Amines, rosin

Endpoint summary

Description of key information

Section R.7.12.2.1, Chapter R.7c of the Endpoint specific guidance on Information Requirements and Chemical Safety Assessment (version 3.0, 2017) provides the guidance on the interpretation of physical-chemical (phys-chem) data regarding oral, inhalation and dermal absorption. The phys-chem properties of the substance influence the ADME of a substance and consequently its effects on human health. Therefore, phys-chem properties may enable qualitative judgments of the toxicokinetic behaviour of the test substance.

 

Absorption is a function of the potential for a substance to diffuse across biological membranes. For UVCB substances, the most useful parameters providing information on absorption potential following exposure by inhalation, skin contact, or ingestion are the octanol/water partition coefficient (logKow) value and the water solubility. For oral route exposure, in general, logKow values between -1 and 4 are favourable for absorption. Nevertheless, a substance with such a logKow value can be poorly soluble in lipids and hence not readily absorbed when its water solubility is very low.

 

No experimental data are available to characterise the toxicokinetic behaviour of Rosin Amine 90.

Experimentally determined results of most relevant phys-chem properties for ADME, for the target substance, Rosin Amine 90 and its read-across chemical, Rosin, are provided in the below table:

Identity	Source Chemical	Target Chemical
	Rosin	Rosin Amine 90
CAS number	8050-09-7	61790-47-4
EC number	232-475-7	263-139-8
Log Kow	3.0 - >6 (pH 7) 1.9 - >6 (pH 2)	5.7
Water solubility	0.9 mg/L at 20°C	At the loading rate of ca. 2.5 mg/L, the water solubility of the test item at 20°C was 0.931 mg/L. The pH of the aqueous samples was 6.8 – 7.2.   At the loading rate of ca. 25 mg/L, the water solubility of the test item at 20°C was 3.14 mg/L. The pH of the aqueous samples was 6.8 – 8.1.
Vapor Pressure	108 mbar at 200°C, equivalent to 0.06 mbar at 25°C.	at 20°C (293K) was 0.00074 Pa and at 25°C (298K) was 0.0014 Pa

Oral route:

 

The absorption of highly lipophilic substances (log Kow of 4 or above) may be limited by the inability of such substances to dissolve into GI fluids and hence make contact with the mucosal surface. Any lipophilic compound may be taken up by micellular solubilisation but this mechanism may be of particular importance for highly lipophilic compounds (logKow>4), particularly those that are poorly soluble in water (1 mg/l or less) that would otherwise be poorly absorbed

 

Absorption of surfactants or irritants may be enhanced because of damage to cell membranes. It may be possible to identify ionisable groups within the structure of the molecule. Groups containing oxygen, sulphur or nitrogen atoms e.g. thiol (SH), sulphonate (SO3H), hydroxyl (OH), carboxyl (COOH) or amine (NH2) groups are all potentially ionisable

 

Conclusion:

Rosin Amine 90 is classified as acute oral tox cat 4, skin irritant cat 2 and skin sensitizer cat 1A according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. As signs of local and systemic toxicity after exposure to Rosin Amine 90 were observed, it is reasonable to expect that the absorption of Rosin Amine 90 via oral route will occur.

 

Inhalation route:

 

As a general guide, the vapour pressure may indicate, whether a substance can be available for inhalation. It is well known, that a vapour of highly volatile substances with a vapour pressure greater than 25 KPa (or a boiling point below 50°C), while the substances with low volatility have a vapour pressure of less than 0.5 KPa (or a boiling point above 150°C).

 

For Rosin Amine 90, the isothermal TGA effusion method was applied for the determination of the vapour pressure of the test item. The vapour pressure of the test item at 20°C (293K) was 0.00074 Pa and at 25°C (298K) was 0.0014 Pa.

Conclusion:

The acute inhalation toxicity information data is not available because of exposure of humans via inhalation is not likely taking into account the vapor pressures of this chemical and the possibility of exposure to aerosols, droplets of an inhalable size.

 

Dermal route:

 

The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore, if the water solubility is below 1 mg/l, dermal uptake is likely to be low. Between 1-100 mg/l absorption is anticipated to be low to moderate. Log Kow Values Above 4, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. for substances with vapour pressures above 100-10,000 Pa (ca. 0.76-76 mm Hg) at 25°C, though the extent of uptake would also depend on the degree of occlusion, ambient air currents and the rate at which it is able to transfer across the skin.

If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration. If the substance has been identified as a skin sensitizer then, provided the challenge application was to intact skin, some uptake must have occurred although it may only have been a small fraction of the applied dose.

 

Conclusion:

Rosin Amine 90 is skin irritant cat 2 and skin sensitizer cat 1A according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. As signs of local irritancy and skin sensitisation occurred after dermal exposure to Rosin Amine 90, it is reasonable to expect that the absorption of Rosin Amine 90 via dermal route will occur.