Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
37.5 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
22.5
Dose descriptor starting point:
LOAEC
Value:
500 mg/m³
Modified dose descriptor starting point:
LOAEC
Value:
844.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

Remark on the starting point :

At 500 mg/m3 one female was sacrificed on day 5 but no further clinical signs were observed during exposure. After exposure, abnormal posture, hunched posture, piloerection, dehydration, lean appearance and/or ptosis were seen among the animals. The surviving animals had recovered from the symptoms by Day 11. No abnormalities were found at macroscopic examination. Therefore, 500 mg/m3 is interpreted as a LOAEC for acute effects.

The corrected inhalatory LOAEC has been calculated considering :

- the difference of exposure conditions between experimental animals and workers (4h/d and 15min/d respectively) by applying the modified Harber's law (Cn* t = k, where ‘C’ is the concentration, ‘n’ is a regression coefficient, ‘t’ is the exposure time and ‘k’ is a constant) and a default value of n=3 for extrapolating from longer to shorter exposure durations : dose at 15min = (500^3 * (240/15))^(1/3) = 1260 mg/m3

- the difference between the standard respiratory volume and the worker respiratory volume for a light activity (i.e. 6.7 m3/person and 10m3 / person respectively) by applying a factor of 0.67

AF for dose response relationship:
3
Justification:
The starting point for the DNEL derivation is a LOAEL.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not applicable when setting an inhalation DNEL based on an inhalation animal study (in accordance with ECHA guidance R8)
AF for other interspecies differences:
2.5
Justification:
For inhalation studies only a factor 2.5 is used, and no correction is made for differences in body size, because extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans; animals and humans breathe at a rate depending on their caloric requirements.
AF for intraspecies differences:
3
Justification:
An overall intraspecies factor of ≤ 3 is justified for workers when local respiratory effects by inorganic metal compounds that do not undergo metabolism are considered (Hattis et al., 1987; Hattis and Silver, 1994; Renwick and Lazarus, 1998; ECETOC 2010).
AF for the quality of the whole database:
1
Justification:
The available information fulfil the requirement of the REACH registration.
AF for remaining uncertainties:
1
Justification:
The global assessment factor applied is considered to be sufficiently protective as it follows the ECHA guidance R8.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.11 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
9
Dose descriptor:
NOAEC
Value:
1.01 mg/m³
AF for dose response relationship:
1
Justification:
The dose descriptor is a NOAEC which is considered as an appropriate starting point.
AF for differences in duration of exposure:
3
Justification:
Local effects such as respiratory tract irritation are more driven by the concentration of the substance rather than the duration of the exposure. Furthermore human data available on cryolite (CAS: 13775-53-6) (substance which can be choosen as an analogue) give no indication for cryolite specific chronic respiratory effects after inhalation exposure (local effects). Therefore taken into account all this information, an assessment factor of 3 for the variability of the time duration appears to be enough conservative.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling should not be applied if the effects are not dependent on metabolic rate or systemic absorption, e.g. in the case of local effects. (According to ECHA guidance R8).
AF for other interspecies differences:
1
Justification:
For respiratory (local) toxicity effects after inhalation of particles of most metal-containing substances in the respirable range, 1-5 µm, rats seem to be more susceptible to toxicity effects than primates or humans (Oberdörster, 1995; Mauderly, 1997; ILSI, 2000; Nikula et al., 2001; Greim and Ziegler-Skylakakis, 2007).
As rats are the most sensitive animal species to the inhalation effects of inorganic particulates, further toxicodynamic adjustments are not needed.
AF for intraspecies differences:
3
Justification:
An overall intraspecies factor of ≤ 3 is justified for workers when local respiratory effects by inorganic metal compounds that do not undergo metabolism are considered (Hattis et al., 1987; Hattis and Silver, 1994; Renwick and Lazarus, 1998; ECETOC 2010).
AF for the quality of the whole database:
1
Justification:
The available information fulfil the requirement of the REACH registration.
AF for remaining uncertainties:
1
Justification:
The global assessment factor applied is considered to be sufficiently protective as it follows the ECHA guidance R8.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

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

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 µg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
36
Dose descriptor:
other: Modified NOAEC as corrected starting point : NOAEC = 1.01 mg/m3 (results of the sub-acute inhalatin toxicity study), corrected for exposure duration in study (6 hrs/day) to default population exposure (24 hrs/day).
Value:
0.25 mg/m³
AF for dose response relationship:
1
Justification:
The dose descriptor is a NOAEC which is considered as an appropriate starting point.
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic (in accordance with ECHA guidance R8)
AF for interspecies differences (allometric scaling):
1
Justification:
No factor for allometric scaling is needed in case of inhalation exposure.
AF for other interspecies differences:
1
Justification:
For respiratory (local) toxicity effects after inhalation of particles of most metal-containing substances in the respirable range, 1-5 µm, rats seem to be more susceptible to toxicity effects than primates or humans (Oberdörster, 1995; Mauderly, 1997; ILSI, 2000; Nikula et al., 2001; Greim and Ziegler-Skylakakis, 2007).
As rats are the most sensitive animal species to the inhalation effects of inorganic particulates, further toxicodynamic adjustments are not needed.
AF for intraspecies differences:
6
Justification:
The critical effect is a direct local effect that is hardly if at all, mainly determined by toxicodynamics and kinetics. Absorption, distribution and elimination play no/a minor role.
An overall intraspecies factor of ≤ 3 is justified for workers when local respiratory effects by inorganic metal compounds that do not undergo metabolism are considered (Hattis et al., 1987; Hattis and Silver, 1994; Renwick and Lazarus, 1998; ECETOC 2010). Using a reduced factor of 6 is therefore justified for general population.
AF for the quality of the whole database:
1
Justification:
The available information fulfil the requirement of the REACH registration.
AF for remaining uncertainties:
1
Justification:
The global assessment factor applied is considered to be sufficiently protective as it follows the ECHA guidance R8.
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:
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The oral route is not relevant for the exposure of lithium cryolite.

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