Accounting for Multiple Comparisons in Statistical Analysis of the Extensive Bioassay Data on Glyphosate

Abstract

Glyphosate is a widely used herbicide worldwide. In 2015, the International Agency for Research on Cancer (IARC) reviewed glyphosate cancer bioassays and human studies and declared that the evidence for carcinogenicity of glyphosate is sufficient in experimental animals. We analyzed 10 glyphosate rodent bioassays, including those in which IARC found evidence of carcinogenicity, using a multiresponse permutation procedure that adjusts for the large number of tumors eligible for statistical testing and provides valid false-positive probabilities. The test statistics for these permutation tests are functions of p values from a standard test for dose-response trend applied to each specific type of tumor. We evaluated 3 permutation tests, using as test statistics the smallest p value from a standard statistical test for dose-response trend and the number of such tests for which the p value is less than or equal to .05 or .01. The false-positive probabilities obtained from 2 implementations of these 3 permutation tests are: smallest p value: .26, .17; p values ≤ .05: .08, .12; and p values ≤ .01: .06, .08. In addition, we found more evidence for negative dose-response trends than positive. Thus, we found no strong evidence that glyphosate is an animal carcinogen. The main cause for the discrepancy between IARC’s finding and ours appears to be that IARC did not account for the large number of tumor responses analyzed and the increased likelihood that several of these would show statistical significance simply by chance. This work provides a more comprehensive analysis of the animal carcinogenicity data for this important herbicide than previously available.

The Potential Effects of Recall Bias and Selection Bias on the Epidemiological Evidence for the Carcinogenicity of Glyphosate

“…Finally, in IARC's determination that glyphosate was probably carcinogenic to humans, IARC concluded that the evidence for the carcinogenicity of glyphosate in humans was “limited,” but the evidence in experimental animals was “sufficient.” Crump, Crouch, Zelterman, Crump, and Haseman () recently completed a thorough reanalysis of data from ten rodent bioassays, which included all the animal studies IARC considered to provide evidence of the carcinogenicity of glyphosate. They found no strong evidence that glyphosate is an animal carcinogen.…”

A Water‐Gated Organic Thin‐Film Transistor for Glyphosate Detection: A Comparative Study with Fluorescence Sensing

“…Glyphosate [ N ‐(phosphonomethyl)glycine] (GlyP) herbicide has attracted attention worldwide due to its potential carcinogenic activity in human bodies. Although an increasing number of countries have already banned the use of GlyP, environmental and biological accumulation of consumed GlyP is a concern because of its potential risks to ecosystems and human health [10] . However, chemosensors for the GlyP detection are still rare [11] .…”

“…Althougha ni ncreasing number of countries have already banned the use of GlyP,e nvironmental and biological accumulation of consumed GlyP is ac oncern because of its potential risks to ecosystems and human health. [10] However,c hemosensors for the GlyP detection are still rare. [11] To detect GlyP by utilizing the WG-OTFT device, we employed ac ompetitive complexation among poly{3-(5-carboxypentyl)thiophene-2,5-diyl} (P3CPT), [8, 9b] GlyP,a nd Cu 2 + .…”

Real-Time Detection of Glyphosate by a Water-Gated Organic Field-Effect Transistor with a Microfluidic Chamber

“…We herein report a real-time monitoring system of targets in aqueous media by the WG-OFET integrated with the microfluidic chamber (Figure ). As a demonstrative analyte, commercially available but potential carcinogenic herbicide glyphosate [ N -(phosphonomethyl)­glycine] (GlyP) was selected. Owing to its wide adverse effects, several countries have prohibited its use and thus the importance of the detection of GlyP is increasing .…”