Important persistent halogenated hydrocarbons (PHA) are polybrominated diphenyl ethers (PBDE), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F), poly-chlorinated biphenyls (PCB), polybrominated biphenyls (PBB), tetrabromobis-phenol-A (TBBPA), DDT, and triclosan. Most PHA are classified as persistent organic pollutants, also known as persistent organic compounds. In addition to intoxicating domestic animals, PHA can be biomagnified in animal tissues especially in body fat and liver, and translocated to the fetus. The occurrence of biomagnification presents a food safety issue of increasing concern. Biomagnification is a process that results in the levels of persistent organic pollutants being concentrated in fat; the levels in fat are a factor higher than dietary levels. PHA are excreted in milk (including breast milk) and eggs.

Etiology

Exposure to PHA occurs from contamination of the indoor environment, atmospheric deposition of PHA on forages, amending agricultural lands with sewage sludge, industrial incidents, contaminated consumer products (eg, herbicides and wood preservatives), and feed contamination. The primary exposure of animals and humans is from the diet. Feeding animal products that include byproducts containing PHA, previously biomagnified in fat and liver by other animals in the food web, is an important source of PHA in animal diets. Ball clay has been identified as being contaminated with PCDD, and contaminated clay has been incorporated in animal diets and used in food processing. All ingredient sources and the level used in diet formulation must be included in assessments. For example, fish meal usage in aquaculture diets may be 2-fold higher than for poultry and pig diets. Exposure of food animals is important because human dietary exposure to PCB and PCCD/F is primarily from ingestion of dairy products and fish, including farmed fish. Cheese in some geographic areas can have PHA levels that approach those found in fish.

Movement of PHA in waste and atmospheric deposition are important in contamination of feedstuffs. Soil can be contaminated by industrial activity, spreading of waste materials on land (eg, land farming of waste and spreading sewage sludge). Spreading sewage sludge on agricultural lands is an important source of PHA in the diet of ruminants and horses. For example, spreading sewage sludge on soil can cause a 50× increase in the soil levels of PCDD congeners. Levels of PBDE in sewage sludge have been reported as 1.1 to 2.3 ppm (DW), and the most consistent PBDE in sewage sludge is the penta-PDE. When soils receive sewage sludge, the primary source of the PCDD/F in forage is considered to come from incorporated soil. Grass silages generally contain more PCDD/F than corn (maize) silage. The congener profile in forage grass can be used to identify sewage sludge and other sources of the PCDD/F. Soil is also consumed during grazing. Domestic and wild animals and birds consume soil when feeding and by geophagy. Grazing cattle or sheep can consume up to 16% or 30% of the dry matter intake as soil, respectively. Ruminants and horses can be exposed to PHA by atmospheric deposition on vegetation. The levels in the atmosphere vary with the season, eg, the levels of the PCDD/F in the atmosphere are generally higher in winter than summer. Some of the PHA are hydrophobic, have low vapor pressure, and absorb to particles. This allows long-range atmosphere transport in dust and worldwide distribution.

Dogs and cats living with people have indoor environmental exposures to PHA. The PBDE are a chemical mixture of congeners and are available in different formulations. There are 209 possible types of PBDE congeners. They contaminate indoor air, migrate from carpets and other synthetic fibers, and are a component of house dust. Triclosan, a polychlorinated hydroxydiphenyl ether, is widely used as broad-spectrum bactericide and is an ingredient in many hygiene products. Domestic surfaces are impregnated with triclosan and these surfaces include cutting boards, food wrappers, refrigerator linings, and surfaces where bacteriocidal action is desired to reduce odors. PHA can be present in feedstuffs fed to dogs and cats. For example, fish oil, which may be used in formulated diets, generally is 2-fold higher in PCDD/F than meat and bone meal. A Japanese study in cats and dogs showed that PHA in the diet are absorbed and can be deposited in tissues. PBDE are added to plastics, textiles, and electronic equipment as flame retardants. PBDE can migrate or leach from products into the surrounding environment during use and leach from plastic after disposal. The lower brominated PBDE generally are more environmentally persistent in food webs, and the higher brominated PBDE can be debrominated by biota to lower brominated PBDE. There is some evidence that PBDE may be converted to polybrominated dibenzo-p-dioxins (PBDD) and dibenzofurans (PBDF). This occurs when plastic material containing PBDE is heated or burned. The PBDD and PBDF have similar toxicity to the chlorinated analogs and have been measured in adipose tissue.

Transmission and Food Safety

PHA are absorbed, can be biomagnified in body fat and liver, translocated to the fetus, and excreted in milk and eggs. Food-producing animals can relay PHA in edible animal products. PHA are in rendered animal fat and other rendered animal products including bone and meat meal. All food-producing animal species that consume PHA can be intoxicated and have residues in their body fat.

