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BPA in canned petfood

  • September 2017
DOI:10.13140/RG.2.2.34540.87681
Authors:
Anton Beynen
Anton Beynen
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Abstract

BPA in canned petfood BPA (bisphenol A) is a component of resins that line the inside of most petfood cans. Quite some dog and cat owners fear that BPA is a danger to their pets. BPA can leach out of the can's coating into the food, while research has identified the synthetic chemical as a disruptor of the body's hormone system, with links to various diseases. In response to the owners' concern, some petfood manufacturers claim that their canned or pouched foods are BPA free. Ingested BPA that enters the dog's bloodstream is then converted by the liver, resulting in detoxification and excretion with urine. The cat neutralizes BPA much slower than the dog does. A toxicity study in dogs found that feeding a dry diet containing as much as 3000 mg BPA per kg had no negative health effects within 90 days. The BPA content of canned food is not higher than 0.2 mg per kg, which equals about 1 mg per kg food when completely dried. Canned food does not cause BPA intoxication in dogs and cats, at least not within a relatively short period of time. Experimental research in laboratory rodents has shown that low intakes of BPA can imitate and oppose some of the body's hormones and thereby modulate hormone-regulated processes. It is conceivable that low dietary BPA levels enhance the development of hormone-related diseases of slow progression, revealing themselves at older age. Circumstantial evidence connects BPA with thyroid disease (hyperthyroidism) in cats. Many dogs and cats receive canned food as part of their total diet. The BPA content of the whole diet does not compromise visible pet health in the medium term. Basic research suggests that low BPA intakes can have negative health effects in the long term, but as yet there is no solid evidence for such impact in dogs and cats.
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Creature Companion 2017; September: 33-34.
Anton C. Beynen
BPA in canned petfood
BPA (bisphenol A) is a component of resins that line the inside of most petfood cans. Quite some
dog and cat owners fear that BPA is a danger to their pets. BPA can leach out of the can’s coating
into the food, while research has identified the synthetic chemical as a disruptor of the body’s
hormone system, with links to various diseases. In response to the owners’ concern, some petfood
manufacturers claim that their canned or pouched foods are BPA free.
Ingested BPA that enters the dog’s bloodstream is then converted by the liver, resulting in
detoxification and excretion with urine. The cat neutralizes BPA much slower than the dog does. A
toxicity study in dogs found that feeding a dry diet containing as much as 3000 mg BPA per kg had
no negative health effects within 90 days. The BPA content of canned food is not higher than 0.2
mg per kg, which equals about 1 mg per kg food when completely dried. Canned food does not
cause BPA intoxication in dogs and cats, at least not within a relatively short period of time.
Experimental research in laboratory rodents has shown that low intakes of BPA can imitate and
oppose some of the body’s hormones and thereby modulate hormone-regulated processes. It is
conceivable that low dietary BPA levels enhance the development of hormone-related diseases of
slow progression, revealing themselves at older age. Circumstantial evidence connects BPA with
thyroid disease (hyperthyroidism) in cats.
Many dogs and cats receive canned food as part of their total diet. The BPA content of the whole
diet does not compromise visible pet health in the medium term. Basic research suggests that low
BPA intakes can have negative health effects in the long term, but as yet there is no solid evidence
for such impact in dogs and cats.
Chemistry
Bisphenol A (BPA) is a high production volume chemical, synthesized by condensation of acetone
(thus the “A”) with two phenol equivalents. BPA is used to produce certain plastics and epoxy resins.
Polymers coating the inside of food cans and pouches can dissociate so that the BPA component
migrates to the can’s content (1, 2). These events extend to other bisphenol compounds (3, 4).
Metabolism
In fasted dogs administered BPA by orogastric gavage, about 50% was absorbed, reached the liver
through the portal vein and underwent glucuronidation (5). In systemic blood, the ratio of
glucuronidated:free BPA was 400:1 (5). Hepatic BPA glucuronidation, which may be more efficient in
dogs than in cats (6, 7), probably inactivates the xenobiotic and steers it towards urinary excretion.
