Propylenediamine

Endpoint summary

Description of key information

No experimental data on absorption, metabolism and distribution are available for the substance. Therefore, the toxicokinetic behavior was evaluated based on the structure and the physico-chemical properties of the substance as well as data from experimental in vivo toxicity studies.

The small molecular weight and the high water solubility favour absorption after oral uptake of the substance. The substance may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. With regard to absorption after inhalation, the target substance is likely to dissolve in the mucus of the upper respiratory tract due to its high water solubility, but absorption is still possible and must be assumed via upper mucosa.

Due to the corrosivity a dermal uptake of 100 % is expected for the undiluted substance. The log Pow points to a poor uptake through the skin at non-corrosive concentrations. Excretion is assumed to take place mainly via urine.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

1.        Chemical and physico-chemical description of the substance

The target substance (CAS 78-90-0) belongs to the chemical class of alphatic amines.

Description of the physico-chemical properties:

- physical state (20 °C): liquid

- vapour pressure (20 °C): 10.8 hPa

- boiling point (at 1013.25 hPa): 119 - 121 °C

- molecular weight: 74.1 g/mol

- log Pow (20 °C): -1.2

- water solubility: 1000 g/L (miscible with water in all ratios at 20 °C)

2.        Toxicokinetic assessment

No experimental data on absorption, metabolism and distribution are available for the substance. Therefore, the toxicokinetic behavior was evaluated based on the structure and the physico-chemical properties of the substance as well as data from experimental in vivo toxicity studies.

2.1.  Absorption:

As the substance is ionizable, it will not readily diffuse across biological membranes. The low molecular weight of 74.1 g/mol and the high water solubility favour absorption after oral uptake of the substance. The substance may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. The log Pow of -1.2 is also favourable for a passive absorption.

Based on study results with structurally analogous substances, propylenediamine is considered as readily biodegradable. Further, according to Kollig et al. (1993), Boethling & Mackay (2000), hydrolysis is not expected to be a relevant degradation process due to the absence of hydrolysable groups. Therefore, no study on hydrolysis was performed and it is assumed, that the parent compound is not hydrolysed in the gastrointestinal tract.

In the acute oral toxicity study available for the substance, a LD50 of ca. 1300 mg/kg was deduced. The effects (gastrorectasis and corrosion effects) appeared at the site of contact and were attributed to the corrosive potential of the substance. However, apart from that, no specific data concerning oral absorption of the test substance are available. Therefore, as a worst case an oral absorption of 100 % is assumed.

With regard to absorption after inhalation, the target substance is likely to dissolve in the mucus of the upper respiratory tract due to its high water solubility, but absorption is still possible and must be assumed via upper mucosa. In an inhalation risk test severe clinical effects were observed (bloody eye and nose discharge, severe dyspnea, reduced breathing during exposure and severe necrosis of the exposed tissues), which are attributed to the corrosivity of the substance. In a 28-day inhalation study in rats local effects in the nasal cavity (acute inflammation, degeneration, necrosis) were observed, too. However, there were no signs of systemic toxicity. Due to the lack of more accurate data as a worst case 100 % absorption is assumed for inhalation as well.

Despite the small molecular weight, the log Pow suggests that the substance is not likely to be sufficiently lipophilic to cross the stratum corneum. Therefore, dermal absorption is likely to be low at non-corrosive concentrations. In an in vivo dermal toxicity study the LD50 was determined at 430 mg/kg body weight. However, no information regarding mortality and clinical signs were given.

On the basis of a skin irritation study in rabbits, which led to the classification for skin corrosivity cat. 1A, a dermal uptake of 100 % is expected for the undiluted substance. At non-corrosive concentrations, where the skin barrier is not destroyed, dermal uptake however will be low.

2.2.  Distribution and accumulative potential:

The physico-chemical information (low molecular weight, good water solubility, log Pow -1.2) point to a wide distribution of the substance throughout the body. According to the log Pow the intracellular compartment might be reached as well. Due to the high water solubility and good distribution accumulation is assumed to be unlikely.

2.3.  Metabolism and Excretion:

With regard to metabolism, no information is available.

As suggested by the small molecular weight of the target substance and its high water solubility, excretion is assumed to take place mainly via urine.