Ethoxyquin

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Peer-reviewed draft assessment report (attached in section 13)

Qualifier:

according to guideline

Guideline:

other: US EPA PAG 161-1

GLP compliance:

yes

Specific details on test material used for the study:

The hydrolysis of ethoxyquin in the dark was studied at 25 °C in sterile aqueous buffered solutions at pH 5, pH 7 and pH 9. The nominal concentration of ring-labelled ethoxyquin was 0.01 mg as/mL for pH 5, 7 and 9. Acetonitrile (< 1.0 % v/v) was used as a cosolvent.

Radiolabelling:

yes

Remarks:

Total recovery of radioactivity was in the range of 98 – 102 %

Analytical monitoring:

yes

Buffers:

sterile aqueous buffered solutions at pH 5, pH 7 and pH 9 with < 1.0 % v/v acetonitrile

Transformation products:

not specified

pH:

5

Temp.:

25 °C

DT50:

3.7 d

Type:

not specified

pH:

7

Temp.:

25 °C

DT50:

6.7 d

Type:

not specified

pH:

9

Temp.:

25 °C

DT50:

9.3 d

Type:

not specified

Details on results:

Under sterile conditions at 25 °C in the dark, ethoxyquin is unstable and undergoes appreciable and rapid hydrolytic degradation in buffered aqueous solutions at pH levels of 5, 7 and 9. Additionally, stability decreases as pH decreases. In all of the samples analysed, one significant radioactive component detected in the organic fractions throughout the sampling intervals was confirmed chromatographically by RP-HPLC and LC/MS to be the parent compound. In addition to parent compound, seven degradates were observed during the course of the study. Deg-1 (except in pH 5 buffer), Deg-2, Deg-3, and Deg-4 (except in pH 7 and 9 buffers) were the major products. Lesser amounts (< 5 %) of Deg-5, Deg-6, and Deg-7 also were detected. Mass spectral data showed the formation of methylation, demethylation, deethylation, quinoline and dimeric ethoxyquin, which indicated that ethoxyquin was degraded primarily via intermolecular rearrangement and dimerisation. The observed halflives of ethoxyquin in pH 5, 7 and 9 test solutions are 3.7, 6.7 and 9.3 days, respectively.

Validity criteria fulfilled:

not specified

Conclusions:

As information was provided via a peer-reviewed assessment report, it can be considered as sufficiently reliable. The hydrolysis of ethoxyquin in the dark was studied at 25 °C in sterile aqueous buffered solutions at pH 5, pH 7 and pH 9. The nominal concentration of ring-labelled ethoxyquin was 0.01 mg as/mL for pH 5, 7 and 9. Acetonitrile (< 1.0 % v/v) was used as a cosolvent. Total recovery of radioactivity was in the range of 98 – 102 %.

Executive summary:

Under sterile conditions at 25 °C in the dark, ethoxyquin is unstable and undergoes appreciable and rapid hydrolytic degradation in buffered aqueous solutions at pH levels of 5, 7 and 9 ( US EPA PAG 161-1, GLP). Additionally, stability decreases as pH decreases. In all of the samples analysed, one significant radioactive component detected in the organic fractions throughout the sampling intervals was confirmed chromatographically by RP-HPLC and LC/MS to be the parent compound. In addition to parent compound, seven degradates were observed during the course of the study. Deg-1 (except in pH 5 buffer), Deg-2, Deg-3, and Deg-4 (except in pH 7 and 9 buffers) were the major products. Lesser amounts (< %) of Deg-5, Deg-6, and Deg-7 also were detected. Mass spectral data showed the formation of methylation, demethylation, deethylation, quinoline and dimeric ethoxyquin, which indicated that ethoxyquin was degraded primarily via intermolecular rearrangement and dimerisation. The observed halflives of ethoxyquin in pH 5, 7 and 9 test solutions are 3.7, 6.7 and 9.3 days, respectively.

Description of key information

-Hydrolysis: hydrolytically unstable; halflives at 25 °C are 3.7 days (pH 5), 6.7 days (pH 7) and 9.3 days (pH 9) (US EPA PAG 161 -1)

Key value for chemical safety assessment

Half-life for hydrolysis:

6.7 d

at the temperature of:

25 °C

Additional information

There is a valid, peer-reviewed US EPA PAG 161-1 study on the hydrolysis of ethoxyquin available, assessed with Klimisch 2 and hence considered as sufficiently reliable to cover this endpoint. It has been observed that ethoxyquin is unstable and undergoes appreciable and rapid hydrolytic degradation in buffered aqueous solutions at pH levels of 5, 7 and 9. Additionally, stability decreases as pH decreases with half-lives at 25°C of 3.6 days (pH 5), 6.7 days (pH 7), and 9.3 days (pH 9). In all of the samples analysed, one significant radioactive component detected in the organic fractions throughout the sampling intervals was confirmed chromatographically by RP-HPLC and LC/MS to be the parent compound. In addition to parent compound, seven degradates were observed during the course of the study. Deg-1 (except in pH 5 buffer), Deg-2, Deg-3, and Deg-4 (except in pH 7 and 9 buffers) were the major products. Lesser amounts (< 5 %) of Deg-5, Deg-6, and Deg-7 also were detected. Mass spectral data showed the formation of methylation, demethylation, deethylation, quinoline and dimeric ethoxyquin, which indicated that ethoxyquin was degraded primarily via intermolecular rearrangement and dimerisation.

There is no reason to believe that this result is not reliable, and consequently, there is no data gap identified.