Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
DNEL related information
DNEL derivation method:
other: A guideline value (the current long-term exposure limit (http://www.hse.gov.uk/pubns/books/eh40.htm)) based on outcome of an epidemiological study.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
28 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Where relevant data are available, local and systemic DNELs for worker exposure to Ash have been developed based on assessment factors recommended by ECETOC (Derivation of Assessment Factors for Human Health Risk Assessment.Technical Report No. 86, pp 86, ECETOC, Brussels, February 2003).

 

Acute systemic effects

A DNEL for acute toxicity should be derived if a hazard leading to acute toxicity (e.g. C&L) has been identified and there is a potential for high peak exposures. The TGD notes that such peaks are normally associated with inhalation exposure but are less common for skin contact and ingestion (ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. Appendix R.8-8). Regarding systemic effects the 28 -day oral toxicity study revealed no toxicologically relevant systemic effects at 2000 mg/kg bw/day. Therefore no acute systemic effects are likely after dermal or inhalation exposure.

 

Acute local effects

Due to high pH (>11.5) of Ash there is a risk for local effects on lungs and skin.

 

Long-term systemic effects

The potential of Ash to cause long-term systemic effects can be judged from results of repeated dose testing.

The following NOAELs / NOAECs are presented in the IUCLID dossier:

sub-acute effects: rat oral NOAEL = 2000 mg/kg bw/day

chronic effects: inhalation: 10 mg/m3. DNEL 10 mg/m3 has been shown to be in agreement with the outcome of the cross-sectional epidemiological study carried out for workers after long-term occupational exposure to pulverized fuel ash (Schilling et al., 1988), and it is the current long-term exposure limit 8-h TWA for pulverised fuel ash issued by the UK Health and Safety Executive(http://www.hse.gov.uk/pubns/books/eh40.htm).

Oral

No oral DNEL is required for Workers.

Dermal

Dose descriptor

A rat oral sub-acute NOAEL of 2000 mg/kg bw/day will be used with appropriate modification to derive a dermal DNEL.

Modification of dose descriptor

In the absence of information to the contrary it is assumed that oral uptake and dermal uptake are identical (ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. Section R.8.4.2, Ad2).

For workers, no modification of the NOAEL is required.

Assessment factors and DNELs

DNELworker-dermal = 2000 / 72 = 28 mg/kg bw/day

Inhalation

Dose descriptor

Assessment factors and DNELs

DNELworker-inhalation = 10 mg/m3. DNEL 10 mg/m3 has been shown to be in agreement with the outcome of the cross-sectional epidemiological study carried out for workers after long-term occupational exposure to pulverized fuel ash (Schilling et al., 1988), and it is the current long-term exposure limit 8-h TWA for pulverised fuel ash issued by the UK Health and Safety Executive(http://www.hse.gov.uk/pubns/books/eh40.htm).

 

Long-term local effects

Due to high pH (>11.5) of Ash there is a risk for local effects on lungs and skin.

Developmental Effects

Oral NOAEL for developmental effects = 1000 mg/kg bw/day (OECD Test Guideline 414)

Oral DNEL

AF interspecies (rat > human) = AS x 2.5 = 4 x 2.5 = 10

AF intraspecies = 10

Oral DNEL general population = 1000 mg/kg bw/day / 10 x 10 = 10 mg/kg bw/day

Oral DNEL worker = 1000 mg/kg bw/day / 10 x 5 = 20 mg/kg bw/day

 

Inhalation DNEL

Oral NOAEL x 1/sRVratx ABSoral-rat/ABSinh-human  

Assumptions

Inhalation bioavailability = 100%

Oral bioavailability = 50%

sRVrat= 0.38 m3                                   

sRVhuman= 0.6.7 m3

wRV = 10 m3

Human body weight = 70 kg

 

 

For workers

Corrected inhalatory NOAEC = Oral NOAEL x 1/sRVratx ABSoral-rat/ABSinh-humanx sRVhuman/wRV

