Slags, elec. furnace smelting, iron silicate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles. Read-across to silicates (major components of the slag).

Data source

Reference

Reference Type:

publication

Title:

Pharmacokinetic study of Zeolite A, sodium aluminosilicate, magnesium silicate, and aluminium hydroxide in dogs

Author:

Cefali E.A, Nolan J.C, McConnell W.R and Lowe Walters D.

Year:

1995

Bibliographic source:

Pharm Res 12, 270-274

Materials and methods

Objective of study:

absorption

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Beagle dogs were given oral doses of sodium aluminosilicate, magnesium silicate, aluminium hydroxide and Zeolite A (an aluminium silicate) and the plasma silicon and aluminium concentrations were followed for 24 h.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

sodium aluminiumsilicate

IUPAC Name:

sodium aluminiumsilicate

Constituent 2

Reference substance name:

magnesium trisilicate

IUPAC Name:

magnesium trisilicate

Constituent 3

Reference substance name:

Zeolite A (an aluminium silicate)

IUPAC Name:

Zeolite A (an aluminium silicate)

Constituent 4

Reference substance name:

Aluminium hydroxide

EC Number:

244-492-7

EC Name:

Aluminium hydroxide

Cas Number:

21645-51-2

IUPAC Name:

aluminum trihydroxide

Details on test material:

Sodium aluminosilicate lot #SR00002922
Magnesium trisilicate lot #BD203
Zeolite A (N-0974) raw material (Ethyl, lot #07)
Concentrated aluminium hydroxide gel, 675 mg/5 ml (lot #911187)

Radiolabelling:

no

Test animals

Species:

dog

Strain:

Beagle

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: 10-13 months
- Weight at study initiation: 7.3-11.6 kg
- Fasting period before study: no data
- Housing: individually in stainless steel cages
- Individual metabolism cages: no
- Diet (e.g. ad libitum): diet available for ca 3 h per day, provided ca 4 h after dosing
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no dara


ENVIRONMENTAL CONDITIONS
- Environmentally controlled room; no other data


IN-LIFE DATES: animals not sacrficed

Administration / exposure

Route of administration:

oral: capsule

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

The animals received a single dose of each test substance. The exposures were carried out with one-week intevals in-between.

Doses / concentrations

Remarks:

Doses / Concentrations:
Sodium aluminosilicate 16 mg/kg (capsule)
Magnesium trisilicate 20 mg/kg (capsule)
Zeolite A 30 mg/kg (capsule)
Aluminium hydroxide gel 675 mg/animal in 5 ml (orally by gavage)

No. of animals per sex per dose / concentration:

12 (the same animals were used for all tests)

Control animals:

yes, historical

Positive control reference chemical:

No

Details on study design:

Dosing of the different test substances was carried out in a randomized, 4-way crossover design.

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood
- Time and frequency of sampling: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h after dosing

Statistics:

One-way ANOVA used for comparison of AUC values and Tmax values.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Mean plasma silicon AUC values, Cmax and Tmax are presented in table 1. Although mean silicon AUC and Cmax values were elevated when compared to baseline, only the AUC from Zelite A was statsitically significantly increased. The Cmax and Tmax values were not significantly different.

There were no significant differences in aluminium absorption from the different substances, although the aluminium concentration in the samples varied. The results are presented in table 2.

Any other information on results incl. tables

Table 1. Silicon bioavailaibility estimates
	Zeolite A	Sodium aluminosilicate	Magnesium trisilicate	Aluminium hydroxide
Silicon dose (mg/kg)	4,66	4,75	4,63	0
Cmax (mg/l)	1.07 ± 1.06	0.67 ± 0.27	0.75 ± 0.31	0.44 ± 0.17
AUC (mg*h/l)	9.5 ± 4.5	7.7 ± 1.6	8.8 ± 3.0	6.1 ± 1.9
Tmax (h)	7.9 ± 6.4	5.8 ± 4.6	6.9 ± 6.3	8.5 ± 3.4

Table 2. Aluminium bioavailaibility estimates
	Zeolite A	Sodium aluminosilicate	Magnesium trisilicate	Aluminium hydroxide
Aluminium dose (mg/kg)	3,36	0,9	0	28
Cmax (µg/l)	29 ± 9	27 ± 14	24 ± 5	29 ± 11
AUC (µg*h/l)	342 ± 111	338 ± 167	315 ± 69	355 ± 150
Tmax (h)	3.5 ± 4.1	4.2 ± 4.3	5.7 ± 7.3	5.0 ± 4.7

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: Silicon was absorbed from the different silicates after single oral administration in dogs. Zeolite A was the only test substane which demonstarted a significantly higher absorption than any other treatment or baseline. No statistically significant absor
Silicon was absorbed from the different silicates after single oral administration in dogs. Zeolite A was the only test substane which demonstrated a significantly higher absorption than any other treatment or baseline. No statistically significant absorption of aluminium occurred.

Executive summary:

Cefali et al. (1995): Beagle dogs were given oral doses of sodium aluminosilicate, magnesium silicate, aluminium hydroxide and Zeolite A (an aluminium silicate), and the plasma silicon and aluminium concentrations were followed for 24 h. Silicon was absorbed from the different silicates after a single oral administration in dogs. However, Zeolite A was the only test substance which demonstrated a significantly higher absorption than any other treatment or baseline. No statistically significant absorption of aluminium occurred.