Nonanoic acid, esters with adipic acid and trimethylolpropane

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Oral (OECD 422, GLP): NOAEL (rat) = 1000 mg/kg bw/day for systemic toxicity and fertility (RA from CAS 126-57-8)

Effect on fertility: via oral route

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).

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Justification for read-across

There are no data available regarding reproduction toxicity of the target substance Nonanoic acid, esters with adipic acid and trimethylolpropane. Therefore, 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, 8.7. 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) 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. Gestation periods were similar in the control and treated groups. In each group, all dams littered between Day 21 and 23 post coitum. The number of Corpora lutea, implantations, and the pre-implantation loss data and the total litter size were similar in control and treated groups. The pre-birth loss was higher in females receiving 1000 mg/kg bw/day when compared with the control group. However, this change was not statistically significant and was attributable to two females. A detailed qualitative examination of the testes was performed in five control and high dose group males. Seminiferous tubules were evaluated with respect to their stage in the sperma-togenic cycle and to the integrity of the various cell types within the different stages; regular layering in the germinal epithelium was noted. Since no treatment-related and adverse effects were observed, the NOAEL (No Observed Adverse Effect Level) was considered to be the highest dose of 1000 mg/kg bw/day for systemic toxicity and fertility in P1 animals.

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 and fertility in P1 animals. Therefore applying the read-across approach similar results are expected for the target substance.

Effects on developmental toxicity

Description of key information

Oral (OECD 422, GLP): NOAEL (rat) = 1000 mg/kg bw/day for the offspring (RA from CAS 126-57-8)

Effect on developmental toxicity: via oral route

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).

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Justification for read-across

There are no data available regarding reproduction toxicity of the target substance Nonanoic acid, esters with adipic acid and trimethylolpropane. Therefore, 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, 8.7. 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) according to OECD 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 to a control group that received only the vehicle (corn oil). 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. Regarding toxicity to the offspring, no differences in total and live litter size or in sex ratio were noted between the control and the treated groups at birth and on Day 4 post partum. Moreover, no abnormalities were recorded in the decedent pups. A malrotated left hindlimb noted in one pup of the low dose group (100 mg/kg bw/day) and tip missing of the tail seen in one pup of the mid-dose group (300 mg/kg bw/day) were considered incidental occurrences and were therefore not treatment-related. Based on these results the NOAEL (No Observed Adverse Effect Level) was considered to be the highest dose of 1000 mg/kg bw/day for the offspring.

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 the offspring. 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.

The available data on toxicity to reproduction with the analogue substances trimethylolpropane tripelargonate (CAS 126-57-8) does not meet the classification criteria according to Regulation (EC) 1272/2008. However, as no prenatal developmental toxicity study is available, the conclusion for classification is ´data lacking`.