Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.8 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
12
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.46 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
2
Dose descriptor starting point:
LOAEC

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:
0.001 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
Overall assessment factor (AF):
1
Dose descriptor:
other: NOAEL

Workers - Hazard for the eyes

Additional information - workers

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

Note 2. All the values (including the dermal one) are provided in the table below.

Note 3. 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 Starting Points were left blank. Further information on the Standard derivation is contained in the documents referenced in the Table below.

Nickel sulfate Table for Workers

Exposure pattern

Route

Descriptors [corrected]

DNEL/DMEL/not quantifiablea

Most sensitive endpoint

Acute-systemic effects

Dermal (mg Ni/kg bw/day)

Not relevant (negligible absorption)

Inhalation (mg Ni/m3)

NOAEC = 120

DNEL = 9.6 (MMAD =3 µm)

Acute Toxicity (Death)

Acute-local effects

Dermal (mg Ni/cm2)

Not irritant at concentration limit < 20%

Inhalation (mg Ni/m3)

LOAEC =0.7

(from 16 d study)

DNEL= 0.28

(MMAD <4 µm)b

Acute Toxicity (Lung inflammation)

Long term-systemic effects

Dermal (mg Ni/kg bw/day)

Not relevant (negligible absorption)

Inhalation (mg Ni/m3)

SCOEL proposed nickel OEL = 0.01

“inhalable”

OEL = 0.05c

Developmental toxicity

Long term -local effects

Dermal (mg Ni/cm2)

NOAEL= 0.00044

DNEL = 0.00044d

Sensitization (skin)

Inhalation (mg Ni/m3)

SCOEL proposed nickel OEL = 0.01

“inhalable”

OEL = 0.05c

Carcinogenicity and repeated toxicity (Respiratory tract-Inhalation)

a.        See Appendix C1-C2 (CSR for Nickel Sulphate) for more details on NOAEL identification and DNEL derivation.

b.        The DNEL based on acute toxicity-local effects (lung inflammation) corresponds to an aerosol of MMAD < 4 µm. This value is not directly comparable to workplace exposures comprised of particles of MMAD >> 4 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 value is used in a direct comparison to workplace exposures with MMAD ≥ 30 µm, this value is likely to overestimate risk by ≥ 4-fold. For more details see Appendix C3.

c. The justification for the use of an inhalable OEL of 0.05 mg Ni/m3is provided in Appendix C3 of CSR for Nickel Sulphate. 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-mm 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.

d. The DNEL for dermal sensitization/elicitation is based on a patch test study where exposure lasted for 48hs under occlusion. This value is likely to overestimate risk compared to workplace 8 h exposure without occlusion.

All data are converted into values suitable for Nickel fluoride by just correcting them with the different Molwculr weight. This approach is conservative as the effect is caused by Nickel and Nickel released by Nickel fluoride is lower ( see 7.1.1 NiF2 Kirby 2008 I and II)

Nickel fluorideTable for Workers

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/m3)

NOAEC = 198

DNEL = 15.8

(MMAD =3 µm)

Acute Toxicity (Death)

Acute-local effects

Dermal (mg Ni/cm2)

Not irritant at concentration limit < 20%

Inhalation (mg Ni/m3)

LOAEC =1.15

DNEL= 0.46

(MMAD <4 µm)

Acute Toxicity (Lung inflammation)

Long term-systemic effects

Dermal (mg Ni/kg bw/day)

Not relevant (negligible absorption)

Inhalation (mg Ni/m3)

SCOEL proposed nickel OEL = 0.01

“inhalable”

OEL = 0.08

Developmental toxicity

Long term -local effects

Dermal (mg Ni/cm2)

NOAEL= 0.00044

DNEL = 0.00072

Sensitization (skin)

Inhalation (mg Ni/m3)

SCOEL proposed nickel OEL = 0.01

“inhalable”

OEL = 0.08

Carcinogenicity and repeated toxicity (Respiratory tract-Inhalation)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 ng/m³
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 ng/m³
Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.011 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.019 mg/kg bw/day
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
Overall assessment factor (AF):
1
Modified dose descriptor starting point:
LOAEL

General Population - Hazard for the eyes

Additional information - General Population

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

Note 2. All the values (including the inhalation one) are provided in the table below:

Note 3. 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 Starting Points were left blank. Further information on the Standard derivation is contained in the documents referenced in the Table below.

