German risk assessor questions EU safety thresholds for toxic insecticide

The opinion, ‘Reconsideration of the human toxicological reference values (ARfD, ADI) for chlorpyrifos’, also outlines the case for re-evaluating the existing safety thresholds for the insectide.

A BfR spokesperson told Foodproductiondaily.com that this process would be initiated by the German Federal Ministry of Food, Agriculture and Consumer Protection (BMELV), the government department that commissioned the opinion.

Risk assessment recommended​

The spokesperson was at pains to point out that “the opinion is a toxicological report regarding the toxicological reference values, not an analysis of chlorpyrifos in food,” ​and said that “a risk assessment should be performed based on actual data on consumer exposure”.​

Chlorpyrifos is used on numerous food and feed crops to kill insects by disrupting their nervous system. Chlorpyrifos binds to and phosphorylates the enzyme acteylcholinesterase, leading to accumulation of acetycholine and ultimately, toxicity.

In summer 2011, the US American Environmental Protection Agency (EPA) revised toxicological reference values for chlorpyrifos, after reviewing new studies and data on the toxicity of the insecticide.

Of particular significance was a study (Marty & Andrus 2010) that measured acteylcholinesterase (AChE) inhibition in rats, after acute and repeated exposure to chlorpyrifos. In this study, the NOAELs (highest experimental dose at which no adverse effects were observed) were 2mg/kg for the brain and 0.5mg/kg for red blood cells.

The acute reference dose (ARfD) for chlorpyrifos in the EU was established in 2005, before much of the recent research on the insecticide was carried out. The current acute reference dose is 0.1mg/kg, on the basis of a NOAEL of 10mg/kg from ‘acute and delayed neurotoxicity studies in rats’ as a point of departure.

Chronic human risk assessment​

In 2005, upon the basis of work done by the European Food Safety Authority (EFSA), the EU also established an acceptable daily intake (ADI) level of 0.01mg/kg on the basis of a NOAEL of 1mg/kg from ‘2-years rats, mice and dogs’ studies as a point of departure.

“The new toxicological studies, mechanistic data, epidemiologic and biomonitoring studies submitted to the US EPA and the new information provided in the literature seem to support NOAELS for acute AChE inhibition of 2mg/kg for brain and 0.5mg/kg for red blood cells, and NOAELS for AChE inhibition after repeated exposure of 0.5mg/kg for brain and 0.1mg/kg for red blood cells,”​ wrote the BfR in its opinion.

Therefore, the BfR concluded, the NOAEL of 10mg/kg which was used for setting the acute reference dose in the EU can no longer be considered an appropriate point of departure for acute human assessment, especially for the protection of infants. Consequently, the acute reference dose of 0.1mg/kg should be reconsidered.

Furthermore, the BfR recommended that both the NOAEL of 1mg/kg, which was used as a point of departure for chronic human risk assessment, and the acceptable daily intake of 0.01mg/kg be reconsidered.