Nevertheless, BPA feeding raised serum total BPA in dogs (8).
Exposure
Three publications report BPA measurements in canned foods. In 11 dog and 15 cat foods, the
ranges were 11 to 206 and 13 to 136 ng BPA/g product (1). Two dog foods were found to contain 12
and 18 ng/g (8) and three dog and three cat foods had <0.2 to 0.3 ng/g (9). The considerable
variation may be caused by analytical inaccuracy. The highest value (206 ng/g) corresponds to about
1 ppm in the dietary dry matter.
Toxicity
In a 90-day toxicity study (10), beagle dogs (4/sex/group) were fed dry foods containing 0, 1000,
3000 or 9000 ppm BPA. The four diets were well tolerated with no overt signs of toxicity. There were
no BPA effects on body-weight gain, food intake, retina condition, blood and urine values and
macroscopically-evaluated tissues. Dogs in the highest dose groups had increased liver weight. Thus,
1000 and 3000 ppm BPA did not induce aberrances.
BPA has been evaluated in three- and two-generation reproductive toxicity studies in rats and mice
(11, 12). Each study included a dry food without or with one of five BPA doses, ranging from 0.015 to
7500 ppm for the rats and 0.018 to 3500 ppm for the mice. Highest BPA levels without effect were
75 and 30 ppm for rats and mice.
Gut bacteria
Switching dogs from a dry food to one of two canned foods led to greater serum BPA
concentrations, which were associated with fecal microbiome changes (8). There was no BPA-free
control treatment, while a dry to wet diet crossover affects gut bacteria anyway. Average serum BPA
increased from 0.7 to 2.2 ng/ml after 14 days (8).
Feline hyperthyroidism
Hyperthyroidism is a common endocrine disorder in older cats. Five case-control studies showed
that more than 50% wet food in the diet is associated with a three-fold higher risk of developing
hyperthyroidism (13-17). Two points twin BPA and the disease. BPA can act as thyroid disruptor (18),
possibly leading to derailments in thyroid cells. Consumption of food from cans with easy-open (pop-
top) lids further increased risk of hyperthyroidism (15). Such cans have more flexible coatings that
may release extra BPA (19).
Low-dose effects
BPA has a complex dose-response curve: biological effects are measurable at low and high doses,
but hardly in between (20, 21). High doses cause intoxication of body cells with exceedance of
reference values, clinical symptoms and death in the short term. Low doses immediately affect the
endocrine system (low-dose effects), with health issues in the long term. Perhaps, BPA accelerates
the development of ageing-related diseases such as feline hyperthyroidism.
Literature
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ResearchGate has not been able to resolve any citations for this publication.
High Bioavailability of Bisphenol A from Sublingual Exposure
Article
Full-text available
Background: Bisphenol A (BPA) risk assessment is currently hindered by the rejection of reported higher-than-expected plasma BPA concentrations in humans after oral ingestion. These are deemed incompatible with the almost complete hepatic first-pass metabolism of BPA into its inactive glucurono-conjugated form, BPA glucuronide (BPAG). Objectives: Using dogs as a valid model, we compared plasma concentrations of BPA over a 24-hr period after intravenous, orogastric, and sublingual administration in order to establish the absolute bioavailability of BPA administered sublingually and to compare it with oral bioavailability. Methods: Six dogs were sublingually administered BPA at 0.05 mg/kg and 5 mg/kg. We compared the time course of plasma BPA concentrations with that obtained in the same dogs after intravenous administration of the same BPA doses and after a 20-mg/kg BPA dose administrated by orogastric gavage. Results: The data indicated that the systemic bioavailability of BPA deposited sublingually was high (70–90%) and that BPA transmucosal absorption from the oral cavity led to much higher BPA internal exposure than obtained for BPA absorption from the gastrointestinal tract. The concentration ratio of BPAG to BPA in plasma was approximately 100-fold lower following sublingual administration than after orogastric dosing, distinguishing the two pathways of absorption. Conclusions: Our findings demonstrate that BPA can be efficiently and very rapidly absorbed through the oral mucosa after sublingual exposure. This efficient systemic entry route of BPA may lead to far higher BPA internal exposures than known for BPA absorption from the gastrointestinal tract.
