Toxicology -Plant Protection Products (Pesticides)
HSE's Chemicals Regulation Division (CRD) refers to the appropriate European guidance documents for most parts of the toxicological assessment of Plant Protection Products (PPPs).
Links to European guidance documents which are used for the toxicology assessment can be found on our Toxicology useful links page.
Specific guidance relating to individual product applications may be delivered directly to the applicant in pre-submission meetings, organised as part of the application process: Applicant Guide - Active Substances guidance document: EU Decision Making Process for Active Substances.
The following subsections are included on this page:
Considerations regarding classification of amateur products
Effective from 01/06/2015, all plant protection products, including those intended for amateur use, must be classified in accordance with Regulation (EC) 1272/2008 (CLP).
HSE's Chemicals Regulation Division (CRD) has previously implemented a policy whereby national authorisation in the UK was not granted for amateur products that were classified as Very Toxic, Toxic, Corrosive or Skin Sensitisers in accordance with the Chemicals (Hazard Information and Packaging for Supply) Regulations (CHIP).
CRD will continue to implement an equivalent policy following the change to compulsory classification of plant protection products under Regulation (EC) 1272/2008 (CLP).
Therefore national authorisation in the UK will not normally be granted for amateur products which are classified in:
- Category 1,2 or 3 for acute toxicity
- Category 1 (1A or 1B) for carcinogenicity, mutagenicity, reproductive toxicity or Specific Target Organ Toxicity (STOT SE/RE)
- Category 1 (1A, 1B or 1C) for skin corrosion/irritation
- Category 1 for eye irritation
- Category 1, 1A or 1B for skin sensitisation
Considerations regarding PPE for amateur products
In addition, authorisation will not normally be granted for amateur products for which the risk assessment demonstrates that the use of personal protective equipment (PPE) is required to ensure safe use. Amateur products may be authorised where there are standard recommendations for PPE in accordance with Regulation (EC) 1272/2008, but PPE was not a requirement to ensure safe use in the risk assessment.
Combined Toxicity for products with multiple active substances
Where two or more active ingredients (including safeners) are present in a formulated product, consideration should be given to the potential for combined toxicity. Combined toxicity should be considered for all areas of the risk assessment, including dietary and non-dietary elements.
CRD has produced a Combined Toxicity Guidance Document,which provides further information and worked examples.
An EU-wide approach to combined toxicity of pesticides is currently being developed. The Scientific Report of EFSA – 'International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals' (2013) provides further information and is available via the EFSA Publications Website.
For the authorisation of plant protection products under Regulation (EC) No. 1107/2009, toxicology data requirements are laid down in the following regulation:
Commission Regulation (EU) No 284/2013 available via The EU Commission Website.
Before conducting in vivo tests on formulated products, consideration should be given to use of the classification-by-calculation approach of the CLP. Where it is necessary to perform toxicological studies, they should be conducted according to the appropriate and current OECD test guidelines or EU test methods and in accordance with GLP(Good Laboratory Practice).
OECD test guidelines can be found on the OECD Website.
EU test methods can be found on the ECHA Website.
Testing On Vertebrate Animals
Regulation (EC) No 1107/2009 applied from 14 June 2011 and lays down a number of requirements aimed at avoiding unnecessary testing on vertebrate animals, including the avoidance of duplicate testing, and for sharing of tests and studies involving vertebrate animals.
In addition, The Regulation states in Article 62 (1) that:
'testing on vertebrate animals for the purposes of this Regulation shall be undertaken only where no other methods are available'.
The Regulation states that dossiers submitted for the approval of active substances and authorisation of plant protection products should include 'for each test or study involving vertebrate animals, a justification of the steps taken to avoid animal testing and duplication of tests and studies on vertebrate animals' (Article 8(1)(d) and Article 33(3)(c) respectively).
When new OECD Test Guidelines become available that can replace in vivo tests, any new studies submitted for the purposes of plant protection regulation should be conducted using these alternatives. In vivo tests conducted before alternative Test Guidelines were adopted by the OECD may be submitted, subject to the requirements of Article 62 regarding data sharing, but no new vertebrate studies should be conducted for the purposes of fulfilling the requirements of the Regulation when there are alternative methods available.
More detailed information on submitting vertebrate studies is given in the pesticides Applicant Guide: Vertebrate Testing Requirements.
The determination of appropriate values for the absorption of pesticide active substances in a product is a critical part of the non-dietary risk assessment for plant protection products.
Dermal absorption values should be determined in accordance with the current EFSA guidance on dermal absorption (2012), which is publically available on the EFSA Publications Website.
HSE's Chemicals Regulation Division (CRD) frequently requests further information from applicants, or make amendments to proposed dermal absorption values, when evaluating plant protection products. Issues which commonly arise are:
- Incorrect interpretation of experimental data:
- Inappropriate exclusion of material found in tape strips
- Unjustified exclusion of outliers
- Failure to make necessary corrections for high experimental variability
- Inappropriate extrapolation to dermal absorption values which were derived for a different formulation, or absence of an acceptable reasoned case to justify any extrapolation.
CRD runs regular dermal absorption workshops which provide further information on this topic. More information can be found on CRD's Events page on the Health and Safety Laboratory (HSL)website.
Some plant protection product formulations may include dyes or colouring agents.
Owing to concerns over the potential genotoxicity and carcinogenicity of certain classes of dyes, for UK national authorisation HSE's Chemicals Regulation Division (CRD) requires that any dyes used in pesticide formulations do not present unacceptable risks.
Acceptable risk can be demonstrated in two ways:
- If the dye used is one that is already approved within the EU for use in cosmetics or foodstuffs, it is considered that the assessment performed prior to gaining approval for food or cosmetic uses will adequately cover pesticide uses. Applicants should provide the name, appropriate Colour Index (C.I.) number, or E number of the approved dye, and a description of the uses for which it is currently approved.
Dyes approved for use in cosmetic products in the EU can be found in Annex IV of Regulation (EC) 1223/2009.
Colours approved for use in foodstuffs in the EU can be found in Part B of Annex II of Regulation (EC) 1333/2008.
- If the dye is not already approved within the EU for use in cosmetics or foodstuffs, the applicant needs to address the potential toxicity of the dye. In particular a reasoned case or data will need to be provided to show an absence of genotoxicity. In most instances this will require negative genotoxicity data to be available on the dye or a closely related compound; in the majority of cases an Ames assay will be sufficient. A justification of no evidence of genotoxicity as a consequence of a particular chemical not having been appropriately tested is unlikely to be adequate without additional scientific argument.
Safety Data Sheets (SDS)
HSE's Chemicals Regulation Division (CRD) requests that applicants who need to submit SDS present them in compliance with the following:
- In English
- Less than 2 years since the last revision date
- In compliance with the EU format (ie according to Annex II and articles 31 & 32 of Regulation (EC) 1907/2006 REACH)