The Skinny on Brazil’s New Dermal Studies

The South American country is the first to adopt a mandatory risk assessment approach for these safety studies, and other Latin American countries will likely follow 

Most, if not all, of the agrochemical products registered in the US and Europe, along with topical medications, undergo dermal absorption studies. Dermal absorption studies provide critical evidence that agencies use to determine product safety when it comes into contact with skin. 

But a paradigm shift in dermal testing is also underway in the Southern Hemisphere, in Brazil, which is one of the leading markets for agrochemical companies, is taking a bolder approach to assessing systemic exposure of agrochemicals once they come in contact with skin. Not only will this lead to more transparent and harmonized decisions by regulators and better public health, but it will also bring Brazil in sync with its US and European counterparts. But it is not without challenges for industries doing business in Brazil. Check out this helpful Q&A for perspective on what this all means for the industrial and agrochemical industries.

What are dermal absorption studies, and why do we need them?

Dermal absorption studies are conducted to estimate how much of the substance penetrates human skin when a substance or the products containing it are handled by humans during occupational exposure. The resulting dermal absorption values, usually expressed as a percentage of the applied dose, are used to calculate the internal dose to which humans may be exposed during a normal working shift. This internal exposure is, in turn, used to estimate the risk the substance may pose to human health by comparing it with the safe levels derived from its toxicological properties. 

How are they typically conducted? 

Dermal absorption studies are usually conducted in vitro using human skin obtained from human donors following surgical procedures (e.g., breast reduction). Following an integrity test, a defined amount of substance is applied to the surface of a skin sample, separating the two chambers (a donor chamber and a receptor chamber) of a diffusion cell to mimic human exposure for a certain period (usually 6 to 8 hours for agrochemicals). Absorption of a test substance is usually measured for 24 hours by the analysis of the fluid from the receptor chamber (receptor fluid) and the distribution of the test substance in different skin layers.

CRL personnel have been conducting these studies for over 35 years, and our dermal absorption team brings more than 200 years of combined experience in testing dermal absorption of (agro-)chemicals across various formulation types, using both radiolabeled and non-radiolabeled test substances. In addition to testing the ‘standard’ concentrate formulation and relevant dilutions thereof, dermal absorption from so-called dried surface/foliar residues can be studied, which is considered a (more) relevant exposure scenario for re-entry workers. (Acceptability of this approach is still under discussion within the EU).

Brazil, the latest country/region to tighten regulations around dermal absorption, is shifting from hazard-based to mandatory risk-based assessment. What factors are driving this change, and why now?  

Brazil has recently undergone a major paradigm shift in agrochemical regulation, moving from a predominantly hazard-based system to a modern, risk-based framework. This framework was introduced by Law 14.785/2023, which now requires addressing the exposure of operators (people applying pesticides to crops), workers (people entering the treated crops for weeding, harvesting etc.), residents (people living near the treated crop fields), and bystanders (people present during the pesticide application). The approach is thought to lead to more transparent and harmonized decisions by regulators, while achieving higher levels of human health protection in real-life exposure conditions and, at the same time, aligning Brazilian regulations with those of its EU and USA counterparts. This, in turn, is thought to facilitate trade and market access, improve regulatory credibility, and reduce international discrepancies for multinational companies. The approach represents a shift in paradigm from “Is this substance intrinsically dangerous?” to “Can the substance be used safely under realistic conditions?”

Are other South American countries contemplating the same? 

Yes, several South American countries have indicated that they are or will be modernizing their regulatory frameworks for plant protection products; among them are Argentina, Colombia, Costa Rica, Ecuador, and Mexico. The objectives are better alignment with international standards, increased use of risk assessment, and improved health and safety protection.

The recent moves by Brazil should bring the country more into alignment with Europe and the US, which have had pretty strict dermal absorption standards for quite some time. But will it also make testing for pesticides and other products more complicated, too?

For companies that already have plant protection products registered on the EU or USA markets, the change in  the Brazilian regulatory framework should not present unexpected challenges, since the risk assessment approach has been at the cornerstone of the authorization process in these regions for a substantial time already. Thus, companies are likely to already have the necessary dermal absorption data. However, for the registration of the new products, the companies must make sure that they conduct necessary dermal absorption studies, develop appropriate exposure scenarios, and use modeling tools recognized by Brazilian authorities to perform risk assessment for the operators and workers. 

What are some of the major questions companies have now regarding the registration of chemicals in Brazil? 

Companies registering agrochemicals in Brazil are currently facing a period of regulatory uncertainty and adaptation, driven by the combination of Law 14.785/2023 and ANVISA RDC 998/2025. This brings a whole bunch of questions, in particular about the applicability of the new law (whether it will apply to only new registrations, or also to existing registrations); the transition timelines for the submission of new risk assessment calculations; the acceptability of existing dermal absorption data; and the experience with the exposure models accepted by Brazilian authorities.

Frank Toner, Wilfred Maas, and Ira Kovel are Charles River SMEs in dermal absorption studies. Frank is Manager of Dermal Services based in Tranent, Wilfred Maas is a Study Director in ‘s-Hertogenbosch, and Ira Koval is Head of Regulatory Affairs, also based in 's-Hertogenbosch.