PIGMENTADDITIV RL

Endpoint summary

Additional information

The toxicokinetic profile of a substance comprises its absorption into the body, its distribution in the body, its metabolism in the body and its excretion from the body. Taking into account the physicochemical properties and the toxicological test results, qualitative estimates for these aspects may be deduced for pigment additive RL.

 

Absorption: a prerequisite for a relevant absorption is that the substance can be dissolved in either aqueous (e.g., gastrointestinal fluid, blood plasma, sweat) or lipophilic (e.g., lipoproteins, lipid membranes, triglycerides) media or in both. Pigment additive RL can be considered to be insoluble in water and only slightly soluble in n-octanol or fat. Therefore, it is unlikely that relevant amounts of pigment additive RL become systemically bioavailable after oral, dermal or inhalation exposure.

 

The results of acute oral toxicity, acute dermal toxicity and repeated oral toxicity studies also give valuable indications with regard to absorption of the test substance.

 

Based on the acute oral toxicity and the 28-day oral toxicity studies, which did not reveal any systemic effects that would indicate that the pigment additive had entered the body, no indications of significant absorption via the gastrointestinal tract has to be assumed.

 

Pigment additive RL does not have particular skin or eye irritating or skin sensitizing properties that would imply a dermal absorptive potential.

 

In the unlikely event of exposure to aerosolized pigment additive in respirable form, the substance is considered likely to behave like an inert dust. Therefore, the deposited pigment additive particles will mostly be cleared from the lung via the mucocilliary transport. As pigment additive RL will not dissolve in the lung surfactant, the only way how pigment additive RL can enter the body is via phagocytosis of pigment additive RL particles by lung macrophages followed by migration of the macrophages into the interstitium and into the draining lymph nodes. However, the internal dose delivered via this mechanism can be considered negligible.

 

Distribution: the 28-day oral repeated dose toxicity study did not indicate any relevant histopathological changes in any of the investigated organs. This may indicate that either the pigment additive does not affect special organs as targets, i.e., is non-toxic, or is not distributed within the body in significant amounts. As indicated above, the physico-chemical parameters of the pigment additive support the conclusion that the pigment additive is not absorbed into the body and thus does not become systemically available. There were also no other signs of deposition of the pigment additive in any organ including excretory organs, like the kidney, indicating that even exposure to high doses of the pigment additive does not lead to bioaccumulation in special compartments of the body. 

 

Metabolism: Since the dissolution of the substance in cellular fluid or cellular membranes is a prerequisite for its metabolism, it is unlikely that the scarcely soluble pigment additive becomes accessible for metabolizing systems in relevant amounts. The results of the mutagenicity tests provide useful indications for qualitative consideration of the metabolic fate of pigment additive RL. In the mutagenicity tests, the pigment additive proved to be non-toxic and non-mutagenic in the absence as well as in the presence of an exogenous metabolizing system, indicating that the pigment additive is not converted into toxic or genotoxic metabolites. This conclusion is also supported by the lack of any morphological and histopathological changes of organs involved in xenobiotic metabolism, such as the liver, in the repeated dose toxicity study.

 

Excretion: the available data indicate that pigment additive RL is not absorbed into the body. In line with this conclusion, the 28-day oral repeated dose toxicity study did not indicate morphological or histopathological effects of the pigment additive on organs involved in excretion of chemicals from the body, such as the kidney. There was no indication that the substance was present in the urine. Moreover, from the repeated oral toxicity studies, it can be concluded that, after oral exposure, the pigment additive is excreted unchanged via the faeces.