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Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

No substance specific data is available for the submission substance. However, there is data available from the structural analogue, 6-hexamethylene diamine (HMD, CAS 124-09-4). Amines such as the submission substance are thought to be bioavailable after dermal or oral exposure. Metabolism includes deamination, oxidation and hydroxylation. The metabolites or the unchanged compound are mostly excreted via the urine and faeces, followed by the lungs. The half-life of amine compounds is short (few hours to 3 days).

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

No substance specific data for toxicokinetic (ADME) considerations are available for 2-methylpentane-1,5-diamine (MPMD).

Nevertheless, as this substance is structurally similar to 1,6-hexamethylene diamine (HMD), data from HMD is thought to be suitable information. Moreover, general information on aliphatic amines was taken as supportive data.

There were specific investigations in humans conducted with HMD. In human volunteers, orally administered HMD is rapidly excreted (within 10 h) in urine as parent compound and 6 -aminohexanoic acid metabolites. Fast acetylators excreted more HMD than slow acetylators. The available human data show considerable inter-individual variation in the elimination of the 6-aminohexanoic acid metabolite, and that the elimination of HMD was based on whether the individuals were fast or slow acetylators (Brorson et al., 1990).

Following oral administration of HMD-1,6-[14C]dihydrochloride (HMD salt; HDDC) to male rats, about 20% of the administered dose was recovered as CO2 after 72 h while urinary and faecal excretion accounted for 47% and 27% of the administered radioactivity, respectively. Two peaks were found in urine with one of them corresponding to 30 % of total radioactivity in urine and comigrating with 1,6-diaminohexane. Of several tissues examined, most residual radioactivity was found in the intestinal mucosal lining, liver, kidney and prostate. At 24h post-administration, the highest concentration of radioactivity was observed in the prostate. However, this result was not considered as relevant for HMD-related effects considering the low absolute values recorded in the prostate. In a read across strategy, the bioavailability of HDDC was likely to be similar as HMD, considering that after ingestion HMD is hydrolysed in the stomach by the gastric hydrochloric acid in the conducting to HDDC (David and Heck, 1983).

The review from Greim et al. (1998) provides data on various primary and secondary amines, which were mostly aliphatic. After dermal application, short chained amines (primary and secondary) appear to be absorbed relatively well through the skin in general. According to the authors, dermal absorption decreases with increasing chain length (i.e. >= C6). The study authors further summarised that after intravenous application of primary aliphatic amines, these were detected in the lung, liver, kidney, heart, spleen and brain. Metabolism found included oxidization via monoamine oxidase (MAO) to aldehydes, followed by quick metabolic oxidation to carboxylic acids via dehydrogenation through aldehyde dehydrogenase (ALDH). Furthermore, beta-oxidation was observed resulting in excretion of CO2. MAO selective binding was reduced with increasing chain length of the amines. Moreover, the excretion via CO2 was found to be dependent on the chain length, too. Primary amines with C6 were shown to have the highest elimination rate via CO2. The rate diminishes with alterations in chain length (increasing as well as decreasing). Some amines are excreted mostly non-metabolised in the urine (e.g., ethylamine or diethylamine; Greim et al., 1998).

Moreover, taking into account the physical-chemical properties and the toxic effects after exposure to the submission substance (summarised below) it is concluded that MPMD becomes systemically bioavailable after ingestion, inhalation or skin contact, but no quantitative conclusions on absorption and bioavailability can be drawn from the available data.

  • Acute toxicity was observed for the substance after oral or inhalation exposure.

  • As well as toxic effects were observed for the submission substance after subacute or subchronic oral application (most conservative oral NOAEL = 50 mg/kg bw/day (OECD 408 Study, LabCorp study no. 8439541, 2022)).

  • Moreover, the physical-chemical characteristics of MPMD (i.e. molecular weight approx. 116.2; water solubility: completely miscible (> 900 g/L at 23.5 °C); partition coefficient 0 > log Kow > 1) are generally in favour of absorption from the gastro-intestinal tract subsequent to oral ingestion as well as dermal absorption after skin contact (remark: amines are very alkaline, pH approx. 12).

  • However, the substance is ionisable: predicted pKa1 and pKa2 (SPARC) are very close (10.66 and 9.59) and based on dissociation degree calculated via Henderson-Hasselbach equation, within the relevant pH range pH 4 (100% dissociation) to pH 9 (97.6% dissociation) the compound is practically completely present as the diammonium cation in the environment and within living organisms, thus the substance does not readily diffuse across biological membranes.


References used, which are included in IUCLID as 'other information':

Brorson T., Skarping G., Sandström J. F. and Stenberg M. (1990). Biological monitoring of isocyanates and related amines. International Archives of Occupational and Environmental Health 62:79-84. Testing laboratory: Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden.


David R. M. and Heck H. d'A. (1983). Localization of 1,6-[14C]diaminohexane (HMDA) in the prostate and the effects of HMDA on early gestation in Fischer-344 rats. Toxicology letters, 17:49-55. Testing laboratory: Department of Biochemical Toxicology, Chemical Industry Institute of Toxicology, USA.


Greim H, Bury D, Klimisch H J, Oeben-Negele M, Ziegler-Skylakakis K (1998). Toxicity of aliphatic amines: structure-activity relationship. Chemosphere, Volume 36, Issue 2, Pages 271–295.