One study in cows showed that cattle absorb 35–88% of dietary PBDE. The PBDE transferred to milk reflect the concentrations in fat tissue except for the most hydro-phobic congeners. In lactating cows exposed to diets naturally contaminated with PBDE, the amount of PBDE in milk is essentially equal to the PBDE absorbed for most congeners.

Studies on the hepta- to deca-BDE were done in dairy cows to provide information on the fate of higher brominated BDE. Cows were exposed to a diet containing forages contaminated with PBDE, PCB, and possibly other PHA. The hepta- to deca-BDE levels in adipose tissue were 9–80 times higher than levels in milk fat. The difference increased with degree of bromination. The food safety message is that meat consumption rather than dairy product consumption can be important in human exposure to the higher brominated BDE present in the environment.

A study in sheep provides insight regarding translocation of PHA to the fetus. The sheep were pastured on land that had previously received sewage sludge. Deposition of PCB in maternal and fetal tissue differed between congeners. For example, the concentration of congener 101 was significantly higher in fetal tissue. PBDE congeners found in maternal and fetal tissues were 47 and 99. The PBDE congener 99 was significantly higher in maternal tissues.

Toxicokinetics of some PHA have been estimated for chickens and pigs. PHA analyzed in chicken fat had biomagnification factors (BMF) ranging from 7–35. For pigs, BMF ranging from <7–15 were observed. The toxicokinetics of PBDE were studied in hens fed a diet containing 3.4 ppm PBDE and 0.95 ppt PCDD. Fecal levels of PBDE increased for 2 wk then decreased to ~0% being excreted. After 2 wk, the BDE-47 excreted represented 62% of quantity ingested, suggesting reductive debromination of PBDE was occurring in the digestive tract. Egg levels of PBDE increased during 5 wk to 24 μg/g fat and then decreased to 3 μg/g fat. Estimated bioconcentration factors for PBDE in abdominal fat varied from 0.7–2.

A study on the transfer of PCDD and PCDF from diet to muscle fat in rainbow trout showed that in the first 13.5 mo of feeding, ~30% of the dietary PCDD and PCDF were transferred to fat located in muscle tissue. At 19 mo, the transfer rate increased slightly to ~34% for male trout and decreased to ~27% for egg-laying female trout. Congener-specific patterns of PCDD and PCDF accumulation were not identified. The levels of PCDD and PCDF in muscle fat increased over the 19-mo feeding period.

Eight PBDE congeners (IUPAC Nos. 28, 47, 99, 100, 153, 154, 183, and 209) were studied in the food web to determine BMF. Three food webs were studied: great tit (Parus major) to sparrowhawk (Accipiter nisus), small rodents (Apodemus sylvaticus, and Clethrionomys glareolus) to buzzard (Buteo buteo), and small rodents to fox (Vulpes vulpes). Congeners, except BDE 28 and 209 (below quantification level), were biomagnified in both predatory bird species. The bioconcentration factors ranged from 2–34 in predatory bird food chain. In the rodent-to-fox food chain, no biomagnification was observed.

Toxicology

PHA have acute and chronic toxicity, and chronic effects can occur over a lifetime. The general toxicology includes disruption of the immune system, altered liver function, and endocrine disruption. It is unlikely that domestic and wild animals are exposed to just one group of PHA. The possible antagonistic, additive, synergistic, and potentiating interactions are not well known.

Binding with the Aryl hydrocarbon receptor is considered important for the immunotoxic effects of the PHA. Immunotoxicity is considered a sensitive parameter for some PCB and TCDD/F congeners. The overall immune effect is reduced native resistance to infectious disease and a likely increased risk for neoplasia. The best-studied immunotoxic effect of PHA is on the lymphocytes and acquired immunity. In dairy herds that were fed silage from PCB-contaminated silos, there was an apparent increase in mastitis and calf mortality. Sled dogs exposed to dietary PCB, PBDE, DDT, other chlorinated hydrocarbon pollutants and mercury through consumption of naturally contaminated minke whale blubber were shown to have reduced cellular immune response.

