Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Due to lack of quantitative data,the default ECHA absorption rates of 100% by inhalation and 50% for oral and dermal routes are assumed.This basically indicates that, although the absorption may be lower it is assumed that inhalation results in twice the exposure that occurs with oral or dermal exposure. Very likely this means an overestimation of the inhalation and dermal absorption compared to oral route. Available studies do not indicate a concern for bioaccumulation.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

Physical-chemical properties

The test substance, N-[3-(dimethylamino)propyl] C6-9 alkyl amides has a molecular weight around 200and is aclear amber liquidat 20°C. Its melting point is considered to be< -30°C, the measured boiling point isnot determined as it decomposes at 360°C at 1013 hPa and a vapour pressure of< 0.1 psi (limit of method), < 689Pa. was measured.The octanol-water partition coefficient (log Pow) ismeasuredto be1.26at 20°C on the basis ofthe shake flask method.The water solubilitywas measured to be 3.19 g/L at 22°C. In physiological circumstances the nitrogen will be positively charged, resulting to a cationic surfactant structure which leads to high adsorptive properties to negatively charged surfaces as cellular membranes. The apolar tails easily dissolve in the membranes, whereas the polar head causes disruption and leakage of the membranes leading to cell damage or lysis of the cell content. As a consequence, the whole molecule will not easily pass membrane structures. Cytotoxicity at the local site of contact through disruption of cell membrane will be considered the most prominent mechanism of action for toxic effects.

Data from acute toxicity studies and irritation studies

Acuteoraltoxicity was evaluated inthe up and down method(OECD 425) study indicating a LD50 of 3129 mg/kg bodyweight. Mortality was observed at5000 mg/kg, where the rats showedhypoactivityabnormal posture and piloerection. At 1750 mg/kg bodyweight, one animal was hypoactive and exhibited facial staining. All animals exhibited ano-genital staining and/or reduced faecal volume. However, these animals recovered by Day 3 and appeared active and healthy for the remainder of the 14-day observation period.

In the acute dermal toxicity study following application, all animals exhibited facial staining and/or ano-genital staining between Days 1 and 2. Also, dermal irritation (erythema, edema, desquamation, hyperkeratosis, discoloration, eschar and/or corrosion) was noted at the dose site of all animals between Days 1 and 14. Gross necropsy of the females revealed red intestines. No gross abnormalities were noted for any of the males when necropsied at the conclusion of the 14-day observation period. Under the study conditions, the acute dermal LD50 of the test substance was greater than 5000 mg/kg bodyweight in male and female rats.

Data from repeated dose toxicity studies

Oral:

Three oral repeated dose toxicity studies were performed with N-[3-(dimethylamino)propyl] C6-9 alkyl amides:

- Repeated Dose 28-Day Oral Toxicity in Rodents (OECD 407)(dietary),

- Combined90 dayRepeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test (OECD 422)(dietary)and

-Preliminary pre-natal development study in rats (oral gavage).

From these studies it can be concluded that:

- Overall there are low to no real systemic effects observed.

- NOAEL systemic effects:175mg/kgbw based onsystemic toxicitywhichwas exhibited at 600 mg/kg/d by clinical findings, lower mean body weights, body weight gains, and food consumption for both sexes and lower absolute and relative-to-brain ovary, uterus, and pituitary weights for the reproductive phase femalesin addition, lower mean live litter size on PND 0, number of pups born and implantation sites, and lower mean pup weights were noted in the 600 mg/kg/daygroup in the presence of excessive maternal toxicity.

The findings observed in these studies suggest that the toxicity of N-[3-(dimethylamino)propyl] C6-9 alkyl amides is rather expressed by local effects than systemic effects.As it was a dietary study and the significantly reduced bodyweight gains at the top dose of 600 mg/kg correlated to the reduced food consumption. This was likely due to unpalatability of the diet due to the test substance. However, there was some indication of reduced food efficiency which could indicate either local or slight systemic toxicity. The reduced nutrition may also explain the reduced number of implants and lower pup weight at birth in the OECD422 study. This lack of any significant systemic effectssupports the lack of bio-accumulating potential of the substance.

 Inhalation:

N-[3-(dimethylamino)propyl] C6-9 alkyl amides is aliquidwith a melting point of< -30°C that is marketed or used in aliquidform. Also, the vapour pressure is< 689 Pa. In addition, the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur.

 Dermal:

No data from repeated dose studies via dermal route. N-[3-(dimethylamino)propyl] C6-9 alkyl amides ismildly irritatingto the skin and is not expected to easily pass the skin.

Absorption, distribution, metabolism, excretion

Data on toxicokinetics for N-[3-(dimethylamino)propyl] C6-9 alkyl amides is not available. Due to the apolar alkyl chain, and its adherence to negatively charged surfaces, the substance does not easily pass biological membranes and dermal uptake is therefore very limited.This was supported by the lack of acute dermal toxicity. Athigh concentrations, the apolar tails easily dissolve in the membranes, whereas the polar head causes disruption and leakage of the membranes leading to cell damage or lysis of the cell content. As a consequence, the whole molecule will not easily pass membrane structures. Cytotoxicity at the local site of contact through disruption of cell membrane will be considered the most prominent mechanism of action for toxic effects. However, due to lack of quantitative data, the absorption rate following oral dosing is considered to bethe ECHA default 50%.

 Dermal absorption

Based on thedermal LD50 being greater than 5000 mg/kgand N-[3-(dimethylamino)propyl] C6-9 alkyl amides,being only mildly irritating to skin,dermal absorption as a consequence of facilitated penetration through damaged skinis notanticipated.

Due to the lack of quantitative absorption data,the ECHA default of 50% absorption is taken as a conservative approach.