Conclusion on the peer review of the pesticide risk assessment of the active substance extract from tea tree 1

Transcription

1 EFSA Journal 2012;10(2):2542 CONCLUSION ON PESTICIDE PEER REVIEW Conclusion on the peer review of the pesticide risk assessment of the active substance extract from tea tree 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy SUMMARY Extract from tea tree is one of the 295 substances of the fourth stage of the review programme covered by Commission Regulation (EC) No 2229/2004 3, as amended by Commission Regulation (EC) No 1095/ Extract from tea tree was included in Annex I to Directive 91/414/EEC on 18 December 2008 pursuant to Article 24b of the Regulation (EC) No 2229/2004 (hereinafter referred to as the Regulation ) and has subsequently been deemed to be approved under Regulation (EC) No 1107/2009 5, in accordance with Commission Implementing Regulation (EU) No 540/2011 6, as amended by Commission Implementing Regulation (EU) No 541/ In accordance with Article 25a of the Regulation, as amended by Commission Regulation (EU) No 114/2010 8, the European Food Safety Authority (EFSA) is required to deliver by 31 December 2012 its view on the draft review report submitted by the European Commission in accordance with Article 25(1) of the Regulation. This review report was established as a result of the initial evaluation provided by the designated rapporteur Member State in the Draft Assessment Report (DAR). The EFSA therefore organised a peer review of the DAR. The conclusions of the peer review are set out in this report. Latvia being the designated rapporteur Member State submitted the DAR on extract from tea tree in accordance with the provisions of Article 22(1) of the Regulation, which was received by the EFSA on 25 October The peer review was initiated on 18 June 2008 by dispatching the DAR for consultation of the notifier (SIA Biomor Latvija ; the new notifier from 04/2010 is Biomor Europe Ltd. ). Subsequently the DAR was dispatched for consultation of the Member States on 24 February Following consideration of the comments received on the DAR, it was concluded that EFSA should conduct a focused peer review in the area of mammalian toxicology and deliver its conclusions on extract from tea tree. 1 On request from the European Commission, Question No EFSA-Q , adopted on 16 December Correspondence: pesticides.peerreview@efsa.europa.eu 3 OJ L 379, , p.13 4 OJ L 246, , p.19 5 OJ L 309, , p.1 6 OJ L 153, , p.1 7 OJ L 153, , p OJ L 37, , p.12 Suggested citation: European Food Safety Authority; Conclusion on the peer review of the pesticide risk assessment of the active substance tea tree oil. EFSA Journal 2012; 10(2):2542. [60 pp.] doi: /j.efsa Available online: European Food Safety Authority, 2012

2 The conclusions laid down in this report were reached on the basis of the evaluation of the representative uses of extract from tea tree as a fungicide on potatoes, carrots, herbs, cucumber, watermelons, tomatoes, pepper and ornamentals as proposed by the notifier. Full details of the representative uses can be found in Appendix A to this report. In the area of identity, physical/chemical/technical properties and methods of analysis data gaps were identified for validation data for the method used in the GLP batch study and spectra for the marker compounds and methods of analysis for appropriate marker compounds in environmental compartments. s for the formulation were identified for accelerated and shelf life storage studies and flash point. s were identified for investigation of the in vitro mammalian cell gene mutation potential of extract from tea tree, providing sufficient toxicological information to allow the derivation of reference values, ADI, ARfD and AOEL. The composition of the batches used in the toxicological studies should be presented, as well as an assessment of the toxicological relevance of impurities and components of the tea tree mixture. As no AOEL could be derived, no conclusion could be reached on the operator, worker and bystander exposure risk assessment. Considering the complete lack of data on toxicokinetic and metabolism, short-term, long-term, reproductive and developmental toxicity, a critical area of concern was identified. There is no conclusion in the residues area. The nature of residues in plants is unknown and a critical area of concern is identified. s have been identified for information to address the route and rate of degradation of extract from tea tree components in soil, surface water and sediment. More specific data gaps for disappearance time (DT) values in soil of the components: tirpenene-4-ol, alpha-terpineol and 1,8- cineole and consequent FOCUS groundwater exposure modelling for these components were also identified along with the need for FOCUS surface water assessments for all extract from tea tree components consequent to the representative uses outdoors in the field. The data gaps lead to the conclusion that the groundwater exposure assessment for tirpenene-4-ol, alpha-terpineol and 1,8- cineole was not finalised, that the soil, groundwater and aquatic exposure assessments from potential soil or aquatic system transformation products of globulol and viridiflorol (should they be formed) could not be finalised and that the aquatic exposure assessment for all 12 components of extract from tea tree could not be finalised for the representative outdoor field uses. The data available for the ecotoxicological assessments were insufficient. The risk assessments for birds and mammals, honeybees and other non-target arthropods, earthworms and non-target soil macro and micro-organisms and for the potential effects on the biological methods of sewage treatment could not be finalised. KEY WORDS Extract from tea tree, peer review, risk assessment, pesticide, fungicide EFSA Journal 2012;10(2):2542 2

