Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
105.79 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:
3 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
2 644.74 mg/m³
Explanation for the modification of the dose descriptor starting point:

There is no relevant experimental data on repeated exposure by inhalation. A conservative approach is used assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting route).

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
30 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:
3 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
3 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. Taken into account the physico-chemical and toxic properties of the substance, dermal absorption is anticipated to be 10% of oral absorption.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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

Worker – Hazard via inhalation route

Step 1: Selection of the relevant descriptor (starting point):

For the risk characterisation an inhalation NOAEC was derived by route to route extrapolation (ECHA CSA R.8, 2012). A DNEL for systemic effects after long-term dermal exposure was derived based on the NOAEL value from a subchronic (90 days) repeated dose study with oral application in rats (NTP, 5701 -307, 1983). The results of this study clearly confirmed the low toxicity of the substance already noted under single-dose conditions. The respective NOAEL for systemic effects was 3000 mg/kg/d (as 100% substance ). At the next dose level (6000 mg/kg), histopathological inspection revealed no specific treatment-related organ lesions, except that two males of the 6000 mg/kg dosage level group suffered from mild mineralization in the heart, and one from moderate bilateral mineralization of the testes, both phenomena considered substance-related.

Step 2: modification into a correct starting point:

Using a conservative approach, a worker DNEL (long-term inhalation exposure) is derived. A conservative approach is used assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting point). This worker DNEL is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected).

 

Relevant dose descriptor (NOAEL): 3000 mg/kg bw/day

Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/day

Frequency of worker: 5 days/week

Oral absorption of the rat/inhalation absorption of humans (ABSoral-rat/ABSinh-human): 0.5

Standard respiratory volume of humans (SRVhuman) for 8 hours: 6.7 m³

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

 

Corrected inhalatory NOAEC for workers

= 3000 mg/kg bw/day x 0.5 x (1/0.38 m³/kg bw/day) x (6.7 m³/ 10 m³) x 5/5

= 2644.74 mg/m³

 

Step 3: Use of assessment factors: 25

Interspecies: Respiratory interspecies differences are fully covered by the modification of the NOAEC

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 2

 

In conclusion, long-term systemic inhalation DNEL, workers = 105.79 mg/m³

 

 

Worker – Hazard via dermal route

Step 1: Selection of the relevant dose descriptor (starting point):

For risk characterisation a dermal NOAEL was derived by route to route extrapolation. The oral NOAEL of 3000 mg/kg bw/day obtained from a 13-week toxicity study in rats with DMDHEU (a surrogate substance of the submission substance; NTP, 5701-307, 1983) was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

 

Step 2: Modification into a correct starting point:

The worker DNEL (long-term dermal exposure) is derived. Based on physic-chemical (Kow = -3.5 to 0.3 at 20 and 23 °C) and toxic properties of the test substance dermal absorption is anticipated to be low. The test substance is not classified as skin irritant or skin sensitizer and therefore no damage to the skin may enhance penetration. Thus, a dermal absorption of 100% of oral absorption is assumed to be worst case.

 

Relevant dose descriptor (NOAEL): 3000 mg/kg bw/day

Frequency of exposure used in the study: 5 days/week

Frequency of exposure of the worker: 5 days/week

ABS (oral rat): 100%

ABS (dermal human): 100%

Corrected dermal NOAEL for worker:

= 3000 mg/kg bw/day x (100/100) * 5/5

= 3000 mg/kg bw/day

 

Step 3: Use of assessment factors: 100

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 2

 

In conclusion, long-term dermal DNEL, worker = 30 mg/kg bw/day

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
no hazard identified
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

No DNELs for the general population were derived due to the facts:

  • that no acute toxicity hazards (leading to C&L) have been identified,
  • that the submission substance is covalently bound to textile and thus reaching the end of the lifecycle,
  • that the covalent binding of the submission substance to the textile excludes exposure of the general population.