Bisphenol-A, an Environmental Contaminant that Acts as a Thyroid Hormone Receptor Antagonist in Vitro, Increases Serum Thyroxine, and Alters RC3/Neurogranin Expression in the Developing Rat Brain
Article
Full-text available
  • Feb 2005
Considering the importance of thyroid hormone (TH) in brain development, it is of potential concern that a wide variety of environmental chemicals can interfere with thyroid function or, perhaps of greater concern, with TH action at its receptor (TR). Recently bisphenol-A (BPA, 4,4' isopropylidenediphenol) was reported to bind to the rat TR and act as an antagonist in vitro. BPA is a high production volume chemical, with more than 800 million kg of BPA produced annually in the United States alone. It is detectable in serum of pregnant women and cord serum taken at birth; is 5-fold higher in amniotic fluid at 15-18 wk gestation, compared with maternal serum; and was found in concentrations of up to 100 ng/g in placenta. Thus, the human population is widely exposed to BPA and it appears to accumulate in the fetus. We now report that dietary exposure to BPA of Sprague Dawley rats during pregnancy and lactation causes an increase in serum total T4 in pups on postnatal d 15, but serum TSH was not different from controls. The expression of the TH-responsive gene RC3/neurogranin, measured by in situ hybridization, was significantly up-regulated by BPA in the dentate gyrus. These findings suggest that BPA acts as a TH antagonist on the beta-TR, which mediates the negative feedback effect of TH on the pituitary gland, but that BPA is less effective at antagonizing TH on the alpha-TR, leaving TRalpha-mediated events to respond to elevated T4.
Hormones and Endocrine Disrupting Chemicals: Low Dose Effects and Non-Monotonic Dose Responses
Article
Full-text available
  • Mar 2012
For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of "the dose makes the poison," because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.
Bisphenol A (BPA) in the serum of pet dogs following short-term consumption of canned dog food and potential health consequences of exposure to BPA
Article
  • Dec 2016
Bisphenol A (BPA) is a widely present endocrine disruptor chemical found in many household items. Moreover, this chemical can bioaccumulate in various terrestrial and aquatic sources; thereby ensuring continual exposure of animals and humans. For most species, including humans, diet is considered the primary route of exposure. However, there has been little investigation whether commercial-brands of dog foods contain BPA and potential health ramifications of BPA-dietary exposure in dogs. We sought to determine BPA content within dog food, whether short-term consumption of these diets increases serum concentrations of BPA, and potential health consequences, as assessed by potential hematological, serum chemistry, cortisol, DNA methylation, and gut microbiome changes, in dogs associated with short-term dietary exposure to BPA. Fourteen healthy privately-owned dogs were used in this study. Blood and fecal samples were collected prior to dogs being placed for two-weeks on one of two diets (with one considered to be BPA-free), and blood and fecal samples were collected again. Serum/plasma samples were analyzed for chemistry and hematology profiles, cortisol concentrations, 5-methylcytosine in lymphocytes, and total BPA concentrations. Fecal samples were used for microbiome assessments. Both diets contained BPA, and after two-weeks of being on either diet, dogs had a significant increase in circulating BPA concentrations (pre-samples = 0.7 ± 0.15 ng/mL, post-samples = 2.2 ± 0.15 ng/mL, p < 0.0001). Elevated BPA concentrations positively correlated with increased plasma bicarbonate concentrations and associated with fecal microbiome alterations. Short-term feeding of canned dog food increased circulating BPA concentrations in dogs comparable to amounts detected in humans, and greater BPA concentrations were associated with serum chemistry and microbiome changes. Dogs, who share our internal and external environments with us, are likely excellent indicators of potential human health concerns to BPA and other environmental chemicals. These findings may also have relevance to aquatic and terrestrial wildlife.
