List of Endpoints
The List of Endpoints presented below is taken from the EFSA Conclusion on the peer review of the pesticide risk assessment of the active substance 6-benzyladenine (EFSA Journal 2010; 8(10):1716).
Metabolism in plants (Annex IIA, point 6.1 and 6.7, Annex IIIA, point 8.1 and 8.6)
Plant groups covered Metabolism study in apple submitted together with scientific review reports on roots vegetables, cereals and pulses and oilseeds
Rotational crops No data available, not required.
Metabolism in rotational crops similar to metabolism in primary crops?
Not applicable
Processed commodities Not required although a processing study has been evaluated for apple pomace.
Residue pattern in processed commodities similar to residue pattern in raw commodities?
No concentration of residues during processing
Plant residue definition for monitoring 6-Benzyladenine Plant residue definition for risk assessment 6-Benzyladenine Conversion factor (monitoring to risk assessment) None
Metabolism in livestock (Annex IIA, point 6.2 and 6.7, Annex IIIA, point 8.1 and 8.6)
Animals covered No data available, not required.
Time needed to reach a plateau concentration in milk and eggs
Not applicable
Animal residue definition for monitoring Not applicable Animal residue definition for risk assessment Not applicable Conversion factor (monitoring to risk assessment) None
Metabolism in rat and ruminant similar (yes/no) Not applicable Fat soluble residue: (yes/no) Not applicable
Residues in succeeding crops (Annex IIA, point 6.6, Annex IIIA, point 8.5)
No study available. Not required, because only uses in seed production and permanent crops are intended.
Furthermore 6-BA rapidly degrades in soil (DT50 1 - 1.2 days).
Stability of residues (Annex IIA, point 6 introduction, Annex IIIA, point 8 Introduction)
Apples at – 18°C:
12 months at 0.025 mg/kg level 18 months at 0.25 mg/kg level
Residues from livestock feeding studies (Annex IIA, point 6.4, Annex IIIA, point 8.3)
Ruminant: Poultry: Pig:
Conditions of requirement of feeding studies Expected intakes by livestock 0.1 mg/kg diet (dry
weight basis) (yes/no - If yes, specify the level)
No No No
Potential for accumulation (yes/no): N/A N/A N/A Metabolism studies indicate potential level of
residues ≥ 0.01 mg/kg in edible tissues (yes/no)
N/A N/A N/A
Feeding studies (Specify the feeding rate in cattle and poultry studies considered as relevant)
Residue levels in matrices : Mean (max) mg/kg
Muscle N/A N/A N/A
Liver N/A N/A N/A
Kidney N/A N/A N/A
Fat N/A N/A N/A
Milk N/A
Eggs N/A
5.1 Summary of residue data
The residue assessment of 6-benzyladenine is based on the Draft Assessment Report (DAR) prepared by France, dated September 2007, the Additional report to the original DAR prepared by UK in October 2009, the EFSA Conclusion on the peer review of the pesticide risk assessment of the active substance 6-benzyladenine (EFSA Journal 2010; 8(10):1716), TNO report (CTB-2006-016-RES-NL, d.d.
June 2006) and Ctgb reports 20040057-sava-res-V01and 20130744-Evaluation report natural background levels of 6-benzyladenine.
5.1.1 Metabolism in plants
Metabolism of [14C]-6-benzyladenine (6-BA) was studied in apple following a foliar application of 0.014 kg as/ha. The application was performed on apples when the fruit was <15 mm in diameter (BBCH 71). Apple samples were collected 0, 7, 50 and 90 Days After Treatment (DAT); leave samples were collected 0, 7 and 90 DAT.
The Total Radioactive Residue (TRR) in leaves and fruit declined rapidly after application. The extractable residues (surface wash and solvent extraction) liberated >79% of the TRR in apple fruit and >67% in leaves. The surface wash TRR decreased extensively with time, indicating: incorporation, growth dilution or rinsing off residue during growth.
