Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

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

Local effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
5.2 µg/m³
Most sensitive endpoint:
carcinogenicity
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
41.6 µg/m³
Most sensitive endpoint:
carcinogenicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

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

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
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

The substance NCA is a homogenous fine black powder that can be described as mixed oxide. NCA (purity 99.1% (w/w)) contains cobalt and nickel as major compounds (>10% (w/w)). In accordance to the analytical report NCA contains 48.0% (w/w) nickel,9.6% (w/w) cobalt, 7.2% (w/w) lithium and 1.4% (w/w) aluminium.

The major toxophores of NCA are cobalt and nickel ions that could potentially be deliberated from the oxide after uptake. The inhalation route is most critical in this regard. The NCA reference value for the inhalative route is derived by using established reference values for nickel and cobalt compounds. As plausibility approach also established DNELs for lithium and aluminium compounds have been taken into account.

Nickel and cobalt ions are carcinogenic, therefore no safe reference value for the alveolar dust fractions were derived. Instead in accordance to the German Exposure-Risk-Relationship (ERB) concept for carcinogenic substances, an acceptance concentration linked to an additional carcinogenic risk of 1:10,000, and a tolerable concentration, linked to a carcinogenic risk of 1:1,000, have been derived and are used for risk management under German legislation for hazardous substances (Technical Rules for Hazardous Substances TRGS 910 and TGRS 561). For nickel compounds furthermore an OEL for the inhalable fraction was derived. For lithium and aluminium the lowest DNELs taken from appropriate REACh registered substances were used (see Table 1).

Table 1: Inhalative reference values (worker, long-term) for metals in NCA

Substance

Reference value

Description

Reference

Li2CO3

0.74 mg Li/m3(alveolar dust fraction)

DNEL long-term worker

REACh dossier

Al2O3

3 mg Al/m3(alveolar dust fraction)

DNEL long-term worker

REACh dossier

Nickel and its inorganic compounds

30 µg Ni/m3(inhalable dust fraction)

OEL (Germany)

TRGS 900

6 µg Ni/m3(alveolar dust fraction)

Acceptance and tolerance conc.

TRGS 910 / 561

Cobalt and its inorganic compounds

0.5 µg Co/m3(alveolar dust fraction)

Acceptance concentration

TRGS 910 / 561

5 µg Co/m3(alveolar dust fraction)

Tolerance concentration

 

As nickel and cobalt are the predominant toxophores and comprise the major metal compounds in NCA, the long-term inhalation threshold was derived using the formula:

DNELNCA,inhalation,worker,long-term= reference valueTable 1÷ concentrationCo or Ni in NCA

=>Using cobalt acceptance concentration: DNEL = 0.5 µg Co/m3÷ 0.096 = 5.21 µg NCA/m3

The same calculation was performed for the above-mentioned metal components and respective derived inhalative reference values for NCA were summarized in Table 2.

Table 2: Derivation of NCA-specific inhalative reference values (worker, long-term)

Basis for NCA reference value

NCA inhalative reference concentration

Lithium content vs. DNEL of Li2O3

10.3 µg NCA/m3(alveolar fraction)

Aluminium content vs. DNEL for Al2O3

214.3 µg NCA/m3(alveolar fraction)

Nickel content vs. OEL for inhalable nickel

62.5 µg NCA/m3(inhalable fraction)

Nickel content vs. acceptance concentration for nickel

12.5 µg NCA/m3(alveolar fraction)

Cobalt in NCA vs. acceptance concentration for cobalt

5.2 µg NCA/m3(alveolar fraction)

 

NCA reference value for long-term exposure (8h): The lowest NCA-specific reference value for the inhalative route was derived using the cobalt acceptance concentration for alveolar dust. Here, an additional carcinogenic risk of 1:10,000 would be linked to the inhalative reference value for NCA. Therefore, the workplace exposure should be below 5.2 µg NCA (A-fraction)/m3 as time-weighted average (TWA; 8h shift). This reference value covers also the other derived metal-specific (lithium, aluminium, nickel) reference values.

As the ratio of nickel and cobalt in NCA is Co : Ni = 1 : 5 it is not possible to derive an acceptable reference value for the inhalable fraction of NCA. Therefore it is recommended to perform workplace measurements for the A-dust fraction and to keep the A-fraction below 5.2 µg NCA (A-fraction)/m3.

NCA reference value for short-term exposure (15 min): As an exceedance factor of 8 is included in the scientific justification for the acceptance concentrations for nickel and cobalt compounds (e.g. TRGS 910 or 561), exposure to NCA in short-term applications could be 8 x 5.2 µg NCA (A-fraction)/m3= 41.6 µg NCA (A-fraction)/m3 four times for 15 min each within one shift.

Nickel and nickel releasing compounds are known dermal skin sensitizers. Data from NiO are taken into account to derive the long-term local dermal DNEL for NCA. According to the REACH dossier the long-term local DNEL for skin sensizisation of NiO is summerized in Table 3 .

Table 3: Nickel Oxide CSR Table for Workers

Exposure pattern

Route

Descriptor

DNEL / DMEL(a)

AF

Corrected Dose descriptor

Most sensitive endpoint

Justification

Long-term - local effects

Dermal

DNEL (Derived No Effect Level)

0.012 mg Ni/cm²

2(g)

NOAEL corrected(h): 0.024 mg Ni/cm² from0.00044 mg Ni/cm² (sulphate)

sensitisation (skin)

 See footnotes

 

g.       AF =2. For the water insoluble compounds like Ni oxide, the uncertainty in the relative bioelution data compared to Ni sulphate relates to the repeatability (within labs) and reproducibility (between labs) of bioelution results and the relevance of the test conditions to the human exposure in the patch test and in the workplace. Based on good repeatability and reproducibility of bioelution data and relevancy of testing conditions to in vivo situation an assessment factor no greater than 2 is justified. The derivation of a DNEL for dermal sensitization by nickel oxide is a conservative approach since no classification appears to be warranted for this endpoint based on Ni release in sweat. The derived DNEL is protective of both acute and long-term local dermal effects.The derived DNEL is likely to overestimate risk compared to workplace 8 h exposure without occlusion.

 

h.       Corrected dose descriptor = 0.024 mg Ni/cm2 [0.44 µg Ni/cm2 x 54 = 0.024 mg Ni/cm2); where 0.44 µg Ni/cm2 is the DNEL for nickel sulphate based on the Fischeret al.(2005) study and 54 is the fold less release of Ni as percent of Ni content from nickel oxide-black than from Ni sulphate after 24 hours, 37C in sweat, KMHC, 2010. This correction was applied because the amount of Ni (II) ions released from one gram of Ni on the skin will be much lower than if the dust is made of nickel oxide than it would be if the dust is made of nickel sulphate (100% dissolved). For nickel oxide, 0.0016 (green) or 0.0184 (black) g of Ni (II) ion/g Ni dust (100% Ni oxide) were released in sweat while 1 g of Ni (II) ion was available per g of Ni applied in the patch test (100% Ni sulphate). The ratios are 1/0.0184 = 54 and 1/0.0016 = 625. The most conservative value of 54 observed for NiO-black was applied to both forms of NiO. This DNEL is protective of both acute and long-term local dermal effects.


The long-term dermal threshold was derived using the formula:

DNELNCA,dermal,worker,long-term= reference value ÷ concentrationNi in NCA

=> DNEL = 12 µg Ni/cm2÷ 0.48 = 25 µg NCA/cm2

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

No DN(M)EL values were derived for the general population as the neat substance will only be used by industry workers and no consumer exposure/indirect human exposure via the environment is anticipated.