Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 251-718-8
CAS number: 33885-52-8
Pinyl Isobutyraldehyde is expected to be readily absorbed, orally
and via inhalation but somewhat less via the dermal route, based on
physico-chemical parameters. The substance also is expected to have some
dermal absorption but this will be limited due to its log Kow of 5.4 and
the dermal absorption will not exceed the oral route. As adverse effects
were observed in the oral repeated dose study, route-to-route
extrapolation will be performed to estimate the dermal and respiratory
Toxicokinetic behaviour of Pinyl Isobutyraldehyde (CAS no.
Pinyl Isobutyraldehyde (CAS no 33885-52-8)contains
analpha pinene unit attached to the
2-position of isobutanal via its allylic 2-methyl group. The pinene unit
is 2,6,6-trimethylbicyclo [3.1.1]hept-2-ene, a bicyclic monoterpene.The
substance is a liquid with a molecular weight of 206.29 that does not
preclude absorption. The substance has a low volatility of 3.4 Pa, a Log
Kow 5.4, and its water solubility is 10.8 mg/L.
Oral: The results of the repeated dose oral
toxicity study (OECD TG 422) with Pinyl Isobutyraldehyde show that the
substance is being absorbed by the gastro-intestinal tract following
oral administration, since renal effects were observed in male rats.
Molecular weights below 500 are favourable for absorption by the
GI tract. The relatively low molecular weight (206.29) and the moderate
octanol/water partition coefficient (Log Kow 5.4) and water solubility
(10.8 mg/l) would favour absorption through the gut. According to
Martinez and Amidon (2002) the optimal log Kow for oral absorption falls
within a range of 2-7. This shows that the substance is likely to be
absorbed orally. As no exact absorption data is available, the oral
absorption of 50% will be used as a default value.
Dermal: Based on the substance having a
molecular weight of 206.29 and the substance being a liquid, dermal
absorption can occur. In view of its log Kow of 5.4 and water solubility
this dermal absorption will not exceed the oral absorption because the
values are outside the optimal range for dermal absorption ( < 100
molecular weight) and in the range of 1-4 log Kow; ECHA guidance, 7.12,
Table R.7.12-3)). The skin absorption will not exceed oral absorption
and 50% dermal absorption will be selected.
Respiratory: Absorption via the lungs is also
indicated based on these physico-chemical properties, though exposure by
inhalation of volatiles is thought minor as a result of the low vapour
pressure. The octanol/water partition coefficient (5.4) indicates that
inhalation absorption is possible. This is supported by the blood/air
(BA) partition coefficient. The blood/air (BA) partition coefficient is
another partition coefficient indicating lung absorption. Buist et al.
2012 have developed BA model for humans using the most important and
readily available parameters:
Log PBA = 6.96 – 1.04 Log (VP) – 0.533 (Log) Kow – 0.00495 MW.
For the substance the B/A partition coefficient would result in:
Log PBA = 6.96 – 1.04 Log (3.4) – 0.533 * 5.4 – 0.00495 * 206.29 =
This means that the substance has a tendency to go from air into
the blood. It should, however, be noted that this regression line is
only valid for substances which have a vapour pressure > 100 Pa. Despite
the substance being out of the applicability domain and the exact B/A
may not be fully correct, it can be seen that the substance will be
readily absorbed via the inhalation route. As a conservative approach,
an absorption percentage of 100% will be taken as a default value.
There are no mammalian data on the metabolism of the substance.
During Phase I metabolism, aldehyde dehydrogenase oxidizes the aldehyde
group to a carboxylic acid, which is predicted using OECD Toolbox
(version 4.1) using simulated rate liver S9 metabolism and is presented
in Fig. 1. Furthermore autoxidation was also predicted to occur for this
substance, which would yield the acid form of the molecule. Based on
information from the biodegradation and bioaccumulation study, the
aldehyde group can also be reduced to an alcohol (see Fig. 1).
During phase 2 metabolism the metabolised molecules can be
conjugated and as such transported to the kidneys.
Figure1According to the OECD Toolbox (4.1 and using simulated rat
liver S9 metabolism) the aldehyde oxidised into an acid. In the
biodegradation and bioaccumulation study the aldehyde can also be
reduced into an alcohol.
The moderate water solubility (10.8 mg/L) of the test substance
may present some distribution in the body via the water channels. The
log Kow (5.4) would suggest that the substance would pass through the
biological cell membrane, and the intracellular concentration may be
higher than extracellular concentration particularly in fatty tissues.
In view of the substance turning into an acid and excretion via the
kidneys the log Kow is not a good parameter for bioaccumulation. A
bioaccumulation study shows that the BCF is < 27 and based on this
result Pinyl Isobutyraldehyde is also considered to not have a
bioaccumulation potential in human. In this bioaccumulation study the
alcohol derivative of Pinyl Isobutyraldehyde had a BCF of 32 and does
not have a bioaccumulation potential either.
In view of the anticipated higher water solubility of the
metabolites the kidney is the main expected route of excretion. The
repeated dose study in rats resulted in effects on the male kidneys.
Tubular degeneration and tubular basophilia were observed. These renal
effects are supportive of the kidneys as the main excretion route.
Pinyl Isobutyraldehyde is expected to be readily absorbed, orally
and via inhalation, based on the mammalian toxicological information and
physico-chemical parameters. The substance also is expected to be
absorbed dermally based on the physico-chemical properties. Though the
molecular weight and the log Kow are slightly outside of the favourable
range for dermal absorption, significant absorption is likely. As
adverse effects were observed in the oral repeated dose study,
route-to-route extrapolation will be performed to estimate the dermal
and respiratory no effect levels.
Oral to dermal extrapolation: There are
adequate data via the oral route and the critical toxic effect is
related to systemic effects and therefore route-to-route extrapolation
is applicable. The toxicity of the substance will be due to the parent
compound but also to its metabolites. The overriding principle will be
to avoid situations where the extrapolation of data would underestimate
toxicity resulting from human exposure to a chemical by the
route-to-route extrapolation. The absorption will be slower via the
skin. Therefore it will be assumed that the oral absorption will be
equal to dermal absorption. Using the asymmetric handling of uncertainty
the oral absorption will be considered 50% (though likely to be higher)
and the dermal absorption will be considered also 50%.
Oral to inhalation extrapolation: Though Pinyl
Isobutyraldehyde is not a volatile substance, inhalation exposure is
considered to be relevant. In the absence of bioavailability data it is
most precautionary that 100% of the inhaled vapour becomes bioavailable.
For the oral route, 50% absorption will be used for route-to-route
extrapolation to be precautionary for the dermal route. For inhalation
absorption 100% will be used for route-to-route extrapolation, because
this will be precautionary for the inhalation route.
Pinyl Isobutyraldehyde is expected to be readily absorbed via the
oral and inhalation route and somewhat lower via the dermal route based
on toxicity and physico-chemical data. Using the precautionary principle
for route to route extrapolation, the final absorption percentages
derived are: 50% oral absorption, 50% dermal absorption and 100%
Buist, H.E., Wit-Bos de, L., Bouwman, T., Vaes, W.H.J., 2012,
Predicting blood:air partition coefficient using basis physico-chemical
properties, Regul. Toxicol. Pharmacol., 62, 23-28.
IGHRC, 2006, Guidelines on route-to-route extrapolation of
toxicity data when assessing health risks of
Martinez, M.N., And Amidon, G.L., 2002, Mechanistic approach to
understanding the factors affecting drug absorption: a review of
fundament, J. Clinical Pharmacol., 42, 620-643.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
På den här webbplatsen används kakor. Syftet är att optimera din upplevelse av den.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again