Zinc bis(benzenesulphinate)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

274 µg/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):

225

Dose descriptor starting point:

LOAEL

Value:

50 mg/kg bw/day

Modified dose descriptor starting point:

LOAEC

Value:

61.7 mg/m³

Explanation for the modification of the dose descriptor starting point:

LOAEL obtained in a combined repeated dose / reproductive toxicity study in rats was selected as the most representative starting dose based on: study duration; presence of adverse effects; type of observations and parameters taken into account to identify effect levels.

 

Starting from an oral dose of 50 mg/kg (LOAEL), a corrected value is obtained, based on: 8-h breathing volume of rat (0.38 m³/kg) and 8-h breathing volume of human (6.7 m³/kg in general population and 10 m³/kg in worker); days per week of exposure in experimental animals (7 d/w) and in humans (5 d/w in workers).

No experimental data on absorption via oral and inhalation route was available. Worst case assumption for absorption was: 50 % orally and 100 % by inhalation.

 

LOAEC = ((50 mg/kg : 0.38 m³/kg) × (6.7 m³: 10 m³)) × (7 d/w : 5 d/w) × 0.5 = 61.7 mg/m³

AF for dose response relationship:

3

Justification:

no NOAEL was identified.

AF for differences in duration of exposure:

6

Justification:

extrapolation from a duration comparable to subacute to chronic.

AF for interspecies differences (allometric scaling):

1

Justification:

implicitly included in the corrected starting point.

AF for other interspecies differences:

2.5

Justification:

toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part).

AF for intraspecies differences:

5

Justification:

workers

AF for the quality of the whole database:

1

Justification:

good quality and reliability.

AF for remaining uncertainties:

1

Justification:

no significative remaining uncertainties.

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:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

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:

no hazard identified

Additional information - workers

In general, the calculation of a DNEL is based on the observed effect level and has to be corrected for the differences between effect assessment data and the real human exposure situation, taking into account variability and uncertainty within and between species. If there is no basis for setting a DNEL or DMEL for a given human health endpoint, i.e. due to the lack of quantitative dose-response information, but there exists toxicity data of a qualitative nature, a qualitative risk assessement is performed. This kind of situation typically occurs with data on irritation/corrosion, sensitisation, acute toxicity, mutagenicity, and carcinogenicity.

INHALATION ROUTE

Systemic effects after long term exposure

The substance is a powder and particle size is between 2 and 23 µm. Considering particle size as well as water solubility and partition coefficient, absorption may not be excluded and a DNEL is derived.

The starting point to derive a long term DNEL for inhalation route was a LOAEC of 61.7 mg/m³ derived from a LOAEL of 50 mg/kg (lowest tested dose in a combined repeated dose / reproductive toxicity study in rats by oral route) properly corrected for route-to-route extrapolation, namely accounting for rat breathing volume and human (worker) breathing volume. Worst case for absorption rate was assumed, namely 50 % by oral route and 100 % by inhalation. Assessment factors were used to derive the DNEL:

- dose response 3, because corrected starting point is derived from a LOAEL

- remaining interspecies differences 2.5

- intraspecies differences 5, for workers

- differences in duration of exposure 6, because the starting value resulted from a subacute study.

Systemic effects after acute exposure

The substance is not classified for acute toxicity according to the CLP Regulation (EC 1272/2008). Therefore, based on ECHA Guidance Chapter R.8, no DNEL for acute toxicity should be derived.

Local effects after acute and long term exposure

The substance is a powder and all particles are inhalable, i.e. particles are below 100 µm size. Mucous lining the respiratory tract may be exposed to the substance. No test on local effects is available, however no irritating effect on mucous is expected since the substance resulted as not irritant to eyes in an in vitro study.

DERMAL ROUTE

Systemic effects after acute and long term exposure

Systemic effects upon dermal exposure were assessed in a skin sensitisation study. The substance gave a positive response in an in vitro skin sensitisation test. As no potency categorisation was possible, a high hazard was associated to the substance.

Local effects after long term and acute exposure

No long term studies upon dermal exposure were available. However, no local effects were noted in a skin irritation study in vitro, thus no local hazard is expected.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

48.3 µg/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):

450

Dose descriptor starting point:

LOAEL

Value:

50 mg/kg bw/day

Modified dose descriptor starting point:

LOAEC

Value:

21.74 mg/m³

Explanation for the modification of the dose descriptor starting point:

LOAEL obtained in a combined repeated dose / reproductive toxicity study in rats was selected as the most representative starting dose based on: study duration; presence of adverse effects; type of observations and parameters taken into account to identify effect levels.

