LD50, toxicity classes and safe pesticide handling
What LD50 and LC50 mean, WHO and GHS hazard classes, ADI, MRL and pre-harvest intervals, formulation toxicity sums, and safe handling of pesticides.
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Pesticides are designed to kill living things, so some are also dangerous to people, livestock, bees and wildlife. Each year many farm workers are poisoned, mostly in low- and middle-income countries, through careless handling, inadequate protection, or storage of highly toxic products in the home. Understanding how toxicity is measured, what the hazard classes and label warnings mean, and how residue limits protect consumers is part of every plant protection course, and part of using pesticides responsibly.
Hazard, exposure and risk
- Toxicity (hazard) is the inherent ability of a substance to cause harm.
- Exposure is how much reaches a person or organism, by mouth, skin or breathing.
- Risk depends on both: a very toxic product handled in a closed system with full protection can be lower risk than a moderately toxic one splashed on bare skin every day.
Most poisonings of farmers happen through the skin during mixing and spraying, and through ingestion, accidental or deliberate.
Measuring acute toxicity
- LD50 (median lethal dose): the single dose, in milligrams per kilogram of body weight, that kills half of a group of test animals, usually rats. The concept was introduced by J. W. Trevan in 1927. It is measured for oral and dermal exposure.
- LC50 (median lethal concentration): the concentration in air (for inhalation) or water (for fish and aquatic invertebrates) that kills half the test organisms over a set time.
The lower the LD50, the more toxic the substance. A pesticide with an oral LD50 of 5 mg/kg is a thousand times more acutely toxic than one with 5,000 mg/kg.
Modern testing methods use fewer animals and estimate ranges rather than precise LD50 values, but the classification system is the same.
Hazard classes
| WHO class | Description | Oral LD50 (rat, mg/kg) |
|---|---|---|
| Ia | extremely hazardous | less than 5 |
| Ib | highly hazardous | 5–50 |
| II | moderately hazardous | 50–2,000 |
| III | slightly hazardous | over 2,000 |
| U | unlikely to present acute hazard | 5,000 or higher |
The WHO classes are linked to the Globally Harmonized System (GHS) acute toxicity categories 1 to 5, which also set pictograms (such as the skull and crossbones) and signal words ("Danger" for the most hazardous, "Warning" for others) printed on labels. Some countries also use coloured label bands.
The FAO and WHO International Code of Conduct on Pesticide Management (2014) recommends phasing out highly hazardous pesticides, including all WHO class Ia and Ib products, where they cannot be used safely. Sri Lanka's bans on the most toxic pesticides from the 1980s onward were followed by a large fall in deaths from pesticide self-poisoning without a fall in agricultural output, an example that has influenced policy in other countries.
Chronic toxicity and residues
Long-term, low-level exposure is assessed differently:
- NOAEL (no-observed-adverse-effect level): the highest daily dose in long-term animal studies that causes no adverse effect.
- ADI (acceptable daily intake): usually the NOAEL divided by a safety factor of 100 (10 for differences between animals and people, 10 for differences among people), in mg per kg body weight per day.
- ARfD (acute reference dose): the amount that can be eaten in one day without appreciable risk.
- MRL (maximum residue limit): the highest legal residue level in a food, set from field trials with good agricultural practice and checked against the ADI. International MRLs are set by the Codex Alimentarius; countries set their own as well, and exports must meet the importer's limits.
- PHI (pre-harvest interval): the minimum days between the last spray and harvest so residues fall below the MRL.
- REI (re-entry interval): the time before workers may re-enter a treated field without protection.
Formulation toxicity and an acceptable daily intake
Toxicity of a formulated product. WHO classes formulations from the LD50 of the active ingredient and its concentration:
LD50 of product = LD50 of active ingredient × 100 ÷ per cent active ingredient.
An insecticide has an oral LD50 of 100 mg/kg (class II). As a 2.5 per cent granule:
- Product LD50 = 100 × 100 ÷ 2.5 = 4,000 mg/kg, class III.
