N-(n-dodecyl)pyrrolidinone

Endpoint summary

Description of key information

The experimental EC10 derived from the FELS test of 0.018 mg/L is in agreement with the QSAR predicted value of 0.015 mg/L based on amides. Hence this value is used to determine the PNEC.

Additional information

An acute toxicity to fish study (Murphy, 1991) is available which is key study. This study showed that 96-hour LC50 of test substance is 0.59 mg/L.

Long-term toxicity to fish was determined by performing a 35 -day Fish Early Life Stage test (Baumann, 2017). This study resulted in an EC10 of 0.018 mg/L for weight as the most sensitive parameter.

An acute Daphnia study (Holmes, 1991) is available which is key study. This study showed that 48-hour EC50 of the test substance is 0.139 mg/L.

A toxicity to aquatic algae study (Lane, 1987) is available which is key study. This study showed 24 -96h EC50 for growth rate of 0.086 mg/L.

An activated sludge respiration Inhibition study (Griffith, 2012) is available which is a key study. This study showed that 3-h EC50 was 36.4 mg/L and 3-h NOEC was 22.2 mg/L.

Chronic toxicity of the three trophic levels was compared applying QSAR estimation and extrapolation. The dossier of N-(n-dodecyl)pyrrolidinone (Surfadone LP-300) contains also data of aquatic toxicity tests with N-(n-octyl)-2-pyrrolidinone (Surfadone LP-100), to support the limited data on chronic exposure to N-(n-dodecyl)pyrrolidinone. Although these two molecules are very similar in their structure, the toxicity of N-(n-dodecyl)pyrrolidinone appeared to be significantly higher in case of aquatic organisms and, at the same time, its solubility in water was lower. Comparing the acute toxicity values based on experiments at the three trophic levels, the differences are a factor of 30, 55 and 117 for fish, Daphnia and algae, respectively (seeTable1). The lowest ATE value of N-(n-dodecyl)pyrrolidinone was 0.053 mg/L for algal growth.

Estimations of the short-term toxicity (ATE) by ECOSAR v.1.11 show that the ATE´s for N-(n-octyl)-2-pyrrolidinone are well predicted based on the neutral organic structure and surprisingly less by the estimations based on the amide grouping, which overall gave more conservative values. Comparing the ECOSAR estimates for N-(n-dodecyl)pyrrolidinone with the experimental data show that these are generally a magnitude higher. Although for acute toxicity of N-(n-dodecyl)pyrrolidinone, algal growth appeared to be most sensitive, it should be noted that the endpoint for fish is mortality and thus not at the same level. When looking at the predicted values for chronic exposure, the fish appear to be most sensitive when the prediction is based on Amides: 0.015 mg/L.

 

Table1: Experimental and QSAR-estimated values for acute and chronic exposure of three aquatic trophic levels in case of exposure to Surfadone LP-100 or LP-300  

	LP-100			LP-300
Species	acute E(L)C50			acute E(L)C50
	Experimental	ECOSAR Version 1.11 Results^1)		Experimental	ECOSAR Version 1.11 Results^1)
		Neutral Organic SAR	Amides		Neutral Organic SAR	Amides
Fish	17.8	11.7	7.28	0.59	3.13	2.68
Daphnia	7.59	7.49	4.47	0.139	2.14	1.160
Algae	6.2	9.06	0.301	0.053	3.46	0.13
	Chronic Value			Chronic Value
		ECOSAR Version 1.11 Results			ECOSAR Version 1.11 Results
	Experimental	Neutral Organic SAR	Amides	Experimental	Neutral Organic SAR	Amides
Fish	0.91	1.32	0.027	0.018	0.381	0.015
Daphnia	2.5	1.01	0.579	0.046 (calculated)	0.352	0.248
Algae	3.2	3.08	0.483	0.046	1.38	0.288

 

Since no experimental data were available for long-term exposure of fish, it was decided to perform a fish early-life-stage (FELS) test on zebra fish. According to the results of the test, the overall NOEC (35 d) was determined to be 12.2 µg/L based on measured concentrations. The EC10 value (35 days) of the most sensitive parameter (fresh weight) was 0.018 mg/L based on measured concentrations (17.7 µg/L with a 95% confidence interval of 13.5 - 21.6).

For invertebrates, the value for long-term exposure was estimated by comparing the available long-term values forN-(n-octyl)-2-pyrrolidinone with its short-term values. Then the same ratio was used to estimate the respective long-term values for N-(n-dodecyl)pyrrolidinone based on its experimental ATE’s (result in Table1). The thus predicted value of 0.046 mg/L is a factor of 5 lower than the values estimated by ECOSAR (0.352 and 0.248 mg/L). The experimental EC10 derived from the FELS of 0.018 mg/L is in agreement with the predicted value of 0.015 mg/L based on amides. Hence this value is used to determine the PNEC.