How does exposure to jet fuels increase the risk of hypothyroidism in individuals, particularly those with prolonged or high-level exposure such as military personnel or airport workers?

Mechanism of Jet Fuel-Induced Hypothyroidism

Direct Thyroid Toxicity Through Polycyclic Aromatic Hydrocarbons (PAHs)

Jet fuels contain polycyclic aromatic hydrocarbons that directly inhibit thyroid peroxidase (TPO), the enzyme essential for thyroid hormone synthesis. 1

• In vitro studies demonstrate that specific PAH compounds found in jet fuels—including pyrene, benzo(k)fluoranthene, and benzo(e)pyrene—reduce TPO activity, blocking the conversion of iodide to thyroid hormones 1
• JP-8 jet fuel, which differs from other fuels due to performance additives, caused reduced T4 levels in mice at doses of 2000 mg/kg, though this exceeds typical environmental exposure levels 1
• The thyroid toxicity appears dose-dependent and correlates with higher PAH content in specific fuel formulations 1

Secondary Hepatic Pathway

Jet fuel exposure causes liver pathology that secondarily disrupts thyroid hormone homeostasis through altered hepatic metabolism. 1

• Heavy fuel oil product F-179 induced thyroid inflammation at 10-55 mg/kg in rats, which co-occurred with liver pathology, suggesting the thyroid effects may be secondary to hepatic dysfunction 1
• The liver plays a critical role in thyroid hormone metabolism and clearance; hepatotoxicity from hydrocarbon exposure can disrupt this balance 1
• This mechanism may be particularly relevant in rodent models but has questionable direct relevance to human exposure patterns 1

Chronic Low-Level Exposure Characteristics

Prolonged dermal and inhalation exposure creates sustained body burden of thyroid-disrupting compounds. 2, 3

• JP-8 is less volatile than its predecessor JP-4, causing liquid fuel to linger on skin and clothing, resulting in prolonged dermal absorption 3
• Over 2 million military and civilian personnel are occupationally exposed annually to kerosene-based jet fuels through dermal absorption, pulmonary inhalation, or oral ingestion routes 2
• Breath samples from Air Force personnel demonstrate demonstrable JP-8 exposure ranging from slight elevations to >100 times control values, indicating substantial systemic absorption 3
• The fuel contains up to 260+ aliphatic and aromatic hydrocarbon compounds (C6-C17+), including benzene, n-hexane, toluene, xylenes, and naphthalenes, creating potential for additive or synergistic thyroid toxicity 2

Epidemiologic Evidence and Clinical Manifestations

The epidemiologic evidence for jet fuel-induced hypothyroidism remains limited but suggestive of association. 4, 5

• A systematic review of 28 epidemiologic studies (18 military, 10 non-military) found slight evidence of associations between jet fuel exposure and neurologic, cognitive, behavioral, respiratory, and cancer outcomes, though thyroid-specific outcomes were not prominently featured 4
• Airport personnel in ground-support functions show biomarkers of exposure and effect, with proximity to running jet engines associated with increased disease risk and hospital admissions 5
• The available epidemiologic data is sparse with low consistency in methods, limiting definitive conclusions about thyroid-specific effects 4

Critical Exposure Factors

The risk of hypothyroidism increases with specific exposure patterns and fuel characteristics. 2, 1

• Exposure typically occurs at concentrations below current permissible exposure limits (PELs), but additive or synergistic interactions among hydrocarbon constituents and up to six performance additives may result in unpredicted thyroid toxicity 2
• Jet fuels with higher aromatic content, particularly elevated PAH levels, carry greater potential for thyroid disruption 1
• The presence of specific additives in military fuels like JP-8 may enhance thyroid toxicity compared to commercial aviation fuels 1

Important Caveats

Most petroleum streams show low thyroid toxicity potential, with effects primarily observed at high doses in animal models. 1

• Of 349 studies of 28-days or longer duration across multiple species, the thyroid was almost invariably not a target organ 1
• Only three rodent studies found thyroid effects, and these occurred at doses substantially higher than environmental exposure levels or involved secondary hepatic effects 1
• Regulatory studies for most chemicals do not include detailed thyroid function or receptor studies, so subclinical effects may exist that were not detectable using conventional pathology or hormone measurements 1
• The overall data indicates low potential for thyroid hormone effects from petroleum stream exposure, especially when aromatic content is low 1

Human epidemiology studies show weak and inconsistent thyroid effects without identification of specific causative chemicals, and confounding variables cannot be excluded as explanations for observed associations. 1

Human Reference: 6, 7, 8