3 TABLE OF CONTENTS Summary... 1 Table of contents... 3 Background... 4 The active substance and the formulated product... 6 Conclusions of the evaluation Identity, physical/chemical/technical properties and methods of analysis Mammalian toxicity Residues Environmental fate and behaviour Ecotoxicology Overview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments Soil Ground water Surface water and sediment Air List of studies to be generated, still ongoing or available but not peer reviewed Particular conditions proposed to be taken into account to manage the risk(s) identified Concerns Issues that could not be finalised Critical areas of concern Overview of the concerns for each representative use considered References Appendices Abbreviations EFSA Journal 2012;10(2):2542 3

4 BACKGROUND Extract from tea tree.is one of the 295 substances of the fourth stage of the review programme covered by Commission Regulation (EC) No 2229/2004 9, as amended by Commission Regulation (EC) No 1095/ Extract from tea tree was included in Annex I to Directive 91/414/EEC on 18 December 2008 pursuant to Article 24b of the Regulation (EC) No 2229/2004 (hereinafter referred to as the Regulation ) and has subsequently been deemed to be approved under Regulation (EC) No 1107/ , in accordance with Commission Implementing Regulation (EU) No 540/ , as amended by Commission Implementing Regulation (EU) No 541/ In accordance with Article 25a of the Regulation, as amended by Commission Regulation (EU) No 114/ the European Food Safety Authority (EFSA) is required to deliver by 31 December 2012 its view on the draft review report submitted by the European Commission in accordance with Article 25(1) of the Regulation (European Commission, 2008). This review report was established as a result of the initial evaluation provided by the designated rapporteur Member State in the Draft Assessment Report (DAR). The EFSA therefore organised a peer review of the DAR. The conclusions of the peer review are set out in this report. Latvia being the designated rapporteur Member State submitted the DAR on extract from tea tree.in accordance with the provisions of Article 22(1) of the Regulation, which was received by the EFSA on 25 October 2007 (Latvia, 2007). The peer review was initiated on 18 June 2008 by dispatching the DAR for consultation of the notifier (SIA Biomor Latvija ; the new notifier from 04/2010 is Biomor Europe Ltd. ) Subsequently the DAR was dispatched for consultation of the Member States on 24 February In addition, the EFSA conducted a public consultation on the DAR. The comments received were collated by the EFSA and forwarded to the RMS for compilation and evaluation in the format of a Reporting Table. The notifier was invited to respond to the comments in column 3 of the Reporting Table. The comments were evaluated by the RMS in column 3 of the Reporting Table. The scope of the peer review was considered in a telephone conference between the EFSA, the RMS, and the European Commission on 20 June On the basis of the comments received and the RMS evaluation thereof it was concluded that the EFSA should organise a consultation with Member State experts in the area of mammalian toxicology. The outcome of the telephone conference, together with EFSA s further consideration of the comments is reflected in the conclusions set out in column 4 of the Reporting Table. All points that were identified as unresolved at the end of the comment evaluation phase and which required further consideration, including those issues to be considered in consultation with Member State experts, and additional information to be submitted by the notifier, were compiled by the EFSA in the format of an Evaluation Table. The conclusions arising from the consideration by the EFSA, and as appropriate by the RMS, of the points identified in the Evaluation Table, together with the outcome of the expert discussions where these took place, were reported in the final column of the Evaluation Table. A final consultation on the conclusions arising from the peer review of the risk assessment took place with Member States via a written procedure in November/December OJ L 379, , p.13 OJ L 246, , p.19 OJ L 309, , p.1 OJ L 153, , p.1 OJ L 153, , p.187 OJ L 37, , p.12 EFSA Journal 2012;10(2):2542 4

5 This conclusion report summarises the outcome of the peer review of the risk assessment on the active substance and the representative formulation evaluated on the basis of the representative uses as a fungicide on potatoes, carrots, herbs, cucumber, watermelons, tomatoes, pepper and ornamentals as proposed by the notifier. A list of the relevant end points for the active substance as well as the formulation is provided in Appendix A. In addition, a key supporting document to this conclusion is the Peer Review Report, which is a compilation of the documentation developed to evaluate and address all issues raised in the peer review, from the initial commenting phase to the conclusion. The Peer Review Report (EFSA, 2011) comprises the following documents, in which all views expressed during the course of the peer review, including minority views, can be found: the comments received on the DAR, the Reporting Table (20 June 2011) the Evaluation Table (12 December 2011) the report of the scientific consultation with Member State experts (where relevant), the comments received on the assessment of the points of clarification (where relevant), the comments received on the draft EFSA conclusion. Given the importance of the DAR including its addendum (compiled version of November 2011 containing all individually submitted addenda (Latvia, 2011)) and the Peer Review Report, both documents are considered respectively as background documents A and B to this conclusion. EFSA Journal 2012;10(2):2542 5