Starting from an oral dose of 50 mg/kg (LOAEL), a corrected value is obtained, based on: 24-h breathing volume of rat (1.15 m³/kg). Exposure conditions of experimental animals and humans (general population) are the same, i.e. 7 days per week. No experimental data on absorption via oral and inhalation route was available. Worst case assumption for absorption was: 50 % orally and 100 % by inhalation.

 

LOAEC = ((50 mg/kg : 1.15 m³/kg) × 0.5 = 21.74 mg/m³

AF for dose response relationship:

3

Justification:

no NOAEL was identified.

AF for differences in duration of exposure:

6

Justification:

extrapolation from subacute to chronic.

AF for interspecies differences (allometric scaling):

1

Justification:

implicitly included in the corrected starting point.

AF for other interspecies differences:

2.5

Justification:

toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part).

AF for intraspecies differences:

10

Justification:

general population.

AF for the quality of the whole database:

1

Justification:

good quality and reliability.

AF for remaining uncertainties:

1

Justification:

no significative remaining uncertainties.

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:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

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:

27.8 µg/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):

1 800

Dose descriptor starting point:

LOAEL

Value:

50 mg/kg bw/day

Modified dose descriptor starting point:

LOAEL

Value:

50 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No extrapolation.

AF for dose response relationship:

3

Justification:

no NOAEL identified; DNEL derived from a LOAEL.

AF for differences in duration of exposure:

6

Justification:

extrapolation from subacute to chronic.

AF for interspecies differences (allometric scaling):

4

Justification:

default value.

AF for other interspecies differences:

2.5

Justification:

toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part).

AF for intraspecies differences:

10

Justification:

general population.

AF for the quality of the whole database:

1

Justification:

good quality and reliability.

AF for remaining uncertainties:

1

Justification:

no significative remaining uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

In general, the calculation of a DNEL is based on the observed effect level and has to be corrected for the differences between effect assessment data and real human exposure situation, taking into account variability and uncertainty within and between species. If there is no basis for setting a DNEL or DMEL for a given human health endpoint, i.e. due to the lack of quantitative dose-response information, but there exists toxicity data of a qualitative nature, a qualitative risk assessment is performed. This kind of situation typically occurs with data on irritation/corrosion, sensitisation, acute toxicity, mutagenicity, and carcinogenicity.

INHALATION ROUTE

Systemic effects after long term exposure

The substance is a powder and particle size is between 2 and 23 µm. Considering particle size as well as water solubility and partition coefficient, absorption may not be excluded and a DNEL is derived.

The starting point to derive a long term DNEL for inhalation route was a LOAEC of 21.74 mg/m³ derived from a LOAEL of 50 mg/kg (lowest tested dose in a combined repeated dose / reproductive toxicity study in rats by oral route) properly corrected for route-to-route extrapolation, namely accounting for rat breathing volume and human (general population) breathing volume. Worst case for absorption rate was assumed, namely 50 % by oral route and 100 % by inhalation. Assessment factors were used to derive the DNEL:

- dose response 3, because corrected starting point is derived from a LOAEL

- remaining interspecies differences 2.5

- intraspecies differences 10, for general population

- differences in duration of exposure 6, because the starting value resulted from a subacute study.

Systemic effects after acute exposure

The substance is not classified for acute toxicity according to the CLP Regulation (EC 1272/2008). Therefore, based on ECHA Guidance Chapter R.8, no DNEL for acute toxicity should be derived.

Local effects after acute and long term exposure

The substance is a powder and, based on the particle size distribution, all particles have diameter below 100 µm.

Mucous lining the respiratory tract may be exposed to the substance. No test on local effects is available, however no irritating effect on mucous is expected since the substance resulted as not irritant to eyes in an in vitro study.

DERMAL ROUTE

Systemic effects after acute and long term exposure

Systemic effects upon dermal exposure were assessed in a skin sensitisation study. The substance gave a positive response in an in vitro skin sensitisation test. As no potency categorisation was possible, a high hazard was associated to the substance.

Local effects after long term and acute exposure

No long term studies upon dermal exposure were available. As no local effects were noted in a skin irritation study in vitro, the substance resulted as non irritant and no local hazard is expected.

ORAL ROUTE

Systemic effects after long term exposure

The starting point to derive a DNEL for oral long-term exposure was a LOAEL of 50 mg/kg obtained in a combined repeated dose / reproductive toxicity study. This was the lowest tested dose.

Assessment factors were used to derive the DNEL:

- dose response 3, because corrected starting point is derived from a LOAEL

- interspecies differences 4, from rat to human

- remaining interspecies differences 2.5

- intraspecies differences 10, for general population

- differences in duration of exposure 6, because the starting value resulted from a subacute study.

Systemic effects after acute exposure

The substance is not classified for acute toxicity according to the CLP Regulation (EC 1272/2008). Therefore, based on ECHA Guidance Chapter R.8, no DNEL for acute toxicity should be derived.