Formation of Heterocyclic Aromatic Amines and Migration Level of Bisphenol-A in Sous-Vide-Cooked Trout Fillets at Different Cooking Temperatures and Cooking Levels
Article
  • Mar 2016
The effects of different cooking temperatures (65°C, 75°C and 85°C) and cooking levels (medium and well) on some quality properties, the formation of heterocyclic aromatic amines (HCAs) and the migration level of bisphenol-A (BPA) in trout fillets cooked by sous-vide were investigated. As a result, as expected, cooking caused a reduction in water content of the samples, while pH, TBARS, L* and b* values increased. Cooking loss values ranged between 14.78-20.51%. While IQ, MeIQ, 7,8-DiMeIQx, 4,8-DiMeIQx, PhIP, AαC and MeAαC could not be detected in the analyzed samples, varying levels of IQx (up to 0.16 ng/g) and MeIQx (up to 5.66 ng/g) were detected. It was determined that total HCAs amount ranged between 1.28 and 5.75 ng/g and all or big part of the total HCAs belonged to MeIQx. In addition, the migration level of BPA in sous-vide cooked samples ranged between 4.93 and 27.11 ng/g.
Molecular basis for deficient acetaminophen glucuronidation in cats
Article
Cats are highly susceptible to acetaminophen toxicity because of deficient glucuronidation of this drug in vivo. The enzyme kinetic basis for this defect is unknown. Therefore, the kinetic properties of acetaminophen UDP-glucuronosyltransferase (acetaminophen-UGT) were investigated, using hepatic microsomes from cats (N = 4) compared with those of species that are less sensitive to acetaminophen intoxication including dogs (N = 4), humans (N = 4), and six other mammalian species (one liver from each). Gunn rats were also studied, since they express defective UGT family 1 isoenzymes and are also prone to acetaminophen toxicity. Acetaminophen kinetics were biphasic in all instances with distinct high and low affinity components. Km values for the high affinity activity in cat microsomes (0.31 ± 0.1 mM; mean ± SEM) were intermediate between those of dogs (0.11 ± 0.02 mM) and humans (0.60 ± 0.06 mM) and other species (0.22 to 6.7 mM; range).On the other hand, high affinity Vmax values were over 10-fold less in cat microsomes (0.025 ± 0.006 nmol/min/mg) than in dogs (0.92 ± 0.09 nmol/min/mg) and humans (0.27 ± 0.09 nmol/min/mg); and over 5-fold less compared with microsomes from other species (range 0.13 to 7.63 nmol/min/mg). Gunn rat microsomes showed a similar 10-fold difference in high affinity Vmax values between the homozygous mutant (0.67 nmol/min/mg) and homozygous normal (6.75 nmol/min/mg) animals. These results demonstrate that, relative to a number of other species, cats have remarkably low hepatic levels of a high affinity acetaminophen-UGT. This difference is sufficient enough to explain poor glucuronidation of acetaminophen in vivo and susceptibility to acetaminophen intoxication.
Feline hyperthyroidism: A descriptive and case-control study
Article
  • Dec 1988
The frequency of diagnosis of feline hyperthyroidism has increased dramatically since the late 1970s. Whether this increase reflects enhanced diagnostic acumen or an actual increase in the incidence of this disease, or both, is unknown. It seems likely, in view of the distinctive nature of the signs and the lack of evidence of thyroid enlargement and clinical signs in previous feline necropsy series, that feline hyperthyroidism is truly occurring with increased frequency today.A case-control study was undertaken to identify possible risk factors for this disease. Owners of 56 cats with feline hyperthyroidism and 117 controls were questioned about their cats' exposure to various potential risk factors (e.g., diet, medications) and these exposures were compared. Elevated odds ratios were associated with regular treatment with flea sprays or powders, living strictly indoors and having reported exposure to lawn herbicides, fertilizers or pesticides. Cases were also more likely to receive canned food and were less likely to be Siamese than controls. The relevance of these factors to the etiology of feline hyperthyroidism is discussed.
