Fatty acids, C18-unsatd., dimers, polymers with 2-ethylhexanol and neopentyl glycol

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Screening test (OECD 421), NOAEL (fertility, systemic) ≥ 1450 (males) mg/kg bw/day (RA CAS 61788-89-4)

The NOAEL is corrected for differences in molecular weight between the source and target substance thus, the mass corrected NOAEL is 942.5 – 3552.5 mg/kg bw/day (males) for Fatty acids, C18-unsatd., dimers, polymers with 2-ethylhexanol and neopentyl glycol

Screening test (OECD 421), NOAEL (fertility, systemic) ≥ 1692 (females) mg/kg bw/day (RA CAS 61788-89-4)

The NOAEL is corrected for differences in molecular weight between the source and target substance thus, the mass corrected NOAEL is 1099.8 – 4145.4 (females) mg/kg bw/day for Fatty acids, C18-unsatd., dimers, polymers with 2-ethylhexanol and neopentyl glycol

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

942.5 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate, reliable study from a reference substance with similar structure. Read-across is justified based on common functional groups and structural similarities (please refer to analogue justification). Taken together, the information from this independent source is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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 available data assessing reproduction toxicity of Fatty acids, C18-unsatd., dimers, polymers with 2-ethylhexanol and neopentyl glycol (CAS 68552-19-2). The assessment of reproduction toxicity was therefore based on studies conducted with the source substance Fatty acids, C18-unsatd., dimers (CAS 61788-89-4) as part of a read across approach, which is in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.7. Read-across is justified based on theoretical hydrolysis of the test substance. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

 

CAS 61788-89-4

A reliable reproduction/developmental toxicity screening test performed according to OECD TG 421 and in compliance with GLP with Fatty acids, C18-unsaturated, dimers (CAS 61788-89-4) is available (Inveresk Research, 2004). Groups of 10 Sprague-Dawley rats of each sex per dose were administered doses of 200, 2000 and 20000 ppm with the diet corresponding to a test substance intake of 14.5, 147 and 1450 mg/kg bw/day and 16.5, 166 and 1692 mg/kg bw/day for males and females, respectively. Males were treated for at least 4 weeks, starting from 2 weeks prior to mating; females were treated for 2 weeks prior to mating, during mating and gestation until at least day 4 of lactation. The animals were monitored for clinical signs, body weight, food consumption, mating and litter performance. All animals were submitted to necropsy, which included weighing of testes and epididymides. Histopathology was conducted on male and female reproductive organs of the control and high dose group. The observed effects were limited to the 20000 ppm males and included slightly decreased body weight gain during the first week of treatment and an increased incidence of piloerection. However, weight gain for males at 20000 ppm was essentially similar to control animals for the rest of the study on weeks 2-4 and the incidence of piloerection lacked any dose-relationship. There were no effects on testes, epididymides and ovaries and on reproductive performance between control and test animals. The fertility index was 100% for males and females in all dose groups. A NOAEL (reproductive toxicity/fertility and systemic) of ≥1450 mg/kg bw/day and ≥1692 mg/kg bw/day for males and females, respectively, was determined based on no toxicologically significant effects at the highest dose tested. The molecular weight ratio of Fatty acids, C18-unsaturated, dimers (MW 564.92 g/mol) and Fatty acids, C18-unsatd., dimers, polymers with 2-ethylhexanol and neopentyl glycol (MW368 - 1386 g/mol) is 0.65 (368/564.92) and 2.45 (1386/564.92). Thus, based on this molecular ratio factor the NOAEL for Fatty acids, C18-unsatd., dimers, polymers with 2-ethylhexanol and neopentyl glycol was calculated to be 942.5 – 3552.5 mg/kg bw/day ((368/564.92)*1450) - ((1386/564.92)*1450) for males and 1099.8 – 4145.4 mg/kg bw/day ((368/564.92)*1692) - ((1386/564.92)*1692) for females, respectively.