6 THE ACTIVE SUBSTANCE AND THE FORMULATED PRODUCT Extract from tea tree is the name of the substance under consideration there is no ISO common name for this mixture of compounds. A number of the constituents of extract from tea tree have one or more asymmetric carbon atoms, so enantiomers and diastereoisomers are present in the mixture as applied. A number of the risk characterisations presented in this conclusion do not address the potential for change in enantiomer ratios of pertinent constituents following use. The representative formulated product for the evaluation was Timorex an emulsifiable concentrate (EC) containing g/l tea tree oil. The representative uses evaluated comprise indoor foliar spraying against powdery mildew in cucumber and tomato and outdoor foliar spraying on potato, carrots, herbs, cucumber, tomato, pepper, ornamentals and watermelon also for powdery mildew control. Full details of the GAP can be found in the list of end points in Appendix A. CONCLUSIONS OF THE EVALUATION 1. Identity, physical/chemical/technical properties and methods of analysis The following guidance document was followed in the production of this conclusion: SANCO/3030/99 rev.4 (European Commission, 2000) The tea tree oil has been shown to comply with ISO 4730:2004. There is no FAO specification. A data gap was identified to validate the method used in the GLP batch analysis study as well as for spectra of the marker compounds. No information was given on the level of microbial contamination and the mechanism for the control of such contamination and its possible increase on storage. The main data regarding the identity of extract from tea tree and its physical and chemical properties are given in Appendix A. It should be noted for the formulation that the data on surface tension and viscosity for R65 classification are not available. s were identified for accelerated and shelf life storage studies and the flash point. Depending on the outcome of the metabolism data gap identified monitoring method for products of plant and animal origin may be a data gap in the future. Methods of analysis for appropriate marker compounds in environmental compartments are a data gap. A method for body fluids and tissues is not required as extract from tea tree is not classified as toxic or very toxic. 2. Mammalian toxicity The following guidance document was followed in the production of this conclusion: SANCO/222/2000 rev. 7 (European Commission, 2004b). Extract from tea tree was discussed at the Pesticides Peer Review Meeting 88 in September EFSA Journal 2012;10(2):2542 6

7 It is unknown whether the toxicological batches are representative of the technical specification as their complete composition is not available. The relevance of impurities and components of the mixture has not been assessed. A data gap has been identified to address this issue. Studies performed with extract from tea tree were limited to acute toxicity and two genotoxicity studies. A short summary of reports regarding some components of extract from tea tree were provided accounting between 8 to 50% of the whole mixture, that could not be assessed in detail. Data gaps were identified for in vitro genotoxicity investigation on mammalian cells gene mutation potential of extract from tea tree, and toxicological information that would allow to set reference values. It is unclear whether an acceptable daily intake (ADI) and acute reference dose (ARfD) are required, once residue data are missing to assess the consumer exposure. No conclusion could be reached regarding operator, worker and bystander exposure risk assessment, as no acceptable operator exposure level (AOEL) could be determined. Considering the complete lack of data on toxicokinetic and metabolism, short-term, long-term, reproductive and developmental toxicity, a critical area of concern was identified. 3. Residues The issue of plant metabolism data was raised in the commenting period by EFSA. In the evaluation table the rapporteur Member State agreed with the data gap proposed by EFSA. It was agreed that without further data no conclusion can be drawn. A valid risk assessment cannot be conducted leading to a critical area of concern for the consumer risk assessment. Subject to the data gap for elucidation of the relevant residue in plants, all of the other data in the residues area will have to be re-assessed. 4. Environmental fate and behaviour Extract from tea tree is made up of the 15 components (see sections 1 and 6 of this conclusion). Information was not available on the route and rate of degradation of any of these components in soil (see section 7 where a consequent data gap is indicated). The available measured and quantitative structure activity relationship (QSAR) estimates of the vapour pressures of these components were considered sufficient to conclude that persistence in soil for 10 of these components would be low (see section 6.1). For the components globulol and viridiflorol, that have lower vapour pressures, it cannot be excluded with the available information, that they would exhibit moderate to high persistence in soil (see section 6.1). Four of these 12 components were immobile in soil with the remaining 8 exhibiting low to slight soil mobility (see section 6.2). The component alpha-terpineol, exhibited very high soil mobility, with tirpenene-4-ol and 1,8-cineole exhibiting high mobility. These mobility classifications are all based on QSAR estimated soil adsorption (K doc ) values. Due to the higher soil mobility of tirpenene-4-ol, alpha-terpineol and 1,8-cineole (these last three making up the balance of the 15 components), to better characterise their leaching potential, data gaps have been identified for soil DT estimates for these components, that would enable FOCUS groundwater simulations to be completed for these three components (see section 7 ). Consequent to these data gaps the groundwater exposure assessment for the components tirpenene-4-ol, alpha-terpineol and 1,8-cineole could not be finalised. Also the need for potential soil transformation products of globulol and viridiflorol (the least volatile components) to be further assessed could not concluded upon. Information was not available on the route and rate of degradation of any of the 15 active substance components in natural sediment water systems (see section 7 where a consequent data gap is indicated). Appropriate predicted environmental concentrations (PEC) in surface water and sediment from the outdoor (field) representative uses applied for were not available as only spray drift as an annual total load had been assessed. To be appropriate, PEC in surface water and sediment from these outdoor uses, need to follow FOCUS (2001) and FOCUS (2008) guidance. This guidance clarifies that in addition to spray drift, short range atmospheric deposition and drainage or runoff from soil have to be assessed. Consequent data gaps are therefore identified in section 7. Consequently the aquatic exposure and risk assessments for the field uses could not be finalised. For the representative protected EFSA Journal 2012;10(2):2542 7

