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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
75
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
185 mg/m³
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.


Starting point:


NOAEL of 150 mg/kg bw/day in a 28-day repeated dose toxicity study in rat.


When correcting an oral NOAEL to inhalation NOAEC the correction factor for worker population would be: 7 day/week (experimental animal exposure) / 5 days/week (worker exposure conditions) = 1.4. 


Conversion of an oral NOAEL into a corrected NOAEC:


For workers (8h exposure/day), the corrected inhalatory NOAEC = oral NOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human * sRVhuman/wRV * 1.4


            = 150 mg/kg bw/day * 1/0.38 m3/kg/8h * ABSoral-rat /ABSinhal-human * 6.7 m3 (8h)/10 m3 (8h) *1.4


            = 150 mg/kg bw/day * 1/0.38 m3/kg/8h  * 0.5 * 6.7 m3 (8h)/10 m3 (8h) *1.4


= 150 mg/kg bw/day /0.38 * 0.5 * (6.7/10) *1.4 = 185 mg/m3.


 


With ABS: Absorption, sRV: Standard Respiratory Volume; wRV: Worker Respiratory Volume;


ABSoral-rat /ABSinhal-human= 50/100= 0.5

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure worker
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point
AF for other interspecies differences:
2.5
Justification:
Factor to correct for toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). No substance-specific information is available to address this aspect more specifically.
AF for intraspecies differences:
5
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
300
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite. Correction dermal NOAEL: 150 mg/kg bw/day x 50/10a = 750 mg/kg bw/day (a % oral/dermal absorption)

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure worker
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
2.5
Justification:
Factor to correct for toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). No substance-specific information is available to address this aspect more specifically.
AF for intraspecies differences:
5
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable study used
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:
high hazard (no threshold derived)
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:
0.43 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):
150
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
65 mg/m³
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.
For the general population (24h exposure/day), the corrected inhalatory NOAEC = oral NOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human
= 150 mg/kg bw/day * 1/1.15 m3/kg * ABSoral-rat /ABSinhal-human
= 150 mg/kg bw/day * 1/1.15 m3/kg * 0.5 = 65 mg/m3
With ABS: Absorption, sRV: Standard Respiratory Volume;
ABSoral-rat /ABSinhal-human= 50/100= 0.5

AF for dose response relationship:
1
Justification:
NOAEL is used
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point
AF for other interspecies differences:
2.5
Justification:
Factor to correct for toxicokinetic differences not related to metabolic rate (small part) and toxic odynamic differences (larger part). No substance-specific information is available to address this aspect more specifically.
AF for intraspecies differences:
10
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
1
Justification:
Reliable study used
AF for remaining uncertainties:
1
Justification:
No remaining differences
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:
DNEL (Derived No Effect Level)
Value:
1.25 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):
600
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite.


Correction dermal NOAEL: 150 mg/kg bw/day x 50/10a =
750 mg/kg bw/day (a % oral/dermal absorption)

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Extrapolation from rat to human
AF for other interspecies differences:
2.5
Justification:
Factor to correct for toxicokinetic differences not related to metabolic rate (small part) and toxic odynamic differences (larger part). No substance-specific information is available to address this aspect more specifically.
AF for intraspecies differences:
10
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
1
Justification:
Reliable study used
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:
high hazard (no threshold derived)
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:
0.25 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):
600
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
2.5
Justification:
Factor to correct for toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). No substance-specific information is available to address this aspect more specifically.
AF for intraspecies differences:
10
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
1
Justification:
Reliable study used
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

NXT Z45 is only used in industrial environments and the general population will not get in direct contact with the test substance. If exposure via the environment occurs, this will be negligible and without any peak exposure.