Small and practically unknown outside laboratories, Parhyale hawaiensis, a crustacean less than one centimeter long, is helping Brazilian scientists answer one of today’s most urgent questions: what are the impacts of chemical contaminants on ecosystems? This is just one of the issues being investigated by Prof. Dr. Gisela de Aragão Umbuzeiro and her team at the Laboratory of Ecotoxicology and Genotoxicity (LAEG), at the School of Technology of the University of Campinas (Unicamp), in Limeira.
To better understand the research that has been bringing the laboratory into international prominence, Farmaco em Foco spoke with Prof. Gisela, postdoctoral researcher Dr. Natália de Farias, PhD candidate Ma. Gabriely Fernanda Groto Militão, master’s student Giovanna Rodrigues de Melo, and undergraduate research students Amanda Rocha Rodrigues, Jéssica Camila Miranda Cardoso, and Julya Cabral de Moura Tavares.
An international reference in ecotoxicology
Prof. Gisela is a biologist with a master’s and a PhD in Genetics from Unicamp. She worked for more than two decades at the Environmental Company of the State of São Paulo (Cetesb), an experience that helped bridge academic research with the real-world challenges of environmental quality management.
Over the course of her career, Gisela has become one of Brazil’s leading experts in environmental mutagenesis, ecotoxicology, and regulatory toxicology. Her work has contributed to understanding the impacts of chemical contaminants on living organisms and ecosystems.
This year, the researcher was once again ranked among the world’s most influential scientists in the field of Environmental Sciences, according to an international survey published by the academic platform Research.com.
She has participated in the development and review of national regulations and has been involved in international initiatives related to the environmental risk assessment of chemical substances. In addition, her research supports public policies related to water quality and environmental protection.
Since 2009, Prof. Gisela has coordinated the Laboratory of Ecotoxicology and Genotoxicity (LAEG) at Unicamp. In addition to investigating the effects of environmental contaminants, the laboratory also develops new methods for monitoring the risks associated with these substances.
Natural does not mean safe
As previously mentioned, Prof. Gisela works in a field called ecotoxicology, which studies how chemical substances and other pollutants affect living organisms and ecosystems. Within this context, she investigates a wide range of chemicals, but one group is the main focus of LAEG: dyes.
Dyes are present in clothing, cosmetics, food, packaging, and countless everyday products. Despite their widespread use, their environmental impacts still receive relatively little attention from the scientific community.
“Dyes have been with us for years and millennia, and it has never become fashionable to study them,” says Prof. Gisela. Over decades of work, her persistence in investigating the topic has made both her and LAEG an international reference in the field.
One of the research focuses is understanding whether certain dyes are toxic and how they cause damage to living organisms. These studies have gained increasing attention from industry, as interest in more sustainable alternatives continues to grow.
At first glance, so-called natural dyes may seem like a more environmentally friendly solution. However, results obtained by LAEG show that the reality is more complex.
In an international project called BioColour, which brought together researchers from Finland, the United States, and Unicamp, LAEG investigated the potential impacts of dyes derived from natural sources.
According to postdoctoral researcher Dr. Natália de Farias, two of the studied compounds (emodin and alizarin) showed concerning results. “They are highly toxic, highly mutagenic, and highly genotoxic,” she reports.
Genotoxic substances alter or damage an organism’s DNA. Mutagenic substances are a specific type of genotoxic agent that, by affecting DNA, produce mutations that can even be passed on to future generations.
These findings reinforce an important scientific message: natural is not synonymous with safe. After all, even snake and scorpion venoms are natural products, yet they remain dangerous.
Beyond toxicity, other factors must also be considered, such as how these dyes are produced. Extracting natural pigments on a large scale may require extensive cultivation areas, high resource consumption, and complex chemical processes.
For example, if a natural dye comes from a plant, several questions must be asked, as Dr. Natália notes: “Will I need a huge plantation? Is that feasible? Do the extraction processes use highly toxic or less toxic solvents?”
This concern is especially relevant for the textile industry, one of the largest water consumers in the world. During dyeing processes, large volumes of effluents containing dyes and other chemicals may be released into the environment.
In addition, in many cases, fixing dyes onto fabrics requires substances known as mordants. These are often metal-based compounds, which in themselves may act as environmental contaminants.
Dr. Natália comments: “Natural dye usually does not bind well to textile fibers, so you typically need a mordant. Is that better or worse than working with synthetic dyes?”
Therefore, understanding the ecotoxicological effects of these substances is essential to determine whether so-called “green” alternatives truly represent a more sustainable solution.
