N-[3-(dimethylamino)propyl]docosanamide

Endpoint summary

Additional information

For the assessment of aquatic toxicity of DIMAPDO short-term toxicity data of DIMAPDO lactate with fish, aquatic invertebrates, algae and microorganisms are available.

 

Short-term toxicity to fish

In a 96-h acute toxicity study according to OECD guideline 203 (Fish, Acute Toxicity Test; 1992) and EU Method C.1 (Acute Toxicity for Fish; 1992), juvenile rainbow trouts (Oncorhynchus mykiss) were exposed to DIMAPDO lactate at nominal concentrations of 1.0, 1.8, 3.2, 5.6 and 10 mg test substance/L (mean measured concentrations of untreated test medium: 0.63, 1.5, 2.9, 4.8 and 9.1 mg/L; mean measured concentrations of centrifuged test medium: 0.32, 0,76, 1.2, 2.6 and 6.6 mg/L) under semi-static conditions. The 96-hour LC50 based on nominal test concentrations was 7.5 mg/L with 95% confidence limits of 5.6 - 10 mg/L. The 96-hour LC50 based on mean measured concentrations of untreated test medium was 6.6 mg/L with 95% confidence limits of 4.8 - 9.1 mg/L.

Because the study was conducted with the lactic acid salt of DIMAPDO, the 96-h LC50 and the NOEC value of DIMAPDO based on mortality and sublethal effects and the concentration analysis of the untreated test solution were calculated as 5.45 mg/L and 3.96 mg/L active ingredient, respectively.

Sub-lethal effects (moribundity) of exposure were observed at a nominal test concentration of 10 mg/L. Due to the approach of substantial severity limit these fish were killed and classed as mortalities at 24 and 48-hour time points respectively.

 

Short-term toxicity to aquatic invertebrates

The 48-hr-acute toxicity of DIMAPDO lactate to Daphnia magna was studied under semi-static conditions according to OECD guideline 202 (April 13, 2004) and Daphnia sp., Acute Immobilization Test stipulated in the "Testing Methods for New Chemical Substances" (November 21, 2003; No. 1121002, Pharmaceutical and Food Safety Bureau, MHLW). Daphnids were exposed to control, and test chemical at measured concentrations of untreated test solution of 0.245, 0.497, 0.999, 1.99, 3.74, 7.82 mg test substance/L for 48 hr. 

Mortality/immobilization and sublethal effects were observed daily. The 48-hour EC50 was 1.41 mg test substance/L.  The 48-hr NOEC based on immobilization was 0.497 mg test substance/L. Because the study was conducted with lactic acid salt of DIMAPDO the EC50 and NOEC values of DIMAPDO based on % immobilization were calculated as 1.16 mg/L and 0.41 mg/L active ingredient.

 

Toxicity to aquatic algae and cyanobacteria

In a 72 hours toxicity study, the cultures of Scenedesmus subspicatus were exposed to DIMAPDO lactate at nominal concentrations of 1.0, 2.0, 4.0, 8.0 and 16 mg/L under static conditions in accordance with the OECD guideline 201 (1984) and EU Method C.3 (Algal Inhibition test; Commission Directive 92/69/EEC). The % growth inhibition in the treated algal culture as compared to the control ranged from 2% to 107%.

The NOEC and EC50 values based on % growth inhibition were 1.0 and 2.7 mg/L, respectively. Based on the geometric mean measured test concentrations of the untreated test media the EC50 was 2.1 mg/L and the NOEC was 0.44 mg/L.

The study was conducted with the lactic acid salt of DIMAPDO. Therefore the EC50 and NOEC values of DIMAPDO based on % growth inhibition and the test concentrations of untreated media were calculated as 1.73 mg/L and 0.36 mg/L active ingredient.

The following abnormalities were noted: After 72 hours there were no abnormalities detected in the control or test cultures at 1.0 mg/L, however some enlarged cells were observed to be present in the test cultures at 2.0, 4.0, 8.0 and 16 mg/L. The test material was observed to form a homogenous dispersion in culture medium.

Toxicity to microorganisms

 

The toxicity of DIMAPDO lactate (99.2% a.i.) to microorganisms was investigated during a ready biodegradation study according to EU Method C.4-C (Determination of the "Ready" Biodegradability - Carbon Dioxide Evolution Test; 1992) and OECD guideline 301 B, 1992 over a period of 28 days and using an inoculum obtained from activated sludge of a predominantly domestic sewage treatment plant. The biodegradation rate was determined by measurement of carbon dioxide evolution.

