Reaction mass of copper oxide and manganese dioxide

Endpoint summary

Description of key information

No data are available for the registration substance. However adequate and reliable studies performed with each of the two constituents of the registration substance are at hand. In all acute toxicity studies no mortalities were observed. In the acute oral toxicity studies recalculated LD50 values in the range of > 2850 to > 11100 mg Hopcalite/kg bw were established. From acute dermal toxicity studies recalculated LD50 values of > 2850 or > 8880 mg Hopcalite/kg bw were derived. The tested materials (both constituents of the reaction mass) and thus also the registration substance itself are considered to be non-toxic.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For details on endpoint specific justification please see read-across report in section 13 or find a link in cross-reference “assessment report”.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 850 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

value calculated based on ratio of MnO2 and CuO in the reaction mass

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was calculated to be > 2850 mg/kg bw for Hopcalite based on the test results obtained for female Wistar rats treated with manganese dioxide orally.

Executive summary:

The acute oral toxicity of MnO2 was investigated in vivo in a study in accordance with the standardised guideline OECD 420. During the study no adverse signs, symptoms and mortality were observed in female Wistar rats. Therefore the tested material was considered to be non-toxic. Results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13 or find a link in cross-reference “assessment report”.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For details on endpoint specific justification please see read-across report in section 13 or find a link in cross-reference “assessment report”.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 11 100 mg/kg bw

Based on:

test mat.

Remarks on result:

other: value recalculated based on the ratio of MnO2 and CuO in the reaction mass

Interpretation of results:

GHS criteria not met

Conclusions:

LD 50 was calculated to be > 11100 mg/kg bw for Hopcalite based on the test results obtained for male Sprague-Dawleyrats treated with copper oxide via oral gavage.

Executive summary:

The study used as source investigated copper oxide. This acute oral toxicity study was performed according to the Acute toxic class method (OECD TG 423) and GLP. Single gavage application of the limit dose of 2000 mg source material per kg bw did not cause lethality or any other signs of toxicity in three male SD rats during the 14 day observation period. All animals showed expected gains in bodyweight and there were no abnormalities noted at necropsy. Based on the provisions of the guideline (see flow chart in annex 2 in OECD TG 423 adopted 17 December 2001) an LD50 of >2500 mg/kg bw was established for the source material, i.e. copper oxide, which is recalculated based on the ratio of MnO2 and CuO within the reaction mass to a LD50 of > 11100 mg/kg bw for Hopcalite.

The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13 or find a link in cross reference "assessment report".

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 850 mg/kg bw

Quality of whole database:

The studies available for both constituents of the reaction mass are performed according to OECD testing guidelines. One study is performed according to GLP, whereas for the other study no details on GLP status are published. The studies thus either have Klimisch score 1 (guieline study with GLP) or 2 (guideline study with GLP status unknown).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For details on endpoint specific justification please see read-across report in section 13 or find a link in cross-reference “assessment report”.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 850 mg/kg bw

Based on:

test mat.

Remarks on result:

other: value recalculated based on the ratio of MnO2 and CuO in the reaction mass

Interpretation of results:

GHS criteria not met

Conclusions:

LD 50 was calculated to be > 2850 mg/kg bw for Hopcalite based on the test results obtained for male and female SD rats treated with manganese dioxide dermally.

Executive summary:

The study used as source investigated manganese dioxide.

Single dermal application of the limit dose of 2000 mg source material per kg bw did not cause lethality in 5 male and 5 female SD rats during the 15 day observation period within this OECD TG 402 study according to GLP, resulting in a recalculated LD50 > 2850 mg Hocalite/kg bw.

The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13 or find a link in cross reference "assessment report".

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For details on endpoint specific justification please see read-across report in section 13 or find a link in cross-reference “assessment report”.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 8 880 mg/kg bw

Based on:

test mat.

Remarks on result:

other: value recalculated based on the ratio of MnO2 and CuO in the reaction mass

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this acute dermal toxicity study the LD50 was recalculated to be > 8880 mg/kg bw for Hopcalite based on the test results obtained for male and female SD rats treated with copper oxide dermally.

Executive summary:

This acute dermal toxicity study used as source was conducted according to OECD TG 402 and in concordance with GLP. The study material investigated was copper (II) oxide, which was applied onto the skin at the limit dose of 2000 mg/kg bw. There were no mortalities, signs of systemic toxicity, or dermal irritation among any of the treated animals. All of them showed expected gains in bodyweight over the study period and there were no abnormalities noted at necropsy.

Based on these results and the ratio of manganese dioxide and copper oxide in the reaction mass the LD50 was recalculated to be > 8880 mg/kg bw for Hopcalite.