8 crop uses, the necessary surface water and sediment exposure assessments (PEC) were carried out using the FOCUS (2001) step 1 and step 2 approach (version 1.1 of the steps 1-2 in FOCUS calculator), which was then modified by post processing the spray drift input results (option no runoff or drainage was selected) to obtain a 0.1 % emission of each extract from tea tree component from greenhouses being re-deposited on adjacent surface water bodies. This approach has been accepted by Member State experts as an assumption that can be used in EU level surface water exposure assessments for greenhouse uses and is referred to in FOCUS (2008) guidance as being appropriate, except when applications are made with ultra low volume application techniques when 0.2% emission is prescribed. It has to be concluded that even for the glasshouse uses, the exposure assessment for potential surface water system transformation products could not be finalised. This conclusion is considered most pertinent for the potential transformation products of the active substance components globulol and viridiflorol, that have the lower vapour pressures. All 15 components of extract from tea tree will be present in the atmosphere as a consequence of their volatilisation from soil and plant surfaces (the relatively high vapour pressures of each component are indicated in section 6.1 or appendix A) or as a consequence of aerosols that may be formed at the time of spraying. Appropriate QSAR calculations following the methods of Atkinson are available to indicate that no component would be expected to be prone to long range atmospheric transport, as all half lives estimated for conditions in the upper atmosphere were less than 48 hours (the longest value was for viridiflorol estimated as ca. 7.hours). PEC are included in appendix A for soil consequent to all representative uses and surface water and sediment consequent to the representative uses requested when crops are grown under protection. 5. Ecotoxicology For the risk assessments the following documents were considered: European Commission 2002a and 2002c. It is noted that it is unknown whether the batches used in the (eco)toxicological studies are representative of the technical specification (see relevant data gap in section 2). It is also noted that given the high volatility of terpenes (the constituents of extract from tea tree), in addition to the standard routes of exposure, the inhalation route of exposure for terrestrial organisms may also be relevant. The available studies revealed relatively low acute toxicity to birds and mammals. Based on the first tier risk assessments, high acute risk to birds however could not be excluded. It is noted however that these assessments based on a study where the exact level of toxicity was not established (there was no mortality observed at the highest dose tested). No short-term or long-them data or the associated assessments were available. Also no assessments for the exposure route via consumption of contaminated water or assessments for the potential bioaccumulation were available. Therefore a data gap was identified for all these issues discussed above regarding the open field uses. For the greenhouse uses the risk to birds and mammals was considered as low. No reliable data were available for aquatic organisms therefore no risk assessments were performed. A data gap for the necessary data and the associated risk assessments was therefore identified. Only an acute oral endpoint was available for honeybees. Based on this data, the risk to honeybees was concluded to be low. A data gap was identified for risk assessments considering the contact route of exposure. No reliable data were available for non-target arthropods and for earthworms or non target soil macro-organisms therefore no risk assessments were performed. Relevant data gaps for these issues were therefore identified. EFSA Journal 2012;10(2):2542 8

9 Regarding the potential effects of the constituents of extract from tea tree to microorganisms, some data (that were submitted for the evaluation of the behaviour of the constituents in soil) indicated that some micro-organisms isolated from soils were capable of degrading several terpenes within a reasonable time frame. Additionally some terpenes were demonstrated as readily biodegradable in activated sludge. Reliable data for soil processes like nitrogen transformation or carbon mineralisation were however not available except for a few constituents of extract from tea tree only for nitrogen transformation. These data indicated no significant impact on the nitrogen transformation in soil. Relevant data gaps for assessments of potential effects of all the constituents of extract from tea tree on nitrogen transformation and carbon mineralization were identified. Also, no specific data or reliable assessments were available for the potential effects of the constituents of extract from tea tree on the biological methods of sewage treatment, although, as discussed above, some available data indicated that some terpenes can be decomposed by microorganisms. Moreover the constituents of extract from tea tree are considered as relatively volatile. Regarding the representative field uses, the exposure of sewage treatment plants was expected to be low. This was however not the case for the greenhouse uses where the sewage might reach the sewage treatment plants directly via closed systems. A data gap for an assessment for the potential effects on biological methods for sewage treatments for the greenhouse uses was therefore identified. The risk regarding the open field uses was considered to be low. The risk to non-target terrestrial plants was considered to be low. EFSA Journal 2012;10(2):2542 9

10 6. Overview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments 6.1. Soil Compound (name and/or code) terpinene-4-ol gamma- terpinene alpha-terpinene alpha-terpineol alpha-terpinolene alpha-pinene Persistence, for DT50 values, considered necessary to address the leaching risk, see 6.2 below. Information not available from studies in soil, but argumentation based on measured vapour pressure (103 Pa at 23.5ºC) was accepted as sufficient to conclude low persistence Information not available from studies in soil, but argumentation based on QSAR estimated vapour pressure (106 Pa at 20ºC) was accepted as sufficient to conclude low persistence, for DT50 values, considered necessary to address the leaching risk, see 6.2 below. Information not available from studies in soil, but argumentation based on QSAR estimated vapour pressure (79 Pa at 25ºC) was accepted as sufficient to conclude low persistence Information not available from studies in soil, but argumentation based on measured vapour pressure (544 Pa at 23.5ºC) was accepted as sufficient to conclude low persistence Ecotoxicology EFSA Journal 2012;10(2):

