# Applied toxicity of chemicals
## Background

The concept of applied toxicity simply uses the fact that the toxicity of chemicals can span several orders of magnitude, i.e. while the herbicide dichlorprop is toxic to terrestrial plants at ~30 mg/ha, the herbicide thiobencarb is only toxic at a concentration of ~30,000 mg/ha and thus is about three orders of magnitude less toxic. Applied toxicity seeks to consider the toxicity of chemicals in order to evaluate how changes in their use affects environmental risks spatio-temporally. It is also used to evaluate how the application of chemicals compares between different geographic entities, i.e. countries or regions. Often evaluations of the changes in the use of chemicals refer to the amount (or mass) of chemicals, yet do not consider the changes in toxicity and thus the potential biological effect. While information on changes in used amounts of chemicals are often relatively easy to obtain, they are of very little use in terms of the potential environmental or human health impact.
The present article uses the example of pesticides, for which applied toxicity has been evaluated recently in a number of contexts. Pesticide use data separated for the different compounds and years are often available and reported by governmental institutions at the national level.

### Total applied toxicity

The Total Applied Toxicity (TAT) of pesticides can be calculated simply by multiplying the inverse acute or chronic toxicity value (here regulatory threshold level, RTL) of each pesticide compound with its annual use (m, kg * yr$^{-1}$) and summing up the results for all pesticide compounds under consideration.
    $TAT=\sum {\tfrac {m}{RTL}}$
The Total Applied Toxicity is a dimensionless estimate, which can be used for comparisons of relative changes over time or of differences between different groups of chemicals (i.e. insecticides, herbicides, fungicides). The absolute Total Applied Toxicity values should be interpreted with great care, since they strongly depend on the input variables used in the calculation. Total Applied Toxicities can be calculated for different species groups (e.g. plants, pollinators or rats as a surrogate species for human toxicity).
The toxicity is a key characteristic of all chemicals which have the potential to get in contact with any form of living organisms. Rough estimations list almost one million chemicals (Ref. Chemical Dashboard) as chemical of potential environmental concern. Environmental health (see also ecotoxicology) deals with the effects of chemicals on aquatic (freshwater, groundwater, marine) or terrestrial (all forms of terrestrial habitats) organisms, including invertebrates (e.g. arthropods, insects, crustaceans, molluscs) and vertebrates (e.g. fish, amphibians, reptiles, birds and mammals). Human health (see also toxicology) is concerned with effects of chemicals on human health and their well-being.

### Toxicity

Toxicity is a substance-specific characteristic measured in ecotoxicological or toxicological tests. In their simplest form, these tests come up with a value for a given chemical that characterises how toxic this chemical is to a certain organism under specific conditions and within a specified time frame. For example, the pesticide chlorpyrifos causes mortality to 50% of a group of tested fish specimens (here rainbow trout) within a time period of 96 h at a concentration of 0.4 mg/L, the 96-LC$_{50}$ is 400 µg/L (LC = lethal concentration). These kind of acute (short term, i.e. up to 96 h) toxicity values (e.g. LC$_{50}$, EC$_{50}$) exist for a tremendous number of chemicals and various aquatic or terrestrial species. For many groups of chemicals (e.g. pesticides, heavy metals or pharmaceuticals) ecotoxicological or toxicological test results do exist, since they are required for risk assessment and registration of use of these kind of chemicals. Toxicity values for mammals such as rat or mice are regularly used to infer to potential human health effects. It is important to keep in mind that a lower toxicity value indicates a higher toxicity, i.e. a LC$_{50}$ of 1 µg/L indicates much higher toxicity compared to a LC$_{50}$ of 1000 µg/L. The advantage of acute toxicity values is that they can be used to compare substances with each other regarding their toxicity to various species groups. The disadvantage is however, that the results of simple acute toxicity tests do not fully represent the complexity of ecosystems and biological responses.

## Environmental health
### Aquatic environmental health

Chemicals enter aquatic ecosystems via point sources (e.g. industrial effluents, wastewater treatment plant inlets) or nonpoint (diffuse) sources (e.g. mining sites, agricultural fields or atmospheric deposition). Due to their position in the landscape as recipient ecosystems, chemicals often end up in aquatic surface waters, groundwater or marine ecosystems either in the water phase, sediment or biota. For instance, due to the widespread application of pesticides in agricultural and urban environments, transport processes such as run-off during strong rainfall events, spray-drift, drainage, direct applications or wastewater entry from the cleaning of spray equipment result in contamination of connected water bodies.
Key aquatic organism groups potentially affected by chemicals and their applied toxicity are primary producers (algae, higher plants), consumers (aquatic invertebrates, fish) or microbial organisms (fungi and bacteria present e.g. as biofilms). Together they represent the aquatic biodiversity, but at the same time provide various ecosystem services, such as provision of biomass via photosynthesis, mineralisation of biomass, self-purification, food provision etc. The extent to which the biodiversity or ecosystem functions are affected depends on both the toxicity and the applied amounts of chemicals which determine the potential exposure of aquatic ecosystems, i.e. the concentrations and frequency of occurrence of chemicals therein.
In order to asses the aquatic environmental health, applied toxicity can be calculated for fish (e.g. rainbow trout, carp or medaka), aquatic invertebrates (e.g. aquatic insect larvae, crustaceans or snails) or aquatic plants (e.g. algae, macrophytes).

