Reaction mass of zinc oxide and zinc peroxide

Endpoint summary

Description of key information

Acute oral toxicity: key studies carried out according to OECD guideline no 401 or 423 indicating LD50 > 2000 mg/kg bw
Acute inhalation toxicity: key study carried out according to OECD guideline no 403 indicating LC50 > 5.7 mg/L/4hrs.    

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target substance Zinc peroxide and the source substances Zinc oxide, Zinc Chloride, Zinc sulfate, Zinc nitrate are ionic and consist of the Zinc2+ cation and the respective anion.
The read-across is based on the assumption that the zinc cation (as measure for dissolved zinc species) is the determining factor for (eco)toxicity.
For further details, see Justification for read-across attached to IUCLID chapter 13

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See Justification for read-across attached to IUCLID chapter 13

3. ANALOGUE APPROACH JUSTIFICATION
See Justification for read-across attached to IUCLID chapter 13

4. DATA MATRIX
See Justification for read-across attached to IUCLID chapter 13

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

act. ingr.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of Zinc Peroxide in rat is >/=2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target substance Zinc peroxide and the source substances Zinc oxide, Zinc Chloride, Zinc sulfate, Zinc nitrate are ionic and consist of the Zinc2+ cation and the respective anion.
The read-across is based on the assumption that the zinc cation (as measure for dissolved zinc species) is the determining factor for (eco)toxicity.
For further details, see Justification for read-across attached to IUCLID chapter 13

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See Justification for read-across attached to IUCLID chapter 13

3. ANALOGUE APPROACH JUSTIFICATION
See Justification for read-across attached to IUCLID chapter 13

4. DATA MATRIX
See Justification for read-across attached to IUCLID chapter 13

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

LC50

Effect level:

>= 5 700 mg/L air

Based on:

act. ingr.

Exp. duration:

4 h

Interpretation of results:

GHS criteria not met

Conclusions:

The 4 h LC50 of Zinc peroxide is >5.7 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 700 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No acute toxicity data are available for the target substance Zinc peroxide. However, reliable data are available for Zinc compounds as well as on hydrogen peroxide. A justification for read-across is attached to IUCLID section 13.

 

Acute oral toxicity

Data on Zinc

In an acute toxicity test Wistar rats (5/sex) were given a single dose of 5 g ZnO/kg bw (in water) by gavage and observed for 14 days. No mortality and signs of toxicity were observed. The LD50 in rats is therefore >5 g ZnO/kg bw.

Several other studies conducted with ZnO reported LD50 values well above 2000 mg/kg bw in rats or mice.

 

Data on hydrogen peroxide

“The oral LD50 values or lethal doses in rats range between 800 mg/kg for 70% H2O2 to more than 5,000 mg/kg for 10% H2O2. There are also a number of reported human incidents by oral

ingestion of H2O2 water solutions, but few reports have given data on the dose. The mechanism of systemic effect has been oxygen embolism. Thus, the substance proved to be harmful if swallowed by a physical mode of action.” (EU RAR, 2003)

 

In the transformation/dissolution test conducted with the target source Zinc peroxide, it was demonstrated, that only low levels of hydrogen peroxide are released. Thus, bolus or high concentration effects of hydrogen peroxide are not relevant for the target substance.

 

Overall, it can be concluded with sufficient reliability, that Zinc peroxide is of low acute toxicity by oral route (LD50 >2000 mg/kg bw).

 

Acute dermal toxicity

The testing of acute dermal toxicity of Zinc peroxide is scientifically not justified based on retrospective data analyses undertaken by Creton et al. (2010) and Seidle et al. (2010) to ascertain the value of regulatory requirements prescribing multiroute testing for acute systemic toxicity. These analyses have examined the concordance among regulatory classifications for acute oral, dermal, and/ or inhalation toxicity for ~500 agrochemical and biocidal active substances and nearly 2000 industrial chemicals. The findings from these two independent reviews have revealed that acute dermal studies of pure substances do not add value above and beyond oral data for hazard classification of pesticides, biocides, or chemicals. According to the COMMISSION REGULATION (EU) 2016/863 of 31 May 2016 amending Annexes VII and VIII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards skin corrosion/irritation, serious eye damage/eye irritation, skin sensitisation and acute toxicity, recent “scientific analysis of available data from in vivo acute toxicity studies have shown that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. Therefore, testing those substances via the dermal route does not provide essential information for their safety assessment.” The oral LD50 was determined to be > 2000 mg/kg bw based on read-across from a closely related substance. Thus, no toxicity via the dermal route is to be expected.  

 

Acute inhalation toxicity

Data on Zinc

In an acute inhalation toxicity study, 10 male and 10 female animals per group were exposed to zinc oxide aerosol (head and nose only) for 4 h. Aerosol concentration was 5.7 mg/l and the particle size distribution had a mass median aerodynamic diameter of 4mm ± 2.9 (GSD). Only one concentration and a control group were tested. All animals survived up to day 14 post exposure. Apart from a dusty fur on the head the day after the exposure, no effects were seen. Body weights developed normally. At pathological examination all organs were normal. The LC50 was >5.7 mg/l.

 

Data on hydrogen peroxide

“Acute inhalation toxicity studies have been performed with aerosols (mice) and vapours (rats and mice). Due to the corrosive nature of the substance after inhalation exposures to highly concentrated aerosols (70% H2O2 as “droplets”), lethality occurs at quite low air concentrations of this substance (0,92-2 mg/l). The lethal event can be attributed to the substance corrosivity rather than its systemic toxicity.” (EU RAR, 2003)

 

In the transformation/dissolution test conducted with the target source Zinc peroxide, it was demonstrated, that only low levels of hydrogen peroxide are released. Thus, bolus or high concentration effects of hydrogen peroxide are not relevant for the target substance.

 

Overall, it can be concluded with sufficient reliability, that Zinc peroxide is of low acute toxicity via inhalation (LC50 >5000 mg/m³).

 

References:

Creton S. et al. Acute toxicity testing of chemicals—Opportunities to avoid redundant testing and use alternative approaches, Critical Reviews in Toxicology, 2010; 40(1): 50–83   

 

EU RAR, 2003.European Union Risk Assessment Report. Hydrogen Peroxide. Volume 38. EUR 20844 EN

 

Seidle T. et al.: Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing, TOXICOLOGICAL SCIENCES 116(2), 382–396 (2010).

Justification for classification or non-classification

Based on the available data, Zinc peroxide is of low acute, dermal and inhalation toxicity not requiring classification and labelling for acute toxicity according to the CLP Regulation (EC) No 1272/2008.