reaction mass of isomers of: C7-9-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Endpoint summary

Description of key information

Summary of 28-day repeat dose study

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

There are 4 studies available for review as follows: detailed in the SNIF file provided by ECHA; giving the following results:

Study 1:Detailed in the SNIF file provided by ECHA, 28-days.

NOAEL: 5 mg/kg/day

Study 2:Detailed in the SNIF file provided by ECHA, 28-days.

NOAEL: 200mg/kg/day

NOEL: < 50mg/kg/day

 

Study 3: Study report on the substance itself, provided by the registrant, 28-days.

 

NOEL: 15 mg/kg/day

 

Study 4: Detailed in the SNIF file provided by ECHA, 90-days.

 

NOEL: 3 mg/kg/day

 

This data is provided from the SNIF file provided by ECHA for data that is >12 years old. In the more detailed study, a NOAEL of 200 mg/kg/day is reported; however the overall conclusion of the report is that the substance is not classified. This is based on the fact that the study observations appears to be adaptive processes only, and are fully reversible. This conclusion appears to be mirrored in all of the repeat dose toxicity studies available for the substance, and is a common theme.

 

As a result, it is considered appropriate to instead to take the NOAEL as 200 mg/kg/day. This is based on the assumption that the full study report has been previously reviewed by an EU member state authority under the 7th Amendment "notification" scheme, and the decision to "not classify" the substance was made at this time. Therefore, no classification is proposed for repeated dose toxicity.

 

The test substance has very low vapour pressure (0.0015 Pa at 20 °C) so the potential for the generation of inhalable forms is low. In addition the use of this substance will not result in aerosols, particles or droplets of an inhalable size. The substance is therefore unlikely to be inhaled and the physicochemical and toxicological properties suggest low potential for significant effects resulting from absorption through the skin. Furthermore the results of laboratory animal studies show negligible acute dermal toxicity. In the 28 - days repeated dose study via oral gavage administration does not appear to exacerbate systemic toxicity effects which suggest bioavailability is low, thereby there is low toxicity potential. This intrinsic property/toxicity potential can be extrapolated to repeated dermal and/or inhalation route administration. Further studies for this endpoint are therefore not appropriate both on predictive toxicology and animal welfare grounds.

 

The following information is taken into account for any hazard / risk assessment:

Assessment of repeat dose exposure by oral route is discussed below.

Value used for CSA (route: oral):

NOAEL: 200 mg/kg bw/day (subacute; rat)

NOEL: 50 mg/kg bw/day (subacute:rat)

Justification for classification or non-classification

The above studies have all been ranked reliability 1 or 2 according to the Klimish et al system. This ranking was deemed appropriate because the studies were all conducted to GLP in compliance with recognised guidelines. The majority of the information has been provided from a migrated nons file referring to studies which are more than 12 years old, with the permission of ECHA.

The above results triggered no classification in the intitial review by an EU Member State Authority under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for repeat dose effects is therefore required.