Inoculum blank, procedural/functional control with the reference substance Sodium benzoate and a toxicity control with reference substance (10 mg C/L) and test substance (9.17 mg C/L) were performed.

The biodegradation in the toxicity control was 81% after 14 d and 100% after 28 d. More than 25% biodegradation occurred within 14 days. Therefore, the test substance was assumed not to inhibit microbial activity at the tested concentration.

Because the study was conducted with the lactic acid salt of DIMAPDO, the 28 d NOEC based on respiratory activity was calculated to be 10.81 mg/L in terms of DIMAPDO.

 

Table 1: Acute and chronic ecotoxicity values for the registration substance DIMAPDO

Test type	Guideline	Species	Endpoint	Value
Short-term toxicity to fish	OECD 203, EU Method C.1	Oncorhynchus mykiss	LC50 (96h)	5.45 mg a.i./L
Short-term toxicity to aquatic invertebrates	OECD 202	Daphnia magna	EC50 (48h)	1.16 mg a.i./L
Toxicity to aquatic algae and cyanobacteria	OECD 201, EU Method C.3	Scenedesmus subspicatus (new name: Desmodesmus subspicatus)	ErC50 (72h) NOEC	1.73 mg a.i./L 0.36 mg a.i./L
Toxicity to microorganisms	OECD 301B, EU Method C.4	Activated sludge	NOEC (28d)	10.81 mg a.i./L

 

 

Justification for not reporting studies performed with DIMAPDO lactate as read-across

All available aquatic toxicity studies were performed with DIMAPDO lactate. DIMAPDO lactate is an ionic chemical compound that dissociates in water under neutral pH conditions almost entirely into DIMAPDO and lactate. This is supported by the observation that at the start of the exposures the test solutions were usually clear and but within the first 24 hours the test solutions became cloudy dispersed solutions. DIMAPDO lactate with its good water solubility dissociates over time into the highly soluble lactate and the only slightly soluble DIMAPDO that forms small micelles in aqueous solutions. Therefore aquatic organisms are mainly exposed to DIMAPDO and lactate and not to DIMAPDO lactate.

Lactate is a normal metabolic intermediate produced and needed by most mammalian cells and micro-organisms and has a low aquatic toxicity (registered substances databank ECHA website). Therefore all toxic effects seen can be attributed to DIMAPDO.

Bowmer et al. published in 1998 a study where they compared the ecotoxicity of lactic acid and its alkyl esters experimentally with the micro alga Selenastrum capricornutum, the crustacean Daphnia magna  and the fish species Danio rerio and Pimephales promelas. The results presented indicate that alkyl lactate esters show some differences in their ecotoxicity when compared to non polar narcotic compounds but that these differences are generally small. For example for octyl lactate the EbC50 for algae (72-96h) was 7.6 mg/L, the daphnia EC50 (48 h) was 41 mg/L and the fish LC50 (96 h) was 24 mg/L. These values are relatively similar to the values of octanol with an EbC50 for algae (72-96h) of 14.6 mg/L, a daphnia EC50 (48 h) of 31.8 mg/L and a fish LC50 (96 h) of 14 mg/L (registered substances database, ECHA website).

CONCLUSION:

Therefore under environmental conditions it is toxicologically not relevant if DIMAPDO or DIMAPDO lactate are introduced in an aquatic medium.

 

Test substance concentration analysis

As the test material was observed to form a dispersion in the test diluent, samples taken from the

test preparations were analysed untreated and after centrifugation (40000 g, 30 minutes) in order to give an indication of the dissolved test material concentration.

The analysed test concentrations of the untreated solution (analysis of dispersed + dissolved test substance) and not of the centrifuged solution (analysis only of dissolved test substance) were chosen as calculation basis for all tests because in the OECD guideline 201 study there was a discontinuity in the analysis of the concentrations of the centrifuged test solution and therefore the calculated values for the centrifuged test media were not valid. Additionally in the OECD guideline 203 study the examination of the dead fish revealed that the dispersed test material had adhered to the gill filaments indicating physical toxicity of the dispersed test material particles that may be also a factor for the toxicity observed in other organisms.

 

 

References:

C.T. Bowmer, R.N. Hooftman, A.O. Hanstveit, P.W.M. Venderbosch & N. van der Hoeven. The ecotoxicity and the biodegradability of lactic acid, alkyl lactate esters and lactate salts. Chemosphere, Vol. 37, No. 7, pp. 1317-1333, 1998