Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

basic toxicokinetics
Type of information:
other: an assessment of toxicokinetic behavior has been conducted to the extent that can be derived from the relevant available information.
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Relevant studies were reviewed with a view to fulfilling the requirements of Annex VIII (8.8.1).

Data source

Reference Type:
other: an assessment of toxicokinetic behaviour has been conducted to the extent that can be derived from the relevant available information.

Materials and methods

Objective of study:
Test guideline
no guideline followed
Principles of method if other than guideline:
In accordance with REACH Annex VIII (8.8.1) an assessment of toxicokinetic behaviour has been conducted to the extent that can be derived from the relevant available information.
GLP compliance:

Test material

Constituent 1
Test material form:
solid: particulate/powder

Results and discussion

Any other information on results incl. tables

The acute toxicity tests showed that the LD50 of the test substance was higher than 2000 mg/kg body weight both after oral administration and after dermal application. The subacute oral toxicity test for 28-days revealed a NOAEL of
1000 mg/kg/day. 

A sub-chronic 90-day study (on a structural analogue substance ) gave a NOAEL of 250 mg/kg bw/day (highest dose tested) and did not show evidence of signifcant absorption of the substance or systemic distribution.

Therefore, an extensive toxicokinetic assessment is considered of limited value. Below, a summary
of the anticipated toxicokinetic behaviour of the test substance is given.

Hydrolysis of two amide bounds in the test substance results (based on main constituent) in the compounds 1,6-diaminohexane (hexamethylenediamine,
CAS# 124-09-4, log Pow =0.02, water solubility : 800 g/L) and 12-hydroxystearic acid (12-hydroxy-octadecanoic acid, CAS# 106-14-9, insoluble in water). Hydrolysis of amide bounds is generally a slow process. Toxicokinetics of these compounds will also be described below.


The water solubility of the test substance is very low, caused by the apolar carbon-hydroxy chain. In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration . Thus, the very low water solubility can be considered as a rate-limiting factor for the absorption of the compound. However, the test substance may be absorbed in the same way as other fatty acids, by diffusion across the
plasma membrane or by active transport. Overall, it is to be expected that the oral bioavailability, and thus the systemic exposure, of the test substance will be low to moderate.

Hydrolysis of the amide bounds may occur in the small intestine. Following hydrolysis, the absorption of 12-
hydroxystearic acid will be high, like other fatty acids. For 1,6-diaminohexane it is known that after oral administration to rats, urinary excretion of diaminohexane-related compounds accounted for 47% of the dose. Thus, in
rats at least half of the dose was absorbed via the gastro-intestinal tract.

Uptake of the test substance via inhalation is not expected to take place, because of the particle size distribution (10% < 12.4 µm).

Since the bioavailability of dermally applied compounds can assumed to be zero for substances with a log Pow below -1
and over 5 or a relative molecular mass over 700, it is not to be expected that the test substance will be absorbed through the skin.


The test substance and 12-hydroxystearic acid will show high volumes of distribution, because of the high lipophilicity
of the compounds. They will be distributed into peripheral tissue, especially fatty tissues. The plasma protein binding
is expected to be high. Distribution of 1,6-diaminohexane will be limited to total body water, because of the
relatively low log Pow. Therefore, a volume of distribution of about 0.7 l/kg is expected. The compound will show
intermediate plasma protein binding.


After absorption of the test substance into the systemic circulation, hydrolysis of the amide-bounds will take place
in the liver. Direct glucuronidation or sulfation takes place on the NH2-groups of 1,6-diaminohexane and on the 12-
hydroxy-group or the acids group of 12-hydroxystearic acid. Following glucuronidation or sulfatation, metabolites
will be excreted in urine or via bile into faeces.


Based on the expected kinetic behavior in the body, as described above, the test substance will show low to moderate absorption after oral administration. The test substance is not expected to be absorbed via dermal
administration or after inhalation. In the gastro-intestinal tract and in plasma and liver, the test substance will be
hydrolyzed to 1,6-diaminohexane and 12-hydroxystearic acid. These compounds will undergo direct glucuronidation or
sulfation and excreted in urine or via bile into faeces.

Therefore, accumulation of the test substance itself in the body during prolonged exposure is highly unlikely. For 12-
hydroxystearic acid, some retention in fatty tissues may take place. For 1,6-diaminohexane, accumulation in fatty
tissues is not anticipated.

Applicant's summary and conclusion

Interpretation of results (migrated information): other: see summary of conclusions
Accumulation of the test substance itself in the body during prolonged exposure is highly unlikely. For 12- hydroxystearic acid, some retention in fatty tissues may take place. For 1,6-diaminohexane, accumulation in fatty tissues is not anticipated.