Risk factors for feline hyperthyroidism in the UK
Article
Previous studies of cats in the USA and New Zealand have identified a number of risk factors for the development of hyperthyroidism including feeding of canned cat food and being non-purebred. The objective of this study was to examine these and other risk factors in cats from London, UK. A questionnaire-based case-control study of hyperthyroidism in cats greater than eight years of age was undertaken. Cases and controls were recruited from two groups of first opinion clinics in London, UK (five locations in total). The two-page questionnaire investigated details of lifestyle, diet and exposure to environmental chemicals. Data analysis included multivariable analysis of risk factors using binary logistic regression. One hundred and nine hyperthyroid cats and 196 control cats were surveyed. Increasing age, non-pure breed, use of a litter box, more than 50 per cent wet food in the diet, a diet that included fish and exposure to food in a can were identified as risk factors for the development of hyperthyroidism using multivariable analysis. Risk factors for hyperthyroidism in cats from the UK appear similar to those of other countries. Exposure to food packaged in a can was identified as the major risk factor for the development of hyperthyroidism.
The toxicity and biotransformation of single doses of acetaminophen in dogs and cats
Article
  • Jul 1984
The biotransformation of single oral doses of acetaminophen (APAP) was studied in dogs an cats. Each animal received APAP at a no-effect (low), mildly toxic (medium), and severely toxic (high) dosage; dosages for each species were selected to produce similar clinical effects at each respective dosage. For dogs, these dosages were 100, 200, and 500 mg APAP/kg, while for cats, the similar effective dosages were 20, 60, and 120 mg APAP/kg. Plasma half-lives in dogs remained constant at the lower two dosages, but nearly tripled at the high dosage. The plasma half-lives in cats rose with increased dosage. Although the cats were given lower APAP dosages than the dogs, the plasma half-lives of cats were greater than those of the dogs at the medium and high dosages. Both species excreted about 85% of the administered single dose within the first 24 hr. APAP-glucuronide was the principal metabolite excreted in the urine of dogs; its fraction of the total metabolites excreted in urine remained constant at the three dose levels. In cats, APAP-sulfate was the major metabolite in urine at all three dosage levels, but the fraction of the total urinary metabolites represented by APAP-sulfate decreased as the dosage increased. Hepatic centrilobular pathology was seen in dogs, while cats had more diffuse liver pathologic changes. The results indicate that the cat is at increased risk from APAP exposure because of impaired glucuronidation and saturation of its sulfate conjugation pathway.
Evaluation of Environmental, Nutritional, and Host Factors in Cats with Hyperthyroidism
Article
  • Jul 1999
The pathologic changes associated with hyperthyroidism (adenomatous hyperplasia, adenoma of the thyroid gland) have been well characterized in cats, but the pathogenesis of these changes remains unclear. In this research, we undertook a case-control study to search for potential risk factors for this disease. Owners of 379 hyperthyroid and 351 control cats were questioned about their cats' exposure to potential risk factors including breed, demographic factors, medical history, indoor environment, chemicals applied to the cat and environment, and diet. The association between these hypothesized risk factors and outcome of disease was evaluated by conditional logistic regression. Two genetically related cat breeds (ie, Siamese and Himalayan) were found to have diminished risk of developing hyperthyroidism. Cats that used litter had higher risk of developing hyperthyroidism than those that did not. Use of topical ectoparasite preparations was associated with increased risk of developing hyperthyroidism. Compared with cats that did not eat canned food, those that ate commercially prepared canned food had an approximate 2-fold increase in risk of disease. When these 4 variables (breed, use of cat litter, consumption of canned cat food, and use of topical ectoparasite preparations) from the univariate analysis were selected for further study as candidate risk factors and analyzed by multivariate conditional logistic regression, a persistent protective effect of breed (ie, Siamese or Himalayan) was found. In addition, results suggested a 2- to 3-fold increase in risk of developing hyperthyroidism among cats eating a diet composed mostly of canned cat food and a 3-fold increase in risk among those using cat litter. In contrast, the use of commercial flea products did not retain a strong association. The results of this study indicate that further research into dietary and other potentially important environmental factors (eg, cat litter) is warranted.