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Administrative data

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Description of key information

A full OECD guideline 417 toxicokinetics study in rats is available for this substance.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
93.5
Absorption rate - dermal (%):
20
Absorption rate - inhalation (%):
100

Additional information

An OECD 417 guideline oral rat ADME study is available for this substance. The results are summarised as follows:

Absorption: The percent absorption of the orally administered dose in the low and high dose groups was at least 92-95%, based on recovery in urine and non-GI tissues for either dose level. Based on this high level of oral absorption, it is assumed that absorption via the inhalation route will be similar.

The dermal penetration of 1, 3 - and 1, 4 -cyclohexanedicarboxaldehyde was estimated using the DERMWIN module of EPI Suite. The estimated dermal permeability (Kp) is 0.00124cm/h for both isomers, indicating that Unoxol dialdehyde is has a potential for dermal absorption. Based on the QSAR dermal prediction estimate via flux values proposed by Moster and Goergens (Mostert and Goergens, 2011), the dermal absorption for Unoxol is estimated as 20% per 8-hr shift.

Distribution: Similar pharmacokinetic parameters were observed in rats for either dose level. The time-course of 14C-1,3- and 1,4-CHDA-derived radioactivity in plasma exhibited a biphasic decline after reaching Cmax and was therefore fit to a two-compartment pharmacokinetic model. Plasma radioactivity declined rapidly during the alpha phase (t½α = ~1.8-3 hours), followed by a slower decline during the terminal beta phase (t½beta = ~6 hours).

Metabolism and Elimination: The reaction mixture was widely metabolized and no parent 1,3 -CHDA and 1,4 -CHDA were detected in the urine and fecal samples. A total of 11 radiochemical peaks were detected in the acidified urine and/or fecal samples across the profiles of all dose levels. Only five major peaks (containing six major metabolites) of the 11 radiochemical peaks accounted for more than 5% of the administered dose. Of these five peaks, two (39 to 45% and 9% of the administered dose respectively), were identified as the cis and trans isomers of 1,3-cyclohexanedicarboxylic acid (1,3-CHD acid) (isomer assignments unknown). Two peaks (17% and 10 -12% of the administered dose respectively) were identified as the cis and trans isomers of 1,4-cyclohexanedicarboxylic acid (1,4-CHD acid) (isomer assignments unknown). Two additional major peaks were tentatively identified as either the cis or trans isomer of 4-(hydroxymethyl)cyclohexanecarboxylic acid (Peak C), which comprised ~7 % to 11 % of the administered dose, and either the cis or trans isomer of 3-(hydroxymethyl)¬cyclohexane carboxylic acid (Peak D-2) which comprised ~9 % of the administered dose The majority (91-94%) of the administered 14C-1,3- and 1,4-CHDA derived radioactivity was rapidly excreted in urine without any difference between the dose levels. The majority of the urinary elimination (91-95%) occurred within the first 12 hours post-dosing. Most of the remaining oral dose (9-13%) was eliminated in feces, with the majority of the fecal elimination (80-91%) occurring within the first 24 hours post-dosing.

Bioaccumulation potential: Less than 0.06% of the orally administered 14C-1,3- and 1,4-CHDA remained in the tissues after 168 hours (7 days) post-dosing in all of the groups, indicating the very low bioaccumulation potential 14C-1,3- and 1,4-CHDA in rats.

Reference

Mostert, V., and A. Goergens. 2011. Dermal DNEL setting: Using QSAR predictions for dermal absorption for a refined route-to-route extrapolation.NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY. 383:90.