Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.87 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
741 mg/m³
Explanation for the modification of the dose descriptor starting point:

An OECD 422 combined 28-day/reproduction screening study resulted to an overall NOAEL of 300 mg/kg/day being the highest dose level tested. The corrected 8 hr inhalation NOAEC for workers is NOAEL(300 mg/kg) * 1.76 mg/m3 = 529 mg/m3. Further correction of 7 d/wk study design to a 5 d/wk worker exposure results to a corrected NAOEC of 741 mg/m3.

No factor 2 route extrapolation from oral to inhalation. The substance is viscous at room temperature with bp > 300°C and a low vapour pressure (< 1.7 x 10-7 Pa, at 25°C, based on FA+DETA considered to have the highest vp among the AAI). Exposure via inhalation may only possible as aerosol if the viscous material is diluted to aqueous solutions. However, in such a case only large droplets need to be considered, as the supported use does not include fine spraying. Such big droplets will deposit mainly on upper airways and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
6
Justification:
ECHA default for sub-acute to chronic. Conservative approach as it concerns an exposure duration around 45 days in an OECD 422 rather than a 28-day.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results within category.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.4 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
420 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

An OECD 422 combined 28-day/reproduction screening study resulted to an overall NOAEL of 300 mg/kg/day being the highest dose level tested. The 8 hr dermal NOAEL for workers involves correction of 7 d/wk study design to a 5 d/wk worker exposure results to a corrected NAOEC of 420 mg/kg bw/d.

This extrapolation from oral NOAEL represents a worst case situation, as dermal absorption is considered to be lower compared to oral absorption.

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
6
Justification:
ECHA default for sub-acute to chronic. Conservative approach as it concerns exposure duration around 45 days in an OECD 422 rather than a 28-day.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling rat to human
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default. Conservative approach as the effects for which the risk assessment is made is based on a local response with expected inherently relative low variation between individuals.
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results within category.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Workers - Inhalation route:

Use of the substance is limited to industrial and professional users. The likelihood of exposure via inhalation is low considering its high boiling point (> 300 °C) and very low vapour pressure (1.7 x 10-7 Pa at 25°C) and use applications that do not involve the forming of aerosols, particles or droplets of an inhalable size.

 

Workers - Dermal route:

No threshold effect: Substance is corrosive and sensitising. Effects following dermal exposures will be characterized by local corrosive and possible sensitising effects that are related to duration, quantity and concentration of the substance, rather than by systemic toxicity due to dermal uptake. Specifically as acute oral toxicity is low.

For corrosive and sensitising substances, the use of protective gloves and other equipment, such as face shields, aprons and good work practices are mandatory. As a result, direct dermal contact occurs only occasionally. Therefore, repeated substantial daily dermal exposure is unlikely. (For properly labelled corrosives, the emphasis in the CSR and ES should be on the presentation of adequate risk management measures, rather than on the assessment of the risks from dermal exposure.)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.74 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
261 mg/m³
Explanation for the modification of the dose descriptor starting point:

An OECD 422 combined 28-day/reproduction screening study resulted to an overall NOAEL of 300 mg/kg/day being the highest dose level tested. The corrected 24 hr inhalation NOAEC for general population following route-to-route extrapolation is NOAEL * 1/1.15 mg/m3 = 261 mg/m3.

No factor 2 route extrapolation from oral to inhalation. The substance is viscous at room temperature with bp > 300°C and a low vapour pressure (< 1.7 x 10-7 Pa, at 25°C, based on FA+DETA considered to have the highest vp among the AAI). Exposure via inhalation may only possible as aerosol if the viscous material is diluted to aqueous solutions. However, in such a case only large droplets need to be considered, as the supported use does not include fine spraying. Such big droplets will deposit mainly on upper airways and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
6
Justification:
ECHA default for sub-acute to chronic. Conservative approach as it concerns an exposure duration of 45 days in an OECD 422 rather than a 28-day.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results within category.
AF for remaining uncertainties:
1
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:
0.5 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):
600
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Extrapolation from oral NOAEL represents a worst case situation, as dermal absorption is considered to be lower compared to oral absorption.

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
6
Justification:
ECHA default for sub-acute to chronic. Conservative approach as it concerns an exposure duration around 45 days in an OECD 422 rather than a 28-day.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling rat to human
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results within category
AF for remaining uncertainties:
1
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:
0.5 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):
600
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As study is based on oral dosing, no route-to-route extrapolation is needed.

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
6
Justification:
ECHA default for sub-acute to chronic. Conservative approach as it concerns an exposure duration around 45 days in an OECD 422 rather than a 28-day.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling for rat to human
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results within category.
AF for remaining uncertainties:
1
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

These substances are only applied in professional or industrial setting in oilfield and mining applications applying adequate PPE. Use results to the inclusion into or onto a matrix. Consequently, consumers/general population will not be exposed.

In order to be able to evaluate possible secondary exposures via environment, additionally long-term systemic DNELs for general population have been derived. (Assessment of indirect exposure is not needed as the tonnage is not above 1000 tpa, and the substance not is classified as CMR or toxic (R48 or STOT-RE).