Carbamic acid, (2-hydroxypropyl)-, compd. with 1-amino-2-propanol (1:1)

Endpoint summary

Description of key information

This toxicokinetic assessment is based on the physico-chemical properties of the substance and on toxicological data. Experimental studies on toxicokinetics were not performed. 

Additional information

The following remarks on toxicokinetics are based on the physico-chemical properties of the substance and on toxicological data. Experimental studies on toxicokinetics were not performed.

Carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) is an equilibrated mixture of the carbamic acid, (2-hydroxypropyl)-, ion (CAS-No. 863242-72-2) and the 1-amino-2-propyl ion. Carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) is extremely unstable and rapidly hydrolyses to1-amino-2-propanol(CAS-No. 78-96-6) under formation of CO₂(see text below). Its use (only industrial use) is based on exactly this unstable property, since the compound serves as foaming agent (via liberation of CO₂) of rigid foam. The molecular weight of carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) is about 194.

The manufacturing process of carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) runs solvent-based in ethylene glycol and the compound has to be continuously dissolved in about 50% ethylene glycol to ensure stability. This is the only form how the active compound carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) can be handled and this is also the only marketed form. The trade name of the stabilized product in ethylene glycol is Zusatzmittel 19IF00 A.
ECHA ‘Guidance for identification and naming of substances under REACH and CLP’ states that solvents have to be separated if possible without affecting the stability of the substance. As given above, removing the solvent in this case would have an impact on the stability of the substance and, therefore, studies are conducted with the substance in the solvent (Zusatzmittel 19IF00 A).

Zusatzmittel 19IF00 A is a colourless, slightly viscous liquid (Neuland, 2011) with the low vapour pressure of 6 hPa at 20°C (Keldenich, 2012). Inhalation to the vapour of the active ingredient is therefore not to be expected. Zusatzmittel 19IF00 A is not used in industrial spray processes.

With a pH-value of about 9.2 in water Zusatzmittel 19IF00 A is a weak base. Under acidic conditions it rapidly disintegrates to the cleavage product1-amino-2-propanolunder formation of carbon dioxide. Hydrolysis studies performed on the basis of OECD TG 111 showed that the substance undergoes complete hydrolysis within 5 minutes at pH 4 and 27°C. Due to the observed spontaneous and complete degradation of the test substance an exact determination of the half-life time is not possible and is therefore set as t_1/2< 5 min (Neuland, 2013; for more details see IUCLID chapter 5.2.1). Thus, such a rapid disintegration can also be expected in the stomach of laboratory animals after oral administration and in the stomach of humans in the unlikely case of in accidental oral ingestion (see IUCLID section 7.12 ‘Justification for Read-across’, Tegethoff 2013, for further information).

As a consequence,1-amino-2-propanolis considered as the relevant disintegration product for human health assessment with regard to all toxicological endpoints with oral uptake (see IUCLID section 7.12 ‘Justification for Read-across’, Tegethoff 2013, for further information).

1-Amino-2-propanol(CAS-No. 78-96-6) is a clear, colorless, slightly alkaline liquid (pKa 9.6 at 20°C) with a molecular weight of 75 g/mole which is soluble in water and organic solvents. Due to its log Kow of about – 1.2 (Wölz, 2012) bioaccumulation is not expected.1-Amino-2-propanolis a naturally occurring compound in the human body as being a physiological cleavage product of the essential amino acid L-threonine, and has been isolated from the urine of untreated rats and of humans (TRGS 900 - ARW-Begründung, 2006,www.baua.de).

1-Amino-2-propanolwas evaluated as high production volume chemical in the ICCA/HPV program as part of the category ‘C1-C13 primary amines’ (published as OECD SIAR, 2011). The toxicokinetic behaviour of the group is described as follows:
‘The C1-C13 primary amines may be absorbed through the skin up to a chain length of about six carbon atoms. The charged form will hinder absorption across biological membranes, and the corrosive properties of the substances may also affect absorption. Dermal exposures to dilute solutions, aerosols and vapors might not have sufficient base capacity to overwhelm the skin's natural acidity and only a few of these molecules exist as the uncharged free base. In situations where the majority of the molecules would exist as the free base on the skin, the individual would experience a chemical burn. At the pH of the GI tract, only limited, non-ionized compound would be absorbed. Following inhalation, the C1-C13 primary amines will be removed by dissolution in the upper respiratory tract and swallowed. Vapors or particulates that get to the deep lungs will be primarily in the charged form which is expected to slow absorption somewhat and contribute to the local metabolism of these C1-C13 primary amines by alveolar and bronchiolar tissues. The major routes of metabolism of C1-C13 primary amines involve various processes including oxidation, conjugation, and other enzyme-catalyzed reactions leading to detoxification and excretion. Additionally, N-acetylation may occur, but represents only a very minor pathway in the metabolism of aliphatic amines.’ (OECD SIDS, 2011)

1-Amino-2-propanolis corrosive to skin and eye (OECD SIDS, 2011). For repeated dose and reproductive toxicity testing the salt of the amine was tested to avoid damage to the gastrointestinal tract following gavage administration due to the caustic mode of action. Testing the salt also provides the ability to distinguish between symptoms caused by local effects such as irritation or corrosion and symptoms that are due to systemic toxicity. The repeated oral toxicity of1-amino-2-propanolhydrochloride in rats is low with a NOAEL of 300 mg/kg bw per day (OECD TG 422). The NOAEL is based on indications of a slight anemic effect in male rats at the limit dose of 1000 mg/kg bw per day (Schneider, 2005). Thus, at least some of the substance must have been systemically available via the oral route. Acute oral dosing of1-amino-2-propanolto rats shows no systemic toxicity resulting in an LD50 of > 2000 mg/kg (e.g. OECD SIDS, 2011).

The log Kow for Zusatzmittel 19IF00A is calculated with - 1.12, thus, the substance has no bioaccumulation potential. Additionally, for substances with log Kow values below zero poor lipophilicity will limit penetration into the stratum corneum and hence dermal absorption. The assumption of negligible dermal absorption is confirmed by the data for acute dermal toxicity (Gillissen, 2012), skin irritation (Leuschner, 2012) and skin sensitization (Vohr, 2012) which do not show systemic effects after dermal exposure.

Zusatzmittel 19IF00 A is not irritating to the skin of rabbits, rats and mice as was shown in studies for skin irritation (Leuschner, 2012), acute dermal toxicity (Gillissen, 2012) and skin sensitization (Vohr, 2012). Zusatzmittel 19IF00 A, however, showed strong irritant properties in two in vitro tests for the detection of eye irritating effects (Vohr, 2012; Wingenroth, 2012c). Based on these in vitro results Zusatzmittel 19IF00 A should be considered as severe eye irritant. 

Based on the results of three in vitro genotoxicity tests performed with Zusatzmittel 19IF00 A with and without metabolic activation (Ames Test, Nern, 2011; in vitro Micronucleus Test, Sutter, 2012; HPRT Test, Wollny, 2012) it can be concluded that-reactive metabolites of the product will not be generated in mammals in the course of hepatic biotransformation. This assumption is supported by in vitro genotoxicity tests on the cleavage product1-amino-2-propanol with negative outcome (OECD SIDS, 2011).