming products from these animals. Fish oil, which may be used in formulating feed, can be twofold higher in PCDD/Fs than in meat and bonemeal.
For the OPFRs, chewing seat cushions and forms used as padding and other synthetic materials and indoor dust are important pathways to dogs and cats. Preening after contact exposure is a route of oral exposure. The oral, dermal, and inhalation routes of exposure to OPFRs are important for household pets.
Exposure assessments for PHPs must include all sources and pathways of PHPs.
Absorption, Biomagnification, Translation, and Food Safety with PHP Poisoning in Animals
Persistent halogenated pollutants are readily absorbed from the gastrointestinal tract and lungs, and (in lesser amounts) through the skin. After absorption, they may be biomagnified in systemic lipids and translocated to the fetus, milk, and eggs. The biomagnification factor generally varies between the chemical groups of PHPs and within chemical groups between animal species. The concentrations of PHPs in milk are higher in the first lactation, and the total body burden of PHPs in females generally decreases with duration of lactation and increasing parity. Egg-laying females generally have a lower body burden of PHPs because PHPs are excreted in the eggs. Males generally have a higher body burden of PHPs than females have.
The PHP concentrations in milk generally are higher during the early part of the first lactation, and colostrum can be substantially higher in PHPs than milk. In dairy cattle, the carryover rate (COR) for PCDD/Fs from diet to milk was calculated in an exposure incident wherein the cattle were exposed to 10.4 ng World Health Organization toxic equivalency (WHO-TE)/kg dry matter. The COR in this incident was from 63% to 46%, and the cattle were considered to be in negative energy balance (some PCDD/Fs likely had been mobilized from lipid depots). For cattle consuming forage with 0.2 ng WHO-TE/kg dry matter, the COR to milk was 13%. A study in lactating goats found that the COR for PCDDs/Fs to milk was from 42% to 1%, with the lower value occurring 20 days after exposure stopped. For the planer PCBs (dioxin-like), the COR to milk was from 73% to 5% for the dioxin-like PCBs and from 3% to 49% for the non-dioxin-like PCBs. Females in their first lactation, because of mobilization from body fat, excrete higher amounts of most PHPs than would be expected from dietary amounts.
In rainbow trout, approximately 30% of the dietary PCDD/Fs are translocated to fat located in muscle tissue.
There is a trend for increased human exposure to OPFRs that is likely due to increasing use. The exposure of household pets likely parallels human exposure. Organophosphorus flame retardants have a low bioconcentration factor, and some of the OPFRs bind with blood proteins. Organophosphorus flame retardants have been observed in breast milk.
Chronic Toxicology of PHP Poisoning in Animals
Persistent halogenated pollutants bioconcentrate in body lipids and are omnipresent in the body. Dose response to PHPs is from the external exposure to environmental PHPs and the internal exposure to PHPs stored in body lipids. Persistent halogenated pollutants cause endocrine disruption, reproductive dysfunction, altered metabolism, and neurotoxicity. Persistent halogenated pollutants also cause up- and downregulation of enzyme systems, especially the hepatic and adrenal CYPs (P450), and the PHPs have epigenetic effects.
There is emerging evidence that low-dose external exposure to endocrine-disrupting PHPs may have increased pathophysiological effects. Endocrine disruption targets for the PHPs include thyroid, reproductive, and adrenal cortical hormones. Exposure in utero to PCBs can increase brain deiodinases, which can be a compensatory response to maintain tissue triiodothyronine (T3) concentrations because of decreased fetal circulating and brain concentrations of thyroxine (T4).
