Potassium dicyanoargentate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.078 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):

225

Dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

17.6 mg/m³

Explanation for the modification of the dose descriptor starting point:

Corrected inhalatory NOAEC:
oral NOAEL*1/sRVrat*ABSoral-rat/ABSinh-human*sRVhuman/wRV

ABS: Absorption; sRV: standard Respiratory Volume; wRV: worker Respiratory Volume

OR:

10 mg/kg/day divided by (0.38 m³.kg^-1x 6.7 m³/10 m³) = 17.6 mg/m³

AF for dose response relationship:

1

Justification:

As the starting point for the DNEL is a NOAEL this default factor is applied

AF for differences in duration of exposure:

6

Justification:

Assumes long-term worker handling is to be expected, but in any case, short-term human exposure is normally assessed using long-term DNELs. In this case the extrapolation is from a subacute animal study to chronic human exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

Appropriate dose descriptor modification has been undertaken

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific toxicodynamic data to demonstrate interspecies differences this default factor is applied

AF for intraspecies differences:

5

Justification:

As a standard procedure for threshold effects this default factor is applied for Worker populations based on the fact that this sub population does not cover the very young, the very old and the very ill.

AF for the quality of the whole database:

3

Justification:

A complete data set in accordance with REACH regulations is not available since some of the study endpoints were waived on the basis of positive results in skin and eye damage tests.

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.011 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):

900

Dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The oral to dermal extrapolation has a default Assessment Factor of 1 in the absence of any specific information on absorption by different routes, and is considered to be a systemic DNEL (the ‘internal dose’ that is expected to be non-hazardous).The relationship between the ‘external’ dose to the skin and the internal systemic dose is dependent on factors such as dermal absorption potential. The REACH guidance for dermal absorption has default values that can be used, or if specific information is available, then modified results are appropriate. The REACH default values are 10% or 100% (which are considered by HERAG not to be relevant for metals). Potassium dicyanoargentate was not subjected to bio-elution studies in dermal fluids, consequently there are no specific details on dermal absorption available. Also, no dermal data is available since the acute study was waived on the basis of the corrosivity displayed in the in vitro skin assay. Therefore, since the substance is also soluble in aqueous media, it is difficult to predict transdermal bioavailability. Pragmatically, therefore, it is considered reasonable to conduct the dermal risk assessment at the arbitrary absorption rate of 100% and no modification of the dose descriptor starting point is necessary in this regard.

AF for dose response relationship:

1

Justification:

As the starting point for the DNEL is a NOAEL this default factor is applied.

AF for differences in duration of exposure:

6

Justification:

Assumes long-term worker handling is to be expected, but in any case, short-term human exposure is normally assessed using long-term DNELs. In this case the extrapolation is from a subacute animal study to chronic human exposure.

AF for interspecies differences (allometric scaling):

4

Justification:

Default value for scaling from oral/dermal. Extrapolates doses according to an assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power 0.75.

AF for other interspecies differences:

2.5

Justification:

In the absence of substance-specific toxicodynamic data to demonstrate interspecies differences this default factor is applied.

AF for intraspecies differences:

5

Justification:

As a standard procedure for threshold effects this default factor is applied for worker populations based on the fact that this sub population does not cover the very young, the very old and the very ill.

AF for the quality of the whole database:

3

Justification:

A complete data set in accordance with REACH regulations is not available since some of the study endpoints were waived on the basis of positive results in skin and eye damage tests.

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

The DNEL calculations were prepared following the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose (concentration)-response for human health. No correction was made for silver content in the test substance.

The DNEL calculations have been conducted only for worker exposure (not consumer). Whilst consumers would be exposed to articles plated with silver as a consequence of using potassium dicyanoargentate during the plating process, the consumer would not actually be exposed to the test substance itself. Also as oral intake is not considered relevant for workers, only the values for dermal and inhalation have been presented using route to route extrapolation.

The DNELs have been derived for a threshold endpoint since the OECD TG422 study has provided some confirmation of this, albeit not to a particularly significant extent.

In the main, default assessment factors have been used to derive the DNELs. Under certain circumstances it may be possible to modify these based on knowledge of exposure conditions, human versus animal sensitivity, etc. and this was exercised in the quality of the database assessment. Many of the studies in the Annex VII and VIII assessment program were waived on the basis of positive results for corrosive potential in the in vitro skin and eye studies. Consequently, the toxicological data is derived from a curtailed data set.

In the in vitro studies potassium dicyanoargentate was found to be significantly corrosive to the skin (OECD431), category 1a, and also significantly damaging to the eye (OECD437), category 1. Consequently, a number of Annex VII and VIII studies were waived as being scientifically unjustifiable:

a)   Acute studies by oral, dermal or inhalation routes of administration;

b)   In vivo skin and eye irritation studies, and

c)   The LLNA skin sensitisation assay.

Dermal DNELs were derived by route to route extrapolation from oral exposure. Generally speaking, a long-term DNEL is protective of acute exposure unless there are peak exposures significantly above the average daily exposure (determined from worker exposure studies), so acute DNELs for workers will not be required. The determination of the inhalation DNEL has been reassessed to take into consideration the Dustiness data for each of the two substances. These data indicated that the particle size and dosimetry would suggest only extremely marginal exposure to the respiratory airways. Consequently, it is considered that the corrected inhalatory NOAEC should remain unaltered.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

The DNEL calculations have been conducted only for worker exposure (not consumer). Whilst consumers would be exposed to articles plated with silver as a consequence of using potassium dicyanoargentate during the plating process, the consumer would not actually be exposed to the test substance.