Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.24 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
other: NAEC
DNEL value:
106 mg/m³
AF for differences in duration of exposure:
2
Justification:
subchronic --> chronic
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
intrahuman AF
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 097 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
other: NAEC
DNEL value:
13 718 mg/m³
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
intrahuman AF

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.141 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
75
Dose descriptor:
other: NAEC
AF for dose response relationship:
3
Justification:
LAEC -- > NAEC
AF for differences in duration of exposure:
2
Justification:
subchronic --> chronic
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
intrahuman AF
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
36 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
38
Dose descriptor starting point:
other: NAEC
AF for dose response relationship:
3
Justification:
LAEC -- > NAEC
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
intrahuman AF

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 015 mg/kg bw/day
AF for differences in duration of exposure:
2
Justification:
subchronic --> chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
intrahuman AF
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40.3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 015 mg/kg bw/day
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
intrahuman AF

Local effects

Long term exposure
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor starting point:
other: NOAEL
AF for intraspecies differences:
5
Justification:
intrahuman AF

Workers - Hazard for the eyes

Additional information - workers

The DNEL for acute dermal effects is based on the subchronic feeding study. Dermal absorption is believed to be as low as gastrointestinal absorption (1%). For systemic effects, an assessment factor (AF) of 50 is composed of 2.5 (toxicodynamic interspecies AF), 4.0 (allometric scaling, rat) and 5 (intraspecies AFs, worker). For local effects on skin, only the intraspecies AF of 5 remains applicable.

The DNEL for acute inhalation effects is based on the subchronic inhalation study study. The typical acute inhalation study comprises an exposure duration of 4 h. In the subchronic study, exposure duration was 6 h/day on a total of 65 days, i.e., a total of 6×65 hours (390 h).

For relatively insoluble dusts like Cr(III) sulphate, the toxicity is correlated with the total lung burden. The NOAEC for systemic effects is ≥ 210 mg/m³. Applying Haber’s “c×t” rule, one can estimate that a systemic 4-h NOAEC in the rat could be 390 / 4 × 210 = 20,475 mg/m³.

This value needs to be corrected for a higher respiratory activity of workers (6.7/10) giving a corrected human 4-h NAEC of 13,718 mg/m³. Likewise, the LOAEC for local lung effects is converted into a human 4-h LAEC of 1372 mg/m³. The AF for local effects is derived by applying a toxicodynamic AF of 2.5, an intrahuman AF of 5, and an additional AF of 3 for extrapolation from an LOAEC to an NOAEC. This gives a total AF of 37.5. For systemic effects, the extra AF of 3 is not needed (clear NOAEC), yielding a remaining AF of 12.5.

The DNEL for skin irritation is based on the skin irritation study. The applied dose is 500 mg/ 6 cm² and represents the NOAEL for Cr picolinate, since the substance is not irritating to skin. Read across to the lower MW of basic Cr(III) acetate monohydrate, the NOAEL is 40 mg/cm². An AF of 5 for intraspecies variability applies.

A DNEL for skin sensitisation cannot be derived since an EC3 could not be determined from the LLNA data (EC3<10%).

A long-term DNEL for systemic effects following dermal exposure is derived by route-to-route extrapolation from a subchronic feeding study. The interspecies AF is 10 for a rat study, the AF for workers is 5 and an extra AF of 2 is applied for extrapolation from subchronic NOAEL to chronic exposure (total AF=100). A local DNEL cannot be proposed because of the skin-sensitizing properties for basic Cr(III) acetate.

The subchronic inhalation LOAEC/NOAEC (local/systemic) are corrected for 8-h exposure (6/8) and for higher respiratory activity (6.7/10) to give an 8-h human local LAEC/ systemic NAEC of 10.6/106 mg/m³. The AF for local effects is derived by applying a toxicodynamic AF of 2.5, an intrahuman AF of 5, and additional AFs of 3 and 2 for extrapolation from LOAEC to NOAEC and for subchronic-to-chronic extrapolation, respectively. This gives a total AF of 75. For systemic effects, the extra AF of 3 is not needed (clearly defined NOAEC), yielding a remaining AF of 25. The DNEL pertains to the alveolar dust fraction.

The existing OEL (Directive 2006/15/EC) for Cr(III) compounds (2 mg Cr/m³, total dust) is equivalent to 8 mg basic Cr(III) acetate monohydrate/m³ (total dust).

The OEL should remain the relevant limit value for total dust, whereas the inhalation DNEL should be used as an upper limit for the alveolar dust fraction.

The supported use of basic Cr(III) acetate is within solid matrices. Exposure of the general population can thus be precluded; DNELs for the general population are not relevant.

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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population