Results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13 or find a link in cross-reference “assessment report”.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 850 mg/kg bw

Quality of whole database:

The studies available for both constituents of the reaction mass are performed according to OECD testing guideline 402 and GLP and have a Klimisch score 1.

Additional information

Acute oral toxicity

In the first key study acute oral toxicity of manganese dioxide was investigated. Accoring to OECD Guideline 420 (Fixed dose method), the test item was administered via single oral gavage to female albino Wistar rats (5 animals/group) at doses of 0 and 2000 mg/kg bw. No treatment-related effects on mortality, clinical signs, body weight changes, food consumption, gross findings, and relative organ weights in Wistar rats treated with a single oral dose of test item were observed during the 14 day observation period. Therefore, the LD50 value of the source material was considered to be over 2000 mg/kg bw for female rats, which is recalculated to > 2850 mg/kg bw for Hopcalite based on the ratio of MnO2 and CuO in the reaction mass.

The second key study used as source investigated copper oxide. This acute oral toxicity study was performed according to the Acute toxic class method (OECD TG 423) and GLP. Single gavage application of the limit dose of 2000 mg source material per kg bw did not cause lethality or any other signs of toxicity in three male SD rats during the 14 day observation period. All animals showed expected gains in bodyweight and there were no abnormalities noted at necropsy. Based on the provisions of the guideline (see flow chart in annex 2 in OECD TG 423 adopted 17 December 2001) an LD50 of >2500 mg/kg bw was established for the source material, i.e. copper oxide, which is recalculated based on the ratio of MnO2 and CuO within the reaction mass to a LD50 of > 11100 mg/kg bw for Hopcalite.

In another study acute oral toxicity of manganese dioxide was investigated, but no detailed description of the study design was published (thus less reliable). Based on the test results obtained for male Sprague-Dawley rats treated with manganese dioxide orally by gavage, the LD50 was calculated to be > 4970 mg/kg bw for Hopcalite and which supports the results from the key studies.

There is a vast variety of studies describing effects after ingestion (mostly via drinking water) of copper compunds. Effects generally observed include e.g. nausea, abdominal pain and vomiting.

The most reliable and relevant dose-response data for acute toxicity come from two well-controlled, oral exposure studies conducted in human volunteers (Araya et al, 2001; Araya et al, 2003). In both of these studies, a concentration-related increase in gastrointestinal symptoms was associated with single oral exposure to copper in drinking water. The NOAEL for gastrointestinal symptoms in adults was 4 mg Cu/litre drinking water (= 22.25 mg hopcalite/ litre drinking water) and the LOAEL was 6 mg/litre (= 33.4 mg hopcalite/ litre drinking water, see IUCLID section 7.10.3 "Direct observations: clinical cases, poisoning incidents and other").

Acute dermal toxicity

There are two acute dermal toxicity studies used as source, which were both conducted according to OECD TG 402 and in concordance with GLP.

In the first study the test material used was manganese dioxide. Single dermal application of the limit dose of 2000 mg source material per kg bw did not cause lethality or any other sign of systemic or local toxicity in 5 male and 5 female SD rats during the 15 day observation period, resulting in a recalculated LD50 > 2850 mg Hocalite/kg bw.

In the second study the test material investigated was copper (II) oxide, which was applied onto the skin of male and female Sprague-Dawley CD rats at the limit dose of 2000 mg/kg bw. There were no mortalities, signs of systemic toxicity, or dermal irritation among any of the treated animals. All of them showed expected gains in bodyweight over the study period and there were no abnormalities noted at necropsy. Based on these results and the ratio of manganese dioxide and copper oxide in the reaction mass the LD50 was recalculated to be > 8880 mg/kg bw for Hopcalite.

Justification for classification or non-classification

Based on the lack of effects observed in reliable acute oral and dermal toxicity studies performed with both of the constituents of the registration substance and in accordance with criteria for classification as defined in Regulation (EC) No. 1272/2008, the registration substance does not require classification with respect to acute oral and dermal toxicity.

However as manganese dioxide is classified for acute oral toxicity category 4 (H302, harmonised classification) and when considering the rules in Regulation (EC) No. 1272/2008 section 3.1.3.6.1, the reaction mass to be classified with regard to acute oral toxicity category 4 (H302), too. This more conservative approach is represented in section 2, GHS classification.

As there are no studies for acute inhalation toxicity reported here, but one of the constituents of this reaction mass, i.e. manganese dioxide, is classified as acute toxic category 4 after inhalation (H332) and after applying the rules in Regulation (EC) No. 1272/2008 section 3.1.3.6.1 the classification as acute toxic category 4 after inhalation (H332) has also to be applied to the reaction mass, too.