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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/m³
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
Value:
506 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
124.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

A systemic NOAEL of 506 mg/kg bw/day elemental chromium was determined in an oral 90 day repeated dose toxicity study in rats (NTP, 2010). This NOAEL can be regarded as worst-case for the registered substance as it is based on elemental chromium. This study was selected as point of departure as in the available repeated dose inhalation study by Derelanko (1999) the local effects clearly prevail over the systemic effects. Therefore no reliable systemic NOAEC could be derived from this study.

The NOAEL of 506 mg/kg bw/day was converted into the corrected inhalatory NOAEC taking into account the standard respiratory factor of 1/0.38 m³/kg/day, the absorption rates (oral 10 % and inhalation 100 % are assumed as worst-case assumptions - please refer to Section 7.1.) and the standard respiratory volume in humans/ worker respiratory volume (6.7 m³ (8 h) / 10 m³ (8 h)) and the correction factor between human and experimental exposure conditions of workers (5 working days vs. 7 days continuous exposure) of 1.4.

NOAEC corrected = 506 mg/kg bw/day * 1/0.38 m³/kg/day * 10%/100% * (6.7 m³/10 m³) * 1.4 = 124.9 mg/m³

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allomoetric scaling needed extrapolating oral-to-inhalation
AF for other interspecies differences:
2.5
Justification:
Default, no route substance specific information on toxicokinetik and dynamic available
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEC
Value:
17 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
32.83 mg/m³
Explanation for the modification of the dose descriptor starting point:

The registered substance is acute toxic by the inhalation route. In an acute inhalation study according to OECD Test Guideline 403 and GLP male and female Han Wistar rats underwent a single 4 -hour nose only inhalation exposure to chromium hydroxide sulphate at a mean atmospheric exposure level of 4.58 mg/L. The test compound was poorly tolerated, causing persistent clinical signs. Seven out of ten animals died during the course of the study. The LC50 is therefore considered to be below 4580 mg/m³. As no actual LC50 value could be derived in this study and no information on sub-lethal effects can be derived from this study, it is not suitable to serve as dose-descriptor starting point for the systemic acute DNEL. In the repeated dose toxicity study by Derelanko et al. (1999) it was shown that the local effects clearly prevail over systemic effects in case of inhalative exposure. In this study a LOAEC of 17 mg/m³ was derived based on local effects on the respiratory tract. As no systemic effects were observed at this dose 17 mg/m³ could be considered as a systemic NOAEC. As this was derived from a chronic daily exposure, this is a clear worst-case assumption for the acute exposure. As in this study rats were exposed 6 h while the acute DNEL represents 15 min of exposure, this value is corrected for time using Haber's Law.

Haber's Law: Cn* t = k,

where ‘C’ is the concentration, ‘n’ is a regression coefficient, ‘t’ is the exposure time and ‘k’ is a constant; a default value of n=3 for extrapolating from longer to shorter exposure durations is used.

(C³ x t) = (C') ³ x t', giving C' = C x (t/t')0.333333. C' is the sought concentration. C' = 17 mg/m³ x (6h/0.25h)0.3333333= 49 mg/m³. The concentration of 49 mg/m³ was adjusted for the differences in the respiratory rates by normal conditions and by light activity: 0.67 (rest / light activity: 6.7 /10)

NOAEC corrected = 49 mg/m³ * 0.67 = 32.83 mg/m³

A total Assessment factor of 12.5 (5 for intra-species and 2.5 for remaining inter-species variability is applied to the corrected starting point of 32.8 mg/m³. The resulting DNEL is 2.6 mg/m³.

As this systemic acute DNEL based on a clear worst-case assumption is lower than the systemic long-term DNEL, the long-term DNEL, which is based on route-to-route extrapolation from a reliable long-term study is used also as short-term DNEL.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.11 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
Value:
8.54 mg/m³
AF for dose response relationship:
3
Justification:
LOAEC to NOAC extrapolation
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not needed for local effects
AF for other interspecies differences:
2.5
Justification:
default for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
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:
7.1 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
Dose descriptor starting point:
NOAEL
Value:
506 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
708 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A systemic NOAEL of 506 mg/kg bw/day elemental chromium was determined in an oral 90 day repeated dose toxicity study in rats (NTP, 2010). This NOAEL can be regarded as worst-case for the registered substance as it is based on elemental chromium.

