Amides, tall-oil fatty, N-[3-(dimethylamino)propyl]

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

75 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Klimisch 1

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In a reproduction / developmental toxicity screening test conducted according to the OECD Guideline 421 and in compliance with GLP, N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18) was administered daily by oral gavage to groups of Wistar rats (10/sex/dose) at the dose-levels of 0, 25, 75 and 200 mg/kg bw/day. The duration of treatment covered premating period of 2 weeks and a mating period (max. of 2 weeks) in both sexes, approximately 1 week post-mating in males, and the entire gestation period as well as 4 days of lactation in females. Parental (F0) animals were mated 13 days after the beginning of treatment to produce a litter (F1 generation pups). F0 animals were examined for their reproductive performance including determination of the number of implantation sites and the calculation of postimplantation loss for all F0 females. Food consumption of the F0 parents was determined weekly during premating and after the mating period and during the gestation and lactation periods in dams. In general, body weights of F0 animals were determined once a week; however, during gestation and lactation, F0 females were weighed on gestation days (GD) 0, 7, 14 and 20, on the parturition day and postnatal day (PND) 4. Pups were sexed on PND 0 and weighed one day after birth and on PND 4. Their viability was recorded until PND 4 when all pups were sacrificed and examined macroscopically for external and visceral findings. All surviving F0 parental animals were sacrificed and assessed by gross pathology. Sex organ weights (testes, epididymides and ovaries) were recorded and a histopathological examination was performed when required.

In parental animals, no test substance-related mortalities occurred in any test group. Clinical signs including salivation; respiration sounds; eyelid-halfclosure and/or piloerection were observed on several days at 200 mg/kg bw/day. Salivation, noted at dose-levels of 75 and 200 mg/kg bw/day, was not considered to be an adverse and toxicologically relevant effect. At 200 mg/kg bw/day, decreased body weight gain was noted in male animals in the first week of treatment (53 %). At dose levels of 75 and 200 mg/kg bw/day, decreased absolute terminal body weights were seen in males (96 and 95 %, respectively) before sacrifice but after a fasting period of 16 -20 hours. No other treatment-related changes were noted at any dose-level in food consumption, reproductive performance, sex organ weights and no gross-finding was observed during gross necropsy.

In pups, viability index decreased significantly by 6 % at 200 mg/kg bw/day however, it is worth noting that the loss of 6 of the 7 pups happened occurred on the first post natal day. In addition, two of the decedents pups came from a litter that started with an exceptional large amount of 17 pups (highest amount in the study), and four came from litter 133 that at birth was already weak with pup weights varying 10-40% below normal and many showing an underdeveloped appearance (Average pup weight about 25% below the overall average pup weight of the high dose group, and three pups that died on day 1 and were not weighed). A relation to treatment was assumed although gross necropsy revealed no relevant findings. No significant treatment-related changes were noted in clinical signs, body weight and at gross-necropsy.

Under the test conditions, the No Observed Adverse Effect Level (NOAEL) of N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18) for reproductive performance and fertility in male and female Wistar rats was considered to be 75 mg/kg bw/day. The NOAEL for general, systemic toxicity was 75 mg/kg bw/day for the F0 parental males based on impaired body weight data (stated 25 mg/kg/day in the study report) and 200 mg/kg bw/day for females. The NOAEL for developmental toxicity was 75 mg/kg bw/day for both sexes as the viability index was decreased at a dose level of 200 mg/kg bw/day.

Short description of key information:
One reproduction/developmental toxicity screening test is available. Under the test conditions, the No Observed Adverse Effect Level (NOAEL) of N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18) for reproductive performance and fertility in male and female Wistar rats was considered to be 75 mg/kg bw/day. The NOAEL for general, systemic toxicity was 75 mg/kg bw/day for the F0 parental males (based on impaired body weight data) and 200 mg/kg bw/day for females. The NOAEL for developmental toxicity was 75 mg/kg bw/day for both sexes as the viability index was slightly decreased at the dose level of 200 mg/kg bw/day.

Justification for selection of Effect on fertility via oral route:
Well performed study according to OECD 421 guideline and under GLP protocol.

Justification for selection of Effect on fertility via inhalation route:
No repeated dose toxicity study via inhalation is available. N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18) is a liquid with a vapour pressure around 1.78 10-7 Pa at 25°C (EPI suite estimation). Also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur.

Justification for selection of Effect on fertility via dermal route:
The substance is corrosive for skin. Therefore, dermal route is not the preferred route for repeated dose toxicity studies.

Justification for classification or non-classification

On the basis of available studies and according to regulation 67-548 EEC and CLP regulation (EC) N° 1272/2008 the substance is not classified as a reproductive toxicant.