Nickel Sulphate Hexahydrate CSR Table for General Population (MvE)

Exposure pattern

Route

Descriptors [corrected]

DNEL/DMEL/not quantifiablea

Most sensitive endpoint

Acute-systemic effects

Dermal (mg Ni/cm2)

Not relevant (negligible absorption)

Inhalation (mg Ni/m3)

Not relevant (negligible acute exposure)

Oral (mg Ni/kg bw/day)

LOAEL = 0.012

DNEL= 0.01b

Oral exacerbation of existing dermatitis

Acute-local effects

Dermal (mg Ni/cm2)

Not relevant (negligible acute exposure)

Inhalation (mg Ni/m3)

Not relevant (negligible acute exposure)

Long term-systemic effects

Dermal (mg Ni/cm2)

Not relevant (negligible absorption)

Inhalation (mg Ni/m3)

Other: CSTEE (ambient air guidelines for Ni) = 0.00002

DNEL = 0.00002c

Reproductive Developmental toxicity

Oral (mg Ni/kg bw/day)

NOAEL =1.1

DNEL = 0.01b

Reproductive Developmental toxicity

Long term-local effects

Dermal (mg Ni/cm2)

Not relevant (negligible exposure)

Inhalation (mg Ni/m3)

Other: CSTEE (ambient air standard) = 0.00002

DNEL-DMEL = 0.00002c

Repeated dose toxicity (lung inflammation)

Carcinogenicity

a.  See Appendix C1-C2 (CSR for Nickel Sulphate) for more details on NOAEL identification and DNEL derivation.

b.  This DNEL value was considered byWHO (World Health Organization, 2007. Background document for development of WHO Guidelines for Drinking-water Quality. © World Health Organization,)in the derivation of the Tolerable Daily Intake for nickel. This value was considered to be protective of sensitive subpopulations, including most nickel sensitive individuals, pregnant women and children.

c.  We used the CSTEE, EU Scientific Committee on Toxicity, Ecotoxicity and the Environment (2001) ambient air recommended nickel value of 20 ng Ni/m3instead of a DMEL based on carcinogenicity or a DNEL based on long term-local respiratory effects. The CSTEE value is based on considerations of both respiratory toxicity and carcinogenicity (see Appendix C1),

 

Sensitive subpopulations. Sensitive subpopulations are not separately addressed as the oral DNEL values used correspond to the TDI calculated by WHO for the general public and the inhalation DNEL-DMEL value used corresponds to the ambient air guidance value derived by CSTEE for the EU general public.

All data are converted into values suitable for Nickel fluoride by just correcting them with the different Molwculr weight. This approach is conservative as the effect is caused by Nickel and Nickel released by Nickel fluoride is lower ( see 7.1.1 NiF2 Kirby 2008 I and II)

Nickel fluorideTable for General Population

Exposure pattern

Route

Descriptors [corrected]

DNEL/DMEL/not quantifiable

Most sensitive endpoint

Acute-systemic effects

Dermal (mg Ni/cm2)

Not relevant (negligible absorption)

Inhalation (mg Ni/m3)

Not relevant (negligible acute exposure)

Oral (mg Ni/kg bw/day)

LOAEL = 0.019

DNEL= 0.016

Oral exacerbation of existing dermatitis

Acute-local effects

Dermal (mg Ni/cm2)

Not relevant (negligible acute exposure)

Inhalation (mg Ni/m3)

Not relevant (negligible acute exposure)

Long term-systemic effects

Dermal (mg Ni/cm2)

Not relevant (negligible absorption)

Inhalation (mg Ni/m3)

Other: CSTEE (ambient air guidelines for Ni) = 0.00003

DNEL = 0.00003

Reproductive Developmental toxicity

Oral (mg Ni/kg bw/day)

NOAEL =1.8

DNEL = 0.016

Reproductive Developmental toxicity

Long term-local effects

Dermal (mg Ni/cm2)

Not relevant (negligible exposure)

Inhalation (mg Ni/m3)

Other: CSTEE (ambient air standard) = 0.00003

DNEL-DMEL = 0.00003

Repeated dose toxicity (lung inflammation)

Carcinogenicity