Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Adequacy of study:
supporting study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test type:
other: Bioelution test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Copper(I) oxide, copper(II) oxide and copper thiocynate from different producers were used. The test materials were supplied in powder form with an average particle size distribution ranging from 3 to 50 μm.

Results and discussion

Any other information on results incl. tables

Refer to Executive Summary.

Applicant's summary and conclusion

Executive summary:

An experimental study was conducted to assess the solubility of two copper oxides and copper thiocyanate in Gamble´s and Gamble´s modified fluids, solutions that simulate interstitial and alveolar milieu conditions. Table 1 shows a summary of the results at 72 h.

 

Table 1.- Dissolved metal @ 72 hours as mg/L (ppm)

 

AAF

AIF

Compound

Cu, mg/L

Cu, mg/L

 

Mean

St. Dev.

Mean

St. Dev.

Cu2O ACh 3-5 μm

22.71

1.10

17.93

1.31

Cu2O ACh 3-5 μm, repetition

22.62

1.01

21.50

0.23

Cu2O ACh 10-11 μm

22.97

0.28

20.16

0.36

Cu2O ACh 50-55 μm

15.13

3.44

18.95

1.75

CuSCN BC unkown

8.80

0.50

6.20

0.74

 

 

 

 

 

 

AAF

AIF

Compound

Cu, mg/L

Cu, mg/L

 

Mean

St. Dev.

Mean

St. Dev.

CuO ACh 3 μm

4.06

0.15

3.98

0.12

CuO ACh 3 μm, repetition

3.44

0.14

4.18

0.11

CuO ACh 10 μm

3.96

0.16

4.51

0.29

CuO AD 3 μm

7.32

0.76

7.86

0.91

CuO AD 50 μm

3.50

0.34

3.09

0.39

 ACh: American Chemet.  AD: ADCHEM. BC: Bardyke Chemicals

 

 The following may be observed:

 

a) In general, no major differences in copper dissolution between fluids at each particle size range were observed. However, some differences were observed at times < 72 h for the dicopper oxide at the smaller particle size range tested, but this did not lead to significative differences in the total copper released after 72 h.

 

b) At each particle size range, dicopper oxide always exhibited higher dissolution rates than copper oxide.

 

c) Comparing within each oxide type, there were no significative differences in dissolution rate between the 3-5 µm and the 10 µm particle size tests. This may be due to overlapping of the particle size distributions of the samples, but we do not have the data to evaluate this possibility.

 

d) Dicopper oxide released significatively more copper in the 3-5 µm and 10 µm tests than in the 50 µm size test. This is the expected result on the basis of the greater surface area of smaller particles at a same mass loading. This was only observed in samples from American Chemet, since no samples of Cu2O from the ADCHEM were provided.

 

e) In the case of copper oxide (CuO), there was also more copper dissolved from the 3-5 µm size particles than from the 50 µm particles. This was observed only in the ADCHEM oxide, since no CuO (50 µm) was provided from American Chemet. Also, no 10 µm particle size CuO was made available for testing.

 

f) A significant difference in copper dissolution rate was observed in the 3 µm particle size tests of copper oxides from the two suppliers. The ADCHEM CuO released approximately two fold the mass of copper compared to the American Chemet CuO. This difference was observed in either fluid type, with three replicate assays for each fluid, and an additional set of replicates of the assay with the American Chemet sample. Furthermore, the standard deviations of the data were quite acceptable. Therefore, it is unlikely that this may be dismissed as experimental error. Possible explanations are:

  • The particle size distributions may be different, but this is unlikely since we observed no differences in dissolution between the 3-5 µm and the 10 µm samples of the dicopper oxide, which suggests that minor differences in this size range should not lead to significative differences in dissolution.
  • There may be surface related differences between the samples. For instance, the presence of more fractures or other irregularities in the ADCHEM oxide particles would result in a greater surface area per mass loading. Alternatively, physicochemical differences associated to the manufacturing procedure might also lead to higher rates of copper reactivity at the surface.

The more relevant conclusions are:

  • The bioelution assays were successfully implemented for the three copper compounds in two biofluid types. The experimental variability was low enough to observe differences between samples of different mean particle sizes and between samples of the same size but from different sources.
  •  The unexpected differences in copper release rates between samples of copper oxide of the same mean particle size but from different suppliers must be addressed and accounted for. This may require surface analysis of the samples. Also, it may be of interest to check whether this is also observed when dicopper oxide samples from different suppliers are compared in this experimental set up.