Registration Dossier

Administrative data

Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 21, 2013 - December 2, 2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study under GLP with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPPTS 830.7840 (Water Solubility)
Deviations:
yes
Remarks:
see extra info under principles of method.
Principles of method if other than guideline:
EPA OPPTS 830.7840 and OECD 105 indicate that solubility test system vials should be agitated at 30°C for a given incubation time, followed by equilibration at the test temperature (ambient) for 24 hours with suggested incubation times of one day, two days, and three days. Because the test material was administered as a neat gas, incubation on an orbital shaker was done at ambient conditions to prevent the vial contents from pressurizing. Incubation times were increased to compensate for the ambient agitation.
GLP compliance:
yes
Type of method:
flask method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: gas
Details on test material:
- Name of test material (as cited in study report: L-21609
- Substance type: Mono-constituent
- Physical state: clear and colorless gas at ambient conditions

Results and discussion

Water solubility
Water solubility:
272 µg/L
Temp.:
22.4 °C
Remarks on result:
other: pH was not measured
Details on results:
Water solubility reported as ng/mL. pH was not measured. Daily average incubation temperatures ranged from 21.7°C-23.3°C. The average temperature over the course of the study was 22.4°C.

Triplicate samples were incubated for five time points (4, 5, 6, 11 and 12 days) at ambient temperature (21.7 - 23.3 °C). Triplicate analysis was performed for each sample at each time point. The average measured solubility for day 4 was 225 (188 -257) ng/mL; the average measured solubility for day 5 was 303 (246 - 420) ng/mL; the average measured solubility for day 6 was 408 (321- 492) ng/mL; the average measured solubility for day 11 was 191 (164 - 256) ng/mL; and the average measured solubility for day 12 was 204 (163- 321) ng/mL. The average %RSD for days 4, 5, 6, 11 and 12 were 12%, 17%, 14%, 39% and 23%, respectively. An overall average value of 272 ng/mL was reported. The overall %RSD was 33% (Table 2).

L-21609 is a gas at ambient temperature. During the twelve-day course of the study, approximately 75% of the dosed test material was lost as indicated by headspace measurements (Table 3). However, the measured headspace concentrations demonstrated that the test substance was present in the test system vials in great excess of what was measured in the water. Therefore, a constant source of L-21609 was available to the test system throughout the twelve-day study and the reported water concentrations represent an equilibrium solubility concentration under the experimental conditions.

Additionally, sample chromatograms detected the presence of a compound suggestive of a fluorinated amide, a possible hydrolysis product of the test material.

Therefore, the solubility values reported here represent the maximum obtainable L-21609 concentration in water under forced conditions (excess test material present in the vial) and represent an equilibrium concentration of two separate processes: transfer of the L-21609 from the headspace into the aqueous phase and the suggested hydrolysis of the heptafluoroisobutyrylnitrile to the heptafluoroisobutyrylamide.

Any other information on results incl. tables

Table 2. Water solubility results of L-21609

Solubility Concentration (ng/mL)(1)

Samples

Time Point 1

(Four Days)

Time Point 2 (Five Days)

Time Point 3

(Six Days)

Time Point 4

(Eleven Days)

Time Point 5

(Twelve Days)

Vial 1, rep 1

257

420

457

193

321

Vial 1, rep 2

207

251

418

256

203

Vial 1, rep 3

226

246

348

175

184

Vial 1 Average

233

306

408

208(2)

236

Vial 1 RSD%

11

32(3)

14

21

31

Vial 2, rep 1

247

290

492

242

178

Vial 2, rep 2

254

325

410

235

181

Vial 2, rep 3

215

266

434

256

196

Vial 2 Average

239

294

445

244

185

Vial 2 RSD%

8.7

10

9.4

4.3

5.3

Vial 3, rep 1

227

320

436

NR

227

Vial 3, rep 2

190

303

321

179

163

Vial 3, rep 3

188

306

354

164

179

Vial 3 Average

202

310

370(2)

172

190

Vial 3 RSD%

11

3.0

16

8.9

18

Intra-day Average

225

303

408

 

191

204

Intra-day %RSD

12

17

14

39(3)

23

Inter-day Average

272

Inter-day %RSD

33(3)

(1) Results are considered accurate to within the calculated analytical method uncertainty for L-21609 of ±31%.

