Hazards and risks of the pesticides chlorpyrifos and chlorpyrifos-methyl: the European Food safety Agency (EFSA) evaluation and consequences for their future use in the E.U.

What are chlorpyrifos and chlorpyrifos-methyl?

Chlorpyrifos (sometimes referred to as chlorpyrifos-ethyl) and chlorpyrifos-methyl are pesticides used to kill insects and mites. They are among the most commonly used in Europe on a range of crops. Their residues are often present in fruits, vegetables, cereals and dairy products, as well as in drinking water.

In the European Union, according to the REACH Regulation on harmonised classification and labelling¹ of chemical products of the European Chemicals Agency (ECHA), chlorpyriphos is classified as “very toxic to aquatic life with long lasting effects and may cause an allergic skin reaction”. By mid-2019, eight countries had already banned the use of the products for agricultural use. Because their approval for the European market expires in January 2020, they were re-evaluated in terms of safety.

In this context, the European Commission asked the experts of the European Food Safety Agency (EFSA) to provide opinions on the updated risk assessments of chlorpyrifos and chlorpyrifos-methyl. EFSA concluded that concerns related to human health exist, in particular in relation to possible genotoxicity and developmental neurotoxicity and that the criteria for renewal were not met. Accordingly, the European Commission voted to not renew the authorization for chlorpyrifos and chlorpyrifos-methyl.

¹ www.echa.europa.eu/information-on-chemicals 

What was the approach used to perform the hazard and risk assessment of chlorpyrifos-methyl?

Initially the approach taken by the experts for the hazard assessment² of chlorpyrifos-methyl was largely based on its structural similarity with chlorpyrifos, even if some differences have uneven consequences leading to variations which could contribute to the differences in toxicity of the two compounds.

Chlorpyrifos‐methyl has a higher acute toxicity than chlorpyrifos, but both have the same level of toxicity after long‐term exposure.

Regarding the two toxicologically relevant impurities that are present in the technical specifications, it is not expected that they would have the potential to add supplementary hazard to that of the parent compounds. The maximum levels of these impurities in the newly proposed technical specifications are in agreement with these requirements.

² Hazard assessment is the identification of the intrinsic properties of the agent considered. To understand more clearly the essential differences between the notions of hazard, risk and safety, watch the short GreenFacts animation video 

What were the main conclusions of the EFSA experts on the safety assessment of chlorpyrifos-methyl?

The main conclusions of the experts of EFSA were:

• For genotoxicity: although the available data did not show any concern, the experts highlighted that the data was very limited and therefore the genotoxic potential of chlorpyrifos and chorpyrifos‐methyl remains unclear. Meanwhile, no evidence for a carcinogenic potential was found upon chlorpyrifos-methyl administration in rats or mice.
• For developmental neurotoxicity (DNT), some effects were observed at low doses for chlorpyrifos, indicating a health concern. The main way through which chlorpyrifos can have an effect on the nervous system is by interfering with cholinesterase, an enzyme involved in the metabolism of choline, an important neurotransmitter. In a conservative approach, the same conclusion was applied to chlorpyrifos-methyl. Meanwhile, chlorpyrifos-methyl did not affect the reproductive performance up to the highest dose tested in a two-generation reproductive toxicity study in rats.
• On the immunotoxic potential of chlorpyrifos-methyl, a data gap was identified as no information has been provided.

Based on the above, it was considered that the approval criteria³ for chlorpyrifos-methyl which are applicable to human health were not met and that this issue represents a critical area of concern.

³ as laid down in Article 4 of Regulation (EC) No 1107/2009

What are the effects of chlorpyrifos-methyl observed regarding human health?

The epidemiological evidence based on the available data supports the developmental neurological concern in children for both chlorpyrifos and chlorpyrifos methyl. Even if EFSA expresses some reservations on this approach, based on the available toxicological data set, the experts considered that chlorpyrifos‐methyl may be expected to meet the criteria for classification in accordance with the criteria set out with Regulation (EC) No 1272/2008 as “Toxic for the reproduction” and ‘May damage the unborn child’. The experts suggested thus to classify chlorpyrifos-methyl as “Toxic for reproduction”⁴. The European Chemical Agency will eventually decide on this matter.

⁴ REPRO 1B, H360D ‘May damage the unborn child’ in accordance with the criteria set out in Regulation (EC) No 1272/2008

Is there a significant health risk from aerial exposure to chlorpyrifos spray drift and what about the presence of chlorpyrifos residues in some fruits?

The Human Health Assessment Branch of the Department of Pesticide Regulation (California Environmental Protection Agency or EPA)⁵ performed a very detailed assessment evaluating the dietary, spray drift, and aggregate risks that accompany exposure to chlorpyrifos from aerial and ground-based applications in the U.S.

When chlorpyrifos is taken in through breathing or on the skin from the spray drift near an application site or through ingestion with food, no risks were identified from exposures to children and women of childbearing age.

When an aggregated risk was calculated by summing all possible exposures to chlorpyrifos (food, drinking water, air and skin contact with residues (horizontal deposition and aerosols associated with spray drift), incidental soil ingestion, ingestion of residues by object-to-mouth, hand-to-mouth), the results of the Californian EPA assessment found that the margin of exposure between the no observed effect level and the estimated exposure, was below the target margin of 100, which suggests a potential risk. There are also studies that suggest that doses smaller than those causing cholinesterase inhibition (AchE) can have neurotoxic effects as well, further suggesting potential risk.

Besides, regarding residue resulting from the existing and the intended uses in particular for kaki/Japanese persimmons and granate apples/pomegranates fruits production, the Europan Food Safety Agency EFSA concludes that the long‐term and short‐term intake of residues of chlorpyrifos‐methyl and its metabolite 3,5,6-trichloropyridinol is unlikely to present a risk to consumer health.

⁵ Final Evaluation of Chlorpyrifos as a Toxic Air Contaminant. Human Health Assessment Branch of the Department of Pesticide Regulation (California Environmental Protection Agency) 2018  www.cdpr.ca.gov/docs/whs/pdf/chlorpyrifos_final_tac.pdf

References:
Statement on the available outcomes of the human health assessment in the context of the pesticides peer review of the active substance chlorpyrifos-methyl – updated statement November 2019. European Food Safety Authority ()EFSA) https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2019.5908
Modification of the existing maximum residue levels for chlorpyrifos‐methyl in kaki/Japanese persimmon and granate apple/pomegranate European Food Safety Authority (EFSA) https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2017.4838
Final Evaluation of Chlorpyrifos as a Toxic Air Contaminant. Human Health Assessment Branch of the Department of Pesticide Regulation (California Environmental Protection Agency) 2018  www.cdpr.ca.gov/docs/whs/pdf/chlorpyrifos_final_tac.pdf