Propane-1,3-diol

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

supporting study

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 Type:

publication

Title:

Unnamed

Year:

1987

Materials and methods

Study type:

clinical case study

Principles of method if other than guideline:

Three patients who died in infancy showed an unusual urinary organic pattern with excessive excretion of 3-hydroxypropionic acid. Propan-1, 3-diol was also present in the urine of all three cases. A fourth patient, also severely ill, showed similar urinary abnormalities. Investigations were conducted to determine the cause of the abnormal urinary profile.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Propane-1,3-diol

EC Number:

207-997-3

EC Name:

Propane-1,3-diol

Cas Number:

504-63-2

Molecular formula:

C3H8O2

IUPAC Name:

propane-1,3-diol

Details on test material:

- Analytical purity: not applicable

Method

Type of population:

general

Subjects:

- Sex: male and female
- Age: infant

Ethical approval:

not applicable

Results and discussion

Any other information on results incl. tables

In all the urines examined the 3-hydroxypropionic acid peak was very prominent, in most cases the largest on the chromatogram. No other metabolites suggestive of propionyl-CoA carboxylase deficiency were present in excess nor was there any indication of other recognised metabolic disease. Examination of the lactic acid peak revealed that it also contained propan-1, 3-diol (as the bis-trimethylsilyl derivative) in a molar ratio to lactate ranging from 0.8 to 3.1.

In patient 4, the urine abnormalities were less marked with, initially, a greater excretion of 1, 3-propandiol than of 3-hydroxypropionic acid. The introduction of a medium-chain triglyceride-rich diet was accompanied by the excretion for the first time of malonic acid, as well as the expected medium-chain dicarboxylic aciduria. While still on this diet the patient was given neomycin (250 mg/kg per day). This resulted in the disappearance of all the abnormal 3-carbon metabolites.

Propan-1, 3-diol has not been reported in human urine before though it has been found in combined form in heart and lung phospholipids. Propan-1, 3-diol can be formed from glycerol by Lactobacillus spp. Its presence in the urine of all four patients is consistent with the idea that overgrowth by some specific type of gut bacterium was the cause of the characteristic urinary organic acid abnormalities. The two unusual metabolites excreted by all four patients, 3-hydroxypropionic acid and propan-1, 3-diol, may be obtained by oxidation or reduction respectively of the aldehyde group of 3-hydroxypropionaldehyde.

Applicant's summary and conclusion

Executive summary:

Three patients who died in infancy showed an unusual urinary organic acid pattern with excessive excretion of 3-hydroxypropionic acid but none of the other metabolites normally associated with propionyl-CoA carboxylase deficiency. Propan-1, 3-diol was present in the urine in all three cases. In the two patients examined propionyl-CoA carboxylase activity was not deficient in cultured skin fibroblasts. A fourth patient, also severely ill, showed similar urinary abnormalities. Feeding a medium-chain triglyceride-rich diet to this patient increased the ratio of 3-hydroxypropionic acid to propan-1, 3-diol and resulted also in the appearance of malonic acid in the urine. These abnormal metabolites disappeared on the administration of neomycin and presumably were produced by gut bacteria.