### Terrestrial environmental health

Chemicals enter terrestrial ecosystems via numerous pathways both intentional and unintentional, such as waste disposal, pesticide applications, sewage sludge fertilisation or accidental spills. Therefore, their concentrations in terrestrial environments depend on the process and applied amounts of chemicals. Resulting environmental harm is characterised by toxicity of chemicals towards key terrestrial organisms (e.g., mammals, vertebrates, higher plants, insects or other invertebrates) compared to their applied amounts. Importantly, toxic effects are (similarly to aquatic environments) manifold, ranging from short term (acute) to long term (chronic) effects and they act simultaneously if multiple chemicals are present. Therefore, the combination of applied amounts and species-specific toxicities provides estimates of the potential harm towards terrestrial ecosystems or species groups therein.
Species groups, and the biodiversity they represent, serve different roles in ecosystems, therefore applied toxicities can impact the provision of ecosystem services (pollination, nutrient processing, carbon storage), but also other organism that are connected to them ecologically. For instance, the reduction of flower intensities due to the widespread application of some herbicides, affects multiple processes or services:
* Seed production and dispersion of affected plants
* Carbon fixation rate of affected plants
* Reduced pollen and nectar production, resulting in lower food availability for pollinating insects
The applied toxicity also directly affects soil health, as applied pesticides or other contaminants (e.g. pharmaceuticals and heavy metals via sludge) are actively applied there. Microbial processes (e.g., nitrification rates) can be altered or soil invertebrates (earthworms, mites, insects) can be impaired, which provide important ecosystems services to farmers:
* Bioturbation of soils
* Aeration of soils
* Predation of pests
In order to asses the terrestrial environmental health, applied toxicity can be calculated for arthropods excluding pollinators (e.g. beetles, moths, butterflies), pollinators (e.g. bees or bumble bees), terrestrial vertebrates (e.g. rats or mice) or terrestrial plants (e.g. flowering plants).

## Human health

Humans are also exposed to various chemicals, e.g. via inhalation, food, or dermal uptake following direct contact. Applied toxicities of chemicals also aid in identifying potential human health risks. Manual pesticide application is one pathway in which operators can be exposed to high doses of toxic chemicals, for instance organophosphorus insecticides which act on the central nervous system (see AChE inhibition). Deriving applied toxicities for specific agricultural crops aids in identifying hot-spots were operator safety training can reduce occupational and accidental human poisonings.
In order to asses the human health, applied toxicity can be calculated for terrestrial mammals, such as rat or mice, which serve as surrogate species to assess the toxicity to humans.

## Data requirements

The minimum set of data to calculate the applied toxicity, using the example of agricultural pesticide use in a country, is pesticide use and toxicity data.
The pesticide use data should e.g. be represented by the annual application of individual pesticide compounds. More generic data such as applied amounts of herbicides or insecticides are not sufficient. Some countries have made substance-specific use data for a number of years publicly available, there might, however, be many more examples of national pesticide use (please add them here!).
The pesticide toxicity data should be acute toxicity values for the groups of species concerned (aquatic, terrestrial, humans). There are various databases available which list acute toxicity data for pesticides. Instead of the (acute) toxicity value itself, the calculation of applied toxicity can also be done using Regulatory Threshold Levels, i.e. toxicity values which have been divided by an assessment factor to account for uncertainties as a result of the fact that these toxicities are the result of standard laboratory tests. Assessment factors are commonly applied during the risk assessment of chemicals, or more specifically of pesticides. A list of RTL values for several hundred pesticides, which can be used to calculate applied toxicities of pesticides for eight different groups of species, can be found here.

## Learning tasks

In the LibreOffice Calc table resp. XLS-table you find for two different countries data on the changes in annual agricultural pesticides (herbicides and insecticides) use (tons per year) over time for a number of pesticides as well as substance specific Regulatory Threshold Levels (toxicity data divided by the respective assessment factor) for aquatic invertebrates, terrestrial plants and terrestrial vertebrates.
* Plot the changes in use and Total Applied Toxicity (separately for aquatic invertebrates and terrestrial plants) over time for all pesticides together as well as specifically for each class herbicides and insecticides.
* What are the differences in changes of use and applied toxicity over time?
* How are pesticide class and species group data related to each other?
* What can you infer for the potential risks to aquatic or terrestrial environments or to human health?