As a 50 per cent concentrate, the product LD50 is 100 × 100 ÷ 50 = 200 mg/kg, still class II but twenty times more hazardous to handle than the granule. Dilution in the spray tank reduces the hazard further, which is why handling the concentrate during mixing is the riskiest step.
Acceptable daily intake. A long-term study finds a NOAEL of 5 mg/kg per day. With a safety factor of 100:
- ADI = 5 ÷ 100 = 0.05 mg/kg per day.
- For a 60 kg adult: 0.05 × 60 = 3 mg per day, a figure that regulators compare with estimated intake from all foods at their MRLs.
Signs of poisoning
Symptoms depend on the class. Organophosphates and carbamates inhibit acetylcholinesterase, causing sweating, salivation, small pupils, vomiting, muscle twitching, breathing difficulty and, in severe cases, death; treatment is with atropine and, for organophosphates, sometimes oximes under medical care. Pyrethroids can cause tingling skin and, at high doses, nerve symptoms. Paraquat causes severe, often fatal lung damage.
First aid: move the person away from exposure, remove contaminated clothing, wash skin with plenty of water, rinse eyes, do not induce vomiting unless the label says so, and seek medical help immediately, taking the label or container.
Safe handling
- Read the label before buying, mixing and spraying.
- Wear the personal protective equipment the label requires: chemical-resistant gloves, long sleeves and trousers, boots, eye protection and, for some products, a respirator. Gloves matter most.
- Mix outdoors or in ventilated areas, measure carefully, and avoid splashes.
- Do not eat, drink or smoke while handling; wash afterwards.
- Store pesticides locked, in original containers, away from food, feed, children and animals.
- Triple-rinse empty containers into the spray tank, puncture them, and return them through collection schemes where available; never reuse them for food or water.
- Respect PHIs, REIs, buffer zones and bee warnings.
Key points
- Risk = hazard × exposure; most farm poisoning happens through skin contact and ingestion.
- LD50 (mg/kg) and LC50 measure acute toxicity; a lower value means more toxic.
- WHO classes: Ia below 5, Ib 5–50, II 50–2,000, III above 2,000, U 5,000 or more (oral, rat).
- Product LD50 = a.i. LD50 × 100 ÷ per cent a.i.
- ADI = NOAEL ÷ 100; MRLs, PHIs and REIs protect consumers and workers.
- The FAO/WHO Code of Conduct recommends phasing out highly hazardous pesticides.
What the exams ask
- School-leaving and entrance papers: what LD50 means, toxicity classes and label warnings, and safety precautions.
- Degree and research-fellowship entrances: LD50 and LC50, WHO and GHS classification, formulation toxicity calculations, NOAEL, ADI, MRL, PHI, and symptoms and antidotes.
- Professional and regulatory examinations: risk assessment, residue monitoring and export compliance, international conventions, and stewardship.
Described in general terms: the kind of examination, not a past paper. Laisha never reproduces exam questions.
Questions people ask
Does a high LD50 mean a pesticide is completely safe?
No. LD50 measures only acute toxicity by one route. A product can have low acute toxicity but cause harm through long-term exposure, to the environment, or to bees and fish.
Why do labels give a pre-harvest interval?
It is the time needed for residues to fall below the legal limit after the last spray. Harvesting earlier can leave residues above the MRL and lead to rejected produce.
What should I do with leftover spray mixture?
Plan to mix only what you need. Small leftovers can usually be applied to the labelled crop within the label rate; never pour them into drains, streams or ditches.
Sources
- World Health Organization. The WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classification, 2019 edition. WHO, 2020.
- FAO and WHO. The International Code of Conduct on Pesticide Management. FAO, Rome, 2014.
- United Nations. Globally Harmonized System of Classification and Labelling of Chemicals (GHS), 10th revised edition. UN, 2023.
- Gunnell, D. et al. "The impact of pesticide regulations on suicide in Sri Lanka." International Journal of Epidemiology 36, 1235–1242 (2007).
- Eddleston, M. et al. "Management of acute organophosphorus pesticide poisoning." The Lancet 371, 597–607 (2008).
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