|
|
|
|
|
|
BIOCIDES |
|
Guideline studies |
+ |
Other reliabe information |
|
Literature data |
Evaluation of reliability and relevance for
' EATS ' endpoints
|
|
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"
� :li
,.,
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|
Assemble lines of evidence |
+ |
Assess lines of evidence |
+ |
Integrate lines of evidence |
•
Evidence for ' EATS ' -mediated adversity and endocrine activity ?
|
|
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'o
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> ,;; "'
" "
,;; "'
.,,
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l"O · s:
|
EATS-mediated parameters ( adversity and ED activity ) sufficiently investieated ? |
•
Observation of EATS-mediated adversity ?
|
Observation of
+ endocrine activity
|
•
Generation of further information necessary on EATS-related adversity and ED activity ?
|
Molecular initiating event ( MIE ) known / plausible in relation to adversity and ED activity ? |
+ |
Sequence of key events ( KEs ) and key event relationships ( KERs ) consistent and understood ? |
Adverse outcome ( s ) plausible and a
+ consequence of ' EATS-mediated ' MIE and KERs >
|
•
Postulation of MoA or generation of targeted information on EATS-related modalities
|
ED activity and EATS-mediated adverse effects observed ?
Biological plausible link between ED activity and EATS-mediated adverse effects ?
YES : ED criteria are met
No : ED criteria are not met
Conclusion not possible : Generation of further data
Figure I :
Figure 1 - Assessment strategy for potential ED properties of active substances used in biocidal & plant protection products
Flow chart on the assessment strategy for
• In vitro mechanistic : In vitro parameters of OECD CF Level 2 , providing information on a potential endocrine mechanism ( i . e ., receptor binding / activation , interaction with hormone production ).
• In vivo mechanistic : In vivo parameters of OECD CF Level 3 , providing information on usually nonadverse endocrine activity .
• EATS-mediated : In vivo parameters contributing to the evaluation of adversity , which are also considered indicative of an EATS MoA and imply underlying in vivo mechanistic information .
• Sensitive to , but not diagnostic of , EATS : In vivo parameters from OECD CF Levels 3-5 which contribute to the evaluation of adversity , but are not sufficiently indicative on their own of any one of the EATS modalities . In accordance with the document , the ED properties assessment comprises five stages ( Figure 1 ): 1 . Gathering of all information and parameters relevant for ED assessment , as listed above 2 . Assembling , assessing and integrating the lines of evidence ,
35