From single-chemical studies to multi-stressor approaches - how environmental toxicology is evolving to address complex planetary health challenges
Imagine a world where scientific detectives don't just look for one culprit at a crime scene, but investigate how multiple suspects interact to cause harm. This is the revolutionary shift happening right now in environmental toxicology and chemistry. For decades, scientists primarily studied how single chemicals affected our environment. Today, they're uncovering a much more complex story where chemicals, microplastics, climate change, and social factors combine in unexpected ways to impact ecosystem and human health 1 .
Traditional toxicology took a somewhat narrow view of environmental threats. Researchers would typically examine one chemical at a time, often at extremely high concentrations, to determine its effects on organisms. While this approach generated valuable data, it failed to capture the complex reality of environmental exposures where organisms simultaneously encounter countless natural and synthetic stressors 1 .
"Assessing (and managing) environmental quality requires understanding the actual or potential impacts of not only chemical but also physical and biological stressors" 1 .
The new approach examines how multiple stressors interact and amplify each other's effects. For example, rising temperatures can increase the toxicity of certain chemicals, while invasive species might introduce new pathogens that make native organisms more vulnerable to pollution 1 .
Traditional toxicology relied heavily on animal testing, which raised ethical concerns and often provided limited information about mechanisms of toxicity. Today, New Approach Methodologies (NAMs) are transforming the field through innovative techniques that are faster, cheaper, and more human-relevant 3 4 .
The United States Environmental Protection Agency (EPA) has been at the forefront of developing and implementing NAMs. Their CompTox Chemicals Dashboard provides public access to chemistry, toxicity, and exposure data for thousands of chemicals, helping researchers predict potential hazards without additional animal testing 3 .
Systems that mimic human organ functions for more accurate toxicity testing without animal subjects.
Automated testing of thousands of chemicals simultaneously to rapidly identify potential hazards.
AI-powered prediction of toxicity based on chemical structure and known biological interactions.
A compelling 2025 study published in Environmental Toxicology and Chemistry illustrates the sophisticated approaches now being employed in the field. Researchers Rosales and Medina critically examined methods for assessing biological effects of microplastics on mouse models, highlighting both advances and limitations in current approaches 8 .
The researchers conducted a systematic review of studies from 2021-2025, focusing on five key parameters often overlooked in earlier research:
The analysis revealed several important limitations in current microplastics research. Perhaps most significantly, most studies used particle properties that were not environmentally realistic—researchers often employed perfectly spherical microplastics of uniform size, while real-world microplastics vary dramatically in shape, size, and chemical composition 8 .
| Characteristic | Environmental Reality | Experimental Tradition | Impact of Discrepancy |
|---|---|---|---|
| Size distribution | Highly heterogeneous | Often uniform sizes | Over-/under-estimation of toxicity |
| Shape diversity | Irregular fragments, fibers, spheres | Mostly perfect spheres | Altered biological uptake and effects |
| Polymer types | Mixed compositions | Single polymer types | Missed synergistic effects |
| Concentration | Generally low but continuous | Often very high doses | Extrapolation challenges |
| Exposure duration | Chronic (lifelong) | Often acute/short-term | Missed cumulative effects |
Modern environmental toxicologists employ an array of sophisticated tools to detect and assess contaminants and their effects. Here are some key research reagents and methodologies advancing the field:
| Tool/Reagent | Primary Function | Application Example |
|---|---|---|
| Silicone wristbands | Passive sampling of personal chemical exposures | Monitoring pesticide exposure in pregnant women 2 |
| High-throughput screening assays | Rapid testing of thousands of chemicals | EPA's ToxCast program evaluating biological activity 3 |
| LC-MS/MS systems | Highly sensitive chemical detection | Identifying plastic-related chemicals in biological samples |
| Organ-on-a-chip devices | Mimicking human organ responses without animal testing | SensOoChip for connected heart and liver modeling 4 |
| CRISPR-based reporters | Detecting specific biological pathways affected by toxins | Identifying endocrine disruptors in chemical mixtures |
| Biosimilars | Reducing animal use in toxicity testing | In vitro-only packages for biosimilar development 4 |
The SensOoChip project recently received £1.6M in funding to integrate sensors into connected heart and liver organ-on-a-chip systems. This innovation allows for real-time multiparametric monitoring of chemical effects on human tissue models without using animals 4 .
Researchers are developing innovative wristband technologies that can detect hundreds of pesticides and other chemicals in personal environments. As one study demonstrated, these wristbands are particularly valuable for monitoring pregnant women's exposures to environmental toxicants 2 .
The future of environmental toxicology will increasingly involve artificial intelligence and computational approaches. As Martyn Smith, a key note lecturer at NIEHS explained, researchers are developing sophisticated tools like the NR-TOXPRED web server that can predict the activity of potentially toxic chemicals 7 .
Smith and colleagues have used computational tools to screen 57,000 chemicals for potential toxicity, identifying numerous environmental chemicals with high affinity for nuclear receptors that control cellular biology. Such large-scale screening would be impossible without advanced computational approaches 7 .
Another promising approach involves the key characteristics framework, which helps organize mechanistic data on how chemicals cause toxicity. Researchers have identified ten key characteristics of cancer-causing agents and similar lists for endocrine disruptors, neurotoxicants, and other harmful substances 7 .
Some characteristics—like oxidative stress and inflammation—appear common to many toxic substances ("umbrella characteristics"), while others are specific to particular organs or effects. This framework helps researchers prioritize chemicals for further investigation and develop targeted testing strategies 7 .
| Toxicity Type | Key Characteristics | Example Chemicals |
|---|---|---|
| Carcinogens | Genomic instability, oxidative stress, inflammation | Benzene, asbestos |
| Endocrine disruptors | Hormone receptor interaction, hormone synthesis alteration | Bisphenol A, phthalates |
| Metabolism disruptors | Insulin signaling alteration, lipid accumulation | PFAS, certain pesticides |
| Neurotoxicants | Neuronal inflammation, oxidative stress, neurotransmitter disruption | Lead, manganese |
| Reproductive toxicants | Steroidogenesis disruption, germ cell depletion | TDCPP, certain pesticides |
The expansion of environmental toxicology and chemistry from a narrow focus on single chemicals to a broad consideration of multiple stressors represents more than just a technical shift—it embodies a fundamental evolution in how we understand our relationship with the environment. This holistic perspective acknowledges that environmental health challenges are rarely simple and require integrated solutions that address chemical, physical, biological, and social dimensions.
As the field continues to evolve, embracing new technologies and collaborative approaches, it moves closer to its ultimate goal: not just identifying environmental threats but understanding them so completely that we can prevent harm before it occurs. In this expanded vision, environmental toxicology becomes not just a science of contamination, but a science of sustainable coexistence with our complex planet.
The journey from studying isolated chemicals to unraveling complex environmental interactions has been transformative. With the continued adoption of New Approach Methodologies, computational toxicology, and cumulative risk frameworks, environmental toxicology is poised to address tomorrow's environmental challenges with unprecedented sophistication and effectiveness.