Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 mg/m³
DNEL related information
DNEL derivation method:
other: The general exposure limit for inhalable dust is applied
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 mg/m³
DNEL related information
DNEL derivation method:
other: The general exposure limit for inhalable dust is applied

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 mg/m³
DNEL related information
DNEL derivation method:
other: The general exposure limit for inhalable dust is applied
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33.3 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):
30
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
according to ECHA guidance
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

Identification of relevant dose descriptor

The test substance is a solid with very low solubility properties and no signs of toxicity in any of the studies performed, indicating that the test article's potential to be systemically available is very low. Nevertheless, DNELs for systemic effects are established for a worst case assessment. In the available combined repeated dose toxicity study with the reproduction / developmental toxicity screening performed with the test item, a NOAEL of 1000 mg/kg body weight was established (highest doses tested). This value was used as point of departure for DNEL calculation.

Calculation of DNELs

Systemic, long-term, dermal:

DNEL = NOAEL (oral) / Sum of assessment factors applicable

The dermal route is typically covered by oral route information in the absence of data for this administration route. Since no data on penetration through skin are available, the dermal absorption property is evaluated based on physic-chemical parameters. The test substance is characerized by low solubility in both water and organic solvents. In addition, the molecular weight is above 500. As a result, absorption via the dermal route is anticipated to be very low. This is taken into account by applying an additional factor of 0.1. The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen:

Intraspecies differences (worker): 5

Interspecies variations: 2.5

Allometric scaling (rat to human): 4

Exposure duration: 6

Oral to dermal route extrapolation factor: 0.1

Dose-response factor: 1

Quality of whole database factor: 1

Overall, an assessment factor of 30 was employed for the dermal route.

DNEL= 1000 mg/kg body weight / 30 = 33.3 mg/kg body weight.

Systemic, long-term, inhalative

Because no inhalation study is available, a route to route extrapolation was performed. The NOAEL (oral) is converted into a NOAEC (corrected) in accordance to guidance on information requirements and chemical safety assessment, Chapter R.8, ECHA, 2012. The NOAEL (oral) has to be divided by a factor of 0.38 m3/kg body weight and corrected for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3). In addition, a default factor of 2 is applied to account for differences in oral and inhalative absorption properties. The corrected starting point is therefore:

NOAEC (corrected) = 1000 mg/kg / 0.38 m3/kg x 0.5 x (6.7 m3/10m3) = 882 mg/m3

The DNEL is calculated as follows: NOAEC (corrected) / Sum of assessment factors applicable.

The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen:

Intraspecies differences (worker): 5

Interspecies variations: 2.5

Exposure duration: 6

Dose-response factor: 1

Quality of whole database factor: 1

The overall assessment factor employed for the inhalation route is therefore 75.

DNEL = 882 mg/m3 / 75 = 11.75 mg/m3

However, since the substance is an insoluble solid for which no systemic hazard was identified by the oral route, the systemic DNEL derived above is considered not relevant. The main hazard results if dusty material is inhaled at doses at which the natural clearance function of the lung is overloaded. To protect against this effect, the general exposure limit of 1.25 mg/m3 for inhalable inert dust is applied.

Systemic, short-term, dermal and inhalative

According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified. Therefore, because the substance is not classified for acute toxicity according to Directive 67/548/EEC and Regulation 1272/2008/EC, no systemic DNELs for short-term exposures were calculated. Regarding exposure by inhalation, the main hazard results if dusty material is inhaled at doses at which the natural clearance function of the lung is overloaded. To protect against this hazard, the general exposure limit for inhalable inert dust is applied. This value is considered to give also sufficient protection for acute effects.

Local, long-term and short-term, inhalative

The main hazard results if dusty material is inhaled at doses at which the natural clearance function of the lung is overloaded. To protect against this effect, the general exposure of limit of 1.25 mg/m3 for inhalable inert dust is applied.

 

Local, long-term and short-term, dermal

Based on the available key toxicological information, the test item is not subject to classification for skin and eye irritation and skin sensitization (according to 67/548/EEC and EC/1272/2008). Accordingly, no DNELs for local effects following acute/short-term or long-term exposure are derived. This is in line with the ECHA guidance document (Chapter R.8).

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:
DNEL (Derived No Effect Level)
Value:
16.7 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):
60
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
according to ECHA guidance
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:
1.67 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
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

Identification of relevant dose descriptor

The dose descriptor chosen is the same as for workers (see above). The NOAEL of 1000 mg/kg was used as starting point to derive the DNELs.

Calculation of DNELs

Systemic, long-term, dermal:

DNEL = NOAEL (oral) / Sum of assessment factors applicable

The dermal route is typically covered by oral route information in the absence of data for this administration route. Since no data on penetration through skin are available, the dermal absorption property is evaluated based on physic-chemical parameters. The test substance is characerized by low solubility in both water and organic solvents. In addition, the molecular weight is above 500. As a result, absorption via the dermal route is anticipated to be very low. This is taken into account by applying an additional factor of 0.1. The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen:

Intraspecies differences (general population): 10

Interspecies variations: 2.5

Allometric scaling (rat to human): 4

Exposure duration: 6

Oral to dermal route extrapolation factor: 0.1

Dose-response factor: 1

Quality of whole database factor: 1

Overall, an assessment factor of 60 was employed for the dermal route.

DNEL= 1000 mg/kg body weight / 60 = 16.7 mg/kg body weight.

Systemic, long-term, oral:

The established oral NOAEL of 1000 mg/kg body weight observed in the combined repeated dose toxicity study was used as starting point for DNEL derivation. The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen:

Intraspecies differences (general population): 10

Interspecies variations: 2.5

Allometric scaling (rat to human): 4

Exposure duration: 6

Dose-response factor: 1

Quality of whole database factor: 1

The overall assessment factor employed for the inhalation route is therefore 600.

DNEL = 1000 mg/kg body weight / 600 = 1.67 mg/kg body weight

Local and systemic, short term and long-term, inhalative

The pure, dusty product is neither intended for use by the general population nor are there any possible use scenarios that might be of interest to the general population. The chemical is embedded in polymer and plastic materials at low concentrations. Based on the very low vapor pressure, evaporation from these materials is not possible. Therefore, no inhalative DNELs for the general population need to be derived.

Systemic, short-term, dermal and oral

According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified. Therefore, because the substance is not classified for acute toxicity according to Directive 67/548/EEC and Regulation 1272/2008/EC, no systemic DNELs for short-term exposures were calculated.

Local, long-term and short-term, dermal

Based on the available key toxicological information, the test item is not subject to classification for skin and eye irritation and skin sensitization (according to 67/548/EEC and EC/1272/2008). Accordingly, no DNELs for local effects following acute/short-term or long-term exposure are derived. This is in line with the ECHA guidance document (Chapter R.8).