2,2-dimethylpropane-1,3-diol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study meets scientific standards with acceptable restrictions (22 glycols tested, partly limited documentation, e.g. no details about test substance & method; no data about other routes of excretion; only 24-h urine analysed).

Data source

Reference

Reference Type:

publication

Title:

Studies in detoxication. 80. The metabolism of glycols

Author:

Gessner PK, Parke DV, Williams RT

Year:

1960

Bibliographic source:

Biochem J 74: 1-5

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

Excretion of the unlabelled test substance and their metabolites via the urine measured in rabbits after gavage.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Details on test material:

The test substance was presented by G.A.H. Buttle and E.E. Connolly of The Distillers Co. Ltd . (Chemical Division), Hull. Boiling points and melting points were
checked with the literature.
No further data available.

Radiolabelling:

no

Test animals

Species:

rabbit

Strain:

Chinchilla

Sex:

not specified

Details on test animals or test system and environmental conditions:

Body weight: 2-3 kg; rabbits kept on a constant diet of 60 g of rat cubes (diet 41; Associated London Flour Millers) and 100 ml of water per day.
No further data available.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

Totally 8 g test substance were given to 4 rabbits.

Duration and frequency of treatment / exposure:

single application

Doses / concentrations

Remarks:

Doses / Concentrations:
Each rabbit gavaged with 1-1.5 g/kg bw (no further data).
No data were given on application volume and concentration.
In the Table on page 3 the authors mentioned a dose of 2 mmole/kg bw which is in contrast to the text on page 2 (8 g test substance were given to 4 rabbits).

No. of animals per sex per dose / concentration:

4 rabbits (sex unknown) received the above mentioned dose.

Control animals:

no

Positive control reference chemical:

no

Details on study design:

No further details

Details on dosing and sampling:

The 24-h urine of the four rabbits (pooled data) brought to pH 10.0 with NH3 solution and then continuously extracted with ether for 6 h; evaporation of the
extract and sublimation of the residue. The residual urine brought to pH 4.0 with HCl and again continuously extracted with ether for 6 hr; evaporation of the extract gave an acidic gum which partly crystallized on keeping at 0°C for a week. Repeated crystallization of this material from ethanol/ether mixtures.

Statistics:

No data

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

62% (range 53-67%) of the applied dose was found in the 24-h urine as the conjugate of glucuronic acid indicating rapid absorption after oral application.

Details on distribution in tissues:

No data

Details on excretion:

Beside the glucuronic acid conjugate (62% of applied dose) also the unchanged test substance was found but only 56 mg or 0.7 % of the applied dose (8000 mg); 150 mg of the metabolite 3-hydroxy-2,2-dimethylpropionic acid were detected (1.9% of applied dose).

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

- glucuronic acid conjugate of neopentyl glycol (62% in 24-h urine)
- 3-hydroxy-2,2-dimethylpropionic acid (1.9%)
- unchanged neopentyl glycol (0.7%)

Any other information on results incl. tables

No further data were presented in the result section.

Applicant's summary and conclusion

Conclusions:

Rapid absorption of the test substance followed by conjugation with glucuronic acid and excretion via urine.

Executive summary:

The study meets scientific standards with accepatable restrictions (22 glycols tested, partly limited documentation, e.g. no details about test substance & method; no data about other routes of excretion; only 24-h urine analysed).

Each of 4 rabbits were gavaged with 1000 -1500 mg/kg bw unlabelled neopentyl glycol and excretion of the test substance and their metabolites via urine was determined the following 24 h (pooled data). 62% (range 53-67%) of the applied dose was found in the 24-h urine as the conjugate of glucuronic acid indicating rapid absorption after oral application. 1.9% of the applied dose was excreted as 3-hydroxy-2,2-dimethylpropionic acid and 0.7% as unchanged neopentyl glycol.

Conclusion: Rapid absorption of the test substance followed by conjugation with glucuronic acid and excretion via urine.