A small crustacean to answer big environmental questions
Understanding the effects of dyes and other contaminants on ecosystems requires the use of living organisms. LAEG has stood out for developing a new ecotoxicology tool: the small marine crustacean Parhyale hawaiensis, also known as an amphipod.
At first glance, the animal may seem like an unusual choice. Few people have even heard of it. However, it has characteristics that make it extremely valuable for scientific research.
For decades, Parhyale hawaiensis has been used in studies of evolution and developmental biology, meaning that a large amount of information is already available about its genetics, physiology, and life cycle.
According to Prof. Gisela, one of the species’ main advantages lies in its genetic richness. The crustacean has a surprisingly large genome, about 30% more DNA than humans. This makes it a species that offers a wide range of biological processes that can be studied in the laboratory.
The story of how the animal arrived at LAEG is quite curious and involves a degree of chance. Initially, the team was searching for another marine organism for their studies. During a sampling trip in Itanhaém, on the coast of São Paulo, researchers collected different species.
The target species did not survive. However, Parhyale hawaiensis did. At first, Prof. Gisela was unfamiliar with the small crustacean and had to identify it. “When I typed Parhyale hawaiensis into Google, I said: my God, this creature came because it really wanted to be studied,” she recalls humorously.
This discovery was especially important because the species naturally occurs in tropical regions, including the Brazilian coastline. This represents a significant advantage for national ecotoxicology research.
Most environmental tests were developed in countries with different climates, such as temperate regions. As a result, they often use organisms that do not fully reflect tropical ecosystem conditions. Parhyale hawaiensis, on the other hand, allows for more representative data for Brazil and other countries of the Global South.
In addition, the development of experimental methods with this species was designed from the beginning to follow New Approach Methodologies (NAMs), a set of approaches aimed at making research more ethical and sustainable.
From environmental model organism to drug screening
As the methods developed by LAEG advance, Parhyale hawaiensis is emerging as a promising tool for the rapid screening of chemical substances. In the past, other organisms were first used in a specific area of research and, over time, their applications were gradually expanded.
The zebrafish (Danio rerio), for example, was initially employed mainly in toxicity and embryonic development studies, but is now also widely used in the discovery and preliminary evaluation of new drugs. According to Prof. Gisela, Parhyale hawaiensis may follow a similar path.
Because Parhyale hawaiensis is a small organism, measuring only a few millimeters in length,it requires very small amounts of the chemical substances being tested. Think of it this way: the amount of anesthetic needed for a kitten is much smaller than the amount needed for an elephant. Now imagine applying that to a tiny animal like Parhyale hawaiensis.
This is extremely advantageous, especially considering that methodologies using Parhyale hawaiensis can also be applied to investigate whether new chemical compounds present toxic or even therapeutic effects, particularly when substances are rare, expensive, or available only in very limited quantities.
This advantage is precisely what is being explored by PhD researcher Ma. Gabriely Militão. She studies so-called New Psychoactive Substances (NPS). Commonly known as “synthetic drugs,” these molecules are designed to produce effects similar to those of known illicit drugs, but with small chemical modifications that often make them difficult to identify and regulate.
In many cases, these NPS are seized in extremely small quantities by law enforcement agencies. For methods that rely on other animals, such as rats and mice, the seized amounts would be insufficient to conduct any meaningful study.
Ma. Gabriely investigates the effects of two NPS representative of classes that have gained global attention. The first is eutylone, a synthetic cathinone, structurally related to amphetamines. The second is MDMB-4en-PINACA, a synthetic cannabinoid, meaning a compound similar to those found in cannabis.
Both NPS studied by Gabriely can act on the central nervous system and are associated with risks that are still poorly understood for both human health and ecosystems.
If the results are promising, Parhyale hawaiensis may become a valuable tool for the initial assessment of new chemical substances, helping researchers quickly identify potentially hazardous compounds.
The challenges of working with a millimeter-sized organism
Despite the enormous scientific potential of Parhyale hawaiensis, turning it into a model organism for ecotoxicology is not a simple task. Unlike species widely used in laboratories around the world, each new method must be developed, tested, and validated almost from scratch.
The first challenge begins even before the experiments. Although the laboratory is located in Limeira, in the state of São Paulo, Parhyale hawaiensis is a marine species. This means that researchers must reproduce, inside the laboratory, conditions similar to those found in the ocean.
“We have to bring the beach to Limeira,” summarizes Prof. Gisela. For the researcher, however, this effort is worthwhile because it reduces the need for continuous collection of animals from nature, which could even put a species at risk of extinction.
