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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.14 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:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
31.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

The substance, TCA, is to be registered in pure solid form, whereas the key study for PoD selection was conducted using the liquid form which constituted 41.5% Gold and 30.2% Chloride. Consequently, it is necessary to express the selected PoD dose levels in terms of pure TCA in order to calculate DNELs for the registered solid material.

Gold MW = 196.97

TCA MW = 339.79

Therefore, the fraction of Gold in TCA = 196.97 ÷ 339.79 = 0.579681568

The percentage Gold in a 1 mg/mL dosing solution in the OECD TG422 study is:
41.5% or 0.415 mg/mL

Expressed in terms of TCA = 0.415 ÷ 0.579681568 = 0.7159 mg/mL

Therefore, the PoD dose level of 50 mg/kg/day expressed as pure TCA = 35.8 mg/kg/day.

The corrected inhalatory NOAEC = oral NOAEL*(1/sRVrat 8hr)*(ABSoral/ABSinh)*(sRVhuman/wRV)

Where; ABS is Absorption; sRV is standard Respiratory Volume; wRV is worker Respiratory Volume

Therefore: NOAEC = (35.8 mg/kg/day)*(1/0.38 m3/kg)*(50/100)*(6.7m3/10m3) = 31.6 mg/m3

AF for dose response relationship:
1
Justification:
As the starting point for the DNEL is assumed to be 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:
Scaling taken into consideration in the dose modification to inhalation exposure
AF for other interspecies differences:
2.5
Justification:
In the absence of substance-specific toxicodynamic data to demonstrate interspecies differences the default factor of 2.5 is applied for systemic effects.
AF for intraspecies differences:
5
Justification:
As a standard procedure for threshold effects the default factor of 5 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:
Data from routes of exposure other than oral (e.g. dermal) are not available due to the corrosivity of the test material. For repeat-dose oral studies the formulation also required neutralisation of pH.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The conduct of an acute inhalation study was waived on the basis that TCA has been classified as skin corrosive (Category 1B). Since there is no established consensus methodology for the establishment of an acute toxicity DNEL and there are no specific data to demonstrate the potential for peak exposures via this route, the most sensitive systemic long-term DNEL together with the risk management measures associated with the CLP skin and eye classifications for these exposure conditions are considered protective of this systemic-acute/short-term exposure.

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.04 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:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
35.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance, TCA, is to be registered in pure solid form, whereas the key study for PoD selection was conducted using the liquid form which constituted 41.5% Gold and 30.2% Chloride. Consequently, it is necessary to express the selected PoD dose levels in terms of pure TCA in order to calculate DNELs for the registered solid material.

Gold MW = 196.97

TCA MW = 339.79

Therefore, the fraction of Gold in TCA = 196.97 ÷ 339.79 = 0.579681568

The percentage Gold in a 1 mg/mL dosing solution in the OECD TG422 study is:
41.5% or 0.415 mg/mL

Expressed in terms of TCA = 0.415 ÷ 0.579681568 = 0.7159 mg/mL

Therefore, the PoD dose level of 50 mg/kg/day expressed as pure TCA = 35.8 mg/kg/day.

DNEL = oral NOAEL(modified)*1/Total Adjustment Factor OR 35.8*1/900 = 0.04 mg/kg/day

AF for dose response relationship:
1
Justification:
As the starting point for the DNEL is assumed to be 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:
Required for scaling from oral administration. 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 the default factor of 2.5 is applied for systemic effects
AF for intraspecies differences:
5
Justification:
As a standard procedure for threshold effects the default factor of 5 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:
Data from routes of exposure other than oral (e.g. dermal) are not available due to the corrosivity of the test material. For repeat-dose oral studies the formulation also required neutralisation of pH.
AF for remaining uncertainties:
1
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:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

The DNELs have been derived for a threshold endpoint since it has been demonstrated in the key OECD TG422 study that data shows a dose-related effect with the neutralised liquid form of TCA.

Default assessment factors have been used to derive the DNELs. Under certain circumstances it is possible to modify these based on knowledge of exposure conditions, human vs animal sensitivity, etc.

The TCA solution is corrosive due to low pH, therefore, DNELs cannot be set for skin and eye irritancy endpoints from the data available. This is confirmed by the classification of skin corrosivity (Category 1B) and of eye damage (Category 1 based on a pH of 1 for the solution). In addition, oral acute toxicity testing of non-neutralised TCA indicates a classification of acute category 4 although this classification is significantly affected by the acidity of the solution which caused some severe clinical effects precluding an accurate assessment of the acute response.