11 p-cymene 1,8- cineole (eucalyptol) limonene aromadendrene delta-cadinene sabinene Information not available from studies in soil, but argumentation based on measured vapour pressure (199.5 Pa at 25ºC) was accepted as sufficient to conclude low persistence, for DT50 values, considered necessary to address the leaching risk, see 6.2 below. Information not available from studies in soil, but argumentation based on measured vapour pressure (202 Pa at 23.5ºC) was accepted as sufficient to conclude low persistence Information not available from studies in soil, but argumentation based on QSAR 15 estimated vapour pressure (3.1 Pa at 20ºC) was accepted as sufficient to conclude low persistence Information not available from studies in soil, but argumentation based on QSAR 16 estimated vapour pressure (0.68 Pa at 20ºC) was accepted as sufficient to conclude low persistence Information not available from studies in soil, but argumentation based on QSAR 17 estimated vapour pressure (726 Pa at 20ºC) was accepted as sufficient to conclude low persistence 15 MPBPWIN v1.43 contained in EPIWEB 4.1 copyright US EPA (presented by EFSA) 16 MPBPWIN v1.43 contained in EPIWEB 4.1 copyright US EPA (presented by EFSA) 17 MPBPWIN v1.43 contained in EPIWEB 4.1 copyright US EPA (presented by EFSA) EFSA Journal 2012;10(2):

12 globulol viridiflorol ledene Information not available from studies in soil, QSAR 18 estimated vapour pressure ( Pa at 20ºC), from the representative uses individual application are up to 26.4 g/ha, therefore PEC soil have been based on annual total dose, persistence needs to be considered moderate to high Information not available from studies in soil, QSAR 19 estimated vapour pressure (0.008 Pa at 20ºC), from the representative uses individual application are up to 26.4 g/ha, therefore PEC soil have been based on annual total dose, persistence needs to be considered moderate to high Information not available from studies in soil, but argumentation based on QSAR 20 estimated vapour pressure (1.57 Pa at 20ºC) was accepted as sufficient to conclude low persistence 6.2. Ground water Compound (name and/or code) Mobility in soil (based on QSAR estimates) >0.1 μg/l 1m depth for the representative uses (at least one FOCUS scenario or relevant lysimeter) Pesticidal activity Toxicological relevance Ecotoxicological activity terpinene-4-ol High mobility K doc 61.5 ml/g Yes, data may be required 18 MPBPWIN v1.43 contained in EPIWEB 4.1 copyright US EPA (presented by EFSA) 19 MPBPWIN v1.43 contained in EPIWEB MPBPWIN v1.43 contained in EPIWEB 4.1 EFSA Journal 2012;10(2):

13 gamma- terpinene Slight mobility K doc 2886 ml/g No, expert judgement based on application amount, mobility classification and vapour pressure. Yes, not required alpha-terpinene Low mobility K doc 1324 ml/g No, expert judgement based on application amount, mobility classification and vapour pressure. Yes, not required alpha-terpineol Very high mobility K doc 7 ml/g Yes, data may be required alpha-terpinolene Slight mobility K doc 2632 ml/g No, expert judgement based on application amount, mobility classification and vapour pressure. Yes, not required alpha-pinene immobile K doc 6495 ml/g No, expert judgement based on application amount, mobility classification and vapour pressure. Yes, not required p-cymene Slight mobility K doc 4732 ml/g No, expert judgement based on application amount, mobility classification and vapour pressure. Yes, not required EFSA Journal 2012;10(2):

14 1,8- cineole (eucalyptol) High mobility K doc ml/g Yes, data may be required limonene Slight mobility K doc 4821 ml/g No, expert judgement based on application amount, mobility classification and vapour pressure. Yes, not required aromadendrene immobile K doc ml/g No, expert judgement based on application amount, mobility classification and vapour pressure. Yes, not required delta-cadinene immobile K doc ml/g No, expert judgement based on application amount, mobility classification and vapour pressure. Yes, not required sabinene Low mobility K doc 1077 ml/g No, expert judgement based on application amount, mobility classification and vapour pressure. Yes, nor required globulol Low mobility K doc 1306 ml/g No, expert judgement based on application amount and mobility classification. Yes, not required EFSA Journal 2012;10(2):

15 viridiflorol Low mobility K doc 1240 ml/g No, expert judgement based on application amount and mobility classification. Yes, not required ledene immobile K doc ml/g No, expert judgement based on application amount, mobility classification and vapour pressure. Yes, not required 6.3. Surface water and sediment Compound (name and/or code) terpinene-4-ol gamma- terpinene alpha-terpinene alpha-terpineol alpha-terpinolene alpha-pinene p-cymene Ecotoxicology 1,8- cineole (eucalyptol) limonene EFSA Journal 2012;10(2):

