Chromium trinitrate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.464 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Modified dose descriptor starting point:

NOAEC

Value:

11.61 mg/m³

Explanation for the modification of the dose descriptor starting point:

no route to route extrapolation, The N(L)OAEC is adjusted taking into account 6h/day exposure in study and respiratory volume adjustment (6.7/10) --> 23.1 mg/m3 *6/8 * 6.7/10 = 11.61 mg/m3 corrected N(L)OAEC

AF for dose response relationship:

1

Justification:

not required as NOAEC for systemic effects

AF for differences in duration of exposure:

2

Justification:

based on a subchronic inhalation study

AF for interspecies differences (allometric scaling):

1

Justification:

not used for inhalation

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

5

Justification:

default factor for worker

AF for the quality of the whole database:

1

Justification:

inhalative and oral data in same range

AF for remaining uncertainties:

1

Justification:

No further uncertainties to be taken into account

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.619 mg/m³

DNEL related information

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.155 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

75

Dose descriptor:

LOAEC

AF for dose response relationship:

3

Justification:

as LOAEC for acute effects is used

AF for differences in duration of exposure:

2

Justification:

based on a subchronic inhalation study

AF for interspecies differences (allometric scaling):

1

Justification:

not used for inhalation

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

5

Justification:

default factor for worker

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not required

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.21 mg/m³

DNEL related information

DNEL extrapolated from long term DNEL

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.32 mg/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):

100

Modified dose descriptor starting point:

NOAEL

Value:

32 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

oral to dermal, no adjustment for absorption made as both, dermal and oral absorption, are considered max. 10%

AF for dose response relationship:

1

Justification:

NOAEL is used as a starting point.

AF for differences in duration of exposure:

2

Justification:

based on a subchronic study

AF for interspecies differences (allometric scaling):

4

Justification:

rats are used in the animal test

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

5

Justification:

default value for worker

AF for the quality of the whole database:

1

Justification:

Available data from substance fulfilling scientific principle is used

AF for remaining uncertainties:

1

Justification:

no other uncertainties needed to be considered.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.32 mg/kg bw/day

DNEL related information

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

As there is no quantitative data available for dermal adsorption of test material, a worst case scenario is assumed in which the absorption rate from dermal route is considered to be same as oral route, and for both routes assumed to be 10%.

No systemic toxicity was observed in rats following a 13-week nose-only inhalation study of basic chromium(III) sulphate, a surrogate substance to chromium trinitrate, also being a very soluble chromium(III) compound. Pathological findings were observed in the respiratory tract and are associated with the deposition of inhaled particulate material. The LOAEC, based on chromium trinitrate nonahydrate in this study for local effects was established at 23.1 mg/m3 air (3 mg/m3 Cr) but for systemic toxicity this value is considered as NOAEC.

Similar physical inflammation reactions were observed in a 4 -6 week inhalative study with chromium trinitrate. In this subacute study also no systemic toxicity was observed but only a limited number of parameters were followed as the study focused on the investigation of lung tissue of rabbits by inhalative exposure. Thus, this study, although performed on the reference substance, is considered supportive and the subchronic study on the surrogate substance is used as key study for inhalative repeated dose toxicity and is used for derivation of systemic and local effects inhalative DNELs.

Another study was conducted to evaluate the toxicity of chromium trichloride in rats exposed to 0, 5, 25, 50, or 100 mg Cr/kg bw in the diet for 20 weeks (estimated to correspond to 0.35–7 mg/kg bw). No morphological changes of liver and renal damage were observed based on histopathological examination of kidneys and did not result in significant alterations in body weight gain at level of 7 mg chromium/kg bw. Moreover, no alterations in testes or epididymis weights were observed in rats at the highest dose.

Therefore, the no-observed-adverse-effects-level (NOAEL) of chromium trichloride is estimated to be 7 mg chromium (III)/kg bw/day. As both, chromium trichloride and chromium trinitrate are very soluble chromium(III) compounds and neither chloride nor nitrate are associated with repeated dose toxicity, a read-across from chromium trichloride to chromium trinitrate is justified and sufficient for hazard and risk assessment. The NOAEL value can be converted to a NOAEL of > 32 mg/kg bw/d based on molecular mass of chromium trinitrate and this value is used for derivation of dermal DNEL for systemic toxicity.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.116 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Modified dose descriptor starting point:

LOAEC

Value:

5.78 mg/m³

Explanation for the modification of the dose descriptor starting point:

no route to route extrapolation, The N(L)OAEC is adjusted taking into account 6h/day exposure in study --> 23.1 mg/m3 *6/24 = 5.78 mg/m3 corrected N(L)OAEC

AF for dose response relationship:

1

Justification:

NOAEC is selected as the starting point for systemic effects

AF for differences in duration of exposure:

2

Justification:

based on the subchronic study

AF for interspecies differences (allometric scaling):

1

Justification:

not applied for inhalation

AF for other interspecies differences:

2.5

Justification:

default factor for interspecies difference

AF for intraspecies differences:

10

Justification:

default factor for general population

AF for the quality of the whole database:

1

Justification:

inhalative and oral data in same range

AF for remaining uncertainties:

1

Justification:

No further uncertainties to be taken into account

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.462 mg/m³

DNEL related information

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.039 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

150

Dose descriptor:

LOAEC

AF for dose response relationship:

3

Justification:

as LOAEC for acute effects is used

AF for differences in duration of exposure:

2

Justification:

based on the subchronic study

AF for interspecies differences (allometric scaling):

1

Justification:

not applied for inhalation

AF for other interspecies differences:

2.5

Justification:

default factor for interspecies difference

AF for intraspecies differences:

10

Justification:

default factor for general population

AF for the quality of the whole database:

1

Justification:

inhalative and oral data in same range

AF for remaining uncertainties:

1

Justification:

No further uncertainties to be taken into account

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.154 mg/m³

DNEL related information

DNEL extrapolated from long term DNEL

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.16 mg/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):

200

Modified dose descriptor starting point:

NOAEL

Value:

32 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

oral to dermal

AF for dose response relationship:

1

Justification:

NOAEL is used as the starting point

AF for differences in duration of exposure:

2

Justification:

based on a subchronic study

AF for interspecies differences (allometric scaling):

4

Justification:

rats are used in the animal test

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

10

Justification:

default for general population

AF for the quality of the whole database:

1

Justification:

available data fullfil scientific principles

AF for remaining uncertainties:

1

Justification:

no other uncertainties need to be considered.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.16 mg/kg bw/day

DNEL related information

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.16 mg/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):

200

Modified dose descriptor starting point:

NOAEL

Value:

32 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

no route to route extrapolation

AF for dose response relationship:

1

Justification:

NOAEL is used as the starting point

AF for differences in duration of exposure:

2

Justification:

based on a subchronic study result

AF for interspecies differences (allometric scaling):

4

Justification:

rats are used in the animal test

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

10

Justification:

default factor for general population

AF for the quality of the whole database:

1

Justification:

available data fullfil scientific principles

AF for remaining uncertainties:

1

Justification:

no other uncertainties need to be considered.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.16 mg/kg bw/day

DNEL related information

DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Although the general population is not exposed to chromium trinitrate as a substance (potential dust exposure as in worker scenarios) and consequently inhalative exposure to it by daily consumption is most unlikely, a DNEL has been derived.

The same data as mentioned above for worker DNELs have been used to derive the DNELs (see above) but assessment factors for general population were used and adjustment of the inhalative NOAEC was done to take account for 24 hours exposure of consumers.