L 130

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

Not applicable

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Theoretical assessment taking all currrently available relevant information into account, based on the REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance. Since this is a theoretical assessment, the Klimisch value cannot be 1.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Guidance for the implementation of REACH. Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. European Chemical Agency, May 2008

GLP compliance:

no

Test material

Test material information

Constituent 1

Details on test material:

Not applicable

Results and discussion

Any other information on results incl. tables

TOXICOKINETIC ASSESSMENT

A substance can enter the body via the gastrointestinal tract, the lungs, or the skin, depending on the exposure route.

 

After oral administration, in general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract. L 130 is considered to be insoluble in water, therefore passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage of such molecules across membranes with the bulk passage of water) is expected to be low. Furthermore, the molecular weight of L 130 (1010 < MW < 1030) will impede fast absorption. Due to its insolubility in water and its limited ability to penetrate biomembranes related to its size, oral absorption is considered to be limited. For risk assessment purposes oral absorption of L 130 is set at 10%. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor.

 

Once absorbed, wide distribution of L 130 throughout the body is not expected based on its high molecular weight (1010 < MW < 1030) and due to its insolubility in water. Absorbed L 130 is most likely excreted via urine. L 130 is not expected to bio-accumulate in the body upon exposure.

 

L 130 has a very low vapour pressure (<0.001 Pa at 25 °C). This implies that exposure via inhalation of vapour of L 130 is not likely to occur. Furthermore, as the density of L 130 has been shown to be relatively high (relative density of 3.74), long-term dust formation is unlikely to occur. On the other hand, L 130 particles are relatively small (on average 27.2 µm) with a narrow size distribution (10% < 4.2 μm, 50% < 14.1 μm and 90% < 25.5 μm). In general, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm can enter the alveolar region of the respiratory tract. This indicates that if L 130 particles would reach the lungs, both the nasopharyncheal region and subsequently the tracheo/bronchial/pulmonary region are potentially exposed. Once L 130 reaches the lung tissue, it will not dissolve within the mucus lining of the respiratory tract due to its insolubility in water. In addition, its limited ability to penetrate biomembranes due to its size will further hamper uptake once deposited in lung tissue. L 130 deposited in the nasopharyngeal region could be eliminated from the body by coughing or sneezing. L 130 deposited in the tracheo-bronchial region is expected to be cleared from the lungs by the mucocilliary mechanism and swallowed. However, a small amount may be engulfed by alveolar macrophages, although its particle size (MMAD = 27.2 µm) does not favour phagocytosis which is more likely to occur with smaller particles (around 1 µm). In case of uptake, macrophages will then either translocate particles to the ciliated airways or carry particles into the pulmonary interstitium and lymphoid tissues. Based on the above data, for risk assessment purposes the inhalation absorption of L 130 is set at 50%.

 

L 130 is a powdery solid. Given the fact that L 130 is insoluble in water, it is not expected to be dissolved in the moisture of the skin and uptake will therefore be limited. Therefore dermal absorption is likely to be low. Furthermore, its molecular size (molecular weight: > 1000 g/mole) and expected low solubility in lipids due to its inorganic nature will further hamper fast uptake. According to the criteria given in the REACH Guidance, 10% dermal absorption will be considered in case MW >500 and log Pow <-1 or >4, otherwise 100% dermal absorption should be used. As L 130 has a high molecular weight (1010 < MW < 1030), but no partition coefficient is known, L 130 only partially meets the criteria for limited dermal absorption. It is however generally accepted that dermal absorption is equal or lower compared to oral absorption, and therefore a dermal absorption of 10% is considered to be more appropriate. Therefore, for risk assessment purposes dermal absorption is set at 10%.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: not expected to bio-accumulate in the body upon exposure
For risk assessment purposes, 10% is used for oral and dermal absorption and 50% is used for inhalation absorption.