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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.98 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA TGD R.8 using the SECO DNEL Tool v. 1.0
Overall assessment factor (AF):
13.75
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
123.42 mg/m³
Explanation for the modification of the dose descriptor starting point:

Bioavailability: 50% oral bioavailability (default) and 100% inhalation bioavailability (default)

Standard respiratory volume:, animal (sRVan): 0.38 m³/kg bw/8h; Standard respiratory volume, human (sRVhu): 6.7 m³/person; Worker respiratory volume (wRV): 10 m³/person; Differences experimental/human exposure conditions: 1.4.

Calculation starting point:

Experimental exposure: 7 days/week; Worker exposure: 5 days/week; Starting point = 100 mg/kg bw/d * 7/5

AF for dose response relationship:
0.55
Justification:
As the test item CXN1-55 is manufactured and handled only as aqueous solution with about 55% concentration, an additional factor of 0.55 is used to derive a DNEL for exposure to the aqueous solution.
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Included in calculation starting point
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
Differences within worker population.
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining differences
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.55 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA TGD R.8 using the SECO DNEL Tool v. 1.0
Overall assessment factor (AF):
55
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
140 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Oral and dermal uptake are considered to be identical.

Calculation of starting point:

Experimental exposure: 7 days/week

Worker exposure: 5 days/week

Starting point = 100 mg/kg bw/d * 7/5 = 140 mg/kg bw/d (human, dermal)

AF for dose response relationship:
0.55
Justification:
As the test item CXN1-55 is manufactured and handled only as aqueous solution with about 55% concentration, an additional factor of 0.55 is used to derive a DNEL for exposure to the aqueous solution.
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
Differences within worker population
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:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

The acute/short-term inhalation DNELs for systemic and local effects were not derived, since the substance is non volatile with a melting point > 300 °C and no generation of aerosol is expected.

The acute/short term exposure dermal DNEL for systemic effects was not derived, since no hazard was identified for Reaction mass of CXN1-55 for dermal toxicity. In the acute dermal toxicity study the LD50 was found to be > 2000 mg/kg bw.

The long-term dermal DNEL for local effects was not derived, since no hazard was identified for Reaction mass of CXN1-55. The substance is not skin sensitizer and not skin irritant in the respective studies.

The short-term dermal DNEL for local effects was not derived, since no hazard was identified for Reaction mass of CXN1-55. The substance is not skin irritating in the respective study.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.58 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA TGD R.8 using the SECO DNEL Tool v. 1.0
Overall assessment factor (AF):
27.5
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
43.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Bioavailability: 50% oral bioavailability (default) and 100% inhalation bioavailability (default)

For the general population (24h exposure/day), the corrected inhalatory NOAEC = oral NOAEC * 1/sRVrat * ABSoral-rat /ABSinhal-human

 

           = 100 mg/kg bw/day * 1/1.15 m3/kg * ABSoral-rat /ABSinhal-human

 

           = 100 mg/kg bw/day * 1/1.15 m3/kg * 0.5 = 43.48 mg/m3

 

With ABS: Absorption, sRV: Standard Respiratory Volume; ABSoral-rat /ABSinhal-human= 50/100= 0.5.

AF for dose response relationship:
0.55
Justification:
As the test item CXN1-55 is manufactured and handled only as aqueous solution with about 55% concentration, an additional factor of 0.55 is used to derive a DNEL for exposure to the aqueous solution.
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation, this is included in dose descriptor starting point
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
Differences within general population.
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No rmaining differences
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:
DNEL (Derived No Effect Level)
Value:
0.9 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA TGD R.8 using the SECO DNEL Tool v. 1.0
Overall assessment factor (AF):
110
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Oral and dermal uptake are considered to be identical.

AF for dose response relationship:
0.55
Justification:
As the test item CXN1-55 is manufactured and handled only as aqueous solution with about 55% concentration, an additional factor of 0.55 is used to derive a DNEL for exposure to the aqueous solution.
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
Differnces within general population
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining differences
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.9 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA TGD R.8 using the SECO DNEL Tool v. 1.0
Overall assessment factor (AF):
110
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
AF for dose response relationship:
0.55
Justification:
As the test item CXN1-55 is manufactured and handled only as aqueous solution with about 55% concentration, an additional factor of 0.55 is used to derive a DNEL for exposure to the aqueous solution.
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
Differences within general population
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining differences
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

The acute/short-term inhalation DNELs for systemic and local effects were not derived, since the substance is non volatile with a melting point > 300 °C and no generation of aerosol is expected.

The acute/short term exposure dermal DNEL for systemic effects was not derived, since no hazard was identified for Reaction mass of CXN1-55 for dermal toxicity. In the acute dermal toxicity study the LD50 was ound to exceed 2000 mg/kg bw.

The long-term dermal DNEL for local effects was not derived, since no hazard was identified for Reaction mass of CXN1-55. The substance is not skin sensitizer and not skin irritant in the respective studies.

The short-term dermal DNEL for local effects was not derived, since no hazard was identified for Reaction mass of CXN1-55. The substance is not skin irritating in the respective study.

The acute/short term exposure oral DNEL for systemic effects was not derived, since no hazard was identified for Reaction mass of CXN1-55 for oral toxicity. In the acute oral toxicity study the LD50 was found to be > 2000 mg/kg bw.