In fruit samples taken close to the time of application (0 & 7 DAT), 6-BA was the major component.
One metabolite (M14) was found 7 DAT at levels above 10 % TRR and 0.05 mg/kg. This metabolite was not found at levels above 10 % TRR and 0.05 mg/kg 50 DAT or at commercial harvest (90 DAT).
Metabolism in the fruit samples 50 DAT was more extensive: apart from 6-BA, 10 other components were detected. Only M10 was above 10% TRR (0.011 mg/kg). At 90 DAT no 6-BA was detected. The two components M5 and M10 were detected above 10% TRR. Nonetheless, the absolute quantities were very low (0.005 mg/kg and 0.007 mg/kg for M5 and M10, respectively) and therefore these metabolites are not considered of toxicological concern.
Significant metabolites found in leaves were also present in fruit suggesting that metabolism was similar in both tissues.
5.1.2 Metabolism in livestock
Based on the available residue data, no significant residues in animal feed (>0.1 mg/kg dry diet) are expected as a result of the intended use, so a livestock metabolism study is not required.
5.1.3 Residue definition (plant and animal) Residue definition in plant and plant products
The metabolism study on apple fruit shows that the TRR is very low at commercial harvest/90 DAT (0.021 mg/kg). The magnitude of the five individual metabolites is <0.01 mg/kg. The TRR of two metabolites is above 10% (21.61% and 30.61% for M5 and M10, respectively). Since the absolute magnitude of both metabolites is very low (0.007 mg/kg), they are considered not relevant for the definition of the residue and further characterisation is considered not necessary.
No significant residue is expected at commercial harvest. Parent 6-BA is the major residue when the application of 6-BA is closer to harvest. Therefore, the residue definition is parent only.
Residue definition in animal products
Based on the available residue data, no significant residues in animal feed (>0.1 mg/kg diet) are expected as a result of the intended use, so a residue definition in animal products is not required.
5.1.4 Stability of residues See List of Endpoints.
5.1.5 Residue data Apple
(cGAP-NL: 1x 0.015 kg as/hL, maximum 0.225 kg as/ha.)
For the application of authorisation, 8 supervised residue trials in apple in Northern Europe have been submitted. Trials were performed under field conditions and GLP. In all trials, the used total dose was substantially higher than the proposed cGAP-NL (two applications at 0.004 kg as/hL and two applications at 0.020 kg as/hL using a spraying volume of 1000 L/ha at an application interval of 7 days). However, none of the trials showed residue levels of parent 6-benzyladenine above the LOQ (0.005 mg/kg) in any sample at harvest time. Therefore, the trials are considered acceptable and a sufficient number of residue trials are available.
During the review of the active substance 6-benzyladenine it was decided to set a PHI of 90 days for the defended uses in apples.
Pear
(cGAP-NL: 1x 0.020 kg as/hL, maximum 0.2 g as/ha)
Residue data in apple can be extrapolated to pear. The PHI of 90 days also applies to pears.
A 90-day PHI is required for the uses of 6-benzyladenine on apples and pears.
“Veiligheidstermijn:
De termijn tussen de laatste toepassing en de oogst mag niet korter zijn dan 90 dagen voor appels en peren.”
5.1.6 Residues in succeeding crops
The intended use for this application for authorisation does concern use in an orchard, where rotational crops are not relevant. Furthermore, there is no risk of significant residues of
6-benzyladenine in succeeding crops given the rapid degradation of this substance in soil. The DT50 range in soil is between 1 and 1.2 days. Therefore, a rotational crop study is not required.
5.1.7 Residues from livestock feeding studies
Based on the available residue data, no significant residues in animal feed (>0.1 mg/kg diet) are expected as a result of the intended use, so a livestock feeding study is not required.
5.1.8 Processing factors
The available residue data show that no analytically determinable residues (<0.005 mg/kg) occur in the plant product to be processed and the Theoretical Maximum Daily Intake is less than 10 % of the ADI. Thus, a processing study is not required.
