Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: accepted QSAR method

Data source

Reference
Reference Type:
other: Model calculation
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Objective of study:
distribution
Principles of method if other than guideline:
The Multiple-Path Particle Dosimetry Model (MPPD, v2.11; CIIT, 2013, available via Internet http://www.ara.com/products/mppd.htm) was used to predict this fractional deposition behaviour in the human respiratory tract.
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide
EC Number:
915-069-0
Molecular formula:
not applicable
IUPAC Name:
Reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide

Results and discussion

Main ADME results
Type:
other: fractional deposition in respiratory tract of total dustiness (119.32 mg/g (11.93 % of total substance mass))
Results:
naso-pharyngeal (head) region: 89.1 %; tracheobronchial region: 1.4 %; pulmonary (alveolar) region: 4.3 %

Toxicokinetic / pharmacokinetic studies

Details on absorption:
not determined
Details on distribution in tissues:
not determined
Details on excretion:
not determined

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
not determined

Any other information on results incl. tables

Particle size distribution of measured total dustiness (119.32 mg/g) was determined in study DMT 2013 (see Technical Dossier Section 4.5, endpoint study record: key_Particle size distribution (Granulometry) DMT GS 3 – 00 005 13rev1) and the calculated MMAD and GSD values were used as input parameters for the prediction of the inhalable amount (94.8% of total dustiness) and its fractional deposition behaviour in the respiratory tract applying the Multiple Path Particle model (MPPD)(ver.2.11).

Only very few amounts of the total dustiness fraction (4.3 %) will reach the pulmonary (alveolar) region. The vast majority of inhaled dust will be withheld in the naso-pharyngeal (head) region (89.1 %) and minor amounts in the tracheobronchial region (1.4 %). Deposits in the alveolar region would not get directly absorbed as the substance is an poorly soluble dust. The alveolar dust deposits would mainly be engulfed by alveolar macrophages. The macrophages will then either translocate particles to the ciliated airways or carry particles into the pulmonary interstitium and lymphoid tissues. Poorly water-soluble dusts depositing in the nasopharyngeal region could be coughed or sneezed out of the body or swallowed. Dusts depositing in the tracheo-bronchial region would mainly be cleared from the lungs by the mucocilliary mechanism and swallowed (c.f. ECHA TGD R7a, R.7.12.2.1).

Thus, direct inhalative systemic bioavailability is highly unlikeley due to the deposition behaviour, crystalline structure and limited solubility.

Applicant's summary and conclusion

Conclusions:
Direct inhalative systemic bioavailability is unlikely due to the deposition behaviour, crystalline structure and limited solubility
Executive summary:

Prediction of respiratory deposition patterns using the MPPD model

MMAD (9.9 µm) and GDS (3.6) were used as distribution parameter for the MPPD model enabling an estimation of deposited dust fractions in the human respiratory tract: Using the derived particle size distribution parameters, it is possible to quantify the deposited fractions of the airborne dust in the human respiratory tract. The Multiple-Path Particle Dosimetry Model (MPPD, v2.11; CIIT, 2013) was used to predict this fractional deposition behaviour for workers.

Particle size distribution of measured total dustiness (119.32 mg/g) was determined in study DMT 2013 (see Technical Dossier Section 4.5, endpoint study record: key_Particle size distribution (Granulometry) DMT GS 3 – 00 005 13rev1) and the calculated MMAD and GSD values were used as input parameters for the prediction of the inhalable amount (94.8% of total dustiness) and its fractional deposition behaviour in the respiratory tract.

Only very few amounts of the total dustiness fraction (4.3%) will reach the pulmonary (alveolar) region. The vast majority of inhaled dust will be withheld in the naso-pharyngeal (head) region (89.1%) and minor amounts in the tracheobronchial region (1.4%). Deposits in the alveolar region would not get directly absorbed as the substance is an poorly soluble dust. The alveolar dust deposits would mainly be engulfed by alveolar macrophages. The macrophages will then either translocate particles to the ciliated airways or carry particles into the pulmonary interstitium and lymphoid tissues. Poorly water-soluble dusts depositing in the nasopharyngeal region could be coughed or sneezed out of the body or swallowed. Dusts depositing in the tracheo-bronchial region would mainly be cleared from the lungs by the mucocilliary mechanism and swallowed (c.f. ECHA TGD R7a, R.7.12.2.1).

Thus, direct inhalative systemic bioavailability is unlikely due to the deposition behaviour, crystalline structure and limited solubility.