Lithium nitrate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Modified dose descriptor starting point:

NOAEC

Value:

14.4 mg/m³

Explanation for the modification of the dose descriptor starting point:

Calculations based on worst case. Performance of the study was waived according to column 2 of REACH Regulation 1907/2006/EC Annex VIII section 8.6.1 (see section 7.5.2).  

AF for dose response relationship:

1

Justification:

NOAEL (human, oral) value was initially used for calculations

AF for differences in duration of exposure:

1

Justification:

Recommended AF (for chronic exposure) ECHA REACH Guidance document R8, 2012

AF for interspecies differences (allometric scaling):

1

Justification:

Not applicable according to ECHA REACH Guidance document R8, 2012

AF for other interspecies differences:

1

Justification:

Not applicable, derived from human data

AF for intraspecies differences:

1

Justification:

Not applicable, see below in "justification and comments"

AF for the quality of the whole database:

1

Justification:

See below in "justification and comments"

AF for remaining uncertainties:

1

Justification:

See below in "justification and comments"

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

41.1 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):

1

Modified dose descriptor starting point:

NOAEL

Value:

41.1 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Calculations based on worst case. Performance of the study was waived according to column 2 of REACH Regulation 1907/2006/EC Annex VIII section 8.6.1 (see section 7.5.2).  

AF for dose response relationship:

1

Justification:

NOAEL (human, oral) value was used for calculations

AF for differences in duration of exposure:

1

Justification:

Recommended AF (for chronic exposure) ECHA REACH Guidance document R8, 2012

AF for interspecies differences (allometric scaling):

1

Justification:

Not applicable, derived from human data

AF for other interspecies differences:

1

Justification:

Not applicable, derived from human data

AF for intraspecies differences:

1

Justification:

Not applicable, see below in "justification and comments"

AF for the quality of the whole database:

1

Justification:

See below in "justification and comments"

AF for remaining uncertainties:

1

Justification:

See below in "justification and comments"

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:

medium hazard (no threshold derived)

Additional information - workers

DNEL derivation for each of the relevant endpoints was based on the most conservative dose descriptors obtained. Assessment factors were assigned accordingly. Thus, the DNELs represent worst-case scenarios.

DNEL long-term inhalation, systemic effects

According to ECHA guidance document CSA: R8, 2012, for dust, if the derived DNEL for inhalation is above the general dust limit (10 mg/m³), then the general dust limit should be applied. As the calculated DNEL long term inhalation was determined to be 14.40 mg LiNO3/m³ (see below *), the DNEL considered for risk characterisation is the general dust limit (10 mg/m³).

* For DNEL long-term inhalation derivation, a NOAEC value was calculated by route-to-route extrapolation (ECHA CSA R8, 2012) from the NOAEL long-term oral (human) value. The NOAEL long-term oral (human) value of lithium nitrate was based on the ADI (Acceptable Daily Intake) value of nitrate (3.7 mg nitrate/kg bw/day) being the toxicological limiting value for lithium nitrate (see IUCLID section 7.5). Thus, the NOAEC (human) calculation for lithium nitrate was based on the NOAEL (human) long-term value of nitrate (3.7 mg nitrate/kg bw/day) corresponding to 259 mg nitrate/person/day (70 kg/person x 3.7 mg Br-/kg bw/day). This value was converted to an inhalation NOAEC (human), assuming 70 kg body weight for worker, 100 % absorption via the lung, 50 % absorption via the oral route and a daily exposure period of 8 hours during light activity (corresponding to breathing volume of 10 m³/day (8 h). Accordingly, a NOAEC of 12.95 mg nitrate/ m³ was calculated which is equivalent to 14.40 mg lithium nitrate/m³.

NOAEC (worker)inhalation = 259 mg nitrate/person/day x (1 / 10 m³/person/day(8h)) x (50 % Abs. / 100 % Abs.) = 12.95 mg nitrate/m³ = 14.40 mg lithium nitrate/m³.

An AF for exposure duration was not applicable as data covered long-term chronic exposure. Interspecies AFs were not applicable as the relevant NOAEL was derived from very reliable and relevant high quality human data. Intraspecies differences were considered not applicable as the NOAEL was based on a toxicological value (ADI of nitrate) which is relevant for worker and general population including sub-populations. The resulting worker DNEL long-term inhalation = 14.40 mg LiNO3/m³ : 1 (AFs) = 14.40 mg LiNO3/m³.

