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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: theoretical approach
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
As the theoretical approach is performed with a substance analogue, in accordance with REACH guidance the maximum reliability for read-across data is 2. Read-across is justified because of the similar chemical nature of the target substance compared to the analogues. The read-across rationale can be found in the analogue approach document attached in Section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Objective of study:
other: Assessment of toxicokinetic behaviour
Principles of method if other than guideline:
A theoretical approach of the toxicokinetic properties of the substance based on the available physicochemical
properties and toxicological data..
GLP compliance:
no
Remarks:
not applicable

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Identification P 93
Substance type Hydrated form
Description White solid
Batch 950530
Purity 99.67%
Test substance storage At room temperature in the dark
Stability under storage
conditions Stable
Expiry date 13 December 1997

Results and discussion

Any other information on results incl. tables

The acute oral toxicity of P93 is low, with LD50 > 2000 mg/kg body. The acute toxicity after inhalation is also low
(4h-LC50 > 5 g/m3). Therefore, an extensive toxicokinetic assessment is considered of limited value. Below, an
assessment of the anticipated toxicokinetic behaviour of P93 is given.

Like most commercially available antacids (compounds therapeutically used to neutralize gastric acid), P93
containes aluminium (Al3+) and magnesium (Mg2+). Moreover, it also contains zinc (Zn2+). Dietary intake of Al3+ is usually in the range of 10 mg daily. About 0.1 - 0.5 mg of Al3+ may be absorbed from a
standard daily doses range from 100 mEq (0.9 g Al3 +/1.2 g Mg2+) - 1000 mEq (9 g Al3+/12 g Mg2+).

Mg2+ is the second most plentiful cation of the intracellular fluids. The average 70-kg adult has about 2000 mEq of Mg2+ in his body and the daily dietary intake is 0.25-0.50 g daily. Approximately one third is absorbed from
the gastro-intestinal tract.

Chronic ingestion of Mg2+ causes only slight increases in plasma concentrations of Mg2+ in individuals with normal
renal function.

The average daily intake of zinc is approximately 12 to 15 mg, mostly from food. It is a nutritionally essential metal
and deficiency result in severe health consequences. About 20 to 30 percent of ingested zinc is absorbed.

Zinc does not accumulated with continued exposure, but body content is modulated by homeostatic mechanisms that act
principally on absorption and liver levels.

The aluminium, magnesium and zinc ions are primarily excreted renally.

The test substance also contains hydroxide and carbonate. These ions are readily neutralized after ingestion.

Dermal absorpiton of the aluminium, magnesium and zinc ions is expected to be low.

The anticipated kinetic behaviour is supported by the acute and semichronic toxicity data.

The observed effects after inhalation of P93 are probably caused by precipitation of the substance in the lungs.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
Based on the Risk Assessment of P93 performed by the Dutch Competent Authorities (BMS071023.03, d.d. 23-10-07), the following values are
considered for absorption:
- oral absorption: 50%
- dermal absorption: 1% (based on the physico-chemical properties)
- inhalation absorption: 1% (considering the particle size inhalation exposure will be negligible)