= 1000 mg/kg bw/d x 1/0.38 m3/kg/d x 50/100 x 6.7 m3(8h)/10 m3(8h) = 882 mg/m3

or

1000 mg/kg bw/d /4 = 250 mg/kg bw/d NAEL human

250 mg/kg bw/d x 70 kg = 17500 mg/person/d

17500 mg/person/d / 10 m3/person/d = 1750 mg/m3

1750 mg/m3x 50/100 = 875 mg/m3 NAEC worker

NAECÞDNEL

Inhalation DNEL for workers = 882 mg/m3/ 2.5 x 5 = 71 mg/m3

As inhalation DNEL (developmental) is much higher than the guideline value 10 mg/m3 used in the CSA, no updates in the CSA are required based on DNEL(developmental)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
DNEL related information
DNEL derivation method:
other: A guideline value (the current long-term exposure limit (http://www.hse.gov.uk/pubns/books/eh40.htm)) based on outcome of an epidemiological study.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Where relevant data are available, local and systemic DNELs for worker exposure to Ash have been developed based on assessment factors recommended by ECETOC (Derivation of Assessment Factors for Human Health Risk Assessment. Technical Report No. 86, pp 86, ECETOC, February 2003).

 

Acute systemic effects

A DNEL for acute toxicity should be derived if a hazard leading to acute toxicity (e.g. C&L) has been identified and there is a potential for high peak exposures. The TGD notes that such peaks are normally associated with inhalation exposure but are less common for skin contact and ingestion (ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. Appendix R.8-8). Regarding systemic effects the oral range-finding study revealed no systemic effects at 1000 mg/kg bw/day for 7 days. Therefore no acute systemic effects are likely after dermal or inhalation exposure.

 

Acute local effects

Due to high pH (>11.5) of Ash there is a risk for local effects on lungs and skin.

 

Long-term systemic effects

The potential of Ash to cause long-term systemic effects can be judged from results of repeated dose testing.

The following NOAELs / NOAECs are presented in the IUCLID dossier:

sub-acute effects: rat oral NOAEL = 2000 mg/kg bw/day

chronic effects: rat inhalation DNEL = 10 mg/m3. DNEL 10 mg/m3 has been shown to be in agreement with the outcome of the cross-sectional epidemiological study carried out for workers after long-term occupational exposure to pulverized fuel ash (Schilling et al., 1988), and it is the current long-term exposure limit 8-h TWA for pulverised fuel ash issued by the UK Health and Safety Executive(http://www.hse.gov.uk/pubns/books/eh40.htm).

 

Oral

Dose descriptor

A rat oral NOAEL of 2000 mg/kg bw /day will be used.

Modification of dose descriptor

In the absence of information to the contrary it is assumed that oral absorption of Ash by humans is identical to that in the rat and, therefore, no modification of the dose descriptor is required.

Assessment factors and DNELs

DNELgeneral population-oral = 2000 / 120 = 17 mg/kg bw/day

 

Dermal

Dose descriptor

A rat oral sub-acute NOAEL of 2000 mg/kg bw/day will be used with appropriate modification to derive a dermal DNEL.

Modification of dose descriptor

In the absence of information to the contrary it is assumed that oral uptake and dermal uptake are identical (ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. Section R.8.4.2, Ad2).

For general population, no modification of the NOAEL is required.

Assessment factors and DNELs

DNELgeneral population-dermal = 2000 / 120 = 417 mg/kg bw/day

 

Inhalation

Dose descriptor

Assessment factors and DNELs

DNELgeneral population-inhalation = 10 mg/m3. DNEL 10 mg/m3 has been shown to be in agreement with the outcome of the cross-sectional epidemiological study carried out for workers after long-term occupational exposure to pulverized fuel ash (Schilling et al., 1988), and it is the current long-term exposure limit 8-h TWA for pulverised fuel ash issued by the UK Health and Safety Executive(http://www.hse.gov.uk/pubns/books/eh40.htm).

 

Long-term local effects

Due to high pH (>11.5) of Ash there is a risk for local effects on lungs and skin.