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Description of key information

Based on its physico-chemical characteristics, Benzylamine (CAS No. 100-46-9) is considered to be bioavailable after oral and dermal absorption. Absorption after inhalation of Benzylamine is expected to be unlikely due to a lack of quantitative exposure or moderate. Following uptake the compound can be distributed through the body thereby a pronounced metabolism is not expected. It is known that Benzylamine and its metabolites will be excreted rapidly via the urine.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
25
Absorption rate - inhalation (%):
100

Additional information

In line with chapter R.7 c (ECHA, 2012) the main toxicokinetic properties of Benzylamine are assessed on the basis of its physico-chemical properties and with special regard to the results of the standard toxicity studies performed with this substance. Specific toxicokinetics or dermal absorption studies are not available for the substance.

 

1.        Relevant physico-chemical properties of Benzylamine

Moleculare weight: 107,16 g/mol

logPow:                    1 (at 25 °C, pH 9.8 - 10.4)

Water solubility:       Miscible with water.

Vapour pressure:    0.06 hPa (20°C)

Boiling point:           185 °C (no data available for the atm. pressure)

Hydrolysis:               No data available.

Surface tension:     Based on chemical structure, no surface activity is predicted.

Particle size:            Substance is a liquid.

 

2.        Absorption:

Based on its low molecular weight, moderate logPow and relatively high water solubility Benzylamine is likely to be absorbed in the GI tract. The moderate logPow value of 1 (at 25 °C, pH 9.8 - 10.4) indicates that the substance is lipophilic, i.e.in the range between -1 and 4, and will thus diffuse well across plasma membranes. In addition, gastrointestinal absorption of Benzylamine is considered to be triggered by passage through aqueous membrane pores or carriage with the bulk passage of water, which is favoured for small (molecular weight < 200 g/mol), water soluble substances. It is unclear whether an active transport for Benzylamine exists. Overall, quantitative gastrointestinal absorption is expected for Benzylamine, based on its physicochemical properties. These assumptions are supported by acute oral toxicity studies (BASF AG, 1971 and Bayer AG, 1977), where death in treated animals was observed as well as clinical signs like sedation, respiratory disorders and tonical cramps. This provides a clear indication for systemic availability after gastrointestinal absorption.)

 

For dermal absorption a substance must be sufficiently lipophilic to cross the stratum corneum. Furthermore, the substance must be adequately soluble in water to partition form the stratum corneum into the epidermis. Since Benzylamine showed a log Pow of 1 and a high water solubility, dermal absorption is most likely. This assumption is supported by the fact that Benzylamine is corrosive to the skin (BASF AG, 1971 and Bayer AG, 1977), which may enhance the penetration through the skin. The ability of Benzylamine to penetrate through the skin barrier was shown in an acute dermal toxicity study (Bayer AG, 1977) performed on rats. During this study mortality and clinical signs of systemic toxicity were observed.

 

With a log Pow value between -1 and 4 and in view of the results obtained in an acute inhalation study where clinical signs on mucous membranes occured (BASF AG, 1971), Benzylamine is considered to be absorbed directly across the respiratory tract epithelium by passive diffusion when its vapour or particles reach the alveolar regions of the lungs. However, based on the low volatility and the high boiling point exhibited by Benzylamine, generally only low amounts of the substance will be available for inhalation under ambient conditions.

 

3.        Distribution/Metabolism:

Benzylamine will be metabolized to benzoic acid, which forms via glycine conjugation hippuric acid, the main metabolite of Benzylamine (Wood et al., 1978; Al-Ani et al., 1979; Mutlib et al., 2002).

 

Generally, metabolism will render a xenobiotic molecule more polar and harmless, leading to fast and quantitative excretion. For Benzylamine, no conversion into a metabolite that was more cytotoxic or more genotoxic than the parent substance was noted when comparing in vitro test results with metabolic activation to in vitro test results without metabolic activation system (genetic toxicity tests). Based on this, a clear indication is given that the formation of reactive metabolites in vivo is unlikely.

 

4.        Excretion:

Benzylamine will be rapidly excreted with the urine as the molecule is good water soluble with a low molecular weight of 107.16 g/mol.

 

Excretion studies in humans showed that Benzylamine will extremely rapidly be metabolised and excreted (> 90%) as hippuric acid in between hours in humans (Wood et al., 1978, Al-Ani et al., 1979) and rats (Mutlib et al., 2002).

 

Substances with log Pow of 3 or less are unlikely to accumulate with the repeated intermittent exposure pattern normally encountered in the workplace but may accumulate if exposures are continuous. Based on its log Pow of 1 (at 20 °C, pH 9.8 – 10.4), the good water solubility and the data from human excretion studies, it can be ruled out that the test substance will not accumulate in the human body under continuous exposure.

 

5. Generic absorption rates

Based on the above information and due to the fact that there are no specific toxicokinetic data available the generic values of 100 % for oral and inhalation absorption as well as 25 % for dermal absorption were established.

 

Reference

- ECHA (2012). Guidance on information requirements and chemical safety assessment, chapter R.7c: Endpoint specific guidance. ECHA-12-6-23-EN.R.7.12 Guidance on Toxicokinetics.

- EFSA (2012). Guidance on dermal adsorption. EFSA Journal: 10 (4) 2665