Reaction mass of 3-(3,3-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal and 3-(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal and 3-(1,1-dimethyl-2,3-dihydro-1H-inden-4-yl)propanal

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-09-01 to 2014-09-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was conducted in accordance with relevant test method and in compliance with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: 2013-06-03/05, Date of signature: 2013-11-05

Type of method:

slow-stirring method

Partition coefficient type:

octanol-water

Analytical method:

gas chromatography

Type:

log Pow

Partition coefficient:

4.37

Temp.:

25 °C

pH:

5.68

Remarks on result:

other: log Kow for isomer 1 = 4.37 ± 0.002 at 25 ± 1°C and pH 5.68

Type:

log Pow

Partition coefficient:

4.46

Temp.:

25 °C

pH:

5.68

Remarks on result:

other: log Kow for isomer 2 = 4.46 ± 0.002 at 25 ± 1°C and pH 5.68

Type:

log Pow

Partition coefficient:

4.32

Temp.:

25 °C

pH:

5.68

Remarks on result:

other: log Kow for isomer 3 = 4.32 ± 0.003 at 25 ± 1°C and pH 5.68

Details on results:

Linearity:
The limit of detection (LOD) of the analyte was determined to be 0.02 mg/L, verified with a signal-to-noise ratio of 3 for isomer 3 (weakest analytical signal).

The system quantification limit of the analyte was designated to be 0.05 mg test item/L, verified by an S/Nratio of 9 for isomer 3. The analytical system gave linear responses in the range of nominal 0.05–4 mg test item/L (7 concentrations; in the range of 0.245–1.93 mg/L for isomer 1, 0.0019–0.159 mg/L for isomer 3 and 0.236 – 1.91 mg/L for isomer 2). The coefficients of determination (r²) were determined to be > 0.992 for all calibration curves used in this study. Representative calibration curves are given in the attached file Section 1.1, chromatograms of the lowest and highest standards are given in Section 1.2.

Limit of Quantification (LOQ):
The limit of quantification (LOQ) was set at nominal 0.2 mg test item/L with a dilution factor of 2 at 1xLOQ, for the aqueous samples as well at nominal 1 g test item/L with a dilution factor of 10000 at 1xLOQ, for the n-octanol samples and checked by means of accuracy. For details of the fortified concentrations for each isomer, please see below.

Accuracy and precision:
The results demonstrate the validity of the analytical method. Mean recovery rates were:
Isomer 1, aqueous: 96% for the 1xLOQ and 94% for the 5xLOQ
Isomer 1, octanol: 100% for the 1xLOQ and 105% for the 5xLOQ
 
Isomer 2, aqueous: 93% for the 1xLOQ and 91% for the 5xLOQ
Isomer 2, octanol: 99% for the 1xLOQ and 104% for the 5xLOQ

Isomer 3, aqueous: 99% for the 1xLOQ and 95% for the 5xLOQ
Isomer 3, octanol: 102% for the 1xLOQ and 106% for the 5xLOQ
 
 
The results indicate sufficient accuracy of the analytical method. Furthermore, the precision of both fortification levels was satisfying because the corresponding coefficients of variation were ≤4.8% for any of the 3 isomers.
 
Specificity:
Three specific ions with an m/z ratio ≥100 were detected for each signal above LOQ level. Response of blank values of control samples was significantly lower than 30% of the LOQ.

Method validation:

The analytical method for the test substance was validated with satisfactory results regarding linearity, limit of quantification, accuracy, precision and specificity.

Partition coefficient determination:

pH check

The pH value at test start was determined for double distilled water, previously saturated with n-octanol, before the adding of the test item. The pH values at test end were determined after the fourth sampling interval.

As the obtained results for the pH values at test end (5.634 to 5.720, av. 5.68) match the pH value at test start (5.682), it can be stated that the test item did not influence the pH value of the aqueous phase.

Stock solution stability testing

The recovery rates of 91-99% for the three isomers indicate sufficient stability of the test item in the n-octanol stock solution during the course of the study.

Mass balance:

The mass balance in the aqueous andn-octanol phases ranges between 94–118%.

Partition coefficient results:

Table 16:Partition Coefficient Results (Isomer1)

 

Replicate	Test	Measured concentration		Kow	log Kow
number	duration [h]	in n-octanol [mg/L]	in aq. Phase [mg/L]		Single	Mean	SD ±	CV
1	41.57	9830	0.414	23744	4.38	4.36	0.03	0.67
	46.78	9370	0.434	21590	4.33
	66.28	10700	0.428	25000	4.40
	71.37	8890	0.402	22114	4.34
2	41.57	10060	0.452	22257	4.35	4.38	0.03	0.72
	46.78	10270	0.436	23555	4.37
	66.28	10390	0.394	26371	4.42
	71.37	9060	0.392	23112	4.36
3	41.57	9620	0.434	22166	4.35	4.36	0.02	0.50
	46.78	9250	0.422	21919	4.34
	66.28	9850	0.404	24381	4.39
	71.37	9440	0.402	23483	4.37
				log KOW,Av		4.37
				slog Kow,Av		0.002

 

aq. Phase = Aqueous phase

K_OW= Partition coefficient (n-octanol / water)

log K_OW= Decadic logarithm of the partition coefficient (n-octanol / water)

SD = Standard deviation

CV = Coefficient of variation [%]

log K_OW,Av= Weighted average value of log K_OW

s_{log Kow,Av}= Weighted standard deviation

 

Regression analysis demonstrated that the slope of the regression line of the log K_OWof the four successive samples was not significantly different from zero.

