Silicone Pet Tags Associate Tris(1,3-dichloro-2-isopropyl) Phosphate Exposures with Feline Hyperthyroidism

Poutasse CM, Herbstman JB, Peterson ME, Gordon J, Soboroff PH, Holmes D, Gonzalez D, Tidwell LG, Anderson KA. Silicone Pet Tags Associate Tris(1,3-dichloro-2-isopropyl) Phosphate Exposures with Feline Hyperthyroidism. Environ Sci Technol. 2019 Jul 10

Hyperthyroidism in cats is characterized by a nodular growth on the thyroid gland that hypersecretes thyroid hormone (thyroxine; T4). This growth is usually benign in nature, however the elevated T4 levels results in an increased metabolic rate, polyphagia, weight loss, muscle wasting, and an elevated heart rate. This progresses to heart, renal, and liver damage and eventually death if untreated. While many treatment and management options for hyperthyroidism exist, the underlying cause of this disease is unknown. First described in the 1970s, it is unclear if the disease existed prior to this and was simply undiagnosed, or if the disease developed at that point. Hyperthyroidism closely mimics the disease “toxic nodular goiter” in humans.

Risk factors for hyperthyroidism have been described, and included non-purebred status, increased age, long hair, female sex, and canned food consumption. It has been repeatedly theorized that exposure to certain flame retardants may be linked to hyperthyroidism. Polybrominated diphenyl ethers (PBDEs) were originally incorporated into furniture, clothing, textiles, computer equipment, and a variety of other substances to prevent and slow the spread of fires. Recently these have been replaced by organophosphate esters (OPEs). The advent of PBDE use coincided with the first diagnoses of hyperthyroidism, and these chemicals are known to bioaccumulate and act as endocrine disruptors.

The purpose of this study was to determine if exposure to flame retardants was associated with hyperthyroidism in cats. The study was designed as a prospective cohort study investigating exposure to hyperthyroidism in cats.

Cats were recruited from multiple veterinary hospitals. All cats were over 7 years old. Cats with a diagnosis of hyperthyroidism were recruited based on clinical signs, elevated thyroxine, thyroid nodules, and positive response to therapy. Cats controlled with medication or previous radioiodine therapy were eligible. Control cats had a normal total T4, free T4, total T3, and TSH and no palpable thyroid nodule.

78 cats were recruited, with 39 in each group. Cats were required to wear a collar with a silicone tag for a 7 day period. The silicone tags were designed to bind flame retardants from the environment. Owners were required to complete a 3 page questionnaire on the cat’s home environment. Data on signalment and thyroid test results were recorded. The silicone tags were analyzed for 44 flame retardant chemicals.

Possible confounding factors including geographic origin of the cat, age, bite marks on the tag, time spent outdoors, multi-cat housing, and sampling season were analyzed and found to not be associated with any flame retardant.

Tags were well tolerated by all cats. All but one survey were returned, though many surveys had at least one question not answered, which were excluded from multivariate analysis. While 24 flame retardant chemicals were detected in at least one tag, only one had a significant association with hyperthyroidism.  The chemical tris(1,3-dichloroisopropyl) phosphate (TDCIPP) with significantly associated with a higher risk of hyperthyroidism. Total flame retardant concentration was not associated with thyroid disease.

Cat tags with higher TDCIPP concentrations also had a higher rate of air freshener use in the home. Homes were more likely to be built since 2005, and the cats were more likely to spend time on upholstered furniture. There was a positive correlation between TDCIPP concentration, fT4, and TT4.

The findings of this study suggest that exposure to TDCIPP is associated with an increased risk of hyperthyroidism.

There are several drawbacks to this study. Among the most significant is that diagnosis of hyperthyroidism and flame retardant exposure were temporally reversed; while it is likely that animals with high exposure post diagnosis also had high pre diagnosis exposure, this study does not prove this. Ultimately, this is a demonstration of correlation and not causation, and while a causational effect may be suspected, further prospective work is needed to determine a causational effect.

See Also

Peterson, M. What’s Causing This Epidemic of Thyroid Disease and Can We Prevent It? J. Feline Med. Surg. 2012, 14 (11), 804−818

Kass, P. H.; Peterson, M. E.; Levy, J.; James, K.; Becker, D. V.; Cowgill, L. Evaluation of Environmental, Nutritional, and Host Factors in Cats with Hyperthyroidism. J. Vet. Intern. Med. 1999, 13 (4), 323−329.

Wakeling, J.; Everard, A.; Brodbelt, D.; Elliott, J.; Syme, H. Risk Factors for Feline Hyperthyroidism in the UK. J. Small Anim. Pract. 2009, 50 (8), 406−414.