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Administrative data

Link to relevant study record(s)

Description of key information

In an in situ study on GI absorption the results indicate that only trace amounts, if any, of test material were absorbed in a 3-hour period. Based on physico-chemical properties and the hazard profile, the substance is not considered to be absorbed. There is no potential for bioaccumulation.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Toxicokinetic assessment

The test substance (molecular weight > 1177 g/mol) is a white powder with a calculated Log Pow of 23, a water solubility of <0.1 mg/L at 20°C and a vapor pressure of 1.33 E-10 Pa at 20°C (estimated).

 

Absorption

Based on the physico-chemical data (low water solubility, molecule size, Log Pow) it is assumed that there is no or only very slow absorption after oral ingestion of the test article. This is supported by an old in situ absorption study. Here it could be shown that only trace amounts, if any, of test material were absorbed in a 3-hour period. In addition, the available acute oral toxicity studies did not reveal any signs of systemic toxicity and resulted in LD50 values of greater than 5000 mg/kg or higher. Furthermore, in the available 90-day feeding study with dogs using dose levels of 1000, 3000, 10000 ppm, no effects on body weight, food consumption, ophthalmology, clinical pathology, organ weights, and on histopathology were reported with a NOAEL of greater than 10000 ppm. In addition, a 2-year chronic feeding study with rats is available, which showed no findings of toxicological relevance up to the highest dose level of 10000 pm. The lack of systemic toxicity in these studies suggests poor bioavailability upon oral ingestion. In support of these findings are the results of an old absorption study performed with rat intestinal loops according to the Levine technique. This study showed that the test article was only absorbed in trace amounts, if at all, after a 3h exposure period. In addition, the diameter of the chemical was determined to be 17.9Å. According to a publication by Opperhuizen et al, a lipophilic particle with a diameter of greater than 9.5 Å has only limited ability to cross biological membranes (Opperhuizen et al, 1985). A second assessment found in ECHA Guidance on information requirements and chemical safety assessment, Chapter R.11, concludes that a substance is possibly not considered to be bioaccumulative if the average maximum diameter is greater than 17 Å and the molecular weight is larger than 1100. Based on this information, it can be assumed that the test article is not likely to cross biological membranes and has no bioaccumulation potential. Therefore, in line with all toxicological data available, systemic availability can be excluded.

Dermal absorption is equally unlikely, due to the size of the chemical, the Log Pow of 22 and the very low water solubility. Highly lipophilic substances that come into contact with the skin can readily penetrate the lipid rich stratum corneum but are not well absorbed systemically. Although they may persist in the stratum corneum, they will eventually be cleared as the stratum corneum is sloughed off. Furthermore, dermal uptake of chemicals with a molecular weight >500 is not favored (ECHA GD 7c). This is in line with the available toxicity data after dermal exposure. In an acute dermal toxicity study no indications of systemic availability after dermal application were detected. In conclusion, dermal penetration is expected to be very low.

In two inhalation toxicity studies, no effects were reported up to the highest doses tested. Given its low water solubility, systemic availability after exposure to dust particle of the test substance is expected to be low. In addition, particle size distribution analysis revealed a mass median diameter of 140.8 µm, therefore, the majority of generated particles will not penetrate into the broncho-alveolar tract.

 

Excretion

In view of the absence of relevant findings and the expected low bioavailability, it can be assumed that the test substance is rapidly excreted. Since the test substance has a molecular weight larger than 500 g/mol and a low solubility in water, it is expected to be excreted predominantly via the feces (ECHA GD 7c).

 

Overall conclusion

The physico-chemical data suggest that the test article cannot cross biological membranes and therefore absorption after oral, dermal and inhalative exposure is expected to be negligible. This is supported by the findings of available toxicity studies, which clearly demonstrated absence of systemic toxicity. The test article has not bioaccumulation potential and rapid excretion via the feces is expected.