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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.113 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Acute/short- and long-term dermal exposure – systemic and local effects

Skin contact is not a relevant route of human exposure for ashes (residues), cenospheres. Based on physicochemical properties (solid ceramic particles of mostly water insoluble compounds) and toxicokinetic behaviour (s. Toxicokinetics), ashes (residues), cenospheres and its main components are not expected to be dermally absorbed and hence bioavailable. Furthermore, for the substance analogue ashes (residues), coal no toxic effects were observed in acute oral and inhalation toxicity studies (s. Acute toxicity); ashes (residues) are not irritating to the skin or eyes and not skin sensitising (s. Irritation and Sensitisation). Therefore, no systemic or local effects are expected after acute/short- or long-term dermal exposure to ashes (residues).

 

Acute/short-term inhalation exposure – systemic and local effects

Based on physicochemical properties and toxicokinetic behaviour, acute/short-term inhalation exposure to ashes (residues), cenospheres is more likely to induce local effects in the lung rather than adverse systemic effects. This applies, however, mainly to respirable particles which are expected to be more slowly cleared upon deposition in the respiratory bronchioles and proximal alveoli.

In rats exposed to coal fly ash particles with a MMAD of 2.5 µm at 1400 mg/m³, 4 h/day for 3 consecutive days, no mortalities occurred and the LC50 was therefore considered to be greater than 1400 mg/m³ for these particles (Smith, 2006). Analyses of bronchoalveolar lavage and blood samples as well as histopathological examinations on lung tissue indicated the induction of inflammatory responses, such as an increase in alveolar macrophages, which are not considered as adverse effects specifically related to ashes (residues), but an adaptive natural response following exposure to a high concentration of insoluble particles.

The animal exposure conditions described correspond to an 8-hour human exposure to ca. 470 mg/m³ of respirable particles (assuming an inhalation volume of 10 m³ under light activity conditions). Such an exposure scenario is unrealistic under normal working conditions considering the current occupational exposure limits for respirable inert dust in the European Union, which range from 3 to 10 mg/m³ (8 h TWA).

Therefore, as no adverse effects are identified, which are based on intrinsic chemical properties of the substance, the minimum OEL value for respirable inert dust in the European Union (3 mg/m³) was adopted as DNEL. This approach is in compliance with the ECHA "Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health", May 2008.

However, it should be noted that the available data on particle size distribution indicate that only < 1.5% of the particles are contained in the respirable (alveolar) fraction of particles with MMAD < 5 µm. Therefore, ashes (residues), cenospheres have in general a low exposure potential to the alveolar region of the lung and most of the inhaled material would presumably intercept in the naso-pharyngeal region.

 

Long-term inhalation exposure – systemic and local effects

The available animal data on the repeated dose toxicity of the analogue substance ashes (residues), coal by inhalation exposure do not provide indications for systemic toxic effects. In fact, long-term inhalation exposure to the respirable fraction of ashes (residues) is most likely to result in local effects considered to be adaptive responses to the inhaled particles, which may become adverse as a result of particle overload at concentrations no longer relevant to humans in current occupational settings.

In a repeated dose inhalation toxicity study, groups of rats were exposed 8 h/day to respirable fly ash particles (MMAD 2 µm) for up to 90 days at 0.6 mg/m³, and up to 180 days at 4.2 mg/m³. No health effects were seen in the lower exposure group and only minor effects were found in the high exposure group. The observed effects included increased number and size of macrophages in bronchoalveolar lavage, and minor changes in secretion of glycoprotein (mucus), or viability, adherence and phagocytic index of ex vivo cultured macrophages. The mild effects were considered natural responses to inhaled particles and not unique to coal fly ash (Raabe et al., 1982). The systemic and local NOAEC for subchronic inhalation exposure to respirable fly ash particles was therefore 4.2 mg/m³. At the same time, this value was considered a local LOEC and local NOAEC, since the induced effects are not regarded as adverse.

The NOAEC value of 4.2 mg/m³ of respirable fly ash particles was selected as the relevant dose descriptor. This dose descriptor needs to be corrected for differences in inhalation absorption between rats and humans as well as for differences in the experimental and human exposure conditions. Additionally, for workers a correction is needed for the difference between respiratory rates under standard conditions and under conditions of light activity.

Corrected NOAEC = inhalatory NOAEC x (inhal. absorption rat/inhal. absorption human) x (exposure conditions rat/exposure conditions human) x (standard 8 h respiratory volume human/8 h respiratory volume worker under light activity)

Ashes (residues), cenospheres are no expected to be systemically absorbed via inhalation. Therefore a correction factor of 1 is applied, assuming no differences between rats and humans.

 

In the Raabe et al. (1982) study, rats were exposed for 8 h/day. Worker exposure is assumed to be 8 h/day. Thus, the dose descriptor is corrected by a factor of 1 (8 h per day /8 h per day).

A modification factor of 0.67 is applied to account for differences in 8 h inhalative volumes between workers in rest (6.7 m³) and workers under light activity (10 m³).

Corrected NOAEC =4.2 mg/m³ x 1 x (8h per day/8h per day) x 6.7m³/10

Corrected NOAEC =2.814 mg/m³

The DNEL for long-term exposure is derived by applying the following assessment factors (AF): an interspecies assessment factor (AF) of 1 for allometric scaling, since allometric scaling should not be applied in cases where doses in experimental animal studies are expressed as concentrations (e.g., in mg/m³ in air) as well as in cases of local effects; an interspecies AF of 2.5 for remaining differences; an intraspecies (human) AF of 5 for worker; an AF of 2 to account for exposure duration (extrapolation subchronic to chronic). This results in a total AF of 25. Applying this total AF to the corrected NOAEC mentioned above, results in an inhalation DNEL for local effects after long-term exposure of 0.113 mg/m³ of respirable ash particles.

The following table summarises the DNEL calculation steps and applied modification/assessment factors.

Step 1) Relevant dose descriptor

Local NOAEC (inhal., rat) = 4.2 mg /m³ of respirable particles

Step 2) Modification of starting point


Correction for differences between rat and human absorption

Correction for differences in the experimental and human exposure conditions

Correction for differences in 8-h inhalative volumes between workers in rest and workers under light activity

 

1

 

8 h per day/8 h per day

 

6.7 m³/10 m³

Step 3) Assessment factors

Interspecies
Intraspecies
Exposure duration (sub to chronic)

Quality of data base



1 x 2.5
5
2
1

DNEL value

0.113 mg/m³ of respirable particles
(4.2 x 1 x (8/8) x (6.7/10) x [1/(1 x 2.5 x 5 x 2 x 1)])

The above mentioned DNEL value applies for the alveolar fraction of ashes (residues), cenospheres particles. A DNEL value for ashes (residues), cenospheres as a whole is derived taking into account the content of respirable particles (< 5 µm).

The available data on granulometry indicates that the respirable (alveolar) fraction of ashes (residues), cenospheres comprises < 1.5% of the total particles. Therefore, the above mentioned DNEL value of 0.113 mg/m³ for respirable particles corresponds to a DNEL value for total ashes (residues), cenospheres of 7.5 mg/m³.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Ashes (residues), cenospheres are used in inclusion into or onto matrices. Therefore a risk potential to the general population is not expected at all.

Since exposure of the general public is not relevant, DNELs for the general population were not derived.