Towards a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny – part II: how can key events of relevant adverse outcome pathways be addressed in toxicological assessments?
Critical Reviews in Toxicology, vol. 51, pp. 328–358
Abstract
assays allow identifying thyroid-related modes-of-action potentially leading to adverse neurodevelopmental outcomes, and the human relevance of effects - in line with the European Commission's Endocrine Disruptor Criteria. The underlying hypothesis is that an understanding of the key events of relevant AOPs provides insight into differences in incidence, magnitude, or species sensitivity of adverse outcomes. The rodent studies include measurements of serum thyroid hormones, thyroid gland pathology and neurodevelopmental assessments, but do not directly inform on specific modes-of-action. Opportunities to address additional non-routine parameters reflecting critical events of AOPs in toxicological assessments are presented. These parameters appear relevant to support the identification of specific thyroid-related modes-of-action, provided that prevailing technical limitations are overcome. Current understanding of quantitative key event relationships is often weak, but would be needed to determine if the triggering of a molecular initiating event will ultimately result in an adverse outcome. Also, significant species differences in all processes related to thyroid hormone signalling are evident, but the biological implications thereof (including human relevance) are often unknown. In conclusion, careful consideration of the measurement (e.g. timing, method) and interpretation of additional non-routine parameters is warranted. These findings will be used in a subsequent paper to propose a testing strategy to identify if a substance may elicit maternal thyroid hormone imbalance and potentially also neurodevelopmental effects in the progeny.
Authors 13
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Affiliation as printed
The Dow Chemical Company, Midland, MI, USA
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Charles River Laboratories (Netherlands)
Affiliation as printed
Charles River Laboratories, Den Bosch, The Netherlands
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Affiliation as printed
Syngenta, Jealott’s Hill, Bracknell, United Kingdom
Syngenta, Jealott's Hill, Bracknell, United Kingdom
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Affiliation as printed
Bayer AG, Monheim, Germany
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Affiliation as printed
Corteva Agriscience, Newark, DE, USA
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Affiliation as printed
Albemarle, Louvain-la-Neuve, Belgium
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Affiliation as printed
BASF SE, Ludwigshafen, Germany
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Affiliation as printed
Scientific Consultancy – Animal Welfare, Neubiberg, Germany
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Affiliation as printed
Bayer Crop Science, Chesterfield, MO, USA
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Affiliation as printed
BASF SE, Ludwigshafen, Germany
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Affiliation as printed
BASF SE, Ludwigshafen, Germany
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Affiliation as printed
Syngenta, Jealott’s Hill, Bracknell, United Kingdom
Syngenta, Jealott's Hill, Bracknell, United Kingdom
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Bennard van Ravenzwaay corresponding
Affiliation as printed
BASF SE, Ludwigshafen, Germany
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