Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
374 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Read-across concept for sulfites, hydrogensulfites, metabisulfites, dithionites and thiosulfates:

The basis for the read-across concept for this project is the equilibrium between sulfites, hydrogensulfites, and metabisulfites in aqueous solutions depending on pHvalue which is clearly described in published literature and summarised in the following equations:[1],[2]

           SO2+ H2O <->`H2SO3´         H2SO3<->H++ HSO3-<->2H++SO32-    2HSO3-<->H2O +S2O52-

As the nature of the cation should make no significant difference in this case concerning toxicity and solubility (all substances are very soluble in water), only the chemical and biological properties of the anion are considered relevant. Based on the described equilibrium correlations, we propose unrestricted read-across between the groups of sulfites, hydrogensulfites and metabisulfites.

Additionally, it is known that sodium dithionite disproportionates in water to form sodium hydrogen sulfite and sodium thiosulfate (equation II) so that this substance can also be added to the read-across concept.[2],[1]It is expected for this case that the substance is not stable enough under physiological conditions to fulfil the requirements of study guidelines and so the products of decomposition have to be considered.

       2 S2O42-+ H2O 2HSO3-+ S2O32-

 

Not completely included in this read-across concept is the substance class of thiosulfates. Although thiosulfates may also disproportionate in aqueous solution to form polythionic acids and SO2(HSO3-), the required conditions are somewhat different (more acidic) and are therefore not strictly comparable with physiological conditions, except for the case of oral application where read-across should be considered unrestricted due to the strongly acidic conditions in the stomach:

       HS2O3-+ H2S2O3 HS3O3- + SO2+ H2O

Nevertheless, read-across for all other routes (dermal, inhalation) should also be considered.

The proposed read-across concept only applies to toxicological and ecotoxicological/environmental fate endpoints.

[1]Hollemann Wiberg, Lehrbuch der Anorganischen Chemie, 101. Auflage

[2]Handbook of Chemistry and Physics, Ed. Lide, DR, 88thedition, CRC Press

Route-to-route extrapolation:

According to regulation (EC) 1907/2006 Annex XI (weight of evidence), testing for sub-chronic inhalation toxicity is not considered to be required. In accordance with ECHA guidance on information requirements and chemical safety assessment-chapter R.8: characterisation of dose [concentration]-response for human health, May 2008, a DNEL for systemic effects could be derived by route-to-route extrapolation from a 90-day oral toxicity study in rats with sodium metabisulfite.

For information on derivation of DNELs please refer to the CSR.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
110 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Read-across concept for sulfites, hydrogensulfites, metabisulfites, dithionites and thiosulfates:

The basis for the read-across concept for this project is the equilibrium between sulfites, hydrogensulfites, and metabisulfites in aqueous solutions depending on pHvalue which is clearly described in published literature and summarised in the following equations:[1],[2]

           SO2+ H2O <->`H2SO3´         H2SO3<->H++ HSO3-<->2H++SO32-    2HSO3-<->H2O +S2O52-

As the nature of the cation should make no significant difference in this case concerning toxicity and solubility (all substances are very soluble in water), only the chemical and biological properties of the anion are considered relevant. Based on the described equilibrium correlations, we propose unrestricted read-across between the groups of sulfites, hydrogensulfites and metabisulfites.

Additionally, it is known that sodium dithionite disproportionates in water to form sodium hydrogen sulfite and sodium thiosulfate (equation II) so that this substance can also be added to the read-across concept.[2],[1]It is expected for this case that the substance is not stable enough under physiological conditions to fulfil the requirements of study guidelines and so the products of decomposition have to be considered.

       2 S2O42-+ H2O 2HSO3-+ S2O32 -

 

Not completely included in this read-across concept is the substance class of thiosulfates. Although thiosulfates may also disproportionate in aqueous solution to form polythionic acids and SO2(HSO3-), the required conditions are somewhat different (more acidic) and are therefore not strictly comparable with physiological conditions, except for the case of oral application where read-across should be considered unrestricted due to the strongly acidic conditions in the stomach:

       HS2O3-+ H2S2O3 HS3O3- + SO2+ H2O

Nevertheless, read-across for all other routes (dermal, inhalation) should also be considered.

The proposed read-across concept only applies to toxicological and ecotoxicological/environmental fate endpoints.

[1]Hollemann Wiberg, Lehrbuch der Anorganischen Chemie, 101. Auflage

[2]Handbook of Chemistry and Physics, Ed. Lide, DR, 88thedition, CRC Press

Route-to-route extrapolation:

According to regulation (EC) 1907/2006 Annex XI (weight of evidence), testing for sub-chronic inhalation toxicity is not considered to be required. In accordance with ECHA guidance on information requirements and chemical safety assessment-chapter R.8: characterisation of dose [concentration]-response for human health, May 2008, a DNEL for systemic effects could be derived by route-to-route extrapolation from a 90-day oral toxicity study in rats with sodium metabisulfite.

For information on derivation of DNELs please refer to the CSR.