PHA can alter endocrine function. Some PHA are known to have an effect on thyroid endocrinology. The PHA (eg, PCB) that induce hepatic uridine diphospho-glucuronosyltransferase or sulfotransferase isozymes increase biliary excretion of conjugated thyroid hormones. PCB or their metabolites may interfere with binding of T₃ to the nuclear receptor. Exposure in utero to PCB can increase brain deiodinases and may be a compensatory response to maintain tissue T₃ concentrations due to decreased circulating and brain concentrations of T₄. Tetrabromobisphenol A has been shown to alter thyroid hormone receptor. The PBDE have been shown in laboratory studies to disrupt thyroid function in mice and American kestrels. One mechanism appears to be competitive displacement of T₄ from its carrier protein by hydroxylated PBDE metabolites. Laboratory studies in mink showed that thyroid vacuolation was increased and cell height was decreased in kits born to mothers orally exposed to a commercial PBDE mixture. There is some evidence that occurrence of diabetes mellitus in humans can be associated with serum levels of PCB and TCDD congeners. It is not known if this association exists in dogs and cats. The effects of PHA on endocrine functions in domestic animals may not be fully appreciated.

PHA can be steroid hormonal agonists and antagonists and can disrupt endocrine homeostasis, altering regulation of metabolism. These disruptions can cause reproductive dysfunctions. A study on PCB in cattle tissues showed that the FSH and LH stimulatory effects on luteal, granulosa, and thecal cells were decreased for secretion of progesterone, estradiol, and testosterone, respectively. In studies in cattle uterine strips, PCB have been shown to increase the force of myometrial contractions and increase endometrial section of PGF₂α. Exposure to PCB and PBB can increase the gestation period in cattle, but the mechanisms have not been established. High doses of triclosan have been shown to cause endocrine disruption and decreased production of spermatozoa. Sled dogs consuming minke whale blubber naturally contaminated with PCB, PBDE, DDT, and other chlorinated hydrocarbon pollutants had increased hepatic activity of ethoxyresorufin-O-deethylase (EROD), epoxide hydroxylase and testosterone metabolism (formation of 6β- and 16β-hydroxy testosterone and androstenedione). The activity of EROD can persist for ≥10 wk after exposure ceases.

There is increasing concern that some PHA can alter hormonal function in utero. Exposure to PHA in utero may alter sexual functions later in life. Pre- and postnatal exposure to PHA, through endocrine disruption mechanisms, may alter mammary gland development and function and increase mammary diseases. Goats exposed to PCB in utero had altered adenyl function that varied with age and sex. The goats had lower basal cortisol levels during prepubertal development, and this effect persisted during their first breeding season. Male goats at 9 mo of age had a greater and prolonged rise in plasma cortisol levels when subjected to moderate stress.

PHA can up-regulate the activities of cytochrome P450 and other enzymes. Changes in drug metabolism can occur. Changes in cytochrome P450 activity can increase the formation of the ultimate toxicant, including carcinogens. PHA can be promoters of carcinogens.

Clinical Findings and Pathology

In chickens, exposure to PHA may cause a sudden drop in egg production followed by reduction in egg hatchability. Ascites and edema may be observed, together with ataxia. Pathology includes degenerative changes in skeletal and cardiac muscle.

Dairy cattle exposed to PHA via contaminated feed develop anorexia, decreased milk production, and increased frequency of urination. Cows bred for 4–6 wk recycle, suggesting early embryonic mortality. Cows in advanced pregnancy may have prolonged gestation, unrelaxed pelvic ligaments, and abnormally large calves. Hematomas progressing to abscesses may be observed, and cows may develop overgrown hooves and alopecia. Pathology findings include hemorrhagic hepatitis, hepatic fatty metamorphosis, hepatic abscesses, acute to chronic interstitial nephritis, and abomasal ulcers. Dairy records in herds fed silage from silos sealed with a PCB-containing sealant or from PCB-contaminated silos show PCB-linked signs of intoxication, including an increase in the rebreeding interval due to anestrus and reduced conception. Some cattle had signs of abomasitis with clinical signs that mimicked those of hardware disease. Calf mortality was increased due to failure to thrive syndrome. The occurrence of infections in calves was also increased, suggesting immune suppression. Surviving calves had decreased weight gains. Milk production was also decreased after feeding from the bottom of upright silos, which were shown to contain the highest concentrations of PCB.

Feeding minke whale blubber naturally contaminated with PHA to sled dogs was shown to increase occurrences of diffuse thickening of the glomerular capillary wall and Bowman's basement membranes. Tubular hyalinization-degeneration and increased chronic interstitial nephritis were also noted.

Diagnosis

Body fat and liver can be assayed for PHA. These levels can be linked to exposure, pathology, and clinical findings to establish a diagnosis.

Treatment/Control

There is no known treatment for PHA intoxication. Supportive care is recommended. Animals should not be fed feedstuffs that are known to contain high levels of PHA. Attention should be given to the indoor environment, feeding utensils, and feed sources to prevent exposure to PBDE. The PHA in body fat are excreted in milk fat and contribute to the body burden of the neonate.

Last full review/revision March 2012 by Robert W. Coppock, BS, DVM, MS, PhD, DABVT, DABT