ED assessment of active substances in PPPs came into effect in November 2018 in the EU. Insights from EFSA’s assessment of the first 65 actives shows how guidance is applied and how waivers are being used. Read on to find out how to negotiate the ED assessment process and when to consider derogations for active substances with ED potential.
内分泌干扰者定义和评估欧盟
2018年6月，欧洲食品安全局（EFSA）和欧洲化学物质局（ECHA）发表guidanceon the identification of Endocrine Disruptors (EDs), which has impacted all active substance renewals in plant protection products (PPPs) since November 2018.1An active substance is classed as an ED if:
- It produces an adverse effect in an intact organism, subpopulation or progeny that results in an impairment of functional capacity or capacity to compensate for additional stress. Or increases susceptibility to other influences.
- It has an endocrine mode of action.
- The adverse effect is a consequence of its endocrine mode of action.
Assessment of ED focuses on the impact of an active substance on the estrogen, androgen, thyroid hormone and steroidogenesis pathways – known as EATS modalities.Table 1显示ECHA / EFSA指导下PPP的标准信息要求。
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Regulation 283/2013 further states that where there is evidence that the active substance may have ED properties, additional information shall be required. The data package of most active substances is likely to contain data derived from older versions of OECD studies; however, this data will only be deemed sufficient for assessing EATS-mediated adversity, if all parameters required in the ED guidance are reported. The following ‘best practice’ parameters should be included in new study protocols and reported fully:
- Anogenital distance of each F1 and F2 pups
- Presence and number of nipples/areolae in all male F1 and F2 pups
- P0和F1成年男性和女性乳腺组织病理学评估
- Sperm parameters measured always by default (regardless of whether they have also been tested in the 90 days)
OECD测试指南的较新版本具有强制性甲状腺激素（TH）测量。但是，有效TH assessment继续证明具有挑战性。
Furthermore, where no mode of action analysis is provided, effects observed on many endocrine organs are considered to be EATS mediated. A plausible link between the adverse effect and endocrine activity is important.
EFSA的ED评估活性物质的现状
In November 2020, EFSA shared details of the first 65 active ingredient ED assessments.2这为欧盟的方法和注册人可能面临的潜在问题提供了宝贵的洞察力。在2020年11月完成的65名ED评估中：2
- 37％需要与人类健康有关的额外数据的额外数据。
- 73% required additional data for EATS modalities relating to non-target organisms.
- 23% (eight) active substances were identified as EDs, of which five were related to the thyroid modality.
It is also noteworthy that a proportion of active substances saw ED data requirements waived during the renewal:
- 18.5% of ED assessments relating to human health
- 12.3％的ED评估与非靶毒性有关
It is the rapporteur Member States that propose the information required to reach an ED conclusion in the draft renewal assessment report. Assessment of most active substances are now in the ‘stop-the-clock’ phase, which allows up to 30 months for registrants to provide missing ED data. Collecting and analyzing data within that timeframe is challenging, especially as studies likeEOGRTSare complex to conduct, due to triggered breeding, and require flexible capacity to house extended generations.
ED assessment waivers and when they apply
In some scientifically justified circumstances, EFSA willwaive ED assessment.3放弃评估的最常见的基本原理涉及活性的内在物理化学和（ECO）毒理学特性。如果这些证实ED评估在科学上不可能或技术上是不可能的，那么它们可能会被免除。EFSA坚持认为，每个豁免应在案例基础上进行科学辩护和制造。这意味着总结了所有相关信息，在ED指导的背景下评估它并制定明确的科学论证。3
Based on the first 65 active substances assessed, ED assessment was waived for human health for actives showing potent anti-cholinesterase inhibition, dose-limiting local irritant effects and dose-limiting induction of methemoglobinemia.2,3授予与非毒性有关的非靶毒性有关的非靶毒性的评估豁免，其具有无毒的作用方式，惰性性质或因为活性物质被消耗作为正常饮食的一部分。2
归类为归类为EDS的活性物质
Even if your active substance is classified as an ED, you may have the option of requesting derogation. During the ‘stop-the-clock’ period, you can request derogation or submit information on the basis that human or non-target organism exposure to an active substance in a PPP, under realistic conditions of use, is negligible. This anticipates that the PPP will be used in a closed system or under other conditions that exclude contact with humans and that the residues do not exceed the default value made inRegulation (EC) No 396/2005. Similarly, its effect on non-target organisms must also be negligible, as stated in Annex II, Points 3.6.5 and 3.8.2.
In addition, applicants should inform the EC of certain serious plant protection dangers that cannot be controlled by any other means. Approval may be granted for a period not exceeding seven years as a candidate of substitution.
According to监管的1109/2009,国家当局还可以授予减损under Article 53 for emergency use in special circumstances. Applicants need to apply to individual member states for authorization of products containing candidates of substitution.
对您的活跃物质的行动方式良好了解，其在农业背景中的使用是成功减损争论的关键。例如，您的活跃物质可能有资格损失：
- It is the only active that offers either a contact or a systemic action and that mode of action is critical for controlling the pest.
- 在抵抗管理计划中使用是重要的，以防止进一步发展抗性菌株。
- It is the only compatible active substance for use within an integrated pest-management program.
- Compared with other methods of controlling the pest or disease, it is the safer alternative.
这不是一个详尽的例子列表，但是说明了如何考虑disogation参数。
Future considerations for ED assessment across all EU legislation
A recentfitness check4of all EU legislation related to ED assessment identified that, although there was no inconsistency in ED identification, risk-management approaches did vary. Consolidation of the principles guiding ED risk management was recommended. Risk management is already built into biocidal product ED assessment and this may be extended to PPPs in future. In addition, the criteria already developed for pesticides and biocides could be further rolled out to other sectors.
The ED assessment mandates the use of animals, with studies like EOGRTS requiring testing on adults and progeny. It is, therefore, not surprising that the fitness check also identified the need to develop ED assessment methods that minimize animal use.
Conclusions
PPP中的活性物质现已在EFSA指南中进行EU的评估。有详细的档案，清楚地秉承ED指导增强了活性物质更新期间成功的机会。在某些情况下，ED评估豁免可能是具有适当物理化学性质和低毒性谱的活性物质的相关性。如果曝光被证明是可忽略的或存在独特的植物保护需要，则损伤可能适用于所在的活性物质，或者被怀疑是曝光的，或者有一个独特的植物保护需要活跃。
对于被归类为EDS的活性物质，批准将被撤销，除非减损被批准，否则他们再也无法销售。
景by Labcorp has been keeping abreast of guideline discussions to anticipate requirements, and we are expanding available capacity to enable clients to meet requirements now and in the future.
For more information about our endocrine disruptor services for crop protection products,点击这里,and to learn more about ED regulatory frameworks in the U.S. and EU,下载我们的电子书。
