Registration Dossier

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

OTNE ED assessment – IFF – IUCLID

Substance name: OTNE (Iso E; Iso E Super; Isocyclemone E)

EC number:915-730-3

Cas number: 54464-57-2 (one of the isomers)

Date: 27ndOctober 2020

 

Executive summary

The endocrine endpoints for OTNE are assessed on Estrogen, Androgen, Thyroid and Steroid activation (EATS).

Human health: In vitro data were found in the Toxcast database of which 49 assays relate to EATS endpoints. For estrogen activity 23 results are available, for androgen activity 9, for thyroid activity 15 and for steroidogenesis 2. All assays were negative when including those where cytotoxicity was exceeding the activity concentration (7 assays). Beside cytotoxicity, 5 assays showed additional flags on which basis the active result was concluded to be negative as well.

Several in vivo repeated dose and reproductive toxicity assays are available: 28-and 90-day studies (OECD TG 407 and 408); 38 to 60-days repeated dose toxicity information from the dose range finder (DRF, eq to OECD TG 421) for the Extended One Generation Reproductive Toxicity test (EOGRT, OECD TG 443), the EOGRT study itself and the developmental toxicity studies (OECD TG 414). On fertility there are the DRF for the EOGRT and the main EOGRT itself. For developmental toxicity, studies in rat and rabbit are available. In all these studies liver is the target organ, increasing in weight up to 50% in rat at around 500 mg/kg bw and up to 80% in mice up to 2000 mg/kg bw (vial dermal/oral (licking)) administration. Liver hypertrophy was also found. In none of the studies effects on fertility or developmental toxic effects were seen.For human health it can be concluded that the substance does not show any endocrine effect in any of the in vivo tests.

 

These in-vivo studies demonstrate that the incidental active findings (in the presence of several confounding factors) in vitro are not reflected in the in vivo apical endpoints.

 

Absence of relevant ED findings in vitro and in-vivo-in mammals can support the absence of ED effects in vertebrates (and invertebrates) because there is ahigh level of conservation of the endocrine system across the taxonomic groups (ECHA guidance, 2018). In addition to this the effects in standard long-term test were assessed for reproductive effects.

 

Environment: Data on vertebrates (two fish species) (and data on invertebrates) are from standard long-term toxicity tests. These data indicate that growth is similarly affected as reproduction. This indicates a general toxic effect and not hormonal or reproductive effects. In addition, the absence of relevant ED findings in the mammalian toxicity tests support the absence of effects in vertebrates in view of the high level of conservation of the endocrine system across the taxonomic groups (ECHA guidance, 2018). Based on these, the conclusion is that there is no indication for endocrine disrupting (ED) effects for environmental species.

Additional information

A full ED report is present in the attachment. Also the Toxcast excell sheet as of October 2020 is also inclueded there.

Categories Display