Effects on developmental toxicity

Description of key information

Screening test (OECD 421), NOAEL (developmental) ≥ 1692 (m/f) mg/kg bw/day (RA CAS 61788-89-4)

The NOAEL is corrected for differences in molecular weight between the source and target substance thus, the mass corrected NOAEL is 1099.8 – 4145.4 mg/kg bw/day for Fatty acids, C18-unsatd., dimers, polymers with 2-ethylhexanol and neopentyl glycol

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 099.8 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate, reliable study from a reference substance with similar structure. Read-across is justified based on common functional groups and structural similarities (please refer to analogue justification). Taken together, the information from this independent source is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 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

Justification for read-across

There are no available data assessing reproduction toxicity of Fatty acids, C18-unsatd., dimers, polymers with 2-ethylhexanol and neopentyl glycol (CAS 68552-19-2). The assessment of reproduction toxicity was therefore based on studies conducted with the source substance Fatty acids, C18-unsatd., dimers (CAS 61788-89-4) as part of a read across approach, which is in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.7. Read-across is justified based on theoretical hydrolysis of the test substance. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

CAS 61788-89-4

A reliable reproduction/developmental toxicity screening test performed according to OECD TG 421 and in compliance with GLP with Fatty acids, C18-unsaturated, dimers (CAS 61788-89-4) is available (Pine Chemical Ass., 2004). Groups of 10 Sprague-Dawley rats of each sex per dose were administered doses of 200, 2000 and 20000 ppm with the diet corresponding to a test substance intake of 14.5, 147 and 1450 mg/kg bw/day and 16.5, 166 and 1692 mg/kg bw/day for males and females, respectively. Males were treated for at least 4 weeks, starting from 2 weeks prior to mating; females were treated for 2 weeks prior to mating, during mating and gestation until at least day 4 of lactation. The animals were monitored for clinical signs, body weight, food consumption, mating and litter performance. All animals were submitted to necropsy. The observed effects were limited to the 20000 ppm males and included slightly decreased body weight gain during the first week of treatment and an increased incidence of piloerection. However, weight gain for males at 20000 ppm was essentially similar to control animals for the rest of the study on weeks 2-4 and the incidence of piloerection lacked any dose-relationship. A NOAEL systemic of ≥1450 mg/kg bw/day and ≥1692 mg/kg bw/day for males and females, respectively, was determined based on no toxicologically significant effects at the highest dose tested. The molecular weight ratio of Fatty acids, C18-unsaturated, dimers (MW 564.92 g/mol) and Fatty acids, C18-unsatd., dimers, polymers with 2-ethylhexanol and neopentyl glycol (MW 368 - 1386 g/mol) is 0.65 (368/564.92) and 2.45 (1386/564.92). Thus, based on this molecular ratio factor the NOAEL systemic for Fatty acids, C18-unsatd., dimers, polymers with 2-ethylhexanol and neopentyl glycol was calculated to be 942.5 – 3552.5 mg/kg bw/day ((368/564.92)*1450) - ((1386/564.92)*1450) for males and 1099.8 – 4145.4 mg/kg bw/day ((368/564.92)*1692) - ((1386/564.92)*1692) for females, respectively. Moreover, a NOAEL (developmental toxicity) of ≥1692 mg/kg bw/day for both sexes was determined. Thus, based on this molecular ratio factor the NOAEL for developmental toxicity for Fatty acids, C18-unsatd., dimers, polymers with 2-ethylhexanol and neopentyl glycol was calculated to be 1099.8 – 4145.4 mg/kg bw/day ((368/564.92)*1692) - ((1386/564.92)*1692) for the offspring.

Justification for classification or non-classification

Based on the analogue read-across approach, the available data from a screening test for reproductive / developmental toxicity with the source substance Fatty acids, C18-unsatd., dimers (CAS 61788-89-4) do not indicate an effect on reproductive performance. However, no final decision on classification for reproductive toxicity according to Regulation (EC) 1272/2008 can be made, as no further information is available.