2,4-D Toxicological Reassessment

Amanda Búlgaro & Luis Ribeiro

Interview with experts from the Brazilian Association of Generic Defensives (Aenda).

2,4-D is a herbicide widely used in agriculture and is one of the most sold in Brazil. Synthesized since 1941, it has an excellent cost-benefit ratio due to its low cost and, due to the mode of action, it does not generate weed resistance. The application of the product requires care in relation to drifting to areas of other crops, which can cause phytotoxicity. Recently, in the state of Rio Grande do Sul, there have been restrictions on the use of the product due to suspected drift contamination.

AgriBrasilis interviewed Luis Ribeiro, State Regulatory Manager and Amanda Búlgaro, Federal Regulation Coordinator, from AENDA (Brazilian Association of Generic Defensives) to discuss this topic.

AENDA, a non-profit oraganization, is the main entity that acted in the origin of the registration of pesticides by equivalence and over the years has shown strength in the involvement of the most diverse issues, such as federal and state regulations, application and use of products, federal and state taxes and fees, patent system, import procedures, among other activities.


AgriBrasilis – What is the 2,4-D market, and who are the main players in it?
Aenda – 
According to the pesticide commercialization reports prepared by IBAMA1, in 2018 2,4-D was the second most sold active ingredient in the country with around 49 thousand tons sold. We yet do not have the figures for 2019, but we believe that the asset is still among the most sold, and it is sold by around 30 companies. Corteva, Nufarm and Adama are the largest players of 2,4-D-based products in the Brazilian market.


AgriBrasilis – What is the dangerousness of 2,4-D?
Aenda – 
Regarding the dangerousness of the active ingredient, with regard to chronic data, there is still
insufficient evidence from observations in humans or studies in experimental animals that 2,4-D causes
some type of chronic damage, according to with ANVISA2.

ANVISA’s analysis, as well as that of other international bodies, show that 2,4-D is safe with regard to chronic dangers and does not fit any characteristic that prevents the registration of pesticides in Brazil because it does not reveal teratogenic, carcinogenic, mutagenic characteristics, nor does it cause hormonal disorders or damage to the reproductive system relevant to humans, according to the results of scientific studies available to date.

Considering the other ANVISA analyzes (occupational risk assessment, dietary risk, residues and other points mentioned in the RDC no. 284/2019), risk mitigations were determined by changing some
application and production recommendations.


AgriBrasilis – At the end of the revaluation of 2,4-D by ANVISA, what are the new guidelines regarding the registration and use of 2,4-D?
Aenda – 
In May 2019, ANVISA published on its website a summary of the new guidelines: Farm worker To protect the health of farm workers, that is, those who deal directly with the application of pesticide 2,4-D,
ANVISA has determined new parameters and limits for its use. One of the parameters is the definition of an exposure limit for rural workers. With this, ANVISA can define specific protection measures for this worker.

For the application made with a tractor, different workers must carry out the preparation and application
of the product. According to a survey carried out with the agricultural sector, this is already a practice
adopted, since the pesticide is authorized only for crops that traditionally are of great extension. The entry of workers in places that received the application of the pesticide will also have defined intervals for each crop. This means that the worker will only be able to enter an area that has been sprayed with 2,4-D after the minimum defined time or with the use of personal protective equipment.

Analysis: For the reassessment of 2,4-D, ANVISA prepared 13 papers, including specific assessments on
occupational risk and for people who transit in areas close to the planted areas. The most recent data from
the Pesticide Residue Analysis Program (PARA), from acute poisoning by pesticides in Brazil, and from the Water Quality Surveillance Information System for Human Consumption (SISAGUA) were also analyzed.

Main changes determined for the application of 2,4-D:
1) For the protection of rural workers:
– Sealing so that the same worker performs the preparation and application of the product when a tractor is used.
– Determination of time intervals, specific to each culture, to allow workers to enter the areas where the
product was applied.

2) For residents in areas close to crops:
– Demarcation of a margin of 10 meters for the interior of the plantation in which the pesticide cannot be applied, if there are buildings less than 500 meters from the field. This margin is also called “border”.
– Obligation to reduce drift, that is, use of equipment and application techniques or change in formulation that prevents the product from dispersing outside the crop.
– Limitation of the maximum application dose to 1.7 kg / hectare costally, that is, when the worker uses the application pump as a backpack. This measure is specific to coffee growing and when drift reduction is not possible.”


