Cerium terbium magnesium undecaaluminum nonadecaoxide (hexagonal) ((Ce, Tb)MgAl11O19) and aluminium oxide (Al2O3) from calcination of Al2O3, CeO2, MgO and Tb4O7

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Toxicokinetic assessment of the substance based on the available data

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: since this is a theoretical assessment, the Klimisch value cannot be 1.

Objective of study:

other: Toxicokinetic assessment of the substance based on the available data

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

Deviations:

not applicable

GLP compliance:

no

TOXICOKINETIC ASSESSMENT

CAT is considered to be insoluble in water. In general a substance needs to be dissolved, before it can be taken up from the gastro-intestinal tract. Thus, the water insolubility can be considered a potentially rate-limiting factor for the absorption of the compound. Also the molecular weight of the main constituent is not favourable for absorption (3). After oral administration, it is unlikely that CAT will show a high systemic exposure (1). In the presence of food and bile salts some systemic exposure might be possible. For risk assessment purposes the oral absorption of CAT is set at 10% as a worst case assumption.

Once absorbed, distribution of CAT throughout the body will be limited due to its water insolubility (3).

Based on the particle size distribution study performed with CAT, particles < 100 μm which have a potential to be inhaled, are present. Particles with an aerodynamic diameter below 50 μm may reach the thoracic regions, whereas particles with an aerodynamic diameter below 15 μm may reach the alveolar region of the respiratory tract. The water insolubility of CAT indicates that CAT will not dissolve into the mucus lining of the respiratory tract and the deposits in the nasopharyngeal region will likely to be coughed or sneezed out of the body, or swallowed. As most of the particles have a size < 10 μm (84.51%), the fraction that will reach the alveolar region of the respiratory tract will be available for absorption. For risk assessment purposes the inhalation absorption of CAT is set at 100%.

CAT being a solid which is considered to be insoluble in water has no real potential for dermal absorption. Also the molecular weight of the main constituent does not favour dermal absorption. Based on these physical/chemical properties of CAT, dermal absorption is considered to be low. Although the criteria for 10% dermal absorption as given in the REACH guidance (2) (MW > 500 and log Pow < -1 or > 4) are not met as data on log Pow are not available for inorganic substances, 100% dermal absorption is considered not relevant for CAT as it is generally accepted that dermal absorption does not exceed oral absorption. For risk assessment purposes therefore, 10% dermal absorption of CAT as default value is considered to be appropriate.

Based on the present available data, no additional conclusions can be drawn on the distribution, metabolism and excretion of CAT after dermal and inhalatory absorption.

References

(1) A. Parkinson. In: Casarett and Doull’s Toxicology, The basic science of poisons. Sixth edition. Ed. C.D. Klaassen. Chapter 6: Biotransformation of xenobiotics. McGraw-Hill, New York, 2001.

(2) 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.

(3) Martinez MN, Amidon GL. Mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals. J Clin Pharmacol 2002; 42: 620-43.

Conclusions:

For risk assessment purposes the following absorption factors were derived: oral absorption factor: 10%; dermal absorption factor: 10%; inhalation absorption factor: 100%

Description of key information

Using a theoretical approach and the available physico-chemical properties and toxicological data, the following absorption factors were derived for risk assessment purposes: oral absorption factor: 10%; dermal absorption factor: 10%; inhalation absorption factor: 100%

Key value for chemical safety assessment

Absorption rate - oral (%):

10

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

CAT is considered to be insoluble in water. In general a substance needs to be dissolved, before it can be taken up from the gastro-intestinal tract. Thus, the water insolubility can be considered a potentially rate-limiting factor for the absorption of the compound. Also the molecular weight of the main constituent is not favourable for absorption. After oral administration, it is unlikely that CAT will show a high systemic exposure. In the presence of food and bile salts some systemic exposure might be possible. For risk assessment purposes the oral absorption of CAT is set at 10% as a worst case assumption.

 

Once absorbed, distribution of CAT throughout the body will be limited due to its water insolubility.

 

Based on the particle size distribution study performed with CAT, particles < 100 μm which have a potential to be inhaled, are present. Particles with an aerodynamic diameter below 50 μm may reach the thoracic regions, whereas particles with an aerodynamic diameter below 15 μm may reach the alveolar region of the respiratory tract. The water insolubility of CAT indicates that CAT will not dissolve into the mucus lining of the respiratory tract and the deposits in the nasopharyngeal region will likely to be coughed or sneezed out of the body, or swallowed. As most of the particles have a size < 10 μm (84.51%), the fraction that will reach the alveolar region of the respiratory tract will be available for absorption. For risk assessment purposes the inhalation absorption of CAT is set at 100%.

 

CAT being a solid which is considered to be insoluble in water has no real potential for dermal absorption. Also the molecular weight of the main constituent does not favour dermal absorption. Based on these physical/chemical properties of CAT, dermal absorption is considered to be low. Although the criteria for 10% dermal absorption as given in the REACH guidance (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) (MW > 500 and log Pow < -1 or > 4) are not met as data on log Pow are not available for inorganic substances, 100% dermal absorption is considered not relevant for CAT as it is generally accepted that dermal absorption does not exceed oral absorption. For risk assessment purposes therefore, 10% dermal absorption of CAT as default value is considered to be appropriate.

 

Based on the present available data, no additional conclusions can be drawn on the distribution, metabolism and excretion of CAT after dermal and inhalatory absorption.