Herbicide used in soybean and sugarcane crops is carcinogenic for rats

Diuron could cause bladder cancer in animals even at doses five times lower than expected.

By José Tadeu Arantes

Agência FAPESP – A study conducted at Universidade Estadual Paulista (Unesp) has identified the method of action of diuron, a herbicide widely used in soybean and sugarcane crops that causes bladder cancer in rats.

“We showed that when eliminated through the urine, diuron and its metabolites cause necrosis at multiple sites in the urothelium, the bladder’s lining. In response, this lining proliferates to replace the damaged areas. The cellular proliferation continues, and it if is maintained for a long time, it ends up leading to successive errors in copies of the DNA, some of which predispose to the development of tumors,” explained Dr. João Lauro Viana de Camargo, a full professor of pathology at Unesp Botucatu Medical School and coordinator of the FAPESP-funded study.

According to the researcher, this method of action proves that diuron is not genotoxic, i.e., it does not initially or directly cause damage to DNA. The damage tends to occur later if exposure is prolonged. The United States Environmental Protection Agency (EPA) had already warned of the carcinogenic potential of this herbicide in humans.

The study was conducted at Unesp by researchers from the Medical School and the Biosciences Institute on the Botucatu campus and the Chemistry Institute on the Araraquara campus. The study also had foreign participation, including researchers from the EPA and the University of Nebraska, with a total of 25 professionals involved. The project confirmed diuron’s carcinogenic potential in rats and showed that the condition could occur even at doses five times lower than the amounts originally considered harmful.

“The changes that diuron caused in rat bladders occurred according to a dose-response relationship, i.e., the higher the dose, the greater the molecular, ultrastructural and histological alterations,” explained Camargo. “Along these lines, we identified the so-called threshold dose – the quantity below which the herbicide is not carcinogenic, even if the animal is exposed to it for a prolonged time.”

According to the researchers, the toxicity of the product manifests early, on the first day of exposure to high doses. “Evaluated based on its genetic expression, the response of the urothelium is apparently adaptive, suggesting that if exposure is interrupted, the bladder will return to normal. A problem will exist if the doses are high and exposure is prolonged,” Camargo affirmed.

Another observation made during the successive studies was that when administered to rats at relatively high doses, diuron causes blood toxicity.

“In this case, the main target is primarily the spleen, an organ related to immunity and the blood supply, which consistently showed higher levels due to excess blood and the accumulation of cellular remains,” commented Camargo. This alteration was also verified in the masculine offspring of pregnant mice that had received diuron at high doses.

The study on diuron was part of a broader study – the Thematic Project “Agricultural pesticides as a risk factor” – conducted with FAPESP funding from 2007-2012. In the Thematic Project, the researchers investigated the effects of five pesticides on rats and mice in addition to diuron. The National Health Surveillance Agency (Anvisa) found the residue of these five pesticides on tomatoes available on the Brazilian market.

“Male rats fed with rations containing that mixture of pesticides at relatively low doses for eight weeks present a potentially more active hepatic biotransformation system for chemical substances,” commented Camargo.

This discovery suggests that the organs of the animals are making an extra effort to rid themselves of strange substances to which they have been exposed. However, the mixture has not promoted the development of liver cancer in rats that have been artificially predisposed to this type of disease.

However, another worrisome effect was discovered. The male mice fed with rations containing the pesticides showed a reduction in the mobility of their spermatozoids. “This finding could indicate that the animals’ fertility has been compromised,” explained Camargo.

His care in saying “could indicate” rather than “indicates” is because changes have not been found in other parameters related to the male reproductive system, such as levels of sexual hormone, sperm morphology, the daily production of spermatozoids, the speed of travel through the epididymis – the duct that collects spermatozoids produced in the testicles – and the histological structure of the testicles and epididymis.

Warnings for authorities and consumers

Using the same caution, Camargo avoids extrapolating the discoveries found in rats to humans. “Although the experimental studies are based on the premise that the laboratory animals responded to chemical insults in the same manner as humans – otherwise, there would be no reason to conduct these experimental studies – the extrapolation of the results must be done carefully, and the relevance of the results must be examined with caution,” he said.

“For rigorous extrapolation, there is a need to compare the metabolic and biological processes that the researched substances undergo and provoke in each species,” stated the Unesp professor.

At any rate, the discovery constitutes an important warning for health authorities and consumers because concern over eating chemical residue-free food, albeit incipient, is growing in Brazil.