Another challenge arises from one of the features that makes the species so attractive: its small size. Investigating such tiny internal structures requires highly specialized techniques that are difficult for researchers to master.
In recent years, the LAEG team has advanced studies that once seemed impossible for an organism of this size, including DNA analyses of sperm cells and assessments of blood-like cells.
“When you look at the size of the organism, you think: it’s impossible,” says Gisela. “These are challenging things even when I just say them, imagine actually doing them.”
Within this effort to expand the available tools for Parhyale hawaiensis, master’s student Giovanna Melo is developing a project aimed at improving methods for assessing cellular and genetic damage in the species.
The proposal includes analyzing the expression of genes involved in DNA repair. This is important because it indicates how the organism is able to correct damage in its genetic material, helping to understand its capacity to resist or recover from exposure to toxic substances.
Giovanna is also working on establishing cell cultures of Parhyale hawaiensis hemocytes. Hemocytes are cells present in the hemolymph (“blood”) of these organisms, with functions similar to immune defense cells in other animals. Culturing these cells would allow researchers to investigate how this defense system responds to contaminants at the cellular level.
Understanding what happens inside the organism
Traditionally, ecotoxicology studies have focused on more visible effects, such as mortality. While this is essential for environmental risk assessment, these outcomes tell only part of the story.
“It’s not enough to just protect the organism if it ends up with impaired behavior and gets preyed upon all the time,” explains Gisela.
In this context, the laboratory has been investing in tools to investigate neurotoxicity in Parhyale hawaiensis. The goal is to understand how different chemical substances can affect the nervous system and, consequently, the behavior of organisms.
According to undergraduate researcher Amanda Rodrigues, who is developing a project in this area, the study is quite ambitious. Amanda aims to evaluate everything from brain and antenna structures to behavioral changes in Parhyale hawaiensis.
This combination of approaches allows the detection of effects that would be invisible in traditional assessments. An organism may survive exposure to a chemical substance but still have difficulty finding food, escaping predators, or reproducing properly. Over time, these changes can compromise entire populations.
Surviving does not mean being healthy
Neurotoxicity studies developed at LAEG show that assessing only organism survival is not enough to understand the real impacts of environmental contaminants.
This is precisely the line of research in which LAEG investigates the effects of 6PPD-quinone, an emerging contaminant that has raised increasing concern among scientists and regulatory agencies worldwide.
This substance is formed from the transformation of 6PPD, an additive widely used in tire manufacturing. As tires wear down during use, microscopic particles are released onto roads. In contact with atmospheric ozone, 6PPD is converted into 6PPD-quinone, which can be carried by rainwater into rivers, streams, and other bodies of water.
International concern about this contaminant increased after it was discovered that it can cause mortality in some salmon species even at extremely low concentrations.
However, researchers believe that mortality is only part of the story. Among LAEG’s findings is a pioneering discovery: evidence that 6PPD-quinone has mutagenic potential, meaning it can induce genetic mutations.
“We were the first group to demonstrate the mutagenicity of 6PPD-quinone,” highlights Prof. Gisela.
One ongoing study is now investigating how this contaminant affects the immune system and embryonic development of Parhyale hawaiensis. The project is led by undergraduate researcher Jéssica Cardoso.
The strategy includes exposing adult organisms to the substance and monitoring their offspring. This allows researchers to investigate whether the effects of contamination can be transmitted from parents to offspring, something preliminary results suggest may be occurring.
These findings may become particularly important in the coming years. Given the evidence of toxicity of 6PPD-quinone, tire manufacturers are already beginning to search for alternatives to 6PPD. When new substitutes are developed, it will be essential to carefully evaluate whether they truly represent a safer option for the environment.
From the laboratory to the sea
If studies with contaminants such as 6PPD-quinone help us understand the effects of specific substances on aquatic organisms, another research front at LAEG addresses an even more complex question: what happens when thousands of different compounds reach the environment simultaneously?
This issue is particularly relevant in Brazilian coastal regions, where a significant portion of domestic sewage is discharged into the ocean through so-called submarine outfalls. These structures consist of long pipelines installed on the seafloor that transport and release waste several kilometers offshore.
“We talk a lot about sanitation, but the so-called advanced solution for much of the coastline is to send sewage into the sea. The beach becomes suitable for bathing, but that does not mean the problem has disappeared,” says Prof. Gisela.
Although wastewater undergoes treatment before discharge, various compounds may still be present. For this reason, PhD candidate M.Sc. Karin Cristine Baudalf has been developing studies that expose Parhyale hawaiensis in cages placed in areas affected by submarine outfalls.
