Establishment of common mechanism groups for pesticides and ...

|[pic] |
|Establishment of common mechanism groups for pesticides and |
|similar substances: |
|A pilot study to establish resource requirements |
|MARCH 2005 | The Institute for Environment and Health was established by the Medical
Research Council at the University of Leicester in 1993. The Institute is
principally funded by UK Government Departments and Agencies by way of
specific research and consultancy contracts. The views expressed here do not necessarily represent those of any
Government Department or Agency.
This report was prepared by the MRC Institute for Environment and Health
for the Food Standards Agency and was issued in March 2005.
Prepared by Karin Koller, Kathryn James, Karen Bradley, Len Levy and Linda
Shuker (Institute for Environment and Health, 2005 MRC Institute for Environment and Health
University of Leicester
94 Regent Road
Leicester
LE1 7DD
UK http://www.le.ac.uk Contents Introduction 5 Background 5 References 6 1 Design of Pilot Study 7 1.1 Selection of pilot compounds 7 1.2 Literature searches 9 2 Completion of Data Record Tables 15 3 Avermectins 16 3.1 Major pilot compound: Abamectin 16 3.2 Minor pilot compound: Selamectin 17 3.3 Additional information of possible relevance to the establishment
of a common mechanism group 18 3.4 Avermectins: Summary 19 4 Conazoles 20 4.1 Major pilot compound: Prochloraz 20 4.2 Minor pilot compound: Triadimenol: 21 4.3 Additional information of possible relevance to the establishment
of a common mechanism group 22 4.4 Conazoles: Summary 23 5 Phenoxy Herbicides 24 5.1 Major pilot compound: 2,4-D 24 5.2 Minor pilot compound: MCPB 25 5.3 Additional information of possible relevance to the establishment
of a common mechanism group 26 5.4 Phenoxy herbicides: Summary 26 6 Pyrethrins and Pyrethroids 28 6.1 Major pilot compound: Deltamethrin 28 6.2 Minor pilot compound: Resmethrin 29 6.3 Additional information of possible relevance to the establishment
of a common mechanism group 30 6.4 Pyrethrins and pyrethroids: Summary 31 7 Triazines 32 7.1 Major pilot compound: Atrazine 32 7.2 Minor pilot compound: Prometryn 33 7.3 Additional information of possible relevance to the establishment
of a common mechanism group 34 7.4 Triazines: Summary 34 8 Conclusions and Recommendations 36 8.1 Assessment of quality of available data on pilot compounds 36 8.2 Recommendations for future data gathering exercises 37 8.3 Assessment of resources required for future data gathering and
analysis 37 9 References 40 9.1 Avermectins 40 9.2 Conazoles 42 9.3 Phenoxy herbicides 43 9.4 Pyrethrins and pyrethroids 45 9.5 Triazines 48 Appendix 1 Candidate compounds and major reviews 52 Appendix 2 Pre-established criteria for data assessment 56 Appendix 3.1 Data record table - ABAMECTIN 58 Appendix 3.2 Data record table - SELAMECTIN 61 Appendix 3.3 Data record table - AVERMECTINS Group reviews/Original
papers 62 Appendix 4.1 Data record table - PROCHLORAZ 63 Appendix 4.2 Data record table - TRIADIMENOL 64 Appendix 5.1 Data record table - 2,4-D (2,4-Dichlorophenoxyacetic
acid) 65 Appendix 5.2 Data record table - MCPB (2-Methyl-4-chlorophenoxy-(-
butyric acid) 68 Appendix 6.1 Data record table - DELTAMETHRIN 69 Appendix 6.2 Data record table - RESMETHRIN 75 Appendix 6.3 Data record table - PYRETHROIDS Group reviews/Original
papers 76 Appendix 7.1 Data record table - ATRAZINE 77 Appendix 7.2 Data record table - PROMETRYN 89 Appendix 8 Revised criteria for data assessment 90
Introduction
Background In 2002 the Committee on Toxicity of Chemicals in Food, Consumer Products
and the Environment (COT) published a report from a COT Working Group on
the Risk Assessment of Mixtures of Pesticides (WiGRAMP) on the risk
assessment of mixtures of pesticides and similar substances (COT, 2002). Many pesticides and veterinary medicines are in use, and some may contain
more than one active ingredient. Individuals may, therefore, be exposed to
a number of different pesticides or veterinary products through dietary and
other routes of exposure. While little is known about any possible human
health risks posed by long-term, combined exposures to trace amounts of
pesticides, the COT report concluded that the likelihood of human disease
arising from such exposure is very low. Nonetheless, there continues to be
concern that the presence of multiple chemical residues in foods may cause
adverse health effects, including effects that would not be predicted from
