Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.05 mg/m³
Most sensitive endpoint:
carcinogenicity
DNEL related information
Explanation for the modification of the dose descriptor starting point:

In most European countries, the occupational exposure limits for Cr(VI) are set at 0.05 mg/m3 (see EU RAR Vol. 53, Table 4.1)

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

Effects are considered to be covered by the Cr(VI) occupational limit (EU RAR Vol. 53)

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.04 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
DNEL related information
Overall assessment factor (AF):
170
Dose descriptor starting point:
NOAEL
DNEL value:
6.8 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
2.5
AF for other interspecies differences:
7
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
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:
0.2 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor:
other: NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Inhalation DNEL / DMEL

Acute inhalation

In some exposure situations peak exposures may occur. Therefore a DNEL for acute toxicity might be needed. This can be derived by CrO3 datas, using the LC50 value of strontium chromate as a starting point. LC50 in the acute inhalation test with strontium chromate was 0.27-0.51 mg/l. When taking the worst case situation as a starting point, the value used was 0.27 mg/l = 270 mg/m3strontium chromate, which corresponds to 69 mg Cr(VI) /m3.

For the extrapolation of the LC50 to a NOAEC an assessment factor of 100 was used.

For intraspecies variation the assessment factor was 10 and for worker inter-individual variability the assessment factor was 5.

This results in a total assessment factor of 5,000.

The DNEL for acute inhalation would thus be 69 mg/m3/ 5,000 = 0.014 mg Cr(VI) /m3(=156 µg zinc tetraoxychromate/m3).

Long term inhalation / carcinogenicity

The genotoxicity of zinc tetraoxychromate as well as the evidence from epidemiologic dose-response data (Park and Stayner 2006) do not allow derivation of threshold doses. Consequently, derived no-effect levels (DNEL) for carcinogenicity of zinc tetraoxychromate cannot be set, and instead, a DMEL has to be derived.

The data from high-quality epidemiologic studies enables the possibility to quantitative risk assessment of Cr(VI). A lot of risk assessment activities on occupational hexavalent chromium exposures were carried out when the background documentation for U. S. OSHA was compiled (see, e.g., Park, Bena et al. 2004; OSHA 2006; Park and Stayner 2006). According to the assessments performed by OSHA, best estimates of lung cancer risks at an eight-hour averaged inhalation exposure level of 0.25 μg Cr(VI) /m3are 0.52–2.3 per 1,000 workers with a working lifetime of 45 years.

The 8-hour time-weighted occupational exposure limit in the (OSHA, based on epidemiological data) was adjusted to 5 μg/m3for Cr(VI) in 2006. This is also the current limit value inand. In other European countries the limit is higher. The level of 5 μg/m3is, however, clearly higher (10x10-3 – 45x10-3) than advised in REACH guidelines. For the great uncertainties rising from the extrapolations to lower exposure concentrations, but taking into account precautionary reasons, a DMEL of 0.5 μg Cr(VI) /m3is suggested for zinc tetraoxychromate.

 

The DMEL calculated for carcinogenicity is clearly lower than the acute inhalation DNEL. Based on this, the acute inhalation effects are considered to be covered by the very low inhalation DMEL derived for carcinogenicity. No DNEL is therefore proposed for acute inhalation.

 

In the registration dossier of insoluble and sparingly soluble zinc compounds, a DNEL of 5 mg/m3has been suggested for inhalation. As this value is much higher than the DMEL suggested for zinc tetraoxychromate, there is no need to take it into consideration in the risk characterisation.

Dermal DNEL

The DNEL for local dermal effects is based on skin sensitisation data. The DNEL calculations were performed according to appendix 8-10 of ECHA guidance R8, and the article of Basketter et al. (2003), which is included under "skin sensitisation", and which is also one of the references listed in appendix 8-10.

The starting point for the DNEL calculations was the results of a number of LLNA: s with potassium dichromate (Kimber et al. 2001). No such tests have been performed with zinc tetraoxychromate and therefore this report with data on a more soluble chromate was selected. This is likely to result in a very precautionary estimate on DNEL.

The EC3 (Effect Concentration 3; concentration that induces a stimulation index of 3 or more) for potassium dichromate was 0.058%, which means that the substance belongs to the category of substances with extreme potency (appendix R.8-10). The EC3 (%) can be converted to µg/cm2(ECHA guidance R8):

0.058*250=14.5 µg/cm2potassium dichromate, corresponding to 5.12 µg Cr/cm2

According to Basketter et al.(2003) this can be used as an NOEL. Chemicals with NOELs (derived from LLNA) ranging from 1 to 10 µg/cm2, have been grouped and a conservative NOEL of 1 µg/cm2should be suggested for this group (Basketter et al. 2003).

For the derivation of DNELs the following assessment factors were used:

- Intraspecies variation: 1 (LLNA data correlates very well with human data, Basketter et al. 2003)

- Inter-individual variability: 5 (workers)

- Matrix effect: 1 (Dermal exposure to zinc tetraoxychromate occurs for example via spraying paint. For this matrix an assessment factor might be needed. However, no AF was used in order to compensate for the the situation that zinc tetraoxychromate is much less soluble (~1 g/l) than potassium chromate (~115 g/l) which was used in the LLNA. Due to the low solubility of zinc tetraoxychromate, its skin penetration, and therefore its sensitisation potential, is likely to be much lower than that of soluble chromates like potassium dichromate.

- Use pattern: 1 (Basketter et al. 2003 used an AF of 3 for the use pattern when calculating acceptable exposure levels for consumer products. However, in the case of zinc tetraoxychromate, the exposure is unintentional and occurs only for very brief periods of time.

Based on the above mentioned NOEL and assessment factor (5), the DNEL for zinc tetraoxychromate can be calculated as 1 µg/cm2/ 5 = 0.2 µg/cm2as Cr(VI) (= 2.2 µg/cm2as zinc tetraoxychromate).

As a comparison, it can be mentioned that the minimal eliciting threshold (MET)10% concentration for chromium allergic patients patch tested with potassium dichromate was 0.03 µg Cr(VI) /cm2/48 hours (Hansen et al. 2003), corresponding to 0.72 µg/cm2/2 hours of exposure (as Cr(VI)).

In appendix 8-10 of ECHA guidance R8, it is stated that 'it is not appropriate to define elicitation thresholds as a function of skin sensitising potency' and the derivation of DNELs for skin sensitisers in the guidance is thus focused only on the induction phase. Accordingly, the DNEL suggested for dermal exposure to zinc tetraoxychromate is based on the LLNA data.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

The general population is not exposed to zinc tetraoxychromate.