Cobalt

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

54.1 µg/m³

Most sensitive endpoint:

carcinogenicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

3

Dose descriptor starting point:

BMCL05

Value:

0.323 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

0.162 mg/m³

AF for dose response relationship:

1

Justification:

default value in ECHA guidance R8, BMDL5 equivalent to a NOAEC is available

AF for differences in duration of exposure:

1

Justification:

default value in ECHA guidance R8, point of departure stems from a chronic study

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not applicable, since effect is not dependent on metabolic rate, the cobalt cation is not metabolised

AF for other interspecies differences:

1

Justification:

Difference in response between rats and humans; can be reduced to 1 in case data is available showing that animals and humans respond to the insult in the same way (see justification in the attached report)

AF for intraspecies differences:

3

Justification:

Difference between workers, can be adjusted case substance-specific data are available (see justification in the attached report)

AF for the quality of the whole database:

1

Justification:

default value in ECHA guidance R8, point of departure stems from a guideline and GLP compliant study

AF for remaining uncertainties:

1

Justification:

not applicable

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:

40 µg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

3

Dose descriptor:

NOAEC

AF for dose response relationship:

1

Justification:

NOAEC available as POD

AF for differences in duration of exposure:

1

Justification:

Chronic human data

AF for interspecies differences (allometric scaling):

1

Justification:

Not required, since POD is taken from studies in workers

AF for other interspecies differences:

1

AF for intraspecies differences:

3

Justification:

This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003). A lower factor of 3 (i.e. closer to the 90th percentile of the distribution of the variability for these datasets) is proposed for the more homogeneous worker population. In the worker population, the more susceptible groups are typically excluded and/or may be protected from specific exposures. Thus, and in consideration of normal hygiene practices at the workplace, a lower value for the assessment factor is considered appropriate for workers.

AF for the quality of the whole database:

1

Justification:

Weight of evidence information provide sufficiently robust data base for hazard assessment purposes.

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:

7 228.9 µg/kg bw/day

Most sensitive endpoint:

carcinogenicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

3

Dose descriptor starting point:

BMCL05

Value:

0.323 µg/m³

Modified dose descriptor starting point:

NOAEL

Value:

21.69 mg/kg bw/day

AF for dose response relationship:

1

Justification:

default value in ECHA guidance R8, BMCL5 equivalent to a NOAEC is available

AF for differences in duration of exposure:

1

Justification:

default value in ECHA guidance R8, point of departure stems from a chronic study

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not applicable, since effect is not dependent on metabolic rate, the cobalt cation is not metabolised

AF for other interspecies differences:

1

Justification:

Difference in response between rats and humans; can be reduced to 1 in case data is available showing that animals and humans respond to the insult in the same way (see justification in the attached report)

AF for intraspecies differences:

3

Justification:

Difference between workers, can be adjusted case substance-specific data are available (see justification in the attached report)

AF for the quality of the whole database:

1

Justification:

default value in ECHA guidance R8, point of departure stems from a guideline and GLP compliant study

AF for remaining uncertainties:

1

Justification:

not applicable

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

During the hazard assessment DNELs -chronic inhalation for local effects were derived for the endpoint repeated dose toxicity (reported in the table above) and carcinogenicity (DNEL derived based on chronic inhalation study in rats = 60.5µg/m³). As laid down in Section 1.1.4, Annex I of Regulation (EC) 1907/2006, the effect which gives rise to the highest concern shall be used, thus the lowest identified DNEL for the same exposure duration and target organ will be used for the risk assessment. Thus, the DNEL(chronic inhalation, local) for the endpoint repeated dose toxicity will be used for the risk assessment of workers.

Further information on the methodology for the DNEL derivation is given in the respective reports, attached to the endpoint summary in section 7 of the IUCLID.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.1 µg/m³

Most sensitive endpoint:

carcinogenicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

10

Dose descriptor starting point:

BMCL05

Value:

0.323 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

0.081 mg/m³

AF for dose response relationship:

1

Justification:

default value in ECHA guidance R8, BMCL5 equivalent to a NOAEC is available

AF for differences in duration of exposure:

1

Justification:

default value in ECHA guidance R8, point of departure stems from a chronic study

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not applicable, since effect is not dependent on metabolic rate, the cobalt cation is not metabolised

AF for other interspecies differences:

1

Justification:

Difference in response between rats and humans; can be reduced to 1 in case data is available showing that animals and humans respond to the insult in the same way (see justification in the attached report)

AF for intraspecies differences:

10

Justification:

default value in ECHA guidance R8

AF for the quality of the whole database:

1

Justification:

default value in ECHA guidance R8, point of departure stems from a guideline and GLP compliant study

AF for remaining uncertainties:

1

Justification:

not applicable

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:

6.3 µg/m³

Most sensitive endpoint:

carcinogenicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

15

Dose descriptor:

BMCL10

AF for dose response relationship:

3

Justification:

adequate data available (BMDL10 instead of NOAEL)

AF for differences in duration of exposure:

1

Justification:

Chronic study available

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

1

AF for intraspecies differences:

5

Justification:

This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003). A lower factor of 3 (i.e. closer to the 90th percentile of the distribution of the variability for these datasets) is proposed for the more homogeneous worker population. In the worker population, the more susceptible groups are typically excluded and/or may be protected from specific exposures. Thus, and in consideration of normal hygiene practices at the workplace, a lower value for the assessment factor is considered appropriate for workers.