consideration of single exposures to individual compounds. WiGRAMP recognised that the regulatory system for pesticides and veterinary
products found in foods does not routinely address the toxic effects of
different substances in combination. The implications, both for risk
assessment and for approval processes, of exposure to mixtures of
pesticides and veterinary medicines are among the topics examined in the
COT report. Among its conclusions, WiGRAMP recommended that the nature and extent of
combined exposure to pesticides and related chemicals, together with the
likelihood of any adverse effects that might result, should be evaluated,
when carrying out risk assessment. Furthermore, a scientific and systematic
framework should be established to decide when it is appropriate to carry
out combined risk assessments of exposures to more than one pesticide
and/or veterinary medicine. WiGRAMP also recommended that groups of
pesticides having common targets of toxicological action should be
identified. Some classes of pesticides and veterinary medicines work, toxicologically,
through the same mechanism. The identification of such common mechanism
groups would, therefore, facilitate combined risk assessments. Combined
exposures to pesticides and veterinary medicines may be both cumulative
(multiple pesticides) and aggregate (multiple pathways), and cumulative
risk assessment is dependent on the identification of common mechanism
groups. Approaches to identifying common mechanism groups for pesticides and
related chemicals are already being established in the USA, and the
International Life Sciences Institute has been developing a framework for
guiding the conduct of cumulative risk assessment, based on five key stages
(EPA, 1999; ILSI, 1999). Some common mechanism groups have already been
proposed by EPA - the organophosphates (EPA, 1998), N-methylcarbamates
(EPA, 2001) and triazines (EPA, 2002). The EPA approach to the establishment of common mechanism groups for
organophosphates and
N-methylcarbamates has been reviewed for the Science Group of the Food
Standards Agency. The Science Group has also prioritised the triazines and
four additional classes of pesticides/veterinary medicines - avermectins,
conazoles, phenoxy herbicides, and pyrethroids and natural pyrethrins - to
be assessed for possible common mechanism grouping. Given the extensive resource requirements to collect and assess the
toxicological and other relevant data necessary to establish common
mechanism groups for these classes of compounds, it was decided to conduct
a scoping study to: . identify the amount of work required to establish common mechanism groups
for each of the prioritised classes of pesticides and veterinary
medicines - this would include an evaluation of the amount and quality of
data available on each substance belonging to each class; . estimate the resources (cost and person years) required to identify and
establish common mechanism groups for the prioritised classes of
pesticides and veterinary medicines. This report describes a project conducted by the MRC Institute for
Environment and Health (IEH), as a pilot study for the scoping exercise.
The pilot study was designed to test procedures for gathering and
evaluating data on a selected number of compounds from each of the five
prioritised classes and to estimate resource requirements for the fuller
scoping exercise. Subsequent to the pilot study and in the light of its results, the Food
Standards Agency decided that the originally planned, larger, scoping study
to identify the resource requirements for establishing common mechanisms
groups would not be necessary. The pilot study was considered to provide
adequate information to guide the data collection and data analysis and to
estimate resources required to identify common mechanism groups for the
prioritised classes of pesticides and veterinary medicines.
References COT (2002) Risk Assessment of Mixtures of Pesticides and Similar
Substances, London, Food Standards Agency, available [October 2004] at
http://www.food.gov.uk/multimedia/pdfs/report(indexed).pdf EPA (1999) Guidance for Identifying Pesticide Chemicals and other
Substances that have a Common Mechanism of Toxicity, Washington DC, Office
of Pesticide Programs, Office of Prevention Pesticides and Toxic
Substances, available [October 2004] at http://www.epa.gov/fedrgstr/EPA-
PEST/1999/February/Day-05/6055.pdf EPA (1998) A Common