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Description of key information

Information on repeated dose toxicity of the sulfide part of the Reaction mass is based on inhalation studies with hydrogen sulfide (as justified elsewhere) and on some sup-porting data. No good quality studies focusing on other than local effects are available on repeated dose toxicity of sodium hydroxide or sodium carbonate. However, under normal handling and use conditions (at locally non-irritating concentrations due to alka-linity) the concentrations of sodium, hydroxide or carbonate ions are not likely to in-crease to levels causing toxicological concern. Also the contribution of sodium hydroxide and sodium carbonate to the toxic effects and the potency of the Reaction mass is negligible, and therefore additional testing of these constituents is not considered neces-sary. 90-day inhalation studies with hydrogen sulfide indicated that olfactory neuronal loss is the most sensitive local effect with NOAEC of 14 mg/m3. The systemic NOAEC was 112 mg/m3. These values will be used as the basis for DNEL derivation of the Reaction mass.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
112 mg/m³
Study duration:
subchronic
Species:
rat

Additional information

Information on repeated dose toxicity of the sulfide part of the Reaction mass is based on inhalation studies with hydrogen sulfide (as justified elsewhere) and on some supporting data. The pKa values for the first and second dissociation steps of H2S are 7.04 and 11.96, respectively. Therefore, at physiological pH values hydrogen sulfide in the non-dissociated form (H2S) and the hydrogen sulfide anion (HS-) are present in almost equimolar proportion, whereas only very small amounts of the sulfide anion (S2-) are present. Under physiological conditions inorganic sulfides, hydrogensulfides and H2S dissociate to the respective species relevant to the pH of the physiological medium, irrespective the nature of the sulfide. Therefore read-across between these substances and H2S is justified without any restrictions.

 No good quality studies focusing on other than local effects are available on repeated dose toxicity of sodium hydroxide or sodium carbonate. However, under normal handling and use conditions (at locally non-irritating concentrations due to alkalinity) the concentrations of sodium, hydroxide or carbonate ions are not likely to increase to levels causing toxicological concern as these ions are ions are normal constituents of the body and their concentrations are physiologically regulated. Therefore the contribution of sodium hydroxide and sodium carbonate to the toxic effects and the potency of the Reaction mixture is negligible, and additional testing of these constituents is notconsidered necessary.

The 90-day inhalation study with hydrogen sulfide did not result in toxicologically relevant alterations in haematology, clinical chemistry or gross pathology in two rat strains and one mouse strain. Therefore, the concentration of 112 mg/m3 H2S is the NOAEC for systemic effects and will be used for DNEL derivation of the Reaction mixture.

The main adverse effect of hydrogen sulfide was an exposure-related increased incidence of olfactory neuronal loss (ONL). The results showed that the rodent nose, and less so the lung, are highly sensitive to H2S-induced toxicity, with 14 mg/m3 H2S representing the NOAEC for local effects following subchronic inhalation exposure.

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

Justification for classification or non-classification

No classification is required under Directive 67/548/EEC or Regulation EC 1272/2008 for repeated dose toxicity.