5.1.9 Calculation of the ADI and the ARfD
During the EFSA Peer Review of the pesticide risk assessment of the active substance
6-benzyladenine, it was initially proposed that 6-benzyladenine is a naturally occurring plant hormone.
In view of this, and given that the available data indicated that residues would be expected to be low, it was proposed that consumer exposure would not be significant. However, during the writing of the EFSA conclusion it was questioned by EFSA whether 6-benzyladenine is naturally occurring, at least in edible crops. A data gap was identified for further quantitative evidence that 6-benzyladenine is a naturally occurring compound and the consumer risk assessment could not be finalized.
In spite of the data gap, 6-Benzyladenine was voted for inclusion on Annex I of 91/414/EEC on 23 November 2010 by the SCFCAH and an ADI of 0.01 was finalised as proposed by the RMS UK in the Additional report to the original DAR. The ADI is based on the NOAEL of 1 mg/kg bw/day in the developmental toxicity study in rabbits. Application of a safety factor for inter- and intraspecies differences of 100 and a safety margin of 10 (taking into account a 2-year dog study and the weak toxicity database including absence of long-term toxicity study in rodents) resulted in an ADI of 0.01 mg/kg bw/day. No Acute Reference Dose (ARfD) value was considered necessary since no consumer exposure was expected for the representative uses.
With particular regard to residues, the review has established that the residues arising from the proposed uses, consequent on application consistent with good plant protection practice, have no harmful effects on human or animal health. Although there were no critical areas of concern in the residues section, the applicant provided a literature study on the natural occurrence of 6-BA
(Heiman, D., B. Baldi and M. Herrero, 2011) to address the data gap identified by EFSA. This literature study was evaluated in Ctgb report 20130744-Evaluation report natural background levels of 6-benzyladenine. The literature study adds little to the data already evaluated in the DAR (September 2007) and in the Additional report (November 2009). Although exact quantitative data on 6-BA levels in food items are limited, the review of the published literature indicate that the aromatic cytokinins, and specifically 6-BA and its conjugates, are naturally present in a multitude of different plants that are utilized as food by humans and many different animals. In addition, in the course of preliminary work toward development of a residue method for 6-BA, Valent BioSciences has found evidence that 6-BA is present in food items that are normal components of European diets. Given that the available data indicate that levels of 6-BA in plant products arising from the approved plant protection product uses would be low, it is not expected that the levels of 6-BA will be higher than the levels which occur naturally.
5.2 Maximum Residue Levels
6-BA is not currently listed in Regulation 396/2005 and therefore the default 0.01 mg/kg value on apple applies. Residue levels arising from the intended use of the product comply with the default MRL of 0.01 mg/kg. Based on the conclusion that 6-BA is proposed as a naturally-occurring
compound, the origin of residues may not be conclusively attributed to the authorised use of 6-BA as a plant growth regulator and fruit thinner. Consideration could be given to inclusion of 6-BA in Annex IV of Directive 396/2005, in which case the compound would be exempted from MRL-setting.
5.3 Consumer risk assessment
6-benzyladenine is a naturally occurring plant hormone and no additional consumer exposure is
with good plant protection practice, have no harmful effects on human or animal health. The Theoretical Maximum Daily Intake (TMDI, UK diet for toddlers) is less than 6 % of the Acceptable Daily Intake (ADI), (calculated according to the EFSA PRIMO model).
Estimates of acute dietary exposure of adults and children have not been conducted since no ARfD value was considered necessary.
Overall, 6-benzyladenine is a chemical analogue of a naturally occurring substance and the levels of 6-BA are not expected to be higher than the levels which occur naturally. In view of this, consumer exposure is not significant.
Conclusion
Based on the assessment for residues, no risk for the consumer due to the exposure to
6-benzyladenine is expected, provided that the product is applied according to the proposed GAP and the PHI is set at 90 days. The product complies with the Uniform Principles.
5.4 Data requirements No additional data required.