Beryllium

Specific investigations: other studies

Administrative data

Endpoint:

chemobiokinetics general studies

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2008-09-26 till 2009-05-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: taylor-made study (fit for purpose), conducted under GLP and well-documented

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2008

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

the dissolution behaviours/kinetics of different beryllium compounds in artificial lung fluids were compared

GLP compliance:

yes (incl. QA statement)

Type of method:

other: cell-free

Endpoint addressed:

basic toxicokinetics

Test material

Test material information

Constituent 1

Reference substance name:

Beryllium

EC Number:

231-150-7

EC Name:

Beryllium

Cas Number:

7440-41-7

Molecular formula:

Be

IUPAC Name:

beryllium

Details on test material:

1.
- Name of test material (as cited in study report): Beryllium Metal Powder
- Substance type: metal
- Physical state: powdered solid
- Analytical purity: 99.4%
- Lot/batch No.: 0-30 H Grade/Blend #051106
- Expiration date of the lot/batch: 2050-12-31
- Storage condition of test material: dry

2.
- Name of test material (as cited in study report): Copper-beryllium alloy powder
- Substance type: alloy
- Physical state: powdered solid
- Analytical purity: 95.9% (1.74% Beryllium)
- Lot/batch No.: BRA3677
- Expiration date of the lot/batch: 2050-12-31
- Storage condition of test material: dry

3.
- Name of test material (as cited in study report): Beryllium Oxide Ceramic Powder
- Substance type: oxide
- Physical state: powdered solid
- Analytical purity: > 96.87%
- Lot/batch No.: TMI#-2008-302
- Expiration date of the lot/batch: 2010-06-01
- Storage condition of test material: dry

4.
- Name of test material (as cited in study report): Beryllium Chloride Powder
- Substance type: salt
- Physical state: powdered solid
- Analytical purity: 99 % (11.4 % Beryllium)
- Lot/batch No.: 05987AH
- Expiration date of the lot/batch: 2010-06-01
- Storage condition of test material: dry

Results and discussion

Details on results:

see table 1 and 2.

Any other information on results incl. tables

Table 1: Dissolution at neutral pH

Gamble's (pH 7.1)	Concentration of beryllium in the supernatant [mg/l] % beryllium dissolved of theoretically available for dissolution
	Day 1	Day 7	Day 14	Day 28
BeO Ceramic Powder
	<LOQ	<LOQ	<LOQ	<LOQ
	n.a.	n.a.	n.a.	n.a.
Be Metal Powder
	0.166	0.311	0.325	0.581
	0.170	0.308	0.318	0.573
BeCl2
	0.807	0.699	0.371	0.514
	7.01	6.29	3.24	4.48
CuBe Alloy Metallic Powder
	0.199	0.706	0.653	0.771
	11.2	40.9	35.0	43.1

Table 2: Dissolution at acidic pH

ALF (pH 4.5)	Concentration of beryllium in the supernatant [mg/l] % beryllium dissolved of theoretically available for dissolution
	Day 1	Day 7	Day 14	Day 28

BeO Ceramic Powder
	<LOQ	0.126	0.209	0.356
	n.a.	0.352	0.561	0.988
Be Metal Powder
	1.01	10.5	18.9	33.9
	1.01	10.6	18.9	32.6
BeCl2
	11.0	11.0	10.2	10.4
	93.9	93.9	87.2	90.6
CuBe Alloy Metallic Powder
	0.709	1.80	1.86	1.80
	40.8	97.5	103	105

Applicant's summary and conclusion

Conclusions:

Beryllium metal, beryllium oxide ceramic and beryllium chloride are largely less soluble in artificail lung fluids compared to beryllium chloride. There are large differences in dissolution behaviour of the individual compounds. Read-across is (with regards to the different bioavailabilities assumed to be present based on these results) considered to be of limited value for beryllium and its compounds.

Executive summary:

The dissolution behaviour (amount and kinetics) of different beryllium compounds in artificial lung fluids was investigated. The dissolution behaviour is considered to have significant influence on toxicokinetics of the individual compounds and the read-across possibilities with regards to toxicological properties of the beryllium compounds. The compounds (beryllium metal, copper-beryllium alloy, beryllium oxide ceramic and beryllium chloride) were grind to fine powders and loaded at the same loading rate into artificial lung fluids at either neutral pH (simulating the normal lung millieu) or at acidic pH (simulating a lysosomal environment). The concentration of dissolved beryllium in the samples (after removal of particulate matter by centrifugation) was determined by atomic absorption spectrometry at day 1, day 7, day 14 and day 28 after start of incubation.

For all compounds, solubility at acidic pH was higher than at neutral pH. Solubility was beryllium chloride >> copper-beryllium alloy > beryllium metal >> beryllium oxide ceramic. For all compounds, the amount of dissolved beryllium stayed either constant or slowly increased with time.