AF for the quality of the whole database:

1

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3 265.2 µg/kg bw/day

Most sensitive endpoint:

carcinogenicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

10

Dose descriptor starting point:

BMCL05

Value:

0.323 mg/m³

Modified dose descriptor starting point:

NOAEL

Value:

32.65 mg/kg bw/day

AF for dose response relationship:

1

Justification:

default value in ECHA guidance R8, BMCL5 equivalent to a NOAEC is available

AF for differences in duration of exposure:

1

Justification:

default value in ECHA guidance R8, point of departure stems from a chronic study

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not applicable, since effect is not dependent on metabolic rate, the cobalt cation is not metabolised

AF for other interspecies differences:

1

Justification:

Difference in response between rats and humans; can be reduced to 1 in case data is available showing that animals and humans respond to the insult in the same way (see justification in the attached report)

AF for intraspecies differences:

10

Justification:

default value in ECHA guidance R8

AF for the quality of the whole database:

1

Justification:

default value in ECHA guidance R8, point of departure stems from a guideline and GLP compliant study

AF for remaining uncertainties:

1

Justification:

not applicable

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.9 µg/kg bw/day

Most sensitive endpoint:

carcinogenicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

10

Dose descriptor starting point:

BMCL05

Value:

0.323 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

0.089 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Note:

Due to an error in the field "Dose descriptor starting point - Value", the BMCL05 is erroneously given as mg/kg bw/day. The correct unit should be mg/m³. The incorrect unit was chosen since otherwise the IUCLID system would identify an error and reject the entry.

AF for dose response relationship:

1

Justification:

default value in ECHA guidance R8, BMCL5 equivalent to a NOAEC is available

AF for differences in duration of exposure:

1

Justification:

default value in ECHA guidance R8, point of departure stems from a chronic study

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not applicable, since effect is not dependent on metabolic rate, the cobalt cation is not metabolised

AF for other interspecies differences:

1

Justification:

Difference in response between rats and humans; can be reduced to 1 in case data is available showing that animals and humans respond to the insult in the same way (see justification in the attached report)

AF for intraspecies differences:

10

Justification:

default value in ECHA guidance R8

AF for the quality of the whole database:

1

Justification:

default value in ECHA guidance R8, point of departure stems from a guideline and GLP compliant study

AF for remaining uncertainties:

1

Justification:

not applicable

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

 

During the hazard assessment DNELs -chronic inhalation for local effects were derived for the endpoint repeated dose toxicity (DNEL derived based on human data = 8.0 µg/m³) and carcinogenicity (reported in the table above). As laid down in Section 1.1.4, Annex I of Regulation (EC) 1907/2006, the effect which gives rise to the highest concern shall be used, thus the lowest identified DNEL for the same exposure duration and target organ will be used for the risk assessment. Thus, the DNEL(chronic inhalation, local) for the endpoint carcinogenicity will be used for the risk assessment of the general population.

 

During the hazard assessment additional DNELs for chronic oral exposure were derived for the endpoint pre-natal developmental toxicity. The DNELs were derived based on the NOAEL identified in a pre-natal developmental toxicity study in rabbits of 5 mg CoCl2 6H2O/kg bw/day for (i) local gastro-intestinal irritation in preganent dams and (ii) increased number of early resorptions. As laid down in Section 1.1.4, Annex I of Regulation (EC) 1907/2006, the effect which gives rise to the highest concern shall be used, thus the lowest identified DNEL for the same route of exposure will be used for the risk assessment. Thus, the DNEL(chronic oral, systemic) for the endpoint carcinogenicity in a chronic inhalation toxicity study in rats will be used for the risk assessment of the general population, using route to route extrapolation as laid down in the ECHA guidance Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1, November 2012).

 

During the hazard assessment additional DNELs for chronic oral exposure were derived for the endpoint repeated-dose toxicity. The DNELs were derived based on the NOAEL identified in a sub-chronic repeated dose toxicity study in rats of 3 mg CoCl2 6H2O/kg bw/day for decreased body weight, erythroid hyperplasia in the bone marrow and altered haematological parameters. As laid down in Section 1.1.4, Annex I of Regulation (EC) 1907/2006, the effect which gives rise to the highest concern shall be used, thus the lowest identified DNEL for the same route of exposure will be used for the risk assessment. Thus, the DNEL(chronic oral, systemic) for the endpoint carcinogenicity in a chronic inhalation toxicity study in rats will be used for the risk assessment of the general population, using route to route extrapolation as laid down in the ECHA guidance Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1, November 2012).

 

Further information on the methodology for the DNEL derivation is given in the respective reports, attached to the endpoint summary in section 7 of the IUCLID.