Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
57 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Additional information - workers

The DNEL for silicic acid, lithium salt for long-term exposure - systemic effects is derived on human data on long-term lithium treatment. Silicic acid, lithium salt contains 3.4% - 7% lithium depending on its molar ratio (MR: 2.8 - 6.3). The DNEL derivation is based on a molar ratio of 2.8 (corresponding to a lithium content of 7%; worst-case assumption)

Lithium is the drug of choice for the treatment of recurrent bipolar disorder for more than 50 years and has gained popularity as a pharmacological option in the treatment of other psychiatric conditions (Aral and Vecchio-Sadus, 2008). In general, plasma lithium levels are monitored during therapy. In lithium long-term therapy the recommended 12-hours serum lithium concentrations are 0.5 - 0.8 mM/L (corresponding to 3.5 - 5.6 mg Li/L). Lithium toxicity correlates with lithium serum levels while levels of 1.2 – 1.6 mM (corresponding to 8.3 – 11.1 mg Li/L) may pose a risk for intoxication (Lagerkvist and Lindell, 2002). Therefore 0.8 mM lithium levels are selected as dose desriptor for deriving a DNEL for long-term systemic effects. 0.8 mM are equivalent to 0.4 mg Li/kg bw/day based on a blood volume of 5 L and a body weight of 70 kg. To reach such lithium serum levels, 5.7 mg silicic acid, lithium salt (MR 2.8)/kg bw/day must be ingested, assuming that all lithium will be bioavailable and recovered in blood serum (worst-case scenario: 100% absorption).

Dermal and inhalative intakes are the possible exposure routes for workers. Thus, the dose descriptor (oral route) is 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 the oral dose descriptor (in mg/kg bw/d) into a dermal NAEL (in mg/kg bw/d), the differences in absorption between routes have to be accounted for. The absorption of silicic acid, lithium salt through skin is considered to be poor. Thus, upon dermal contact the bioavailibility is expected to be negligible. However, the conservative factor of 10% absorption is assumed when performing oral to dermal extrapolation (factor 10). This assumption results in the following NAEL for the dermal exposure route:

 NAEL dermal (corr) = oral dose descriptor x 10 = 57 mg/kg bw/day

 

The conversion of the oral dose descriptor into an inhalation dose descriptor is performed using the following equation:

For workers (8 h/exposure/d, light activity):

Corrected inhalatory dose descriptor = oral dose descriptor x 6.7m³/10m³

 

Based on the assumption, that all ingested silicic acid, lithium salt will be recovered in blood serum, no further default factor for absorption is used.

 

Assessment factors:

No inter-species assessment factor is needed, when human data are used for derivation of DNELs. In addition, no assessment factor for duration extrapolation is used, since the dose descriptor is based on long-term lithium treatment. No intra-species assessment factors are used, since according to generally acknowledgement, workers are healthier and/or more resistant than the general population and certainly than patients receiving lithium drugs and since no difference in absorption rates are applicable (100% "worst-case" absorption considered).

 

Thus a DNEL of 3.8 mg/m³ for long-term systemic effect via inhalation and a DNEL of 57 mg/kg bw/day for long-term system effects via the dermal route are derived based on a therapeutic lithium serum concentration of 0.8 mM.

   

The existing OEL (TRGS 900, June 2008) for dust is 3 mg/m³ (alveolar fraction) and 10 mg/m³ (respirable fraction). The more critical value of 3 mg/m³ is based on effects (5% elevation of the prevalence for chronic bronchitis and lung emphysema) observed in epidemiological studies taking into account a typical dust density at the workplace of 2.5 mg/cm³.

As the derived DNEL for inhalation is higher than the existing OEL for dust, long-term systemic effects caused by silicic acid, lithium salt are not expected to occur as long as the OEL is complied with.

However, because of the alkalinity of silicic acid, lithium salt, local irritation on mucous membranes, e. g. eyes have to be accounted for. Since no adequate dose descriptor for the corrosion/irritation effects could be derived, no DNEL is calculated for local effects. Appropriate risk management measures will be identified.

 

 

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

Silicic acid, lithium salt is used in inclusion into or onto matrices. Therefore a risk potential to the general population is not expected at all.

Since exposure for the general public is precluded, DNELs for the general population are not relevant and thus not derived.