Diphenylphosphate

Diphenyl phosphate (DPHP) is a urinary metabolite of triphenyl phosphate (TPHP) and other organophosphate flame retardants (OPFRs), widely used in consumer products such as electronics, furniture, and cosmetics. 

As human exposure to OPFRs increases, DPHP is a biomarker for recent exposure, with research suggesting potential endocrine, neurodevelopmental, and reproductive health risks.

What is Diphenyl Phosphate (DPHP)?

Diphenyl phosphate (DPHP) is a urinary metabolite of organophosphate flame retardants (OPFRs), specifically triphenyl phosphate (TPHP) and other phenyl-containing organophosphates. 

These chemicals are commonly used as flame retardants and plasticizers in consumer products such as electronics, furniture, textiles, automotive interiors, and personal care products (e.g., nail polish).

With the phase-out of polybrominated diphenyl ethers (PBDEs) due to toxicity concerns, OPFRs have become increasingly prevalent, leading to widespread human exposure. DPHP is a biomarker for recent exposure, as it is rapidly metabolized and excreted in urine.

Potential Health Risks

New research demonstrates the potential health risks of increased exposure to chemicals such as DPHP. Potential health risks may include:

Endocrine Disruption 

Some organophosphorus flame retardants (OPFRs), including triphenyl phosphate (TPHP), can cause endocrine-disrupting effects, including thyroid hormone dysregulation and reproductive hormone effects.

Neurotoxic Effects

While this has not been confirmed, TPHP may have potential neurotoxic effects through noncholinergic mechanisms, including endocrine disruption and oxidative stress.

Neurodevelopmental Impact

The CHAMACOS study, which included 537 live births, provides epidemiological evidence suggesting a potential association between prenatal TPHP (via its metabolite DPHP) exposure and lower cognitive function in children, specifically reduced Full-Scale IQ and Working Memory scores at age 7. 

However, while the study identifies statistically significant correlations, it does not definitively validate a causal link between TPHP exposure and neurotoxicity, as other confounding factors and the limitations of single urine sample measurements could impact results. Further research is warranted to establish causation.

Pregnancy Complications

Higher maternal DPHP levels have been linked to altered gestational duration.

Who Should Get Tested for DPHP?

DPHP testing is not a routine clinical test but may be relevant for:

Occupational Monitoring: workers in plastics, electronics, automotive, furniture, firefighters, and those in nail salon industries may have higher exposure due to handling OPFR-containing materials.

Environmental Health Studies: researchers assessing population-level exposure to OPFRs, particularly in vulnerable groups such as pregnant individuals and children.

Suspected High Exposure Cases: individuals with a history suggesting significant recent exposure, especially if they also present with unexplained endocrine symptoms, metabolic or neurological changes, or suspected toxicant exposure, may benefit from DPHP testing as part of a broader toxicology panel.

Test Procedure and Interpretation

Sample Type: Urine

Methodology: Isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS)

Sensitivity: Limit of detection (LOD) = 0.05–0.16 ng/mL

Reference Ranges

Median DPHP concentration in U.S. adults (NHANES 2013–2014): ~0.92 ng/mL

However, higher levels are noted in women (likely due to cosmetic exposure) and children (higher dust ingestion, hand-to-mouth behaviors)

Clinical Significance of High DPHP Levels

Elevated DPHP levels indicate recent OPFR exposure, particularly from triphenyl phosphate (TPHP)-containing products. Research demonstrates: 

General Population Exposure

92% of U.S. participants aged 6+ years had detectable DPHP levels, confirming widespread exposure.

Higher Levels in Women and Children

Women had significantly higher levels, likely due to cosmetic use (e.g., nail polish). Children exhibited higher levels than adults, suggesting increased susceptibility due to dust exposure.

The ECHO study demonstrated DPHP in the urine of 99.5% of pregnant participants, highlighting near-universal exposure.

Clinical Significance of Low DPHP Levels

Minimal or no detectable levels of OPFR metabolites in biological samples suggest little to no recent exposure. However, the absence of high levels does not rule out chronic low-level exposure, which may still contribute to cumulative endocrine or neurological effects over time. 

Given the widespread use of OPFRs in consumer products and indoor environments, background exposure is common across the general population, making it important to consider long-term, low-dose exposure when assessing potential health risks.

Key Clinical Considerations

DPHP levels should be interpreted in context—they reflect exposure, not direct toxicity.

Higher exposure groups (women, children, occupational workers) may require further monitoring.

Reducing exposure through lifestyle modifications, such as avoiding OPFR-containing personal care products, improving indoor air quality, and minimizing dust accumulation, may help mitigate risk.

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