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Administrative data

Link to relevant study record(s)

Description of key information

Based on physico-chemical properties and toxicological data, absorption, distribution, accumulation and metabolism of UMA121 is not expected. The unabsorbed test substance will be excreted via faeces.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

There are no toxicokinetic studies available for UMA121. Whenever possible, the toxicokinetic properties of the substance were assessed, taking into account the available information on physico-chemical and toxicological characteristics, according to ‘Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance’ (ECHA, 2012).

UMA121 is a resin with a molecular weight > 538.6 g/mol.The substance was found to have a vapour pressure < 10E-8 Pa at 20 °C and a water solubility of 0.4 mg/L at 20 °C. The partition coefficient (log Pow) was determined to be in the range of 3.9 to 7.0 at 25 °C resulting from the different chain lengths of its constituents.

In order to allow testing, UMA121 had to be pre-cooled and then ground to a fine powder. The application of the fine powdered test substance does not reflect the actual use situation. Therefore, the results obtained from studies applying the ground test substance represent a worst case with respect to effects and values observed.

 

Absorption

Absorption is a function of the potential for a substance to diffuse across biological membranes. In addition to molecular weight the most useful parameters providing information on this potential are the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow value provides information on the relative solubility of the substance in water and octanol and is a measure of lipophilicity (ECHA, 2012).

 

Oral

The smaller the molecule, the more easily it will be taken up. In general, molecular weights below 500 are favorable for oral absorption. Solids have to dissolve before they can be absorbed (ECHA, 2012). Only marginal absorption after oral ingestion is expected due to the molecular weight of < 538.6 g/mol and when the “Lipinski Rule of Five” (Lipinski et al., 2001) is applied to the test substance as two of the rules are not fulfilled (the molecular weight and the log Pow).

As the substance is an insoluble solid, the substance is not expected to be taken up after oral ingestion. Additionally, there are experimental data available, investigating the acute and subacute oral toxicity of UMA121 (Takawale, 2012; Takawale, 2013). No mortality was observed and no signs of toxicity occurred. No test substance-related effects were noted in gross pathological and histopathological examinations. These results support the assumption that the test substance will not be taken up.

In summary, absorption after ingestion of UMA121 is not expected.

 

Inhalation

UMA121 has a vapour pressure of < 10E-8 Pa at 20 °C thus being not volatile. Furthermore, the substance is a resin, which is not used in spraying, drilling and grinding applications and the use is limited to professional and industrial applications. 

In conclusion, the substance is a non-volatile resin and there is no availability for absorption via the inhalation route.

 

Dermal

The smaller the molecule, the more easily it may be taken up. In general, a molecular weight below 100 favours dermal absorption, above 500 g/mol the molecule may be too large.Log Pow values between 1 and 4 favour dermal absorption particularly if water solubility is high(ECHA, 2012). As UMA121 is an insoluble solid with a molecular weight of > 538.6 g/mol and a log Pow in the range of 3.9 to 7.0, dermal absorption of the substance is not likely.

Additionally, QSAR prediction for the skin absorption potential of UMA121 resulted in a very low dermal absorption potential of about 1% (Mostert and Goergens, 2011; Potts and Guy, 1992).

Moreover, investigations regarding the acute dermal toxicity of UMA121 resulted in a low toxicity with a LD50 value of > 2000 mg/kg bw (Takawale, 2012). No signs of systemic toxicity or irritation were observed.

In summary, a dermal absorption of UMA121 is not expected.

 

Accumulation

Lipophilic substances tend in general to concentrate in adipose tissue and depending on the conditions of exposure may accumulate. Moreover, lipophilic substances that come into contact with the skin can readily penetrate the lipid rich stratum corneum but are not well absorbed systemically. Although there is no direct correlation between the lipophilicity of a substance and its biological half-life, it is generally the case that substances with high log Pow values have long biological half-lives (ECHA, 2012). The high log Pow in the range of 3.9 to 7.0 implies that UMA121 may have the potential to accumulate in adipose tissue and in stratum corneum. However, as UMA121 is considered not to be absorbed after ingestion, there is no possibility for accumulation.

 

Distribution

Distribution within the body depends on the molecular weight, the lipophilic character and water solubility of a substance. In general, the smaller the molecule, the wider is the distribution. If the molecule is lipophilic, it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues (ECHA, 2012). Due to the molecular weight of > 538.6 g/mol and insolubility in water, distribution of the substance in the body is considered to be limited. Since the substance is very lipophile, distribution particularly in fatty cells is likely. However, as UMA121 is considered not to be absorbed after ingestion, there is no possibility for distribution.

 

Metabolism

Based on the molecular weight of > 538.6 g/mol, the high log Pow, the insolubility in water and the physical state of UMA121, absorption of relevant substance amounts is not expected and therefore, metabolism into chemically reactive compounds under in vivo conditions is not expected.

The test substance was not found to induce genotoxic effects in Ames test, mouse lymphoma assay and chromosome aberration assay (Donath, 2012; Zeller, 2013; Hofman-Hüther, 2013). Furthermore, there is a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test according to OECD 422 available (Takawale, 2013) which did not reveal any test substance-related effect. No mortality and no adverse clinical signs were observed. Body weights, food consumption, ophthalmoscopy, haematology, clinical chemistry, urinalysis and investigations on neurobehaviour revealed no adverse effects. In addition, gross pathology, organ weight determination and histopathology were without any adverse finding.

 

Excretion

As UMA121 is considered not to be absorbed after ingestion, it is expected that the unabsorbed substance will be excreted via faeces. The portion of the substance which has penetrated the lipid rich stratum corneum after dermal application is considered to be sloughed off with the skin cells.