Reaction product of fatty acids C14-18/C16-18 unsaturated with dihydrogendioxide and Ammonia

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

There are valid sub acute / chronic study data available to assess the repeated dose toxicity of Reaction product of fatty acids C14-18/C16-18 unsaturated with dihydrogendioxide and Ammonia.

Studies according to OECD guidelines:

A study according to OECD guideline 421 (BASF.80R0774/11X309, 2012) was conducted to provide data on the possible effects of Reaction product of fatty acids C14-18/C16-18 unsaturated with dihydrogendioxide and Ammonia on the reproductive performance of Wistar rats (four groups of 12 males and 12 females each) and the development of pups . The test item was administered as a dilution in tap water by daily oral gavage at levels of 0, 200, 600 or 2000 mg/kg body weight, during a premating period of 2 weeks and during mating (1 week), gestation and lactation until postnatal day 4. The high dose level of 2000 mg/kg bw was selected considering the content of the active substance (approximately 50%). The dose volume was 5 ml/kg bw/day. Based on mortality and respiratory related clinical signs (regurgitation of test item maybe due to gavage procedure), the high-dose level was reduced to 1000 mg/kg body weight from day 4 of dosing.

No signs of parental toxicity were noted in any of the surviving rats. Occasionally, a grunting respiration was noted after dosing, but there were no adverse effects of treatment on general condition, body weights, growth and feed intake during the premating, gestation or the lactation period. There were no treatment-related changes in organ weights, macroscopic examination at necropsy or microscopy of testes, epididymides, ovaries and gross lesions. No treatment-related effects were observed on mating index, male and female fertility indices, gestation index, duration of gestation, number of corpora lutea, implantation sites, lost implantations. No effects were observed on litter size, pup sex and weight and pup survival.

Based on the absence of any signs of systemic toxicity in surviving rats, the No Observed Adverse Effect Level (NOAEL) for parental toxicity is considered to be 1000 mg/kg bw/day (a.i. 500mg/kg bw/day). No treatment-related effects were observed on fertility and developmental parameters. Therefore, the NOAEL for fertility and development is established at the high-dose of 1000 mg/kg bw/day (a.i. 500mg/kg bw/day).

As the study is conducted accordning to actual guidelines under GLP and therefore high reliable and no other further study is available the study was assigned as key study.

According to the results the substance shows not treatment / substance specific effect up to the tested dosage of 500 mg/kg bw/day (active ingredient). This is also confirmed in a 90 day study (HENKEL/COGNIS.R9400320, 1995) with rat.

Short description of key information:
Reprotoxicity screening, rat, OECD 421 (BASF 2013): NOAEL parental toxicity= 1000 mg/kg bw/day test item (a.i. 500mg/kg bw/day)
NOAEL fertility and development = 1000 mg/kg bw/day test item (a.i. 500mg/kg bw/day).

Justification for selection of Effect on fertility via oral route:
Reliable and adequate conducted study according to actual guidelinies

Effects on developmental toxicity

Description of key information

No teratogenicity study available.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Additional information

As no maleformation are found in a OECD 421 study (BASF.80R0774/11X309, 2013) up to the highest test dosage (500mg/kg bw/day active ingredient) no additional information is expected if a teratogenicity test is performed at that concentration. According to Annex XI REGULATION (EC) No 1907/2006 chapter 1.2 "weigh of evidence .... Where sufficient weight of evidence for the presence or absence of a particular dangerous property is available:.....—further testing on vertebrate animals for that property shall be omitted...." further testing (two generation or teratogenicity study) is not strongly suggested and therefore not proposed.

Justification for classification or non-classification

As the lowest NOAEL obtained was 500 mg/kg bw/day (AS 100%) and no parental, fertility or F1 maleformations could be observed at this concentration (no higher concentration was tested) a classification according to GHS (Regulation (EU) 1272/2008) as toxic for reproduction or an additional classification according to DPD (67/548/EEC) as harmful R60-63 is not indicated or justified.

 

Labelling for reproductive toxicity:

GHS: no additional labelling

DSD: no additional labelling