Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.18 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1
Modified dose descriptor starting point:
NOAEC
Value:
16.18 mg/m³
Explanation for the modification of the dose descriptor starting point:

Inhalative toxicity studies with zinc dipropionate are not available. For the assessment of toxicological effects of zinc dipropionate and the respective DNEL derivation, read-across of existing toxicity data on its two individual moieties zinc and propionate is applied. The hazard assessment is based on the most toxic moiety, i.e. the zinc cation, and the respective DNEL respectively starting point is recalculated for zinc dipropionate based on a maximum zinc content of 30.9 %. Please refer to the section for the respective assessment entity.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 343 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
1
Modified dose descriptor starting point:
NOAEL
Value:
1 343 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal toxicity studies with zinc dipropionate are not available. For the assessment of toxicological effects of zinc dipropionate and the respective DNEL derivation, read-across of existing toxicity data on its two individual moieties zinc and propionate is applied. The hazard assessment is based on the most toxic moiety, i.e. the zinc cation, and the respective DNEL respectively starting point is recalculated for zinc dipropionate based on a maximum zinc content of 30.9 %. Please refer to the section for the respective assessment entity.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

In order to evaluate toxicological properties of the substance zinc dipropionate, information on the assessment entities zinc cation and propionate anion were considered. For a documentation and justification of that approach, please refer to the separate document attached to section 13, namely "Read-across concept Category approach for Zinc dipropionate".

In brief: Zinc dipropionate is a metal carboxylate. Metal carboxylates are salts consisting of metal cations and carboxylic acid anions.

EFSA in its Scientific Opinion on the re-evaluation of propionic acid (E 280), sodium propionate (E 281), calcium propionate (E 282) and potassium propionate (E 283) as food additives (2014) noted that in the gastrointestinal tract, sodium propionate, calcium propionate and potassium propionate will be dissociated into sodium ion, potassium ion or calcium ion and propionate ion. Comparable behaviour can also be expected for zinc dipropionate. The dissociation is not limitet to the gastrointestinal tract, but can also be expected to occur in other physiological (and environmental) liquids. Thus, zinc diporopionate liberates its moieties zinc and propionate under physiological relevant conditions.

Since zinc ions and propionate ions behave differently in respect of their toxicity, a separate assessment of each assessment entity is performed. Please refer to the data as submitted for each individual assessment entity. In order to evaluate toxicological properties of the substance zinc dipropionate, except of local irritation which is addressed with data on the substance itself, information on the assessment entities zinc cation and propionate anion were considered.

The zinc cation is selected as most toxic moiety, as in studies in which humans were supplemented with zinc (as zinc gluconate), at a LOAEL of 2.5 mg Zn/kg bw/day (150mg/day) decreased ESOD activity and effects are seen as a result of copper imbalance. The NOAEL= 0.83 mg/kg bw/day (50mg/day). Whereas the effects of propionic acid in repeated dose toxicity studies are limited to local site-of-contact effects triggered by the caustic properties of the acid. Systemic effects of propionic acid are lacking although doses far exceeding the limit dose of of the relevant guidelines were administered. The local site-of-contact effects of propionic acid are considered not relevant for zinc dipropionate: (1) Because the irritant activity of this salt is much less pronounced than the irritant activity of the acid. Propionic acid is classified in skin corrosion category 1B, which indicates that already a single exposure time of less than 1 h  may produces destruction of (skin) tissue. Whereas zinc dipropionate is not classified for skin irritating / skin corrosive activity as in an in vivo study according to OECD guideline 404 it induced neither edema nor oedema. However zinc dipropionate is classified for eye effects category 1 based on an in vitro test result. (2) If the dose descriptor for repeated dose effects of the acid (733 mg/kg bw/d) is read across to zinc propionate, the recalculated value for zinc dipropionate would exceed the guidelines limit dose. And also for this, it can be concluded that zinc dipropionate does not pose a repeated dose toxicity hazard and thus, in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment Part D: Framework for exposure assessment Version 2.0 August 2016, D.2.2, p 19, the determination of the concentration of zinc dipropionate below which adverse toxic effects of concern are not expected to occur (derivation of a DNEL) based on the propionate moiety dose descriptor is irrelevant.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1
Modified dose descriptor starting point:
NOAEC
Value:
8.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