This method is called active biomonitoring. Unlike conventional analyses, which evaluate only water or sediment, this approach allows researchers to observe what actually enters organisms and accumulates in their tissues.
Initial results have revealed important findings. In some cases, chemical substances were detected in organisms even when they were not found in water samples collected at the site.
“We observe compounds that appear in the little body of the animal but not in the water,” says Gisela. “This shows the importance of active biomonitoring.”
From victims of contamination to heroes
While studies involving submarine outfalls show how contaminants and residues can accumulate in Parhyale hawaiensis, another research line at LAEG seeks to address the problem at its source: finding new ways to reuse waste before it reaches the environment.
The project investigates an unusual application for Parhyale hawaiensis: transforming waste from the textile industry into high-value raw material. Tons of waste are generated daily during the manufacturing and disposal of clothing. Among them are cotton fibers, which often end up in landfills or aquatic environments in the form of microfibers.
Although cotton is a natural and biodegradable material, this does not mean that its degradation occurs quickly. Chemical treatments applied during textile processing can increase its persistence in the environment, making its disposal an environmental challenge.
A little-explored characteristic of Parhyale hawaiensis may offer a solution to this problem. Studies show that this organism can produce enzymes capable of degrading cellulose, the main component of cotton fibers. In other words, Parhyale hawaiensis could “eat” these fibers.
The hypothesis is simple but ambitious: what if this organism could be used to consume textile waste and transform it into a useful material?
This is the question guiding the undergraduate research project of student Julya Tavares. She is investigating whether Parhyale hawaiensis can survive, grow, and reproduce when fed diets containing cotton fibers.
The body of Parhyale hawaiensis contains a very interesting compound: chitin. From it, chitosan can be produced, a material widely used in pharmaceutical, biomedical, cosmetic, and environmental applications. Thus, chitin could be extracted from animals grown on cotton fiber-based diets and then used for different purposes.
The researcher emphasizes that large-scale cultivation of the organism is not merely a theoretical possibility. In other countries, Parhyale hawaiensis is already produced for use as fish feed.
In addition, undergraduate researcher Amanda Rodrigues is also investigating how dyes present in cotton fibers may cause toxic effects in Parhyale hawaiensis. After all, if this organism can feed on these fibers, this represents another pathway through which dyes may pose a risk.
Science to protect what sustains life
From dyes to emerging contaminants, from submarine outfalls to the search for sustainable solutions for textile waste, the research developed at LAEG converges toward a single concern: understanding how human activities are transforming ecosystems and how these impacts may, in turn, affect society itself.
Studying environmental issues is also studying quality of life. After all, ecosystem health is directly linked to food security, water supply, coastal economies, and human well-being.
“We are forgetting the air we breathe and the water we drink,” warns Prof. Gisela.
In this context, scientific research plays a fundamental role. By revealing invisible risks, developing new monitoring tools, and proposing more sustainable solutions, studies such as those conducted at LAEG help build the knowledge needed to protect not only species and ecosystems, but also the natural resources on which society itself depends.
The research presented in this article was funded by FAPESP (grant numbers 23/10693-5, 25/00020-9, 25/07242-7, 25/06744-9, 24/20219-1, 24/23631-0, 25/17338-1, 25/10258-2, 25/15626-0, and 24/20276-5).
This article was produced with support from the São Paulo Research Foundation (FAPESP), Brazil. Grant number 25/17158-3. The opinions, hypotheses, conclusions, or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of FAPESP.
For more information:
Prof. Gisela’s YouTube channel
Master’s dissertation discussing the use of Parhyale hawaiensis (DOI: 10.47749/T/UNICAMP.2015.945921)
Dissertation on genotoxicity in Parhyale hawaiensis (DOI: 10.47749/T/UNICAMP.2024.1402283)
Natural dyes (DOI: 10.1016/j.chemosphere.2023.140174)
Alizarin (DOI: 10.1002/em.70046)
Emodin (DOI: 10.1016/j.fct.2024.114749)
Chronic toxicity in Parhyale hawaiensis (DOI: 10.1016/j.marpolbul.2023.115375)
6PPD-quinone (DOI: 10.1002/em.22560)
CICTA2021 conference and environmental discussions (DOI: 10.1016/j.scitotenv.2023.162436)
Written by:
Mia Schezaro Ramos
Pharmacist. Ph.D. in Pharmacology. Science journalist, illustrator, trans, Nintendo enthusiast, K-pop fan, and dependent on physical exercise to stay sane.