Reaction mass of Amines, coco alkyl and β-Alanine, N-(2-carboxyethyl)-, N-coco alkyl derivs. and β-Alanine, N-coco alkyl derivs.

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

A repeated dose/reproductive toxicity screening study (OECD 422) is available. The NOEL for fertility is 200 mg/kg/day and the NOAEL for toxic effects on progeny is 67 mg/kg/day.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

67 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

GLP study which meets the Annex IX chapter 8.7.1 requirements.

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 substance was tested in a repeated dose/reproductive toxicity screening study (OECD 422). The test item was administered daily by oral gavage to male and female Sprague-Dawley rats, for 2 weeks before mating, during mating, and for females throughout gestation and until day 5 post-partum, at dose-levels of 22, 67 or 200 mg/kg/day. Based on the experimental conditions of this study: - the NOEL for reproductive performance was considered to be 200 mg/kg/ day in the absence of any treatment-related effect on mating and fertility at this dose-level and the NOAEL for toxic effects on progeny was considered to be 67 mg/kg/day based on clinical signs recorded in pups at 200 mg/kg/day. The clinical signs in the pups (thin appearance, cold to the touch and desquamation) were considered to be the consequence of altered/reduced maternal care. . The NOAEL for parental toxicity was considered to be 67 mg/kg/day based on microscopic examination findings (acanthosis/hyperkeratosis with ulcer and inflammation in the forestomach in both sexes which were considered as adverse at 200 mg/kg/day).

Justification for selection of Effect on fertility via oral route:
Only one study available. Study compliant with GLP and testing guidelines.

Effects on developmental toxicity

Description of key information

A prenatal developmental toxicity study in rat is available. The NOAELs for maternal parameters and for embryo-fetal development were established to 170 mg/kg/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

170 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

GLP study which meets the Annex IX chapter 8.7.1 requirements.

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

Three groups of 24 time-mated female Sprague-Dawley rats received the test item at 0 (corn oil), 60, 170 or 500 mg/kg/day by oral route (gavage) once daily from Days 6 to 20 p.c. Formulation concentrations were checked in the first and last weeks of treatment in the study. The animals were checked daily for mortality and clinical signs. Body weight and food consumption were recorded every 2 to 3 days. On Day 21 p.c., females were sacrificed and submitted to a macroscopic post-mortem examination of principal thoracic and abdominal organs. Hysterectomy was performed and the numbers of corpora lutea, implantations, uterine scars, early and late resorptions, live and dead fetuses were recorded. The fetuses were sexed, weighed and examined for external, soft tissues and skeletal (cartilages + bones) abnormalities.

 

The test item concentrations in the dose formulations analyzed were within the acceptable range of variations

At 500 mg/kg/day, maternal toxicity (poor health condition, absence of food intake and body weight loss) found in a few females resulted in one death on Day 19 p.c. Otherwise, ptyalism was the main clinical sign in this group. There was also low mean food consumption throughout the treatment period associated with low mean body weight. These effects correlated with the low mean carcass weight and mean net body weight change from Day 6p.c.at necropsy. There were also associated low mean gravid uterus weight, low mean fetal weight and fetal ossification delays.

At 60 and 170 mg/kg/day, there were no adverse findings in dams and litters.

 

Under the experimental conditions and results of this study:

.         the No Observed Adverse Effect Level (NOAEL) for maternal parameters was considered to be 170 mg/kg/day in view of poor general condition, death and effect on body weight and food consumption at 500 mg/kg/day,

.         the NOAEL for embryo-fetal development was considered to be 170 mg/kg/day based on decreased mean fetal weight at 500 mg/kg/day. 

Justification for classification or non-classification

The effects on the progeny at 200 mg/kg/day observed in the combined repeated dose toxicity /screening reproductive toxicity study were considered to be the consequence of altered/reduced maternal care (which in turn was a consequence of maternal toxicity) and not true reproductive toxicity. In addition, no embryo-fetal development toxicity was observed in absence of maternal toxicity in the prenatal developmental toxicity study in rat.

Therefore, no clasification would be proposed according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) or the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.