Mono Dimer Trimer FA TETA PAA

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

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:

Reliable screening study providing multiple endpoints.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

The effects of Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine on fertility have been investigated in a combined repeated dose/reproductive screening toxicity study conducted according to OECD Test Guideline 422 (Perks, 2013).

In the study groups of male and female Crl:WI(Han) rats (10 animals/group) were administered with the test substance orally by gavage, at dose levels of 100, 300 and 1000 mg/kg bw/day. Dose levels were selected based on the results of a 14-day range finding study. Male rats were dosed once daily for two weeks prior to pairing, during the pairing period and a further two weeks before necropsy. Males were treated for a minimum of 6 weeks prior to necropsy. Female rats were dosed for two weeks prior to pairing, during pairing and until Day 4 post-partum, inclusive at total of approximately 7 weeks. The females were allowed to litter and rear their offspring to Day 4 post-partum.

There were no treatment related deaths during the study. No treatment-related clinical signs, changes in bodyweight gains, histopathological changes or functional changes were observed in the study. The No-Observed-Adverse-Effect-Level (NOAEL) for the general or systemic toxicity in male and female rats was considered to be 1000 mg/kg bw/day (i.e the highest dose tested).

 

No developmental effects, effects on reproductive parameters or treatment-related signs of systemic toxicity were observed in the study. No treatment-related effects were observed on mating, fertility or fecundity indices; the majority of animals mated within one oestrous cycle. No treatment-related adverse effects were observed on gestational length, the number of implantation sites or pups born, pup survival or body weight gain. Pup necropsy data were unremarkable. Based on this study, The No-Observed-Adverse-Effect-Level (NOAEL) for the effects of the substance on fertility in male and in female rats and for developmental toxicity was considered to be 1000 mg/kg bw/day (i.e. the highest dose tested).

There were no adverse findings from a 90-day repeated dose oral toxicity study or a pre-natal developmental toxicity study that highlight any reproductive hazard potential of Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine. The NOAEL for repeat dose toxicity was 1000 mg/kg bw/d on the OECD 408 90 -day Repeat dose toxicity study, with no effect on the reproductive organs.

In accordance with Column 2 of Annex X of the REACH regulation, a waiver is proposed for the extended one generation reproductive toxicity study. No adverse effects or indication of systemic exposure were observed in a combined repeated dose toxicity with reproduction/developmental toxicity screening test (OECD 422) at dose levels up to and including the limit dose. Also, according to Lipinski’s Rule of Five, the substance is not predicted to be bioavailable (OECD QSAR Toolbox). No additional testing is therefore considered necessary on scientific grounds and in the interests of avoiding unnecessary animal testing in accordance with EU Directive 86/609/EEC.

Short description of key information:
No evidence of an effect on the reproductive organs was seen in a combined repeated dose and reproductive/developmental screening study (OECD 422) or a 90 -day repeat dose toxicity study (OECD 408) in rats after repeated oral doses upto 1000 mg/kg bw/day.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

35 mg/kg bw/day

Study duration:

subacute

Species:

rabbit

Quality of whole database:

Study was conducted to the relevant guideline and in a GLP compliant laboratory, with certificate

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

No effects on developmental parameters were observed in a combined repeated dose and reproductive/developmental toxicity study conducted using Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine following oral doses upto 1000 mg/kg bw/day (Perks, 2013). Based on this study, the NOAEL for developmental toxicity was considered to be 1000 mg/kg bw/day (i.e. the highest dose tested)

A pre-natal developmental toxicity study using Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine in the rat (OECD Test Guideline 414) was conducted to evaluate the developmental hazard potential of the substance. No reproductive toxicity was observed in a combined repeated dose and reproductive and developmental toxicity screening study (OECD Test Guideline 422) conducted using Dimer trimer FA TETA PAA. In the study, rats were administered the substance by oral gavage at 0, 100, 300 or 1000 mg/kg bw/day. No signs of reproductive or developmental toxicity were observed at doses up to 1000 mg/kg bw/day. The NOAEL for effects on fertility and developmental effects was considered to be 1000 mg/kg bw/day (i.e. the highest dose tested).

No developmental toxicity was observed in prenatal developmental toxicity studies in the rat or rabbit (OECD Test Guideline 414) conducted using Dimer trimer FA TETA PAA.

In the study conducted in the rat, the test item was administered by oral gavage at 100, 300 or 1000 mg/kg bw/d. No signs of developmental toxicity or teratogenicity were observed at doses up to 1000 mg/kg bw/d. The NOAEL for fetal developmental toxicity and teratogenicity was established as 1000 mg/kg bw/d

In the study conducted with the rabbit, the test item was administered by oral gavage at 15, 35 and 75 mg/kg bw/d. There were no signs of developmental toxicity or teratogenicity, in the absence of maternal toxicity. The NOAEL for developmental toxicity and teratogenicity was established as 75 mg/kg bw/d.

As the most sensitive endpoint, the calculations for DNEL derivation and the risk assessment have used 75 mg/kg bw/d as their starting value. Rabbits are known to be sensitive to handling and stress during repeat dose studies, and the use of this lowest NOAEL is seen as conservative for use as the starting point for risk assessment and protective of human health and the environment.

Justification for classification or non-classification

No classification is proposed: relevant data do not show need for classification.