Inhalative toxicity studies with zinc dipropionate are not available. For the assessment of toxicological effects of zinc dipropionate and the respective DNEL derivation, read-across of existing toxicity data on its two individual moieties zinc and propionate is applied. The hazard assessment is based on the most toxic moiety, i.e. the zinc cation, and the respective DNEL respectively starting point is recalculated for zinc dipropionate based on a maximum zinc content of 30.9 %. Please refer to the section for the respective assessment entity.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 343 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
1
Modified dose descriptor starting point:
NOAEL
Value:
1 343 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal toxicity studies with zinc dipropionate are not available. For the assessment of toxicological effects of zinc dipropionate and the respective DNEL derivation, read-across of existing toxicity data on its two individual moieties zinc and propionate is applied. The hazard assessment is based on the most toxic moiety, i.e. the zinc cation, and the respective DNEL respectively starting point is recalculated for zinc dipropionate based on a maximum zinc content of 30.9 %. Please refer to the section for the respective assessment entity.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.69 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1
Modified dose descriptor starting point:
NOAEL
Value:
2.69 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Oral toxicity studies with zinc dipropionate are not available. For the assessment of toxicological effects of zinc dipropionate and the respective DNEL derivation, read-across of existing toxicity data on its two individual moieties zinc and propionate is applied. The hazard assessment is based on the most toxic moiety, i.e. the zinc cation, and the respective DNEL respectively starting point is recalculated for zinc dipropionate based on a maximum zinc content of 30.9 %. Please refer to the section for the respective assessment entity.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

In order to evaluate toxicological properties of the substance zinc dipropionate, information on the assessment entities zinc cation and propionate anion were considered. For a documentation and justification of that approach, please refer to the separate document attached to section 13, namely "Read-across concept Category approach for Zinc dipropionate".

In brief: Zinc dipropionate is a metal carboxylate. Metal carboxylates are salts consisting of metal cations and carboxylic acid anions.

EFSA in its Scientific Opinion on the re-evaluation of propionic acid (E 280), sodium propionate (E 281), calcium propionate (E 282) and potassium propionate (E 283) as food additives (2014) noted that in the gastrointestinal tract, sodium propionate, calcium propionate and potassium propionate will be dissociated into sodium ion, potassium ion or calcium ion and propionate ion. Comparable behaviour can also be expected for zinc dipropionate. The dissociation is not limitet to the gastrointestinal tract, but can also be expected to occur in other physiological (and environmental) liquids. Thus, zinc diporopionate liberates its moieties zinc and propionate under physiological relevant conditions.

Since zinc ions and propionate ions behave differently in respect of their toxicity, a separate assessment of each assessment entity is performed. Please refer to the data as submitted for each individual assessment entity. In order to evaluate toxicological properties of the substance zinc dipropionate, except of local irritation which is addressed with data on the substance itself, information on the assessment entities zinc cation and propionate anion were considered.

The zinc cation is selected as most toxic moiety, as in studies in which humans were supplemented with zinc (as zinc gluconate), at a LOAEL of 2.5 mg Zn/kg bw/day (150mg/day) decreased ESOD activity and effects are seen as a result of copper imbalance. The NOAEL= 0.83 mg/kg bw/day (50mg/day). Whereas the effects of propionic acid in repeated dose toxicity studies are limited to local site-of-contact effects triggered by the caustic properties of the acid. Systemic effects of propionic acid are lacking although doses far exceeding the limit dose of of the relevant guidelines were administered. The local site-of-contact effects of propionic acid are considered not relevant for zinc dipropionate: (1) Because the irritant activity of this salt is much less pronounced than the irritant activity of the acid. Propionic acid is classified in skin corrosion category 1B, which indicates that already a single exposure time of less than 1 h  may produces destruction of (skin) tissue. Whereas zinc dipropionate is not classified for skin irritating / skin corrosive activity as in an in vivo study according to OECD guideline 404 it induced neither edema nor oedema. However zinc dipropionate is classified for eye effects category 1 based on an in vitro test result. (2) If the dose descriptor for repeated dose effects of the acid (733 mg/kg bw/d) is read across to zinc propionate, the recalculated value for zinc dipropionate would exceed the guidelines limit dose. And also for this, it can be concluded that zinc dipropionate does not pose a repeated dose toxicity hazard and thus, in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment Part D: Framework for exposure assessment Version 2.0 August 2016, D.2.2, p 19, the determination of the concentration of zinc dipropionate below which adverse toxic effects of concern are not expected to occur (derivation of a DNEL) based on the propionate moiety dose descriptor is irrelevant.