Polyamide wax

Endpoint summary

Description of key information

No experimental toxicokinetic studies are available on the substance. However, as cited in the REACH guidance document R7.C, information on absorption, distribution, metabolism and excretion may be deduced from the physicochemical properties.
Based on the toxicological data and the physicochemical properties, a very low absorption of the substance is expected by the oral and dermal routes while the physical form of the substance will favour the deposition on the surface of the lower respiratory tract.

Key value for chemical safety assessment

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

No experimental toxicokinetic study is available on the substance but information on absorption, distribution, metabolism and excretion may be deduced from the following physicochemical properties:

-Molecular weight: the molecular weight of the three major components are 681, 665 and 964 g/mol (present at 65.5, 15.2 and 12.7 % w/w respectively in the typical composition) and more than 96% w/w of the substance has a molecular weight above 600g/mol.

-Water solubility: the water solubility is below 0.0055 µg/L at 20°C. the substance is therefore considered as insoluble (Sydney, 2004)

-Partition coefficient Log Kow: Log Kow estimated values by QSAR modeling for the three major components are above 13.28

-Particle size:the mass median aerodynamic diameter (MMAD) is 8.4 µm and approximately 57% by mass of the particles have an aerodynamic diameter less than 10 µm.

Absorption

The value of the log Kow, the extremely low water solubility, the molecular weight and the solid form of the test substance suggest a very low absorption into the gastro-intestinal tract after oral absorption. Indeed the absorption of highly lipophilic substances may be limited by the inability of such substances to dissolve into GI fluids. The 'particle' form also limits the absorption because of the time taken for the particles to disssolve, this is further accentuated for this poorly water-soluble substance.

This assumption of a very low oral absorption is confirmed in the oral toxicity studies: no systemic effects or mortalities were observed in rats treated at 2 000 mg/kg bw in an acute toxicity study and at 1000 mg/kg bw/day in a 28 -day repeated-dose toxicity study.

However, an oral absorption of 100% is taken into account for risk assessment (worst case scenarios).

With extremely low water solubility, a high value of log Kow and a molecular mass above 600 g/mol, dermal absorption is also anticipated to be very low.

This assumption is confirmed in the dermal toxicity studies: no systemic effects or mortalities were observed in rats treated at 2000 mg/kg bw in an acute toxicity and there were no effects in dermal irritation. Nevertheless, the substance exhibited a sensitizing potential. According to the prediction done by HI SKin Perm, the dermal absorption is very low. 10% of dermal absorption is used for risk assessment.

Regarding the inhalation route, the size of the particles will favour the deposition on the surface of the lower respiratory tract. As the particles are poorly water-soluble, those deposited in the alveolar region will mainly be engulfed by macrophages. The macrophages may either translocate particles to the ciliated airways for elimination or carry particles into the pulmonary intersticium. Thus, absorption should be very limited.

The assumption of a very low absorption by inhalation is confirmed in the acute inhalation toxicity study : no systemic effects or mortalities were observed in rats exposed to the test substance for four hours up to the maximal practical concentration of 4060 mg/m3 and up to 26.0 mg/m3 air for six hours per day, five days per week in a 90-day repeated dose toxicity study.  100% of inhalation absorption is used for risk assessment.

Distribution and Metabolism

By the dermal route, since the substance is highly lipophilic, it may persist in the lipid rich stratum corneum and will eventually be cleared as the stratum corneum is sloughed off. By the inhalation route, since the particles of the substance are poorly water-soluble, they may stay in the pulmonary intersticium and clearance will depend mainly upon solubilisation and other mechanisms. No specific data is available on the metabolism of the substance.

Elimination

Due to the extremely low water solubility and a relatively high molecular mass, the excretion of the substance in urine is not expected. An excretion via bile and faeces is possible.