Dialuminium nickel tetraoxide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.05 mg/m³

Most sensitive endpoint:

developmental toxicity / teratogenicity

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

520 mg/m³

Most sensitive endpoint:

acute toxicity

DNEL related information

Overall assessment factor (AF):

7.5

Modified dose descriptor starting point:

NOAEC

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.05 mg/m³

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.9 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

1

Dose descriptor starting point:

NOAEC

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.024 mg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

Overall assessment factor (AF):

1

Dose descriptor:

other: NOAEL

Additional information - workers

Nickel aluminate CSR Table for Workers

Note 1. Exposures are always given in terms of mg nickel and NOT as mg substance.

Note 2. In cases where existing standards (OELs in case of workers, ambient air standards in case of general public) are used instead of DNEL/DMEL, the fields for Assessment factors and Dose descriptor were left blank. Further information on the air Standard derivation is contained in the documents referenced in the Table below.

Note 3. Acute systemic and local effects are relevant for short-term worker’s exposure (peak exposure of 15 minutes to a few hours). Long-term systemic and local effects are relevant to long-term worker’s exposure defined as 8 hours/day and 5 days per week for a working life.

Exposure pattern	Route	Descriptors [corrected]	DNEL/DMEL/not quantifiable	Most sensitive endpoint
Acute-systemic effects	Dermal (mg Ni/kg bw/day)	Not relevant (negligible absorption)
	Inhalation (mg Ni/m^3)	NOAEC=3900 (MMAD=2.8 µm)	520 (MMAD = 2.8 µm)	Acute Toxicity (Death)
Acute-local effects	Dermal (mg Ni/cm^2)	Not relevant
	Inhalation (mg Ni/m^3)	NOAEC= 3.9 (MMAD=2.9 µm)	3.9 (MMAD=2.9 µm)^a	Repeated Dose Toxicity (Lung inflammation)
Long term -systemic	Dermal (mg Ni/cm^2)	Not relevant (negligible absorption)
Long term -systemic	Inhalation (mg Ni/m^3)	SCOEL proposed nickel OEL = 0.01 “inhalable”	OEL = 0.05^b	Developmental toxicity
Long term - local effects	Dermal (mg Ni/cm^2)	NOAEL= 0.024	DNEL=0.024^c	Sensitization (skin)
Long term - local effects	Inhalation (mg Ni/m^3)	SCOEL proposed nickel OEL=0.01 “inhalable”	OEL = 0.05^b	Carcinogenicity and repeated toxicity (Respiratory tract-Inhalation)

a.   The DNEL for nickel aluminate based on acute toxicity-local effects (lung inflammation) corresponds to aerosols of MMAD = 2.9 µm. This value should be compared to workplace exposures comprised of particles of MMAD = 2.9 µm. The proper comparisons should take into account the equivalent deposited doses per unit surface area in the respiratory tract of rats exposed to experimental aerosols and of humans exposed to workplace aerosols. If this DNEL values are used in a direct comparison to workplace exposures with MMAD ≥ 30 µm, these values are likely to overestimate risk by ≥ 4-fold. For more details see Appendix in the CSR.

b.   The justification for the use of an inhalable OEL of 0.05 mg Ni/m³is provided in the Appendix of the CSR. This value is based on the SCOEL proposed OEL for nickel of 0.01 mg Ni/m³(March 2009) with further adjustments for differences in particle size distributions between animal experiments and workplace exposures and differences in sampling efficiency between 37-mmm and inhalable samplers. The SCOEL value and the IND-revised value are based on toxicity local effects observed on the lungs of rats after inhalation and carcinogenicity effects in the respiratory tract observed in human studies. Both values consider nickel compounds to be genotoxic carcinogens with a practical threshold. These values are also protective against possible reproductive effects. When exposure are solely to metallic and nickel oxide dusts, without exposure to any other forms of nickel, and the mean particle size of the aerosol is greater than 10 µm aerodynamic equivalent diameter (≤ 10% of aerosol mass in respirable fraction), inhalable exposure levels up to 0.2 mg Ni/m³could be reasonably assumed to be safe (see Appendix). When handling powders of particle equivalent aerodynamic diameter below 10 µm, exposures (8h TWA) to these powders should be kept under 0.01 mg Ni/m³.

c.   The DNEL for dermal sensitization/elicitation is based on a patch test study where exposure lasted for 48 hours under occlusion. Correction for differences in Ni release rates in sweat from nickel sulphate and oxide were applied.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20 ng/m³

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

312 mg/m³

Most sensitive endpoint:

acute toxicity

DNEL related information

Overall assessment factor (AF):

12.5

Modified dose descriptor starting point:

NOAEC

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20 ng/m³

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.9 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

1

Dose descriptor starting point:

NOAEC

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - General Population

Nickel Aluminate CSR Table for General Population

Note 1. Exposures are always given in terms of mg nickel and NOT as mg substance.

Note 2. In cases where existing standards (OELs in case of workers, ambient air standards in case of general public) are used instead of DNEL/DMEL, the fields for Assessment factors and Dose descriptor were left blank. Further information on the air Standard derivation is contained in the documents referenced in the Table below.

Note 3. Acute systemic and local effects are relevant for short-term exposure (peak exposure of 15 minutes to a few hours). Long-term systemic and local effects are relevant to long-term exposure defined as 24 hours/day and 7 days per week for a life-time.

Exposure pattern	Route	Descriptors [corrected]	DNEL/DMEL/not quantifiable^a	Most sensitive endpoint
Acute-systemic effects	Dermal (mg Ni/cm^2)	Not relevant (negligible exposure and absorption)
	Inhalation (mg Ni/m^3)	Not relevant – compliance with more conservative acute-local effects DNEL is also protective against acute systemic effects
	Oral (mg Ni/kg bw/day)	Not relevant (negligible exposure)
Acute-local effects	Dermal (mg Ni/cm^2)	Not relevant (negligible exposure and absorption)
	Inhalation (mg Ni/m^3)	NOAEC= 3.9	3.9		Repeated dose toxicity (lung inflammation)
Long term-systemic effects	Dermal (mg Ni/cm^2)	Not relevant (negligible absorption)
	Inhalation (mg Ni/m^3)	Other: CSTEE (ambient air guidelines for Ni) = 0.00002	DNEL = 0.00002^b	Exacerbation of existing dermatitis
	Oral (mg Ni/kg bw/day)	Not relevant (negligible exposure)
Long term-local effects	Dermal (mg Ni/cm^2)	Not relevant (negligible exposure and absorption)
	Inhalation (mg Ni/m^3)	Other: CSTEE (ambient air standard) = 0.00002	DNEL-DMEL = 0.00002^b	Repeated dose toxicity (lung inflammation) Carcinogenicity

a.      See Appendices of the CSR for more details on NOAEL identification and DNEL derivation.

b.      We used the CSTEE, EU Scientific Committee on Toxicity, Ecotoxicity and the Environment (2001) ambient air recommended nickel value of 20 ng/m³instead of a DNEL based on long term-local respiratory effects. This value is also protective from the most sensitive of systemic effects: exacerbation of existing dermatitis (see Appendix).

 

Sensitive subpopulations. Sensitive subpopulations are not separately addressed as the inhalation DNEL-DMEL value used corresponds to the ambient air guidance value derived by CSTEE for the EU general public.