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Link to relevant study record(s)

Description of key information

There are no specific studies available on absorption, distribution, metabolism or excretion of Reaction Mass of Amines, coco alkyl and ß-Alanine, N-(2-carboxyethyl)-, N-coco alkyl derivatives and ß-Alanine, N-coco alkyl derivatives. Assessment of toxicokinetic properties is based on the physico-chemical properties of the substance and experimental data.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

TOXICOKINETIC BEHAVIOUR

 

Physico-chemical properties:

‘Reaction Mass of Amines, coco alkyl and ß-Alanine, N-(2-carboxyethyl)-, N-coco alkyl derivatives and ß-Alanine, N-coco alkyl derivatives’ (EC number 915-790-0) is a pale solid brown paste. A mean molecular weight has been calculated as approximately 283 g/mol. The mean measured Log P (octanol-water) is estimated at 2.51 at 20 degC and the water solubility has been determined as 45.1 mg/L at 20.5 degC.The vapour pressure value is 0.21Pa at 20 degC which is indicative that the substance is not volatile at room temperature and pressure, therefore inhalation exposures are not a concern. The melting point is between -5 and 50.5 degC and the substance decomposes at 95-100 degC.

Absorption:

There are no directly measured ADME data by any route for this substance.

 

Oral: In the key study for acute oral toxicity (Manciaux, 2001), the item was administered as a 69% formulation in 28% isopropanol/3% water to a dose level of 1380 mg/kg (technical substance). LD50 was >1380 mg/kg as no signs of systemic toxicity were observed in this study. It is unknown as to whether the material had absorbed across the gut in this form. In the combined repeat dose and reproductive (OECD 422) toxicity study (Spezia, 2012), the substance was administered by gavage as a suspension up to 200 mg/kg in corn oil. There were signs of toxicity (ulcers and inflammation in the gut) observed in this study and the NOEL was set at 67 mg/kg, based on these local gut effects seen at 200 mg/kg. This material is an irritant and there were observed impacts on food consumption rates in the treated animals. It is unknown as to whether the test material has absorbed to some degree. Thus, default absorption factors recommended in REACH guidance R.8, have been used and the absorption rate following oral dosing is considered to be 50%.

 

Inhalation: no data, as the substance is not volatile and not expected to be inhaled. However in absence of specific data, the absorption rate following inhalation is considered to be 100% (as recommended in REACH guidance R.8).

 

Dermal: In an acute dermal toxicity study (Silvano 2012), the test material was applied as an unchanged paste at 2000 mg/kg. There were no clinical signs systemically, but there were signs of local effects (scabs and varying grades of erythema). Given the material was applied in paste form, it is expected that dermal absorption would have been very low in this study. However in absence of specific data, the absorption rate following inhalation is considered not to be higher than the oral rate, i.e. 50% (as recommended in REACH guidance R.8).

 

Distribution:

There are no specific data on differential distribution to organs by the oral, inhalation or dermal routes.

 

Metabolism:

There are no specific data on metabolism of this substance per se, although it is expected that coco alkyl amines can be extensively metabolised if they enter the systemic circulation. There is evidence to show that alkyl amines are oxidatively deaminated by monoamine oxidases (MAOs) with concomitant formation of ammonia and the corresponding alkyl amine aldehyde (Tenne M et al., 1985; Tominaga T et al., 1987; Tynes RE et al., 1986 as cited in Section 5.1.1.3 of ECHA, 2011). The MAOs are present and can rapidly metabolise alkylamines in the blood (Gallagher B et al. 1977b as cited in Section 5.1.1.3 of ECHA, 2011). The aldehyde products formed may be oxidised by aldehyde dehydrogenases to the corresponding carboxylic acids, which can be effectively cleared from the body (Fowler JS et al., 1976a; Tominaga T et al., 1987 as cited in Section 5.1.1.3 of ECHA, 2011).

There is no evidence from in vitro genotoxicity studies to suggest that metabolism plays a role in the genotoxic properties of this substance. The ‘Reaction Mass of Amines, coco alkyl and ß-Alanine, N-(2-carboxyethyl)-, N-coco alkyl derivatives and ß-Alanine, N-coco alkyl derivatives’ showed cytotoxic responses in in vitro genotoxicity assays but is non genotoxic in the absence and presence of metabolic activation.

 

Excretion:

No specific data are available for the substance per se to determine the exact pathways or extent of excretion. However, fatty amines are mainly oxidised to and excreted as CO2 via the lungs. This has been shown for n-dodecylamine administered orally in mice (Iwata Y et al., 1987; Fowler JS et al., 1976a as cited in Section 5.1.1.3 of ECHA, 2011) and rabbits (Fowler JS et al., 1976b as cited in Section 5.1.1.3 of ECHA, 2011).

 

Reference

ECHA (2011) Committee for Risk Assessment RACAnnex 1.Background documentto the Opinion proposing harmonised classification and labelling at Community level of amines, coco alkyl. ECHA/RAC/CLH-O-0000002195 -77 -01/A1