This value was converted into the corrected dermal NOAEL taking into account the the correction factor between human and experimental exposure conditions of workers (5 working days vs. 7 days continuous exposure) of 1.4. No correction for absorption rates is needed as the absorption rates for the dermal and oral route are the same (10 %).

NOAEL corrected = 506 mg/kg bw/day * 1.4 = 708 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.88 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
506 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
44 mg/m³
Explanation for the modification of the dose descriptor starting point:

A systemic NOAEL of 506 mg/kg bw/day elemental chromium was determined in an oral 90 day repeated dose toxicity study in rats (NTP, 2010). This NOAEL can be regarded as worst-case for the registered substance as it is based on elemental chromium. This study was selected as point of departure as in the available inhalation study by Derelanko (1999) the local effects clearly prevail over the systemic effects. Therefore no reliable systemic NOAEC could be derived from this study.

This value was converted into the corrected inhalatory NOAEC taking into account the standard respiratory factor of 1/1.15 m³/kg/day and the absorption rates (oral 10 % and inhalation 100 % are assumed as worst-case assumptions - please refer to Section 7.1.)

NOAEC corrected = 506 mg/kg bw/day * 1/1.15 m³/kg/day * 10%/100% = 44 mg/m³

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not needed for inhalation endpoint as already included in the corrected starting point
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.96 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
17 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
49 mg/m³
Explanation for the modification of the dose descriptor starting point:

The registered substance is acute toxic by the inhalation route. In an acute inhalation study according to OECD Test Guideline 403 and GLP male and female Han Wistar rats underwent a single 4 -hour nose only inhalation exposure to chromium hydroxide sulphate at a mean atmospheric exposure level of 4.58 mg/L. The test compound was poorly tolerated, causing persistent clinical signs. Seven out of ten animals died during the course of the study. The LC50 is therefore considered to be below 4580 mg/m³. As no actual LC50 value could be derived in this study and no information on sub-lethal effects can be derived from this study, the repeated dose toxicity study by Derelanko et al. (1999) is used to derive an acute systemic DNEL for the inhalation route. In this study a LOAEC of 17 mg/m³ was derived based on local effects on the respiratory tract. As no systemic effects were observed at this dose 17 mg/m³ is considered to be a systemic NOAEC. As this was derived from a chronic daily exposure, this is a clear worst-case assumption for the acute exposure. As in this study rats were exposed 6 h while the acute DNEL represents 15 min of exposure, this value is corrected for time using Haber's Law.

Haber's Law: Cn* t = k,

where ‘C’ is the concentration, ‘n’ is a regression coefficient, ‘t’ is the exposure time and ‘k’ is a constant; a default value of n=3 for extrapolating from longer to shorter exposure durations is used.

(C³ x t) = (C') ³ x t', giving C' = C x (t/t')0.333333. C' is the sought concentration. C' = 17 mg/m³ x (6h/0.25h)0.3333333= 49 mg/m³.

NOAEC corrected = 49 mg/m³

AF for dose response relationship:
1
Justification:
not needed as NOAEC was used as staring point
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not applicable for inhalation
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
sufficient quality of database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.03 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
Value:
4.25 mg/m³
AF for dose response relationship:
3
Justification:
LOAEC to NOAC extrapolation
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not needed for local effects
AF for other interspecies differences:
2.5
Justification:
default for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.09 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
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:
2.53 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
Dose descriptor starting point:
NOAEL
Value:
506 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
506 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A systemic NOAEL of 506 mg/kg bw/day elemental chromium was determined in an oral 90 day repeated dose toxicity study in rats (NTP, 2010). This NOAEL can be regarded as worst-case for the registered substance as it is based on elemental chromium.

No correction for absorption rates is needed as the absorption rates for the dermal and oral route are the same (10 %).1.7

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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:
DNEL (Derived No Effect Level)
Value:
2.53 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
Dose descriptor starting point:
NOAEL
Value:
506 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
506 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A systemic NOAEL of 506 mg/kg bw/day elemental chromium was determined in an oral 90 dayrepeated dose toxicity studyin rats (NTP, 2010). This NOAEL can be regarded as worst-case for the registered substance as it is based on elemental chromium.

This value does not have to be corrected as the oral absorption rate of rats and humans are considered to be identical (10 % as worst-case assumption).

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
sufficient quality of the database
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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