1,1'-iminodipropan-2-ol

Specific investigations: other studies

Administrative data

Endpoint:

cell culture study

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

2008

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Principles of method if other than guideline:

Examination of incorporation of DIPA into phospholipids and effects of DIPA upon choline uptake and phospholipid synthesis in CHO cells.

GLP compliance:

not specified

Type of method:

in vitro

Endpoint addressed:

other: choline uptale and phospholipid synthesis

Test material

Test material information

Constituent 1

Reference substance name:

1,1'-iminodipropan-2-ol

EC Number:

203-820-9

EC Name:

1,1'-iminodipropan-2-ol

Cas Number:

110-97-4

Molecular formula:

C6H15NO2

IUPAC Name:

1,1'-iminodipropan-2-ol

Details on test material:

TS-Freetext:
1,1'-iminodipropan-2-ol, pure

Test animals

Species:

other: In vitro: CHO cells

Administration / exposure

Route of administration:

other: In vitro: Incubation of cell culture

Results and discussion

Details on results:

DIPA displayed a dose-related cytotoxicity to CHO cells resulting in near complete lethality at 3000 ug/ ml in the absence of significant changes in osmolality or pH. A dose-related inhibition of choline uptake by CHO cells was also observed at nontoxic concentrations of DIPA which was roughly 2-fold less potent than what has been reported for diethanolamine (DEA). In contrast to DEA, however, DIPA did not cause changes in the synthesis rates of 33P-phosphatidylethanolamine, 33P-phosphatidylcholine or 33Psphingomyelin at either nontoxic or toxic concentrations. Finally, only very small amounts, approximately 0.004%, of 14C-DIPA was metabolically incorporated into phospholipids at either nontoxic or toxic concentrations. This was over 30-fold less than the incorporation of 14C-DEA under similar conditions.
Overall, the data provided by the present in vitro study and previous toxicity data obtained in vivo suggests that DIPA is distinct from DEA in several toxicologically significant ways. Despite the potential of DIPA to decrease the uptake of choline by cultured CHO cells, the lack of effects upon 33Pphosphatidylcholine synthesis suggests a lack of severe choline deficiency in treated cells. In addition, the minimal incorporation of 14C-DIPA into phospholipids suggests a relatively low potential to form aberrant lipids.

Applicant's summary and conclusion

Executive summary:

The study was undertaken to examine the potential incorporation of diisopropanolamine (DIPA) into phospholipids (PLs) of cultured Chinese Hamster Ovary (CHO) cells and potential effects of DIPA upon choline uptake and phospholipid synthesis in vitro. Where appropriate, results were compared and contrasted with those generated using a related secondary alcohol amine, diethanolamine (DEA), whose toxicity has been associated with its metabolic incorporation into phospholipid headgroups and depletion of choline pools. CHO-K1-BH4 cells cultured using standard methods were utilized.

The following were evaluated: DIPA-related cytotoxicity; uptake of 3H-choline by cells; synthesis of 33Pphosphatidylethanolamine (PtdEA), 33P-phosphatidylcholine (PtdCho), and 33P-sphingomyelin (SM); and metabolic incorporation of 14C-DIPA into PLs.

DIPA displayed a dose-related cytotoxicity to CHO cells resulting in near complete lethality at 3000 mg/mL in the absence of significant changes in osmolality or pH. A dose-related inhibition of choline uptake by CHO cells was also observed at nontoxic concentrations of DIPA which was roughly 2-fold less potent than what has been reported for DEA. In contrast to DEA, however, DIPA did not cause changes in the synthesis rates of PtdEA, PtdCho or SM at either nontoxic or toxic concentrations. Finally, only very small amounts, approximately 0.004%, of 14C-DIPA was metabolically incorporated into PLs at either nontoxic or toxic concentrations. This was over 30-fold less than the incorporation of 14C -DEA under similar conditions.

Overall, the data provided by the present in vitro study and previous toxicity data obtained in vivo suggests that DIPA is distinct from DEA in several toxicologically significant ways. Despite the potential of DIPA to decrease the uptake of choline by cultured CHO cells, the lack of effects upon PtdCho synthesis suggests a lack of severe choline deficiency in treated cells. In addition, the minimal incorporation of 14C-DIPA into PLs suggests a relatively low potential to form aberrant lipids.