Reaction mass of Dimethyl [3-[(hydroxymethyl) amino]-3-oxopropyl] phosphonate and Dimethyl (3-amino-3-oxopropyl)phosphonate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25.03.1992 - 30.11.1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Name: DMPPA_701-402-5
Batch No.: EN 746916/1991
Aggregate State: liquid
Colour: white
Stability: pure: stable for years in solvent: >2 hours in H20, ethanol, methanol, acetone, DMSO, and DMF
Storage: at room temperature
Expiration Date: September, 1996

Analytical monitoring:

yes

Details on sampling:

1 ml aliquot of the sample solution was filled up to 50 ml with HPLC water and analysed by HPLC.

Buffers:

Sterile buffer solutions for experiments:
pH 4.0: 0.40 ml 0.1N NaOH + 50 ml potassium biphthalate (0.1 mol/1) to 100 ml
pH 7.0: 29.63 ml 0.1N NaOH + 50 ml monopotassium phosphate (0.1 mol/1) to 100 ml
pH 9.0: 21.30 ml 0.1N NaOH + 50 ml boric acid (0.1 mol/1) to 100 ml

The buffer solutions are purged with nitrogen for 5 minutes and heated to 122 °C in an autoclave for 20 minutes for CO2 remove and sterilisation.
The pH of each buffer solution was checked with a calibrated pH meter at required temperature to a precision of at least ± 0.1.

Duration:

120 h

Temp.:

50 °C

Remarks:

Preliminary test at pH 4, 7 and 9

pH:

7

Remarks:

tested at 50, 60 and 70 °C

pH:

9

Remarks:

tested at 50 and 30 °C

Positive controls:

no

Negative controls:

no

Preliminary study:

Hydrolysis after 2.4 h at
pH 4: <5 %,
pH 7: 13 %,
pH 9: 49 %

Hydrolysis after 5 days at
pH 4: < 5 %,
pH 7: 42 %,
pH 9: 2 %

DMPPA_701-402-5 is considered hydrolytically stable at pH 4.0 because no hydrolysis reaction was observed until 5 days reaction time (t% >1 year). Therefore, no further tests were performed at pH 4.0.

Transformation products:

not measured

Key result

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

The preliminary study indicates that the substance is hydrolytically stable and no further study was performed.

Table: Results of the hydrolysis of DMPPA_701-402-5 at pH 7.0

Test no.	Temp [° C]	Time [h]	Conc. (µ.g/ml)	Hydrolysis [%]	k* [h^-1]	T1/2 [h]
1	50	0 48 72 96 192 264 354	2623 2318 2013 1809 1320 981 764	12** 23 31 50 63 71**	0.0026 0.0037 0.0039 0.0036 0.0037 0.0035	269.4 188.7 179.0 193.7 186.0 199.0
3	60	0 21 29	2365 1593 1411	33 40	0.0188 0.0178	36.8 38.9
3	70	0 6.5 12 21	2570 1991 1217 668	23** 53 74	0.0393 0.0623 0.0641	17.7 11.1 10.8

slope = k = 0.0037 h^-1

intercept = 0.0055

coefficient of regression = 0.999

t_1/2 = 0.693/k = 189 h

Table: Results of the hydrolysis of DMPPA_701-402-5 at pH 9.0

Test no.	Temp [° C]	Time [h]	Cone.(µ.g/ml)	Hydrolysis [%]	k*[h^-1]	T1/2 [h]
		0 0.5	2585 2467	5**	0.0934	7.4 4.4 4.3 4.3 4.4 4.4 4.5
1	50	1	2206	15**	0.1586
		2	1869	28	0.1622
		3	1592	38	0.1615
		4	1366	47	0.1594
		5	1174	55	0.1578
		6	1020	61	0.1551
	30	0 43	2711 1652	39	0.0115	60.1
3		48	1597	41	0.0110	62.9
		72	1229	55	0.0110	63.1

slope = k = 0.1517 h^-1

intercept = 0.0266

coefficient of regression = 0.999

t_1/2 = 0.693/k = 4.6 h

Validity criteria fulfilled:

yes

Conclusions:

DMPPA_701-402-5 is hydrolytically stable at pH 4.0, hydrolyses rather slow at pH 7.0 (t1/2 = 189 h), while hydrolysis was relatively fast at pH 9 (t1/2 = 4.6 h).

Executive summary:

The assessment of hydrolysis of DMPPA_701-402-5 was assessed in a study conducted according to OECD Guideline 106 and EU Method C.7. In the preliminary study, the hydrolysis was assessed at 50 ± 0.1 °C at each of pH 4.0, 7.0, and 9.0. The percentage of hydrolysis was found to be less than 10 % after 5 days (t_1/2 >1 year) at pH 4.0, while further testing was needed at at pH 7.0 and 9.0.

DMPPA_701-402-5 is thus considered hydrolytically stable at pH 4.0. During further testing at pH 7.0, the hydrolysis of DMPPA_701-402-5 was found to be rather rather slow (t_1/2 = 189 h ). While the hydrolysis reaction of DMPPA_701-402-5 was found to be relative fast at pH 9.0 (t_1/2 = 4.6 h).

Description of key information

DMPPA_701-402-5 is hydrolytically stable at pH 4.0, hydrolyses rather slow at pH 7.0 (t1/2 = 189 h), while hydrolysis was relatively fast at pH 9 (t1/2 = 4.6 h).

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

50 °C

Additional information

The assessment of hydrolysis of DMPPA_701-402-5 was assessed in a study conducted according to OECD Guideline 106 and EU Method C.7. In the preliminary study, the hydrolysis was assessed at 50 ± 0.1 °C at each of pH 4.0, 7.0, and 9.0. The percentage of hydrolysis was found to be less than 10 % after 5 days (t1/2 >1 year) at pH 4.0, while further testing was needed at pH 7.0 and 9.0.

DMPPA_701-402-5 is thus considered hydrolytically stable at pH 4.0. During further testing at pH 7.0, the hydrolysis of FAT 80001/I was found to be rather slow (t1/2 = 189 h). While the hydrolysis reaction of DMPPA_701-402-5 was found to be relative fast at pH 9.0 (t1/2 = 4.6 h).