Manganese dioxide

Endpoint summary

Description of key information

Regarding repeated dose toxicity adverse effects were observed for oral exposure (LOAEL mouse= 275 mg/kg/bw) and for inhalator exposure (LOAE = 0.7 mg/m^3). No data of repeated dose dermal toxicity are available. 
However, according to CLP Regulation (EC n.1272/2008) manganese dioxide is not classified for repeated dose toxicity.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

275 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Quality of whole database:

SIDS Dossier of MnO2 approved at SIAM 25 (17 -18 October 2007)

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEC

0.7 mg/m³

Study duration:

subchronic

Species:

monkey

Quality of whole database:

SIDS Dossier of MnO2 approved at SIAM 25 (17 -18 October 2007)

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral exposure

As reported in SIDS Dossier of MnO2 approved at SIAM 25 (17 -18 October 2007) with reference to Komura J and Sakamoto M, Short-term oral administration of several manganese compounds in mice: physiological and behavioral alterations caused by different forms of manganese.Bulletin of environmental contamination and toxicology, 46(6): 921-928, 1991, the oral LOAEL on male mice was 276 mg/kg/day based on hematological effect. The ddy mice were exposed either to a control diet containing 130 mg Mn/kg, or a diet supplemented with an additional 2000 mg Mn/kg as MnO2. The duration of treatment was 100 days. This value was confirmed by another study of chronical dietary toxicity of 1992-see Komura J and Sakamoto M, Effects of manganese forms on biogenic amines in the brain and behavioral alterations in the mouse: long-term oral administration of several manganese compounds.Environmental Research,57: 34-44,1992 reported in SIDS Dossier of MnO2 approved at SIAM 25 (17 -18 October 2007). From this study the oral LOAEL on male mice was 275 mg/kg/day based body weight gain and locomotor activity. The study was conducted feeding control and test group with 130 and 2000 mg Mn/kg, respectively, for 12 months.

Inhalator exposure

As reported in SIDS Dossier of MnO2 approved at SIAM 25 (17 -18 October 2007) with reference to Suzuki, Effects of the inhalation of manganese dioxide dust on monkey lungs.Tokushima Journal of Experimental Medicine, 25:119-125, 1978, the inhalator LOAEL on Rhesus monkey is 0.7 mg/m^3 based on inflammation in the lung. Rhesus monkeys were exposed in a repeated inhalation toxicity study to manganese dioxide dust at the concentrations of 0.7 and 3 mg Mn/m^3 for 22 hours daily for a duration of 10 months. During histological examination damages in the lung were fund. Data of chronic toxicity of manganese dioxide after inhalator exposure are supported also by a human study (see section 7.10 IUCLID).

Dermal exposure

Data on dermal repeated dose toxicity are not available.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Study conducted according to internationally accepted testing guidelines.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Study conducted according to internationally accepted testing guidelines.

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: lung

Justification for classification or non-classification

According to CLP Regulation (EC n.1272/2008) manganese dioxide is not classified for repeated dose toxicity. According to the available data, there may be a concern deriving from inhalation exposure. However, the substance is used under strictly controlled conditions and there is no exposure to workers. Further details on guidance of safe use are reported in section 11 of IUCLID.