Since the substance, TCA, is to be registered as a pure solid, an extrapolation of the DNELs calculated for the neutralised material to account for the difference in purity was considered appropriate. Therefore, the Worker inhalation and dermal DNELs have been calculated from the PoD from the key oral OECD TG422 study, adjusted to reflect the pure TCA content. Under the calculation criteria, it is considered that the systemic chronic DNEL can be protective of the acute exposure scenario for pure TCA and is relevant for the inhalation and dermal hazards beyond the initial corrosivity. The additional caveats relating to the pure solid form of TCA would be based on the physico-chemical aspects relating to bioavailability/absorption as well as, specifically for inhalation exposure, “dustiness” and “respiratory tract deposition modelling”. However, due to the hygroscopic nature of the solid form of TCA, it is unlikely that “Dustiness” or particle size dosimetry could be conducted.

The dermal exposure of workers to pure solid material will be covered by the application of adequate risk management measures because of the corrosivity properties determined for the liquid form.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.035 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):
600
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
15.66 mg/m³
Explanation for the modification of the dose descriptor starting point:

The substance, TCA, is to be registered in pure solid form, whereas the key study for PoD selection was conducted using the liquid form which constituted 41.5% Gold and 30.2% Chloride. Consequently, it is necessary to express the selected PoD dose levels in terms of pure TCA in order to calculate DNELs for the registered solid material.

Gold MW = 196.97

TCA MW = 339.79

Therefore, the fraction of Gold in TCA = 196.97 ÷ 339.79 = 0.579681568

The percentage Gold in a 1 mg/mL dosing solution in the OECD TG422 study is:
41.5% or 0.415 mg/mL

Expressed in terms of TCA = 0.415 ÷ 0.579681568 = 0.7159 mg/mL

Therefore, the PoD dose level of 50 mg/kg/day expressed as pure TCA = 35.8 mg/kg/day.

Scaling from rat to human and from oral to inhalation = 35.8 mg/kg/day*1/4 = 8.95 mg/kg/day NAEL human; 8.95*70 = 626.5 mg/person/day; 626.5*1/20m3per person = 31.325 mg/m3NAEC (24 h). As for Workers extrapolation was also applied from 50% bioavailability by the oral route to 100% bioavailability by the inhalation route, therefore, the adjusted NAEC human (24 h) is 31.325*50/100 = 15.66 mg/m3.

AF for dose response relationship:
1
Justification:
As the starting point for the DNEL is assumed to be 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:
Already taken into account for the dose modification
AF for other interspecies differences:
2.5
Justification:
In the absence of substance-specific toxicodynamic data to demonstrate interspecies differences the default factor of 2.5 is applied for systemic effects.
AF for intraspecies differences:
10
Justification:
As a standard procedure for threshold effects the default factor of 10 is applied for the general population.
AF for the quality of the whole database:
3
Justification:
Data from routes of exposure other than oral (e.g. dermal) are not available due to the corrosivity of the test material. For repeat-dose oral studies the formulation also required neutralisation of pH.
AF for remaining uncertainties:
1
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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
no hazard identified

Additional information - General Population

Since the test substance is to be registered as a pure solid, an extrapolation of the inhaltory DNEL calculated for the neutralised material to account for the difference in purity was considered appropriate. Therefore, the General population inhalation DNEL has been calculated from the PoD from the key oral OECD TG422 study, adjusted to reflect the pure test substance content. The additional caveats relating to the pure solid form of the test substance would be based on the physico-chemical aspects relating to bioavailability/absorption as well as, specifically for inhalation exposure, “dustiness” and “respiratory tract deposition modelling”. However, due to the hygroscopic nature of the solid form of the test substance, it is unlikely that “Dustiness” or particle size dosimetry could be conducted.

The oral route of exposure is not considered relevant for the general population. Also, for the general population, whilst dermal exposure to articles plated with gold as a consequence of using tetrachloroauric acid in the plating process, the consumer would not actually be exposed to the substance via this route. However, there was considered to be a requirement to assess potential exposure to the general public within a certain distance from stack emissions at manufacturing plants. Therefore, general population inhalation DNEL has been calculated.

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