Deficiency in thyroid hormones can cause abnormal neurologic development. Some PCBs or their metabolites may interfere with binding of thyroid hormones to transporter proteins and the cell nuclear receptor. Exposure to PHPs may be associated with hyperthyroidism in cats; it is conjectured that PBDEs may act as goitrogens via thyroid-stimulating hormone (TSH) stimulation or as direct mitogens1, although current opinions are conflicted. Some naturally occurring hydroxyl forms of PBDEs target thyroid endocrinology. These can be present in aquatic-source pet foods, and there is evidence that cats have increased risk. Polychlorinated biphenyls likely alter thyroid hormones in dogs, the net effect being hypothyroid function. Other PHPs may cause or contribute to hypothyroid function in dogs. The PBDEs disrupt thyroid function in American kestrels.
There is evidence that total serum concentrations of PHPs are linked to feline acromegaly. Some PHPs can be steroid hormonal agonists and antagonists and can disrupt endocrine homeostasis. Exposure to PCBs and PBBs can delay onset of parturition in cattle. There is increasing concern that some PHPs can alter hormonal function in utero. Prenatal and early postnatal exposure to PHPs, through endocrine disruption mechanisms, may alter mammary gland development and function and increase the risk of mammary diseases. Some evidence suggests that OPFRs can alter prolactin secretion, especially in males.
There is a growing general consensus that increased diagnosis of obesity in humans and companion animals cannot be completely explained by genetics, lifestyle, and energy balance. Evidence suggests that PHPs and other persistent nonhalogenated chemicals can have pathophysiological effects on metabolomics. An emerging opinion is that obesity in humans and companion animals is caused by multiple factors, including exposure to PHPs. In utero and neonatal exposure to some PHPs is linked to obesity in the offspring. Feline obesity is associated with PFAS exposure and living indoors. When an animal is in negative energy balance, the blood concentrations of bioconcentrated PHPs increase because these persistent chemicals are liberated during catabolism of fatty tissues. Thus, blood concentrations of PHPs can be dynamic with weight loss, and this phenomenon is considered internal dosing. In humans, plasma concentrations of bioconcentrated PHPs can increase by 388% with a weight loss of 46%. Stores of PHPs in adipose tissue should be considered in managing weight loss in obese patients.
Persistent halogenated. Until the neonatal transition, the fetus can be epigenetically programmed for a lifetime, with the harmful epigenetic effects being expressed at specific stages during the postpartum biological life history (eg, infancy, preadolescence stages, adolescence, puberty, and adult life stages and events). Obesity in humans is being linked to in utero exposure to PFAS.
References
Mensching DA, Slater J, Scott JW, et al. The feline thyroid gland: a model for endocrine disruption by polybrominated diphenyl ethers (PBDEs)? J Toxicol Environ Health A 2012; 75: 201–212.
Clinical Findings, Lesions, and Diagnosis of PHP Poisoning in Animals
Acute exposure of chickens to PCDDs causes a sudden drop in egg production, followed by reduced egg hatchability. Ascites, edema and ataxia may be evident. Lesions include degenerative changes in skeletal and cardiac muscle. Altered thyroid function is associated with anomalous development in birds and mammals, and altered thyroid function is linked to dietary PHPs. Chewing and ingesting foam impregnated with OPFRs can be fatal to dogs. Seizures can occur, and pieces of foam and OPFRs have been identified in gastrointestinal contents. Persistent halogenated pollutants can upregulate the activities of cytochrome P450 enzymes (CYPs) and other enzymes. Unpredictable changes in drug pharmacokinetics and pharmacodynamics can occur.
Prevention and Treatment of PHP Poisoning in Animals
There is no known specific treatment for acute poisoning by PHPs. Supportive care is recommended. For chronic exposure to PHPs, attention should be given to prevent exposure to known sources of PHPs. Using biosourced materials in home finishing and furniture generally reduces the overall indoor exposure to flame retardants. Using metal feed and water bowls also reduces exposure to toxic substances that leach out of synthetic materials. For the one-health model, intoxication with radioisotopes and chemical agents must be a reportable disease. This regulation is important for food and feed vigilance. There are public concerns regarding exposure to PHPs in animal-source foodstuff and feed.