16 aromadendrene delta-cadinene sabinene globulol viridiflorol ledene 6.4. Air Compound (name and/or code) terpinene-4-ol gamma- terpinene alpha-terpinene alpha-terpineol alpha-terpinolene alpha-pinene p-cymene Toxicology 1,8- cineole (eucalyptol) limonene EFSA Journal 2012;10(2):

17 aromadendrene delta-cadinene sabinene globulol viridiflorol ledene EFSA Journal 2012;10(2):

18 7. List of studies to be generated, still ongoing or available but not peer reviewed This is a complete list of the data gaps identified during the peer review process, including those areas where a study may have been made available during the peer review process but not considered for procedural reasons (without prejudice to the provisions of Article 7 of Directive 91/414/EEC concerning information on potentially harmful effects). Validation of the method used in the GLP batch analysis study (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 1) Spectra for the marker compounds (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 1) Flash point of the formulation (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 1) Accelerated and shelf life storage studies for the formulation (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 1) Methods of analysis for appropriate marker compounds in environmental compartments (relevant for all edible crop uses evaluated; submission date proposed by the notifier: unknown; see section 1) Plant metabolism data, subject to the outcome of this data further data gaps may be identified (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 1 and 3) Composition of the batches used in the toxicological studies and an assessment of the toxicological relevance of impurities and components of tea tree oil mixture (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 2) Sufficient toxicological information to allow the derivation of reference values ADI, ARfD, AOEL, including an investigation of in vitro mammalian cell gene mutation potential (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 2) Information on the route and rate of degradation of components of extract from tea tree in soil or information on natural background levels that may be present in soil that were eligible to be considered by the peer review were not available (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 4) Information on the route and rate of degradation of components of extract from tea tree in natural surface water systems or information on natural background levels that may be present in such systems that were eligible to be considered by the peer review were not available (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 4) Appropriate PEC in surface water and sediment from the outdoor (field) representative uses applied for were not available that include short range atmospheric deposition and drainage or runoff from soil (currently only spray drift as an annual total load has been assessed), (relevant for all representative uses outdoors; submission date proposed by the notifier: unknown, though it has been indicated that for the EU level assessment field uses are no longer defended; see section 4) Information on the potential for groundwater exposure for soil transformation products of components of extract from tea tree were not available. Soil DT estimates for components of extract from tea tree that are less strongly adsorbed (terpinene-4-ol, alpha-terpineol & 1,8-cineole), EFSA Journal 2012;10(2):

19 are necessary to finalise the groundwater exposure assessment, that when completed should follow up to date FOCUS groundwater guidance (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 4) Long-term and short-term risk assessments for birds and long-term risk assessment for mammals. Additionally, the risk assessment for acute scale for birds should be further addressed (relevant for all representative uses outdoors; submission date proposed by the notifier: unknown; see section 5) Reliable toxicological data set for aquatic organisms and the subsequent risk assessments (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 5) Risk assessment for honeybees considering the contact route of exposure (relevant for all representative uses evaluated; submission date proposed by the notifier: it was indicated that a new study is already available on a formulation; see section 5) Risk assessment for non-target arthropods (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 5) Risk assessment for earthworms and non target soil macro-organisms (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 5) Risk assessment for non target soil micro-organisms (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 5) Risk assessment for biological methods for sewage treatments (relevant for the greenhouse uses evaluated; submission date proposed by the notifier: unknown; see section 5) 8. Particular conditions proposed to be taken into account to manage the risk(s) identified None. 9. Concerns 9.1. Issues that could not be finalised An issue is listed as an issue that could not be finalised where there is not enough information available to perform an assessment, even at the lowest tier level, for the representative uses in line with the Uniform Principles of Annex VI to Directive 91/414/EEC and where the issue is of such importance that it could, when finalised, become a concern (which would also be listed as a critical area of concern if it is of relevance to all representative uses). 1. The consumer risk assessment cannot be finalised as the identity of the residue is unknown. 2. The groundwater exposure assessment for tirpenene-4-ol, alpha-terpineol and 1,8-cineole could not be finalised 3. The groundwater and soil exposure assessments from potential soil transformation products of globulol and viridiflorol (if any would be formed) could not be finalised. Consequently the risk assessment to soil dwelling organisms from exposure to transformation products of globulol and viridiflorol for the representative uses could not be finalised. EFSA Journal 2012;10(2):

