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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: expert statement
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Well documented expert statement. This expert statement has been based on a series of physicochemical, environmental and toxicology studies with octane-1,2-diol performed according to technical guidelines and in compliance with GLP in internationally recognized contract research organizations. In addition, this expert statement has been based on read-across from studies with structurally similar substance analogues and published literature.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012

Materials and methods

Objective of study:
absorption
bioaccessibility (or bioavailability)
excretion
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Expert statement based on a series of physicochemical, environmental and toxicology studies with the target chemical, octane-1,2-diol, and on read-across from a number of subacute repeated dose oral and reproduction/developmental toxicity studies with the substance analogue source chemicals, butane-1,2-diol (EC 209-527-2), hexane-1,2-diol (EC 230-029-6) or decane-1,2-diol (EC 214-288-2). Technical guidelines followed in these experimental studies are cited in the respective endpoint study records.
GLP compliance:
no
Remarks:
Considered unnecessary for expert statement

Test material

Constituent 1
Chemical structure
Reference substance name:
Octane-1,2-diol
EC Number:
214-254-7
EC Name:
Octane-1,2-diol
Cas Number:
1117-86-8
Molecular formula:
C8H18O2
IUPAC Name:
octane-1,2-diol
Radiolabelling:
no

Test animals

Species:
other: Detailed in endpoint study records of in-vivo studies referred to in the present expert statement
Strain:
other: Detailed in endpoint study records of in-vivo studies referred to in the present expert statement
Sex:
male/female
Details on test animals or test system and environmental conditions:
Detailed in the endpoint study records of in-vivo studies referred to in the present expert statement.

Administration / exposure

Route of administration:
other: Detailed in endpoint study records of in-vivo studies referred to in the present expert statement
Vehicle:
other: Detailed in endpoint study records of in-vivo studies referred to in the present expert statement, if appropriate
Details on exposure:
Detailed in endpoint study records of in-vivo studies referred to in the present expert statement.
Duration and frequency of treatment / exposure:
Detailed in endpoint study records referred to in the present expert statement.
Doses / concentrations
Remarks:
Doses / Concentrations:
Detailed (as appropriate) in endpoint study records referred to in the present expert statement.
No. of animals per sex per dose / concentration:
Detailed in endpoint study records of in-vivo studies referred to in the present expert statement.
Control animals:
other: Detailed in endpoint study records referred to in the present expert statement, if applicable
Positive control reference chemical:
Detailed in endpoint study records referred to in the present expert statement, if applicable
Details on study design:
Detailed in endpoint study records referred to in the present expert statement, if applicable
Details on dosing and sampling:
Detailed in endpoint study records referred to in the present expert statement, if applicable
Statistics:
Detailed in endpoint study records referred to in the present expert statement, if applicable. Not applicable for the present expert statement.

Results and discussion

Preliminary studies:
Not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Based on the physical-chemical properties of octane-1,2-diol [moderately high water solubility of 7.5 g/L (at 20°C), a partition coefficient value Log10Pow of 2.1 and a relatively low molecular weight of 146] it is expected that after oral dosing the substance is well absorbed by passive diffusion in the gastro-intestinal tract and becomes systemically available [1].

Likewise, water solubility (ca. 230 g/L to 0.40 g/L) [2], partition coefficient values (Log10Pow of ca. –0.8 to +2.4) [2] and relatively low molecular weights (90 to 174) [2] changing with increasing carbon chain length for the structurally similar substance analogues used for read-across [butane-1,2-diol (EC 209-527-2), pentane-1,2-diol (EC 226-285-3), hexane-1,2-diol (EC 230-029-6) or decane-1,2-diol (EC 214-288-2)] favour systemic absorption after oral gavage administration [1]. This is consistent with the finding of slightly reduced locomotor activity in the two 28-day oral toxicity studies with octane-1,2-diol and decane-1,2-diol and in the reproduction and developmental toxicity screening study (combined with some repeat dose toxicology endpoints) with butane-1,2-diol, being an indication of systemic exposure.

The above physical-chemical properties of octane-1,2-diol also favour dermal uptake [1]. However, systemic availability after dermal uptake is considered to be lower than after gastro-intestinal absorption. In an in-vitro trial in which octane-1,2-diol was incubated for 24 h with and without cut up pig skin, 50% of the octane-1,2-diol was lost in the presence of skin when compared with two samples without pig skin [2]. It was concluded that chemical or metabolic degradation took place in the presence of the skin.

