Registration Dossier

Administrative data

Description of key information

Oral (OECD 422, GLP, read across): NOAEL (rat, systemic, m/f) = 1000 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose (refer to the endpoint discussion for further details).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for read-across

There are no data available regarding repeated dose toxicity of the target substance Nonanoic acid, esters with adipic acid and trimethylolpropane. Thus, read-across from the appropriate structural analogue substance trimethylolpropane tripelargonate (CAS 126-57-8) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard information requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.6. Common functional groups and structural similarities combined with similar toxicokinetic properties of the source and target substances are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

CAS 126-57-8

A combined repeated dose toxicity study with the reproduction / developmental screening test was available with the analogue substance trimethylolpropane tripelargonate (CAS 126-57-8); the study was performed according to OECD guideline 422 and GLP (RTC, 2014). Both male and female rats were treated for approximately 5 weeks. Three different doses were tested (100, 300 and 1000 mg/kg bw/day) and compared with a control group that received only the vehicle (corn oil). No mortality occurred throughout the study. No differences in body weights and food consumption were observed in treated animals compared with the control group. No clinical signs were observed during the study. No adverse findings were recorded in clinical pathology investigations (haematology, clinical chemistry and urine analysis) apart for lymphocytosis, which was recorded in a number of males dosed at 300 and 1000 mg/kg bw/day. Lymphocytes mean group values were 36% and 41%, respectively, above controls. The other statistically significant differences between control and treated animals (mean corpuscular haemoglobin concentration in males dosed with 100 mg/kg bw/day, erythrocytes in females of the same group and basophils in females dosed with 1000 mg/kg bw/day) were of minimal severity and/or not dose-related, therefore considered of no toxicological significance. No findings were recorded in the absolute and relative organ weights of treated animals, when compared with the control. No treatment-related changes were noted during the macroscopic and microscopic examinations. Regarding functional observation battery, motor activity and sensory reaction to stimuli measurements recorded at the end of treatment were comparable between control and treated groups in animals of both sexes. Variations recorded in mean grip strength in males receiving 1000 mg/kg bw/day and mean landing foot splay in males receiving 300 and 1000 mg/kg bw/day were considered incidental, since they were observed in one sex only and without correlation with the dose. Based on the results the NOAEL (No Observed Adverse Effect Level) for systemic toxicity was considered to be the highest dose of 1000 mg/kg bw/day.

Overall conclusion

The available data with the analogue substances trimethylolpropane tripelargonate (CAS 126-57-8) resulted in a NOAEL (No Observed Adverse Effect Level) of 1000 mg/kg bw/day for systemic toxicity. Therefore applying the read-across approach similar results are expected for the target substance.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Nonanoic acid, esters with adipic acid and trimethylolpropane, data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach, the available data on repeated dose toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.