Table 4 Summary of undisclosed DNT studies: timeline, study results, and regulatory impact. DER – Data Evaluation Record. PoD – Point of departure. Bw – body weight. f – female, m – male. “---” – we have no access to this information. Laboratories: Bayer: Bayer CropScience LP Toxicology. Stilwell, KS, USA. CTL: Central Toxicology Laboratory, Macclesfield, Cheshire, UK. Huntingdon: Huntingdon Life Sciences, Ltd., Huntingdon, Cambridgeshire, England, UK
Companies and regulatory timeline | DNT study conclusions | Regulatory impact of DNT study | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
by test laboratory | by agency | ||||||||||||||||
Substance name | Sponsor/ test laboratory | DNT study report | Annex I inclusion, applicants | Applicants Annex I renewal (AIR), dossier submitted | AIR outcome | Dose levels | Off-spring NOAELa | Offspring critical effecta | Offspring NOAEL | Offspring critical effect | Mater-nal NOAEL | Source | When/how did EFSA become aware of DNT study? | Most recent PoD (NOAEL) for ADI mg/kg bw/day | Most recent PoD (NOAEL) for ARfD, mg/kg bw/day | Source for PoDs | Regulatory consequences of DNT study |
Abamectin | Syngenta/CTL | 2005 + 2007 | Syngenta 2009 | Five companies not incl. Syngentab 2016 | Renewal 2023 | 0, 0.12, 0.2, 0.4 mg/kg bw/day | --- | --- | < 0.12 | Decreased bw, delayed sexual maturation in f | 0.4 | EFSA RAR 2020 | RMS requested, RAR 2020 | 0.12 (DNT rat, LOAEL) | 0.12 (DNT rat, LOAEL) | EFSA Conclusion 2022 | yes |
Buprofezin | ---/--- | approximately 2002 | Nihon Nohyaku 2011 | Nihon Nohyaku 2020 | pending | --- | --- | --- | --- | --- | --- | --- | Sept. 2022, by us | 0.9 (2-y rat) | 50 (developmental rat) | EFSA Conclusion 2010 | unknown |
Ethoprophos | Bayer/Bayer | 2004 | Bayer 2007 | AMVAC 2016 | Non-renewal 2019 | 0, 3, 30, 180 ppm | 3 | AChE inhibition | < 3 | motor activity PND 17 m | < 3 | EFSA final RAR 2018 | EFSA found, Peer Review Report 2018 | not set - genotox potential | not set - genotox potential | EFSA Conclusion 2018 | yes |
Fenamidone | Bayer/Bayer | 2005 | Bayer 2003 | Bayer 2013 | Non-renewal 2018 | 0, 60, 250, 1000, 4700 ppm | 1000 | decreased bw (gain) | 1000 | decreased bw (gain). Increased motor activity on PND 13 + 17 in top two dose groups c | 4700 | EPA DER | Oct. 2022, by us | not set - genotox potential | not set - genotox potential | EFSA Conclusion 2016 | potential: offspring < maternal NOAEL, possible motor activity effects at maternal NOAEL |
Fenamiphos | Bayer (?)/ Bayer | 2004 | Irvita 2007 | AMVAC 2016 | Non-renewal 2020 | 0, 2.5, 10, 50 ppm | --- | --- | 10 (2.1 mg/kg bw/day) | RBC ChE inhibition | 2.5 | EFSA conclusion 2019 | public consultation 2018, our comment | 0.083 (chronic dog) | 0.25 (acute neurotox dog) | EFSA Conclusion 2019 | no |
Fluazinam | ISK: Ishihara Sangyo Kaisha/ Huntingdon | 2005 | ISK 2009 | Five companies incl. ISKd 2016 | pending | 0, 2, 10, 50 mg/kg bw/ day | 2 | decreased bw (gain). | 2 | decreased bw (gain). Delayed sexual maturation in m. Decreased non-perfused brain weights m/f in top two dose groups c | 50 | EPA DER | EFSA or RMS found, included in draft RAR 2021 | 1 (2-y mouse) | 7 (developmental rabbit) | EFSA Conclusion 2008 | potential: offspring NOAEL < PoD for ARfD, offspring < maternal NOAEL |
Glyphosate (-trimesium) | Syngenta/CTL | 2001 | Four com-panies incl. Syngentae 2002 | Glyphosate renewal group incl Syngenta and Bayer 2020 | pending | 0, 10, 25, 100 mg/kg bw/ day | 25 | decreased survival; bw; memory in high dose m on PND 62 | 10 | decreased PND 14 motor activity in f/m | 100 | EPA DER, ECHA RAC opinion | March 2022, by us | 10 (2-y rat) | 150 (developmental rabbit) | RAR 2021 | potential: offspring NOAEL < PoD for ARfD |
Pymetrozine | Syngenta/CTL | 2003 | Syngenta (Novartis) 2001 | Syngenta 2012 | Non-renewal 2018 | 0, 100, 500, 2500 ppm | 100 | Mortality, litter size, survival | < 100 (< 8.1 mg/kg bw/day) | brain morphometric changes in f PND 12 and m PND 63 offspring | 100 | EPA DER | RMS found, approx. 2017 | 3 (90-d + 1-yr, dog) | 10 (developmental rabbit) | EFSA Conclusion 2014 | yes |
Pyridaben | Nissan Chemical/ Huntingdon | 2007 | Nissan Chemical 2011 | Nissan Chemical 2020 | pending | 0, 25, 50, 100 ppm | 50 | decreased bw | 25 (= 2.2 mg/kg bw/day) | decreased bw. Increased PND24 auditory startle pre-pulse inhibition at all dose levels in f/m c | 25 | EPA DER | Sept. 2022, by us | 1 (2-y rat) | 5 (developmental study/maternal, rabbit + rat) | EFSA Conclusion 2010 | potential: offspring NOAEL < PoD for ARfD, possible auditory startle effects at maternal NOAEL |