A recent ecological study (Dhar M, Ahn S, Fu W, Goldner W, Monaghan M, van Gerwen M. Endocrines. 2026;7(3):43) explored potential associations between 2,4-D and thyroid health. Its findings should be interpreted within limitations of this study design and considered alongside the broader scientific and regulatory evidence base evaluating 2,4-D.
What did the study find?
The study compared county-level 2,4-D use, estimated by the U.S. Geological Survey (USGS) from crop acreage data, with thyroid cancer incidence reported by the U.S. Centers for Disease Control and Prevention (CDC) for the period 2017–2021, applying both 5- and 10-year exposure lags. No statistically significant association was observed in nationwide analyses, either overall or in sex-stratified models. However, a statistically significant positive association was identified when analyses were restricted to rural counties (p = 0.004 and p = 0.006). The authors interpreted these findings cautiously, noting that agricultural context may influence the observed associations and did not identify any mechanistic and longitudinal studies determining causality.
What can a study of this design establish?
Ecological studies compare group-level exposures and outcomes rather than measuring exposure and outcomes in the same individuals. In this study, 2,4-D exposure was estimated from modeled agricultural use, not direct measurements, and no individual-level exposure or diagnosis data were available. As a result, the findings are useful for generating hypotheses but cannot establish individual risk or causality.
The design also cannot distinguish the effects of 2,4-D from other factors that may occur alongside its use, such as other pesticides, nitrate exposure, differences in healthcare access, or geographic variation in cancer detection. In addition, the analysis assumes that people were diagnosed where they were exposed, despite potential population movement over time.
Have regulators considered this before?
Yes. Regulators address the biological premise of the study. The paper’s rationale rests on the possibility that 2,4-D can act as an endocrine disruptor, which regulatory assessments of 2,4-D have consistently challenged.
What does the evidence say about 2,4-D and endocrine effects?
EPA, EFSA and Health Canada’s PMRA have specifically examined whether 2,4-D interferes with thyroid and other hormone pathways. Their reviews have not concluded that 2,4-D meets the evidence threshold for an endocrine disruptor. EPA, EFSA and PMRA have all reached conclusions inconsistent with treating a thyroid-mediated carcinogenic mechanism as established.
Does 2,4-D disrupt the body’s hormone system?
EPA examined this question directly in its Endocrine Disruptor Screening Program assessment. After considering dedicated endocrine tests together with the broader toxicology database, EPA concluded that there was “no convincing evidence of potential interaction with the estrogen, androgen or thyroid pathways.” EPA did not require additional higher-tier mammalian endocrine testing because a comprehensive extended one-generation study was already available.[1]
What did the most comprehensive animal study find?
The extended one-generation reproductive toxicity study examined reproduction, development and endocrine-related effects across multiple life stages. It found some small, temporary thyroid-hormone changes at high doses, around levels where the body’s ability to eliminate 2,4-D becomes saturated. It did not find adverse thyroid pathology or an overall pattern supporting a thyroid-mediated endocrine effect.[2] In other words, the study found no adverse endocrine effects at real world levels; the only changes appeared at high doses near the point where the body’s normal elimination of 2,4-D becomes saturated.
Did Health Canada look at this question when approving 2,4-D?
Yes. PMRA has reviewed or revisited the health evidence for 2,4-D three times over the past two decades. Its 2008 review reported “no evidence for effects on the endocrine system” in the toxicology database.[3] In 2013, after reviewing additional studies including the extended one-generation study, PMRA concluded that no further changes to its regulatory decision were required.[4] In 2017, after considering newer epidemiology and cancer assessments, including IARC’s evaluation, PMRA maintained that 2,4-D did not pose an unacceptable cancer risk under current conditions of use.[5]
What have European regulators concluded most recently?
In 2023, EFSA assessed 2,4-D against the EU’s updated endocrine-disruptor criteria. It found no pattern of estrogen-, androgen-, steroidogenesis- or thyroid-mediated adversity and concluded that the endocrine-disruptor criteria were not met for humans or non-target organisms.[6]
Citations
[1] U.S. EPA, Endocrine Disruptor Screening Program, 2015
[2] Marty et al., extended one-generation reproductive toxicity study of 2,4-D
[3] Health Canada PMRA, Re-evaluation Decision: 2,4-D, 2008
[4] Health Canada PMRA, Re-evaluation Update: 2,4-D, 2013
[5] Health Canada PMRA, Re-evaluation Note: 2,4-D, 2017
[6] EFSA, Assessment of confirmatory data following renewal of approval of 2,4-D, 2023