20 4. The exposure assessment for aquatic systems (for all active substance components and potential transformation products of globulol and viridiflorol, if any would be formed in soil or surface water systems) could not be finalised for the representative outdoor field uses. Consequently the aquatic risk assessment for the representative outdoor field uses could not be finalised. 5. The exposure assessment for aquatic systems for potential transformation products of globulol and viridiflorol, (if any would be formed in soil or surface water systems) could not be finalised for the representative protected uses. Consequently the aquatic risk assessment from exposure to transformation products of globulol and viridiflorolfor the representative protected uses could not be finalised. 6. The ecotoxicological risk assessment for birds and mammals, aquatic organisms, honeybees and other non-target arthropods, earthworms and non-target soil macro and micro-organisms for the representative outdoor uses could not be finalised. 7. The ecotoxicological risk assessment for aquatic organisms honeybees and other non-target arthropods, earthworms and non-target soil macro and micro-organisms and for the potential effects on the biological methods of sewage treatment for the representative protected uses could not be finalised Critical areas of concern An issue is listed as a critical area of concern where there is enough information available to perform an assessment for the representative uses in line with the Uniform Principles of Annex VI to Directive 91/414/EEC, and where this assessment does not permit to conclude that for at least one of the representative uses it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater or any unacceptable influence on the environment. An issue is also listed as a critical area of concern where the assessment at a higher tier level could not be finalised due to a lack of information, and where the assessment performed at the lower tier level does not permit to conclude that for at least one of the representative uses it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater or any unacceptable influence on the environment. 8. No reference values could be derived due to the insufficient toxicological data base, considering the complete lack of data on toxicokinetic and metabolism, short-term, long-term, reproductive and developmental toxicity. 9. Operator, worker and bystander exposure risk assessment and the consumer risk assessment could not be assessed as no reference values could be derived. EFSA Journal 2012;10(2):

21 9.3. Overview of the concerns for each representative use considered (If a particular condition proposed to be taken into account to manage an identified risk, as listed in section 8, has been evaluated as being effective, then risk identified is not indicated in this table.) All columns are grey as the technical material specification proposed could not be compared to the material tested. Representative use Field application to potato Field application to carrots Field application to herbs Field application to cucumber Field application to watermelon Risk identified Operator Assessment not risk finalised Risk identified Worker risk Assessment not finalised Risk identified Bystander Assessment not risk finalised Risk identified Consumer Assessment not risk finalised Risk to wild Risk identified non target Assessment not terrestrial finalised vertebrates Risk to wild Risk identified non target terrestrial Assessment not organisms finalised other than vertebrates Risk to Risk identified aquatic Assessment not organisms finalised Groundwate Legal parametric r exposure value breached active Assessment not substance finalised Legal parametric value breached Groundwate Parametric value r exposure of 10µg/L (a) metabolites breached Assessment not finalised Comments/Remarks X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 1,8 X 1,8 X 1,8 X 1,8 X 1,8 X 6 X 6 X 6 X 6 X 6 X 3,6 X 3,6 X 3,6 X 3,6 X 3,6 X 4,6 X 4,6 X 4,6 X 4,6 X 4,6 X 2 X 2 X 2 X 2 X 2 X 3 X 3 X 3 X 3 X 3 The superscript numbers in this table relate to the numbered points indicated in sections 9.1 and 9.2 Where there is no superscript number see sections 2 to 6 for further information (a): Value for non relevant metabolites prescribed in SANCO/221/2000-rev 10-final, European Commission, 2003 EFSA Journal 2012;10(2):

22 Representative use Field application to tomato Field application to pepper Field application to ornamental s Application to protected cucumber Application to protected tomato Operator risk Worker risk Bystander risk Consumer risk Risk to wild non target terrestrial vertebrates Risk to wild non target terrestrial organisms other than vertebrates Risk to aquatic organisms Groundwate r exposure active substance Groundwate r exposure metabolites Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Legal parametric value breached Assessment not finalised Legal parametric value breached Parametric value of 10µg/L (a) breached Assessment not finalised X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 8,9 X 1,8 X 1,8 X 1,8 X 1,8 X 6 X 6 X 6 X 3,6 X 3,6 X 3,6 X 3,7 X 3,7 X 4,6 X 4,6 X 4,6 X 5,7 X 5,7 X 2 X 2 X 2 X 2 X 2 X 3 X 3 X 3 X 3 X 3 The superscript numbers in this table relate to the numbered points indicated in sections 9.1 and 9.2 Where there is no superscript number see sections 2 to 6 for further information (a): Value for non relevant metabolites prescribed in SANCO/221/2000-rev 10-final, European Commission, 2003 EFSA Journal 2012;10(2):

