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Administrative data

Link to relevant study record(s)

Description of key information

There are no specific studies available for the assessment of the absorption, distribution, metabolism or excretion of N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18). However, information issued from available acute and subacute studies indicate a low bioaccumulation potential.

Key value for chemical safety assessment

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

Additional information

Physical-chemical properties

The test substance, N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18) has a molecular weight around 366.64 and is a brown liquid at 20°C. Its melting point is considered to be ‑10.5 °C, the measured boiling point could not be measured due to its decomposition at 163°C at 1013 hPa and an estimated vapour pressure of 1.7810-7Pa at 25°C (EPI suite) has been calculated. The octanol-water partition coefficient (log Pow) is considered to be 6.1 at 25°C. The water solubility expressed as the critical micelle concentration (CMC, a solubility limit) since the substance forms micelles in water is 26 mg/mL at pH 7.0 at 23°C. In physiological circumstances both 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

Acute oral toxicity was evaluated in rats according to an OECD 401 study. The test substance was administered undiluted by gavage at the dose of 2000 mg/kg. Three out of five males and 1/5 females died during the study between day 2 and day 8. Hypoactivity or sedation, piloerection, dyspnea, hypersalivation and swollen abdomen were recorded in these animals prior to death as well as in the surviving animals from day 1. No apparent abnormalities were observed at necropsy in any animals.

The substance is corrosive when applied topically on rabbits and is not expected to easily pass the skin in view of its ionised form at physiological conditions. However, as this is not quantitatively evaluated, 100% dermal absorption is considered as worst case assumption.

 

Data from repeated dose toxicity studies

Oral:

In a 28-days repeated dose oral toxicity study conducted according to the OECD Guideline 407 and in compliance with GLP, N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18) was administered daily to groups of Wistar rats at doses of 0, 10, 50 and 150 mg/kg bw/day over a period of 28 days by gavage. No deaths occurred during the study and only slight signs of toxicity were observed at 150 mg/kg bw/day: salivation was observed in all male and female animals and respiration sounds were observed after treatment in 3 male animals and 4 female animals on several days between Day 7 and 28. No significant treatment-related changes were noted in the body weight gain, food and water consumption, ophthalmological examinations, hematological parameters, urinalysis and neurotoxicological parameters at any dose-level. No treatment-related effects were noted on organ weights or necropsy and microscopic findings.

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 at the dose-levels of 0, 25, 75 and 200 mg/kg bw/day. In parental animals, no test substance-related mortalities occurred in any test group. Clinical signs including salivation; respiration sounds; eyelid-half closure and/or piloerection were observed on several days at 200 mg/kg bw/day. Salivation was noted at dose-levels of 75 and 200 mg/kg bw/day. At 200 mg/kg bw/day, decreased body weight gain was noted in male animals in the first week of treatment (53 %). 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 although gross necropsy revealed no relevant findings. No significant treatment-related changes were noted in clinical signs, body weight and at gross-necropsy.

In conclusion, taken together these data, it can be concluded that N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18) is of low toxicity and that no bio-accumulating potential is expected. 

Inhalation:

N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18) is a liquid at room temperature with a vapour pressure around 1.7810-7Pa. In addition, the use of this substance will not result in aerosols, particles or droplets, so exposure to humans via the inhalation route will be unlikely to occur.

Dermal:

No data from repeated dose studies via dermal route is available. N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18) is corrosive to the skin and is not expected to easily pass the skin at non corrosive dose-levels.

 

 

Absorption, distribution, metabolism, excretion

Data on toxicokinetics for N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18) is not available. Due to the apolar alkyl chain, and its adherence to negatively charged surfaces, the substance does not easily pass biological membranes at low, non corrosive dose-levels and dermal uptake is therefore very limited. At corrosive dose-levels, 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 be 100%.

 

Dermal absorption

Based on the corrosive properties of N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18), dermal absorption as a consequence of facilitated penetration through damaged skin can be anticipated

Due to the lack of quantitative absorption data, 100% absorption is taken as a conservative approach.