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Key value for chemical safety assessment

Effects on fertility

Description of key information

Fertility information (OECD 408, with extended protocol)

NOAEL systemic = 100 mg/kg bw/day

NOAEL fertility ≥ 1000 mg/kg bw/day

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2) is a substance in Cramer class I, indicating low concern with respect to systemic toxicity. In the 28-day repeated dose toxicity study, no toxicologically relevant effects were observed up to and including the highest dose level of 1000 mg/kg bw/day (Pitterman, 1993). In a developmental study with a study protocol similar to OECD 414, the test substance was administered to pregnant rats on gestation day 6-15 in doses up to 1000 mg/kg bw/day (Pitterman, 1997). No treatment-related effects on reproduction parameters or systemic toxicity were noted in the P-females, and no developmental effects were observed in the F1-pups up to and including the highest dose level of 1000 mg/kg bw/day (limit dose).

Futher in a GLP-compliant subchronic toxicity study in the rat via the oral route (OECD 408, GLP) (BASF SE 2018) an extended standard protocol with additional sperm motility parameters was performed and careful examination of reproductive organs/tissues to assess the potential effects of isononanoic acid isononanoate on fertility was performed. In summary there were no effects observed which influence the fertility up to and including the highest tested dosage of 1000 mg/kg bw/d.

The available data indicate that no toxicity to reproduction is expected. Unnecessary testing on vertebrate animals is discouraged under Regulation (EC) 1907/2006, Annex XI, subparagraph 1.2, in favour of a weight-of-evidence approach. Therefore, no additional studies on toxicity to reproduction are currently justified for this endpoint.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.


Short description of key information:
Developmental toxicity study (OECD 414), rat, oral:
NOAEL systemic (P females, F1) ≥ 1000 mg/kg bw/day
NOAEL fertility (P) ≥ 1000 mg/kg bw/day
NOAEL reproduction (P) ≥ 1000 mg/kg bw/day

Fertility information (OECD 408, with extended protocol)

NOAEL systemic = 100 mg/kg bw/day

NOAEL fertility ≥ 1000 mg/kg bw/day

Effects on developmental toxicity

Description of key information
Prenatal developmental toxicity study (OECD 414), rat, oral:
NOAEL teratogenicity (F1) ≥ 1000 mg/kg bw/day
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfill the standard information requirements set out in Annex VIII-IX, 8.7 of Regulation (EC) 1907/2006.
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

Toxicity to reproduction – (pre-natal) development

The potential of isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2) to cause developmental toxicity was assessed in a study performed using a study protocol similar to OECD guideline 414 (Pitterman, 1997). 23-24 pregnant female Sprague-Dawley rats/dose level were administered 0, 100, 300 and 1000 mg/kg bw/day of the test substance by gavage on gestation Day 6 to 15.

No signs of systemic toxicity were observed in the P-females and no treatment-related effects were observed. One female in the high-dose group had blood in the uterine horn, but this is not considered to be treatment-related as no related effects were observed. One female in each of the control group and the low-dose group did not become pregnant, while all the pregnant females had viable foetuses. No treatment-related effects on the reproductive parameters (number of corpora lutea, implantation sites, pre-implantation loss, post-implantation loss, embryonic deaths, embryonic resorptions, foetal resorptions, live foetuses, dead foetuses) were observed.

The external examination of the F1-foetuses did not reveal any treatment-related macroscopic findings. The skeletal examination showed a statistically significant increase in the number of foetuses with 6 ossified sternebrae in the mid-dose group (300 mg/kg bw/day). As there were no increases in ossification anywhere else and no overall increase in abnormal findings for this group, the result is considered to be incidental. The results for the remaining offspring parameters (body weight, placental weight, sex ratio) were comparable between the control and treatment groups. 

The NOAEL developmental is considered to be ≥ 1000 mg/kg bw/day.

The most recent version of OECD guideline 414, adopted in January 2001, stipulates that the dams should be dosed from implantation (gestation Day 0) to the day prior to scheduled caesarean section (around gestation day 19 for rats). The study was performed according to the previous version of OECD guideline 414, adopted in May 1981, which recommended exposure during organogenesis; gestation Day 6-15 for rats. The available data on repeated dose toxicity and developmental toxicity is of high quality and does not show treatment-related adverse effects at dose levels up to and including the highest dose of 1000 mg/kg bw/day, indicating that adverse effects are unlikely to occur in the period prior to Day 6 of gestation (Pitterman, 1993, 1997). Based on the available it is not considered necessary to perform an additional, dedicated, developmental toxicity study.

Conclusions for developmental toxicity

A developmental toxicity study performed with isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2), using a protocol similar to OECD guideline 414 is available (Pitterman, 1997). Pregnant rats were administered the test substance from gestation Day 6-15. No effects on development (survival, body weight, sex ratio, external appearance, skeletal development) in the P1-pups were observed up to and including the highest dose level of 1000 mg/kg bw/day.

Thus, isononanoic acid, C16-18 alkyl esters is not considered to cause adverse effects on intrauterine development.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.


Justification for selection of Effect on developmental toxicity: via oral route:
There is only one study available.

Justification for classification or non-classification

The available data on the toxicity to reproduction of the substance do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

Additional information