Herbicide Exposure and Kidney Cancer Risk
Based on the most recent and highest quality evidence, occupational exposure to specific herbicides does increase the risk of kidney cancer, particularly with agents like 2,4,5-T, atrazine, and related compounds containing dioxin (TCDD). 1, 2
Evidence for Herbicide-Associated Kidney Cancer
Strongest Evidence - TCDD-Containing Herbicides
The International Agency for Research on Cancer (IARC) has upgraded the evidence for kidney cancer from "limited" to "sufficient" for TCDD exposure (a contaminant in certain herbicides like Agent Orange), classifying it as a Group 1 carcinogen with a strong association to renal cell carcinoma. 1
TCDD induces chronic inflammation and acts through multiple carcinogenic mechanisms including metabolic activation to electrophilic compounds and immunosuppressive effects that impair cancer surveillance. 1
Patients with occupational exposure to TCDD-containing herbicides (such as chemical plant workers, agricultural workers exposed to contaminated products) should be considered at increased risk for renal cell carcinoma according to the American College of Occupational and Environmental Medicine. 1
Specific Herbicide Associations from Prospective Studies
The Agricultural Health Study, a large prospective cohort of 55,873 pesticide applicators followed from 1993-2015, provides the strongest evidence for specific herbicides: 2
2,4,5-T (a component of Agent Orange) showed the strongest association with kidney cancer, with a nearly 3-fold increased risk among highest users (RR=2.92,95% CI: 1.65-5.17) in unlagged analyses and even higher risk with 20-year lag (RR=3.37,95% CI: 1.83-6.22). 2
Atrazine exposure demonstrated a significant exposure-response relationship with kidney cancer risk (RR for highest quartile=1.43,95% CI: 1.00-2.03) in 20-year lagged analyses. 2
Cyanazine showed elevated risk in the highest exposure quartile (RR=1.61,95% CI: 1.03-2.50) with 20-year lag. 2
Paraquat exposure above the median was associated with nearly doubled risk (RR=1.95% CI: 1.03-3.70). 2
Canadian Population-Based Evidence
A large Canadian case-control study of 1,279 renal cell carcinoma cases found: 3
Occupational herbicide exposure in males was associated with a 60% increased risk of renal cell carcinoma (OR=1.6,95% CI: 1.3-2.0). 3
Risk increased with duration of herbicide exposure, demonstrating a dose-response relationship. 3
The association was independent of other occupational chemical exposures. 3
Important Caveats and Clinical Context
Atrazine Classification Nuance
Despite the positive associations in prospective studies, atrazine itself was classified by IARC in Group 3 (inadequate evidence) in 1998 and has not been reevaluated. 4
Updated follow-up of the Agricultural Health Study with twice the number of cancer cases found no clear association of atrazine with cancer risk at most sites when examining lifetime use. 4
However, this apparent contradiction is resolved by understanding that the kidney cancer associations emerged specifically in analyses examining high cumulative exposure and recent use patterns, not just ever/never use. 2, 5
Kidney Function Effects
Beyond cancer risk, herbicide exposure affects kidney function: 5
Atrazine use was associated with 3.7% lower estimated glomerular filtration rate (eGFR) and 80% increased odds of chronic kidney disease (OR=1.8,95% CI: 1.0-3.0). 5
Pendimethalin showed similar associations with reduced kidney function and elevated CKD risk. 5
Long-term atrazine exposure causes kidney fibrosis through activation of Wnt/β-catenin signaling pathways, epithelial-mesenchymal transition, and oxidative stress. 6
Risk Assessment Algorithm
For patients with occupational herbicide exposure, assess kidney cancer risk using this hierarchy:
Highest risk: Exposure to 2,4,5-T or TCDD-contaminated herbicides (e.g., Agent Orange, chemical manufacturing workers) - consider these patients at 2-3 fold increased risk. 1, 2
Moderate-high risk: Prolonged high-intensity exposure to atrazine, cyanazine, or paraquat (>20 years of agricultural application) - approximately 1.5-2 fold increased risk. 2
Moderate risk: General occupational herbicide exposure in males with duration >10 years - approximately 1.6 fold increased risk. 3
Lower concern: Brief or low-intensity herbicide exposure, or exposure to herbicides not specifically implicated (though general pesticide safety practices still apply). 4
Key Confounders to Consider
Tobacco smoking is a major confounder that must be assessed, as it independently increases kidney cancer risk. 4
Trichloroethylene (TCE) co-exposure is common in agricultural and industrial settings and is itself a Group 1 carcinogen for kidney cancer - the herbicide associations are independent of TCE. 4, 1
Combined exposures to multiple chlorinated compounds appear to confer highest risk. 1
Bottom Line for Clinical Practice
Occupational exposure to herbicides, particularly TCDD-containing agents like 2,4,5-T and high-intensity exposure to atrazine, does cause kidney cancer. The evidence is strongest for renal cell carcinoma with clear exposure-response relationships in prospective studies. 1, 2 While not all herbicides carry equal risk, and the evidence for some agents remains inadequate, clinicians should recognize herbicide exposure as an established occupational risk factor for kidney cancer when taking exposure histories, particularly in male agricultural workers and chemical industry employees with prolonged high-intensity exposures. 3