Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.9 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):
30
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
176.32 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL is 1000 mg/kg bw/day. This is converted to 176.32 mg/m3 based on ECHA guidance:

To convert the rat NOAEL (NoObservedAdverse Effect Level) to human NoAEL (No Adverse Effect Level) for interspecies variation (rat to human), a factor of0.38will be applied to account for the standard breathing volume of the rat for 8 hours, as per the ECHA Guidance (ECHA, 2008).

An additional conversion for workers of6.7m3/10m3to account for caloric demand during light activity will be applied.

An adjustment of x10/100%(oral absorption/inhalation absorption) will be applied to account for assumed bioavailability via the inhalatory route compared with the oral route. (i.e. low oral absorption as low toxicity seen via this route and has to pass into blood stream from the intestines versus high absorption straight from the lungs) (IGHRC, 2006).

1000 mg/kg bw/day * 1 / 0.38 mg3/kg/day * 0.1 abs oral/inhalation * 6.7 m3 / 10 m3 = 176.32 mg/m3

AF for dose response relationship:
1
Justification:
Value is a NOAEC so no additional AF needed
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic based on ECHA Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
Taken into account with modified dose descriptor starting point
AF for other interspecies differences:
1
Justification:
Taken into account with modified dose descriptor starting point
AF for intraspecies differences:
5
Justification:
ECHA guidance for workers
AF for the quality of the whole database:
1
Justification:
N/A
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.3 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
DNEL value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The dose response factor is 1 since the value is a NOAEL and not a LOAEL.
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic AF based on ECHA guidance
AF for interspecies differences (allometric scaling):
4
Justification:
Worker interspecies differences based on ECHA guidance
AF for other interspecies differences:
2.5
Justification:
other interspecies differences based on ECHA guidance
AF for intraspecies differences:
5
Justification:
Intraspecies differences AF based on ECHA guidance
AF for the quality of the whole database:
1
Justification:
N/A
AF for remaining uncertainties:
1
Justification:
N/A
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

Alkanolamine polyborates (MEA polyborates and DEA polyborates) are of low acute toxicity via the dermal route and are not sensitisers. A sub‑acute or chronic dermal study are not available.

The United Kingdom Interdepartmental Group on Health Risks from Chemicals document entitled ‘Guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals’ (IGHRC, 2006) states that oral to dermal extrapolation is common for industrial chemical and pesticide exposure. This document assumes that dermal bioavailability is less than oral (i.e. less substance will be absorbed via the skin due to its barrier properties), therefore, using the oral data is precautionary, providing that the skin is not compromised by the substance being a severe irritant and causing increased absorption through a more permeable barrier. MEA and DEA polyborates are not considered to be irritants, therefore, equivalent bioavailability can be assumed for oral and dermal exposure to provide a precautionary DNEL. The approach used in the IGHRC document is that used in the ECHA Guidance and is widely referenced.

A sub-acute (short-term) NOAEL of1000 mg/kg bw/dayhas been identified from a 28 day repeat dose oral study.

Worker

Long-term

A safety assessment factor of10will be applied to account for interspecies (rat to human) variation, as per the ECHA Guidance (ECHA, 2008).

A safety assessment factor of5will be applied to account for intraspecies variation (between workers, therefore not including sensitive sub-populations), as per the ECHA guidance.

In the absence of any long-term repeat dose studies, a safety assessment factor of6will be applied to account for use of a sub-acute NOAEL for a chronic DNEL, as per the ECHA Guidance.

Derived No Effect Level (DNELLong-term) for dermal exposure = 1000/(10x5x6) = 3.3 mg/kg bw/day

It should be recognised that in addition to defining a dermal DNEL, consideration should be given to whether it would be more relevant to assess and control the risk(s) of dermal exposure.

A sub-acute or chronic inhalation study is not available. In order to derive an inhalation DNEL, data can be converted from oral studies.

A sub-acute (short-term) NOAEL of1000 mg/kg bw/dayhas been identified from a 28 day repeat dose oral study.

Worker

Long-term

To convert the rat NOAEL (NoObservedAdverse Effect Level) to human NoAEL (No Adverse Effect Level) for interspecies variation (rat to human), a factor of0.38will be applied to account for the standard breathing volume of the rat for 8 hours, as per the ECHA Guidance (ECHA, 2008).

An additional conversion for workers of6.7m3/10m3to account for caloric demand during light activity will be applied.

An adjustment of x10/100%(oral absorption/inhalation absorption) will be applied to account for assumed bioavailability via the inhalatory route compared with the oral route. (i.e. low oral absorption as low toxicity seen via this route and has to pass into blood stream from the intestines versus high absorption straight from the lungs) (IGHRC, 2006).

A safety assessment factor of5will be applied to account for intraspecies variation (between workers, therefore not including sensitive sub-populations) (ECHA, 2008).

In the absence of any long-term repeat dose studies, a safety assessment factor of6will be applied to account for use of a sub-acute NOAEL for a chronic DNEL, as per the ECHA Guidance.

Derived No Effect Level (DNELLong-term) for inhalation exposure = [1000/(0.38x5x6)]x0.67x0.1 = 5.9mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.4 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):
60
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
86.96 mg/m³
Explanation for the modification of the dose descriptor starting point:

To convert the rat NOAEL (NoObservedAdverse Effect Level) to human NAEL (No Adverse Effect Level) for interspecies variation (rat to human), a factor of1.15will be applied to account for the standard breathing volume of the rat for 24 hours, as per the ECHA Guidance (ECHA, 2008).

