Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

The following information is taken into account for any hazard / risk assessment: 
One in vivo study was taken into account to predict toxicokinetic pathways for MPD.
According to the data available, MPD does not seem to accumulate in the body.
Methylpentane-1,5-diol adminstered to rabbits yielded large amounts of methylglutaric acid in the urine.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

Absorption:


oral


MPD which is fully water miscible is likely to be readily absorbed via oral route. From read across of other glycols an absorption percentage of more than 50 % can be taken into account for this route. As a worst case an absorption rate of 100% is used for the assessment.


 


dermal


No experimental data on dermal absorption of MPD are available. From read across of similar glycols a moderate dermal adsorption between 5 and 50% can be assumed. For the present assessment a worst case of 100% is assumed.


 


inhalation


MPD which is fully water miscible is likely to be readily absorbed via the inhalation route. From read across of other glycols an absorption percentage of 100 % can be taken into account for this route.


 


Distribution:


The acute toxicity dosis for oral application (8 g/kg in rats) is four times higher than that for the intraperitoneal route (2 g/kg in mice), which again is 7 times higher than the acute toxicity for intravenous application (0.32 g/kg in mice). It can therefore be assumed that MPD is readily absorbed but does not accumulate in blood. It is readily routed to the liver and kidneys, which is in agreement with the results of repeated dose toxicity studies (see section 7.5 for further details).


 


Metabolism:


The metabolism of MPD has been investigated together with a series of glycols starting from ethylene glycol to hexane 1,6 -diol. Urine excretion analysis identified metabolites for MPD as follows: 1 - 2 days after administration14.5% (w/w) of the dose was recovered as unmetabolized parent compound, while 30% was recovered as 3 -methyl glutaric acid. It can be concluded that the main metabolic pathway is oxidation leading to 3 -methyl glutaric acid. Glucurono- and sulfo-conjugation has not been identified but is assumed to contribute only to a smaller amount. At high dose, saturation of the metabolic pathways leads to urinary elimination of MPD as such.


It should be noted, that 3- methylglutaric acid (CAS 626 -51 -7) as the main metabolite of MPD is a human endogenous substance metabolized from food. 3 -methyl glutaric acid is further metabolitzed to acetic acid CoA and acetylacetate.


 


Excretion:


From the available in-vivo study on MPD it is concluded that urine excretion contains metabolites for MPD as follows: 1 - 2 days after administration 14.5% (w/w) of the dose was recovered as unmetabolized parent compound, while 30% was recovered as 3 -methyl glutaric acid.