For log K_OW vs. Time plot including 95 % confidence intervals, see figure 11 (attached)

Table 17:Partition Coefficient Results (Isomer 3)

 

Replicate	Test	Measured concentration		KOW	log Kow
number	duration [h]	in n-octanol [mg/L]	in aq. Phase [mg/L]		Single	Mean	SD ±	CV
1	41.57	810	0.0394	20558	4.31	4.31	0.03	0.70
	46.78	771	0.0402	19179	4.28
	66.28	872	0.0388	22474	4.35
	71.37	728	0.0370	19676	4.29
2	41.57	833	0.0428	19463	4.29	4.33	0.04	0.84
	46.78	853	0.0398	21432	4.33
	66.28	849	0.0356	23848	4.38
	71.37	744	0.0354	21017	4.32
3	41.57	794	0.0410	19366	4.29	4.31	0.02	0.51
	46.78	767	0.0382	20079	4.30
	66.28	811	0.0372	21801	4.34
	71.37	779	0.0376	20718	4.32
				log KOW,Av		4.32
				slog KOW,Av		0.003

 

aq. Phase = Aqueous phase

K_OW= Partition coefficient (n-octanol / water)

Log K_OW= Decadic logarithm of the partition coefficient (n-octanol / water)

SD = Standard deviation

CV = Coefficient of variation [%]

log K_OW,Av= Weighted average value of log K_OW

s_{log Kow,Av}= Weighted standard deviation

 

Regression analysis demonstrated that the slope of the regression line of the log K_OW of the four successive samples was not significantly different from zero.

For log K_OW vs. Time plot including 95 % confidence intervals, see figure 12 (attached)

 

Table 18:Partition Coefficient Results (Isomer 2)

 

Replicate	Test	Measured concentration		KOW	log KOW
number	duration [h]	in n-octanol [mg/L]	in aq. Phase [mg/L]		Single	Mean	SD ±	CV
1	41.57	9690	0.326	29724	4.47	4.46	0.03	0.68
	46.78	9240	0.346	26705	4.43
	66.28	10460	0.338	30947	4.49
	71.37	8730	0.320	27281	4.44
2	41.57	9870	0.358	27570	4.44	4.47	0.03	0.70
	46.78	10080	0.346	29133	4.46
	66.28	10170	0.312	32596	4.51
	71.37	8880	0.310	28645	4.46
3	41.57	9440	0.342	27602	4.44	4.46	0.02	0.52
	46.78	9060	0.334	27126	4.43
	66.28	9710	0.318	30535	4.48
	71.37	9250	0.320	28906	4.46
				log KOW,Av		4.46
				slog KOW,Av		0.002

 

aq. Phase = Aqueous phase

K_OW= Partition coefficient (n-octanol / water)

Log K_OW= Decadic logarithm of the partition coefficient (n-octanol / water)

SD = Standard deviation

CV = Coefficient of variation [%]

log K_OW,Av= Weighted average value of log K_OW

s_{log Kow,Av}= Weighted standard deviation

 

Regression analysis demonstrated that the slope of the regression line of the log K_OWof the four successive samples was not significantly different from zero.

For log K_OWvs. Time plot including 95 % confidence intervals, see figure 13 (attached)

Conclusions:

The substance has potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow >4).

Executive summary:

The log Kow of the isomers have been determined using a relevant test method and in compliance with GLP.

Log Kow of 4.37 ± 0.002 for isomer 1, 4.32 ± 0.003 for isomer 3 and 4.46 ± 0.002 for isomer 2 at 25 ± 1°C and pH 5.68 were obtained.

The results are considered to be reliable.

Description of key information

Partition Coefficient: 4.37 ± 0.002 (isomer 1), 4.46 ± 0.002 (isomer 2) and 4.32 ± 0.003 (isomer 3) at 25 ± 1°C and pH 5.68

Additional information

Log Kow values of 4.37 ± 0.002 (isomer 1), 4.46 ± 0.002 (isomer 2) and 4.32 ± 0.003 (isomer 3) at 25±1°C and pH 5.68 for the constituents of the submission substance were determined using the slow-stirring method in accordance with OECD Test Guideline 123 and in compliance with GLP. The results are considered to be reliable and key study.