(2) The laboratory matrix spike recovery associated with this test system vial was less than 70%.

(3) The measured precision did not meet the acceptance criteria set forth in the study protocol: intra-day and inter-day %RSD <25%.

Table 3. Measured Headspace Concentrations of L-21609.

L-21609 Headspace Concentration (ng/cc)

Samples

Time Point 1

(Four Days)

Time Point 2

 (Five Days)

Time Point 3

(Six Days)

Time Point 4

(Eleven Days)

 

Time Point 5

(Twelve Days)

Vial 1, rep 1

6,410,000

5,680,000

3,430,000

2,210,000

1,940,000

Vial 1, rep 2

6,110,000

4,750,000

3,110,000

2,090,000

2,000,000

Vial 1 Average

6,260,000

5,220,000

3,270,000

2,150,000

1,970,000

Vial 1 RSD%

4.9

18

9.6

5.3

2.9

 

Vial 2, rep 1

5,720,000

4,540,000

2,540,000

2,370,000

2,080,000

Vial 2, rep 2

5,900,000

4,980,000

3,430,000

2,210,000

1,940,000

Vial 2 Average

5,810,000

4,760,000

2,940,000

2,270,000

1,980,000

Vial 2 RSD%

3.2

9.3

27

8.9

10

 

Vial 3, rep 1

6,320,000

4,170,000

2,490,000

1,890,000

1,810,000

Vial 3, rep 2

6,180,000

4,660,000

3,280,000

1,850,000

1,910,000

Vial 3 Average

6,250,000

4,410,000

2,890,000

1,870,000

1,860,000

Vial 3 RSD%

2.3

11

27

2

5.4

 

Intra-day Average

6,110,000

4,800,000

3,030,000

2,100,000

1,940,000

%RSD (N=6)

4.2

11

14

9.5

4.9

% Theoretical Neat Gas(1)

76.6

60.2

38

26.3

24.3

(1) Concentration of the neat gas dosed into the test system vial = 7,980,000 ng/cc.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): slightly soluble (0.1-100 mg/L)
Under conditions of this study, the average measured water solubility of L-21609 is 272 ng/mL.
Executive summary:

The solubility of L-21609 in Milli-Q water was determined using a modified Shake Flask method according to OPPTS 830.7840. Triplicate samples were incubated for 4, 5, 6, 11 and 12 days at ambient temperature (approximately 22 °C). Samples were equilibrated at room temperature for 30 minutes prior to analysis. Concentrations were analyzed in triplicate using a purge and trap gas chromatography/mass spectrometry (GC/MS).

 

L-21609 has an average measured water solubility of 272 ng/mL at approximately 22˚C, as an average of day 4, 5, 6,11 and 12 measurements. The overall %RSD was 33%.

 

L-21609 is a gas at ambient temperature. During the twelve-day course of the study, approximately 75% of the dosed test material was lost as indicated by headspace measurements. However, the measured headspace concentrations demonstrated that the test substance was present in the test system vials in great excess of what was measured in the water. Additionally, sample chromatograms detected the presence of a compound suggestive of a fluorinated amide, a possible hydrolysis product of the test material. Therefore, the solubility values reported here represent the maximum obtainable L-21609 concentration in water under forced conditions (excess test material present in the vial) and represent an equilibrium concentration of two separate processes: transfer of the L-21609 from the headspace into the aqueous phase and the suggested hydrolysis of the heptafluoroisobutyrylnitrile to the heptafluoroisobutyrylamide.

 

This is a modified guideline study conducted under GLP compliance. The modification was necessary to accommodate gaseous samples. The method had a ± 31% uncertainty. Therefore, it is considered reliable with restrictions.