AgriBrasilis – Who are the responsibles for implementing and monitoring these new guidelines?
Aenda – 
When we talk about inspection, the federal constitution, federal law and its regulatory decree determine the competences over who legislates and who inspects certain matters. It is up to the federal government to inspect products in their manufacture, import and transport between states. It is up to the states to supervise storage, internal transport, if the recommendation for use is being carried out through
agronomic prescription, trade and use of the product.

All information contained on the product labels and package inserts must be updated in the state plant defense agencies in accordance with the determinations of the federal registration agencies (MAPA3, ANVISA e IBAMA). Municipalities can have their pesticide laws and inspect where the state is unable to act.


AgriBrasilis – How are companies organizing themselves to adapt to the new established standards?
Aenda – 
All 2,4-D based product registration companies are adapting their technical products and formulated in accordance with the new ANVISA recommendations and, in addition to the recommendations contained in the new asset monograph and the changes in the recommendation for the application and use of products, should also institute training and information dissemination programs for farmers. Companies are also responsible for monitoring the results of these programs and forwarding
annual reports to ANVISA with product sales records, detailing how the risk mitigation measures were
disseminated and the results obtained.

As a result, in 2019 the “2,4-D Post-Reassessment Task Force” was formed to develop joint training programs. The TF is coordinated by Aenda and consists of 23 companies, as shown below. We set up a face-to-face training plan in the states of Tocantins, Espírito Santo, Alagoas, Minas Gerais and Santa Catarina for 2020.

The locations chosen are the result of a cross between IBGE4 data, Intoxication notifications and ANVISA
data about 2, 4-D. Besides, a video was also developed for instruction and guidance on the safe application in addition to face-to-face training that can be accessed on the website:

Due to COVID-19, unfortunately, live training is suspended and we are currently encouraging the dissemination of the training video, seeking help from other partners and institutions in the sector.


AgriBrasilis – What is the role of Aenda?
Aenda – 
AENDA is coordinating the TF and is in contact with the agricultural departments of the states to
work together and also with ANDAV5 aiming at a wide dissemination of the work being done by TF.


AgriBrasilis – In the case of noncompliance with what is established by ANVISA, is there a penalty?
Aenda – 
According to ANVISA, in accordance with art. 7th of the DRC No. 284/2019, “Failure to comply with the provisions contained in this Resolution constitutes an infraction, pursuant to Law No. 6437, of August 20, 1977, Law No. 7802, of July 11, 1989, and art. 31 of the Resolution of the Collegiate Board – RDC No. 221, of March 28, 2018, without prejudice to the applicable civil and criminal penalties.”


AgriBrasilis – Do the Federation units follow ANVISA standards or have their own standards?
Aenda – 
In accordance with Law No. 7802 / 89 and its regulatory Decree No. 4074 / 2002, each State has issued its own pestcide reguçation. There are state regulations that are prior to the federal law and are
still in force, as in the states of Rio Grade do Sul and Paraná. All state regulations provide that state health
agencies observe what ANVISA approved at the time of the state registration of pesticides, to be subsequently released for sale.

Each state has its particularities and may request companies to supplement information in the labeling to be in compliance with any determination.


AgriBrasilis – Do these new guidelines have an impact on the price of the product?
Aenda – 
What regulates price are the conditions of purchase value of the components for formulation, in the event the product is formulated in the country or the price of the finished / formulated product that comes ready for use from abroad. All of these are dollarized, the commercialization and business conditions are different for each company.


AgriBrasilis – Will this impact product consumption?
Aenda – 
We believe not, because the product is well known and the producer understands the need to have it as a tool in crop management. We understand that risk mitigations and training programs can contribute to the safe application of the product and thus avoid intoxications and cases of drift to neighboring cultures, not affecting sales, but bringing more security to the applicator and final consumer.

¹IBAMA: Brazilian Institute of Environment and Renewable Natural Resources
²ANVISA: National Health Surveillance Agency
³MAPA: Ministry of Agriculture, Supply and Livestock
⁴IBGE: Brazilian Institute of Geography and Statistics
5ANDAV: National Association of Agrochemical and Veterinary Products Distributors