Zeolite, silica rich, without aluminium, crystalline, synthetic, non fibrous

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3 mg/m³

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - workers

Long term exposure - systemic effects: Dermal DNEL in mg/kg bw/day: 2.5 -3.0

In principle, if there is no dose descriptor for the dermal exposure route available, the available dose descriptor (oral route, systemic effect) can be converted into a correct starting point by route-to route extrapolation according to the ECHA guidance document "Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health", May 2008.

To convert an oral N(L)OAEL (in mg/kg bw/d) into a dermal N(L)OAEL, the differences in absorption between routes as well as differences in dermal absorption between rats and humans have to be accounted for. Since the oral bioavailablility of zeolites in beagle dogs is less than 3.5 % (Cefali et al. 1996, see chapter 7.1), the bioavailability can be neglected. On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral to dermal extrapolation. Furthermore the same bioavailability for experimental animals and humans is assumed (no default factor, i.e.factor 1). This assumptions results in the identical N(L)OAEL for the oral and dermal exposure route.

As the synthetic zeolites exposure at the workplace is neither regulated on the EU level nor in any of the member states, the limits for the exposure at the workplace are derived from the generic dust limits. The generic dust limits for inorganic dust is defined in Germany in TRGS 900 chapter 2.6, taking into account particle size, solubility and density of the substance. The AGW (workplace exposure limits) are defined as 10 mg/m³for inhalable and 3 mg/m³for respirable dust. It is proposed to adopt the more critical value of 3 mg/m³ 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.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.75 mg/m³

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

200

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

200

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - General Population

Long term exposure - systemic effects: Oral and dermal DNEL in mg/kg bw/day: 1.25 -1.5

In principle, if there is no dose descriptor for the dermal exposure route available, the available dose descriptor (oral route, systemic effect) can be converted into a correct starting point by route-to route extrapolation according to the ECHA guidance document "Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health", May 2008.

To convert an oral N(L)OAEL (in mg/kg bw/d) into a dermal N(L)OAEL, the differences in absorption between routes as well as differences in dermal absorption between rats and humans have to be accounted for. Since the oral bioavailablility of zeolites in beagle dogs is less than 3.5 % (Cefali et al. 1996, see chapter 7.1), the bioavailability can be neglected. On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral to dermal extrapolation. Furthermore the same bioavailability for experimental animals and humans is assumed (no default factor, i.e.factor 1). This assumptions results in the identical N(L)OAEL for the oral and dermal exposure route.

As already discussed for the worker´s inhalation, the general tendency of Zeolites to form agglomerates and the fast settling behavior of air borne dust as well as the long term monitoring of workers health conditions (with regard to the read across substance Zeolite, cuboidal, crystalline, synthetic, non-fibrous) strongly support the existing exposure limits of 10 mg/m³inhalable and 3 mg/m³respirable dust. Therefore the DNEL can be derived using the more critical OEL of 3 mg/m³respirable dust taking into consideration the higher respiratory volume and the higher sensitivity of a consumer (according to the ECHA guidance document "Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health", May 2008).