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Rotenone: Mechanism, Hazards and Lab Handling Limits

What rotenone is, how it inhibits mitochondrial complex I, and how its hazard classifications and exposure limits differ by source.

Written and maintained by CASRAI Editorial Board

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Rotenone is a naturally derived pesticide and a classic mitochondrial complex I inhibitor. It blocks the respiratory chain at the start of electron transport, which is why it is used as a fish-management tool in fisheries and as a reagent in mitochondrial research. It is acutely toxic as a concentrated powder, and its hazard labels differ by database. This page is general reference, not medical or regulatory advice.

What is rotenone?

Rotenone (CAS 83-79-4) is described by NIOSH as a colorless to red, odorless crystalline solid. Its two best-known uses sit far apart: wildlife agencies apply it to manage fish populations, and laboratories use it to shut down complex I of the mitochondrial electron transport chain in cells and isolated mitochondria. The two settings involve very different concentrations and exposure routes, so facts from one do not transfer to the other.

Rotenone mechanism of action

The WHO Poison Information Monograph cited in PubChem states that rotenone inhibits the mitochondrial respiratory chain between NAD(H) and flavin, which stops NADH from being reoxidised. The Krieger Handbook of Pesticide Toxicology (2nd ed.) identifies complex I as the primary site and describes two binding sites, with the 23 kDa PSST subunit important for high-affinity binding.

That is the reason it appears in respirometry. In a mitochondrial stress test, a complex I inhibitor is added alongside a complex III inhibitor to remove mitochondrial respiration and reveal non-mitochondrial oxygen consumption. See the Seahorse assay guide for the full injection sequence, and mitochondria and function for the underlying biology.

How toxic is rotenone?

Toxicity depends on dose and route. The Alaska Department of Fish and Game (ADF&G) health-effects page reports that the WHO rates rotenone as moderately hazardous, that inhaling the concentrated powder is the most direct risk, and that the EPA concluded use according to the label does not pose an unreasonable risk to human health or the environment. The same page reports no evidence of birth defects, reproductive effects, mutations or cancer.

Rotenone and Parkinson’s disease

ADF&G states that high exposure may damage nerve cells, but that rotenone has not been shown to cause Parkinson’s disease; it describes animal studies as inconclusive and their exposure routes as not relevant to fishery use. Neurotoxicity research on rotenone exists in the peer-reviewed literature, but that research does not establish a cause for any individual’s condition.

Hazard and exposure values by source

The same substance carries different classifications and limits depending on which database or agency you read. This is the main thing to check before relying on any single label or number.

Source What it states
PubChem GHS summary Signal word Danger; pictograms GHS06 and GHS09 (some notifiers also GHS07 and GHS08)
EU CLP / ECHA (as listed in PubChem) H301, H315, H319, H335, H400, H410
NITE-CMC, Japan (as listed in PubChem) Adds H300, H310, H370, H372, H373 to the set above
NIOSH REL 5 mg/m³ time-weighted average
OSHA PEL 5 mg/m³ time-weighted average
ACGIH TLV (1993-1994 listing on NIOSH page) 5 mg/m³ time-weighted average
NIOSH revised IDLH 2,500 mg/m³

The IDLH figure needs a caveat. NIOSH states that no inhalation toxicity data exist for rotenone; the value is based on an estimated fatal human oral dose of about 200 g (Lehman 1949) and on being 500 times the REL and PEL. It is a respirator-selection benchmark, not a measured inhalation threshold. For the meaning of H-codes and pictograms see GHS classification of chemicals, and for reading the supplier document that applies to your own stock see how to read a safety data sheet.

Fishery use versus laboratory use

  • Fishery use: ADF&G notes that applicators are certified in Alaska and that label restrictions cover drinking water and contact. It reports EPA figures of under 90 ppb as safe for human contact and under 40 ppb as safe for drinking water.
  • Laboratory use: the hazard that matters is the concentrated solid or stock solution, which is where the SDS classification and the occupational limits above apply. Handling, storage and disposal instructions come from the supplier’s SDS and your institution’s plan; see OSHA SDS requirements and the chemical hygiene plan entry.

Common misunderstandings

  • “Safe at fishery concentrations means safe on the bench.” The ppb values above refer to treated water, not to powder or stock solutions.
  • “Every database gives the same hazard label.” As the table shows, the H-code set differs between ECHA and NITE-CMC entries.
  • “A high IDLH means low risk.” The value rests on an oral estimate and no inhalation data, and it is a respirator-selection figure, not a safe level.

Frequently asked questions

What is rotenone?

A naturally derived pesticide and complex I inhibitor, used in fish management and in mitochondrial research.

How much does rotenone cost?

The sources used here state no price. Cost varies by supplier, grade and pack size, so quotes should come from the supplier directly.

How toxic is rotenone?

The WHO rates it moderately hazardous, per ADF&G, and GHS entries carry the Danger signal word. Inhaling the concentrated powder is the most direct risk. See the table above for classification differences.

Can you eat fish killed by rotenone?

ADF&G states that eating such fish is not considered harmful, but that the EPA does not recommend it because no tolerance (residue level) has been set.

Why was rotenone banned?

The sources read for this page do not describe a general ban. ADF&G describes use under EPA-reviewed label conditions by certified applicators. Current registration status for a given use or country should be checked with the relevant regulator.

Sources

  • Alaska Department of Fish and Game, Rotenone: Health Effects (read 2026-11-07).
  • CDC NIOSH, Rotenone IDLH documentation (read 2026-11-07).
  • NCBI PubChem, rotenone compound record (CID 6758), GHS classification and mechanism-of-action sections, citing WHO PIM 474 and Krieger, Handbook of Pesticide Toxicology, 2nd ed. (read 2026-11-07).

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