23 REFERENCES Latvia, Draft Assessment Report (DAR) on the active substance extract from tea tree prepared by the rapporteur Member State Latvia in the framework of Directive 91/414/EEC, October Latvia, Final Addendum to Draft Assessment Report on extract from tea tree., compiled by EFSA, November EFSA (European Food Safety Authority), Peer Review Report to the conclusion regarding the peer review of the pesticide risk assessment of the active substance extract from tea tree. European Commission, Review Report for the active substance extract from tea tree finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 1 August 2008 in view of the inclusion of extract from tea tree in Annex I of Directive 91/414/EEC, SANCO/2609/08 rev. 1, 1 August 2008 European Commission, 2002a. Guidance Document on Terrestrial Ecotoxicology Under Council Directive 91/414/EEC. SANCO/10329/2002 rev.2 final, 17 October European Commission, 2002c. Guidance Document on Risk Assessment for Birds and Mammals Under Council Directive 91/414/EEC. SANCO/4145/2000. European Commission, Guidance Document on Assessment of the Relevance of Metabolites in Groundwater of Substances Regulated under Council Directive 91/414/EEC. SANCO/221/2000- rev final, 25 February European Commission, 2004b. Guidance Document on Dermal Absorption. SANCO/222/2000 rev. 7, 19 March FOCUS (2001). FOCUS Surface Water Scenarios in the EU Evaluation Process under 91/414/EEC. Report of the FOCUS Working Group on Surface Water Scenarios, EC Document Reference SANCO/4802/2001-rev pp. FOCUS (2008). Pesticides in Air: Considerations for Exposure Assessment. Report of the FOCUS Working Group on Pesticides in Air, EC Document Reference SANCO/10553/2006 Rev 2 June JMPR, Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues Rome, Italy, September 2004, Report 2004, 383 pp. JMPR, Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues Geneva, Switzerland, September 2007, Report 2007, 164 pp. OECD (Organisation for Economic Co-operation and Development), Guidance Document on Overview of Residue Chemistry Studies. ENV/JM/MONO(2006)32, 10 October EFSA Journal 2012;10(2):

24 APPENDICES APPENDIX A LIST OF END POINTS FOR THE ACTIVE SUBSTANCE AND THE REPRESENTATIVE FORMULATION Identity, Physical and Chemical Properties, Details of Uses, Further Information Active substance (ISO Common Name) Function (e.g. fungicide) Tea Tree Oil Fungicide Rapporteur Member State Latvia Co-rapporteur Member State Identity (Annex IIA, point 1) Chemical name (IUPAC) Tea Tree Oil is a complex mixture of chemical substances. List of endpoints is limited to 4 major constituents: terpinene-4-ol (30-48%) 1-methyl-4-isopropyl-1-cyclohexen-4-ol gamma-terpinene (10-28%) 1-methyl-4-isopropyl-1,4-cycloheyadiene alpha-terpinene (5-13) 1-methyl-4-isopropyl-1,3-cyclohexadiene 1,8-cineole (0.1-15%) 1,33-trimethyl-2-oxabicyclo[2.2.2]octane Chemical name (CA) CIPAC No Not applicable CAS No Tea Tree Oil terpinene-4-ol gamma-terpinene alpha-terpinene ,8-cineole EC No (EINECS or ELINCS) Tea Tree Oil terpinene-4-ol gamma-terpinene FAO Specification (including year of publication) Minimum purity of the active substance as manufactured alpha-terpinene ,8-cineole Not applicable terpinene-4-ol 300 g/kg gamma-terpinene 100 g/kg alpha-terpinene 50 g/kg 1,8-cineole 1 g/kg EFSA Journal 2012;10(2):

25 Identity of relevant impurities (of toxicological, ecotoxicological and/or environmental concern) in the active substance as manufactured Molecular formula - Not relevant for Tea Tree Oil terpinene-4-ol C 10 H 18 O gamma-terpinene C 10 H 16 Molecular mass Structural formula alpha-terpinene C 10 H 16 1,8-cineole C 10 H 18 O Not relevant for Tea Tree Oil terpinene-4-ol g/mol gamma-terpinene g/mol alpha-terpinene g/mol 1,8-cineole g/mol Not relevant for Tea Tree Oil terpinene-4-ol OH gamma-terpinene OH alpha-terpinene 1,8-cineole O EFSA Journal 2012;10(2):

26 Physical and chemical properties (Annex IIA, point 2) Melting point (state purity) Boiling point (state purity) Temperature of decomposition (state purity) Appearance (state purity) Vapour pressure (state temperature, state purity) Not available for Tea Tree Oil (TTO is known to be a liquid at ambient temperature, therefore, melting point is ambient temperature) Not available for Tea Tree Oil (based on the available data for the components Tea Tree Oil is expected to have a boiling point of ca 200 C) Not specified Clear liquid (technical Tea Tree Oil) Not available for Tea Tree Oil (based on the values reported for the individual components TTO is expected to be volatile). terpinene-4-ol 53.2 Pa at 20 C * 14.9 Pa at 20 C (97%) (experimental) gamma-terpinene 93.1 Pa at 20 C * 103 Pa at 23.5 C alpha-terpinene Pa at 20 C * 1,8-cineole 253 Pa at 25 C alpha terpineol 5.69 Pa at 23.5 C * (98%) (experimental) * calculations using EPI suite Henry s law constant Not available for Tea Tree Oil terpinene-4-ol 4.64 Pa m 3 mol -1* Pa L mol -1 (based on experimental values gamma-terpinene 1476 Pa m 3 mol -1* alpha-terpinene 2485 Pa m 3 mol -1* 1,8-cineole 71 Pa m 3 mol -1* * calculations of water solubility and/or vapour pressure Solubility in water (state temperature, state purity and ph) Not available for Tea Tree Oil terpinene-4-ol 1767 mg/l * 3280 mg/l (20 C, 97%, ph 5.85) (experimental) gamma-terpinene 8.72 mg/l at C alpha-terpinene 5.92 mg/l * 1,8-cineole 552 mg/l * * calculations using EPI suite EFSA Journal 2012;10(2):