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:
DNEL (Derived No Effect Level)
Value:
88.1 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:
no hazard identified
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:
medium 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 = 133.3µg/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:
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:
13.9 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).
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:
no hazard identified
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:
66 µg/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):
25
Dose descriptor starting point:
NOAEL
AF for dose response relationship:
1
Justification:
adequate data available
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Metabolism of cobalt as an inorganic substance can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between rats and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 instead of using the respective default factors of 4
AF for other interspecies differences:
2.5
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 intra-species 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 intra-species variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003). Specifically for the cobalt substances, it has been shown that faecal clearance has been noted to decrease as cobalt particle solubility increases. In baboons, guinea-pigs, rats (HMT and Fischer-344), mice and hamsters (Andre et al. 1989, Bailey et al. 1989, Collier et al. 1989, Patrick et al. 1989, Talbot et al. 1989), oral exposure to tricobalt tetraoxide (with 57Co tracer) resulted in little gastrointestinal absorption and a rapid elimination in faeces (>96%). No significant differences in tricobalt tetraoxide elimination were observed among species. Furthermore, it was concluded in this study series, that no organs were found to accumulate cobalt significantly following ingestion or injection administration. Cobalt dichloride, which is more soluble, was excreted primarily via faeces (70–83% of the administered dose) in rats, with urinary excretion accounting for the remainder of the dose (Gregus, Z.; Klaassen, C.D. 1986).
AF for the quality of the whole database:
1
Justification:
no need for a further assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium 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 = 17.6µg/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 consumers.

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 repeated dose toxicity based on haematological findings in a sub-chronic oral repeated dose toxicity study in rats will be used for the risk assessment of consumers.

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.