An adjustment of x10/100%(oral absorption/inhalation absorption) will be applied to account for assumed bioavailability via the inhalatory route compared with the oral route (i.e. low oral absorption as low toxicity seen via this route and has to pass into blood stream from the intestines versus high absorption straight from the lungs) (IGHRC, 2006).

A safety assessment factor of10will be applied to account for intraspecies variation (between humans in the general population, to include sensitive sub-populations) (ECHA, 2008).

AF for dose response relationship:
1
Justification:
dose descriptor is a NOAEC
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic based on ECHA guidance
AF for interspecies differences (allometric scaling):
1
Justification:
accounted for in modificaiton of dose descriptor
AF for other interspecies differences:
1
Justification:
accounted for in modificaiton of dose descriptor
AF for intraspecies differences:
10
Justification:
ECHA guidance for General Population
AF for the quality of the whole database:
1
Justification:
N/A
AF for remaining uncertainties:
1
Justification:
N/A
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:
1.7 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
DNEL value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
ECHA Guidance on sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA Guidance on rat to human
AF for other interspecies differences:
2.5
Justification:
ECHA Guidance
AF for intraspecies differences:
10
Justification:
ECHA Guidance on General Population
AF for the quality of the whole database:
1
Justification:
N/A
AF for remaining uncertainties:
1
Justification:
N/A
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

A sub-acute (short-term) No Observed Adverse Effect Level (NOAEL) of1000 mg/kg bw/dayhas been identified from a 28 day repeat dose oral study.

General population

Long-term

A safety assessment factor of10will be applied to account for interspecies (rat to human) variation, as per the ECHA Guidance (ECHA, 2008).

A safety assessment factor of10will be applied to account for intraspecies variation (between humans in the general population, to include sensitive sub-populations) as per the ECHA Guidance.

In the absence of any long-term repeat dose studies, a safety assessment factor of6will be applied to account for use of a sub-acute NOAEL for a chronic DNEL, as per the ECHA Guidance.

Derived No Effect Level (DNELLong-term) for oral exposure = 1000/(10x10x6) = 1.7 mg/kg bw/day

Alkanolamine polyborates (including MEA and DEA polyborates) are of low acute toxicity via the dermal route and are not sensitisers. A sub‑acute or chronic dermal study are not available.

The United Kingdom Interdepartmental Group on Health Risks from Chemicals document entitled ‘Guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals’ (IGHRC, 2006) states that oral to dermal extrapolation is common for industrial chemical and pesticide exposure. This document assumes that dermal bioavailability is less than oral (i.e. less substance will be absorbed via the skin due to its barrier properties), therefore, using the oral data is precautionary, providing that the skin is not compromised by the substance being a severe irritant and causing increased absorption through a more permeable barrier. MEA and DEA polyborates are not considered to be irritants, therefore, equivalent bioavailability can be assumed for oral and dermal exposure to provide a precautionary DNEL. The approach used in the IGHRC document is that used in the ECHA Guidance and is widely referenced.

A sub-acute (short-term) NOAEL of1000 mg/kg bw/dayhas been identified from a 28 day repeat dose oral study.

General population

Long-term

A safety assessment factor of10will be applied to account for interspecies (rat to human) variation, as per the ECHA Guidance (ECHA, 2008).

A safety assessment factor of10will be applied to account for intraspecies variation (between in the general population, to include sensitive sub-populations) as per the ECHA Guidance.

In the absence of any long-term repeat dose studies, a safety assessment factor of6will be applied to account for use of a sub-acute NOAEL for a chronic DNEL, as per the ECHA Guidance.

Derived No Effect Level (DNELLong-term) for dermal exposure = 1000/(10x10x6) = 1.7 mg/kg bw/day

A sub-acute or chronic inhalation study is not available. In order to derive an inhalation DNEL, data can be converted from oral studies.

A sub-acute (short-term) NOAEL of1000 mg/kg bw/dayhas been identified from a 28 day repeat dose oral study.

General population

Long-term

To convert the rat NOAEL (NoObservedAdverse Effect Level) to human NAEL (No Adverse Effect Level) for interspecies variation (rat to human), a factor of1.15will be applied to account for the standard breathing volume of the rat for 24 hours, as per the ECHA Guidance (ECHA, 2008).

An adjustment of x10/100%(oral absorption/inhalation absorption) will be applied to account for assumed bioavailability via the inhalatory route compared with the oral route (i.e. low oral absorption as low toxicity seen via this route and has to pass into blood stream from the intestines versus high absorption straight from the lungs) (IGHRC, 2006).

A safety assessment factor of10will be applied to account for intraspecies variation (between humans in the general population, to include sensitive sub-populations) (ECHA, 2008).

In the absence of any long-term repeat dose studies, a safety assessment factor of6will be applied to account for use of a sub-acute NOAEL for a chronic DNEL, as per the ECHA Guidance.

Derived No Effect Level (DNELLong-term) for inhalation exposure = [1000/(1.15x10x6)]x0.1 = 1.4mg/m3