The partition coefficient Log10Pow of 2.1 of octane-1,2-diol and its moderately high water solubility of 7.5 g/L (at 20°C) are favourable for absorption directly across the respiratory tract epithelium by passive diffusion [1]. However, in view of the rather low volatility of octane-1,2-diol (vapour pressure of 0.28 Pa at 25°C, 0.15 Pa at 20°C) and being described as a viscous liquid with a melting point of 28-31°C the likeliness of exposure to its vapour or to inhalable particles is rather low.



References:
[1]: ECHA 2008, Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7c: Endpoint specific guidance.
[2]: On the Safety Assessment of 1,2-Glycols as Used in Cosmetics. Final Report Cosmetic Ingredient Review Expert Panel, June 28, 2011
Details on distribution in tissues:
There are no data on the distribution of octane-1,2-diol in tissues. In view of the findings of reduced locomotor activity in rats treated by oral gavage for 28 days at 1000 mg/kg bw/day effects on the central nervous system and therefore, passage of the blood/brain barrier by octane-1,2-diol or possible metabolites cannot be ruled out.
Details on excretion:
There are no data on the excretion of octane-1,2-diol. After i.v. infusion of the structural substance analogue, butane-1,2-diol (EC 209-527-2), at 1000 mg/kg bw into rabbits, its metabolism was described as slow and 1,2-butanediol was excreted in the urine either as the glucuronide or unchanged [1].

Reference:
[1]: On the Safety Assessment of 1,2-Glycols as Used in Cosmetics. Final Report Cosmetic Ingredient Review Expert Panel, June 28, 2011

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
Experimental data on the metabolism of octane-1,2-diol or any of its structurally similar substance analogues are not available. From metabolism modelling on hexane-1,2-diol (EC 230-029-6), octane-1,2-diol, decane-1,2-diol (EC 214-288-2) and dodecane-1,2-diol (EC 214-289-8) it was concluded that С-oxidation, C-hydroxylation, glucuronidation and beta-oxidation may take place to form corresponding metabolites, whereby C-hydroxylation and beta-oxidation are more likely to be favoured metabolic pathways for the longer alkyl chain length compounds, 1,2-decanediol and 1,2-dodecanediol, than for 1,2-hexanediol and 1,2-octanediol [1].

Reference:
[1]: On the Safety Assessment of 1,2-Glycols as Used in Cosmetics. Final Report Cosmetic Ingredient Review Expert Panel, June 28, 2011

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: No bioaccumulation potential. Conclusion of submitter from the present expert statement.
No specific study was performed on the absorption, distribution, metabolism and/or excretion (ADME) of octane-1,2-diol.

Absorption and systemic availability of octane-1,2-diol or metabolites after oral administration has been concluded from its moderately high water solubility of 7.5 g/L (at 20°C), a partition coefficient value Log10Pow of 2.1, a relatively low molecular weight of 146 and the finding of slightly reduced locomotor activity in rats treated in a 28-day oral (gavage) toxicity study at 1000 mg/kg bw/day. The three physicochemical properties also favour dermal uptake, although the systemic availability of octane-1,2-diol after dermal uptake is considered to be lower than after gastro-intestinal absorption.

The attained partition coefficient and moderately high water solubility of octane-1,2-diol favour absorption directly across the respiratory tract epithelium by passive diffusion. However, the risk of exposure by the inhalation route is considered to be low, because of its relatively low vapour pressure (0.28 Pa at 25°C, 0.15 Pa at 20°C).

All available experimental study results gave no indication regarding the metabolic pathway, distribution or excretion of octane-1,2-diol itself, but for the structural substance analogue, butane-1,2-diol (EC 209-527-2), excretion in the urine as its glucuronide or unchanged was demonstrated after i.v. infusion to the rabbit. Based on metabolism modelling on C6-, C8-, C10- and C12-alkane-1,2-diols С-oxidation, C-hydroxylation, glucuronidation and beta-oxidation were identified as possible pathways for forming corresponding metabolites, whereby hydroxylation and beta-oxidation are more likely to be favoured for the metabolic pathways of the latter two substance analogues.

Bioaccumulation was not investigated, but in view of its Log10Pow of 2.1, octane-1,2-diol is not considered to be bioaccumulative.