DNEL long-term dermal, systemic effects

The NOAEL long-term dermal of 41.1 mg (LiNO3)/kg bw/day was calculated from the NOAEL long-term oral of 4.11 mg (LiNO3)/kg bw/day considering a conservative 10 % absorption through the skin (ECHA document R.7c, 2012, 7.12).

NOAEL long-term dermal = 4.11 mg/kg bw/day x 100 : 10 = 41.1 mg/kg bw/day.

An AF for exposure duration was not applicable as data covered long-term chronic exposure. Interspecies AFs were not applicable as the relevant NOAEL was derived from very reliable and relevant high quality human data. Intraspecies differences were considered not applicable as the NOAEL was based on a toxicological value (ADI of nitrate) which is relevant for workers and general population.

The resulting DNEL long-term dermal = 41.1 mg LiNO3/ kg bw/day : 1 (AFs) = 41.1 mg LiNO3/ kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.12 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Modified dose descriptor starting point:

NOAEC

Value:

6.12 mg/m³

Explanation for the modification of the dose descriptor starting point:

Calculations based on worst case. Performance of the study was waived according to column 2 of REACH Regulation 1907/2006/EC Annex VIII section 8.6.1 (see section 7.5.2).  

AF for dose response relationship:

1

Justification:

NOAEL (human, oral) value was initially used for calculations

AF for differences in duration of exposure:

1

Justification:

Recommended AF (for chronic exposure) ECHA REACH Guidance document R8, 2012

AF for interspecies differences (allometric scaling):

1

Justification:

Not applicable, derived from human data

AF for other interspecies differences:

1

Justification:

Not applicable, derived from human data

AF for intraspecies differences:

1

Justification:

Not applicable, see below in "justification and comments"

AF for the quality of the whole database:

1

Justification:

See below in "justification and comments"

AF for remaining uncertainties:

1

Justification:

See below in "justification and comments"

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

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:

41.1 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):

1

Modified dose descriptor starting point:

NOAEL

Value:

41.1 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Calculations based on worst case. Performance of the study was waived according to column 2 of REACH Regulation 1907/2006/EC Annex VIII section 8.6.1 (see section 7.5.2).  

AF for dose response relationship:

1

Justification:

NOAEL (human, oral) value was used for calculations

AF for differences in duration of exposure:

1

Justification:

Recommended AF (for chronic exposure) ECHA REACH Guidance document R8, 2012

AF for interspecies differences (allometric scaling):

1

Justification:

Not applicable, derived from human data

AF for other interspecies differences:

1

Justification:

Not applicable, derived from human data

AF for intraspecies differences:

1

Justification:

Not applicable, see below in "justification and comments"

AF for the quality of the whole database:

1

Justification:

see below in "justification and comments"

AF for remaining uncertainties:

1

Justification:

See below in "justification and comments"

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:

4.11 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):

1

Modified dose descriptor starting point:

NOAEL

Value:

4.11 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation required

AF for dose response relationship:

1

Justification:

NOAEL used for calculations

AF for differences in duration of exposure:

1

Justification:

Recommended AF (for chronic exposure) ECHA REACH Guidance document R8, 2012

AF for interspecies differences (allometric scaling):

1

Justification:

Not applicable, derived from human data

AF for other interspecies differences:

1

Justification:

Not applicable, derived from human data

AF for intraspecies differences:

1

Justification:

Not applicable, see below in "justification and comments"

AF for the quality of the whole database:

1

Justification:

See below in "justification and comments"

AF for remaining uncertainties:

1

Justification:

See below in "justification and comments"

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Value:

12.33 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

DNEL derivation for each of the relevant endpoints was based on the most conservative dose descriptors obtained. Assessment factors were assigned accordingly. Thus, the DNELs represent worst-case scenarios.

DNEL long-term inhalation, systemic effects

For DNEL long-term inhalation derivation, a NOAEC value was calculated by route-to-route extrapolation (ECHA CSA R8, 2012) from the NOAEL long-term oral (human) value. The NOAEL long-term oral (human) value of lithium nitrate was based on the ADI (Acceptable Daily Intake) value of nitrate (3.7 mg nitrate/kg bw/day) being the toxicological limiting value for lithium nitrate (see IUCLID section 7.5). Thus, the NOAEC (human) calculation for lithium nitrate was based on the NOAEL (human) long-term value of nitrate (3.7 mg nitrate/kg bw/day) corresponding to 222 mg nitrate/person/day (60 kg/person x 3.7 mg nitrate/kg bw/day). This value was converted to an inhalation NOAEC (human), assuming 60 kg body weight for general population, 100 % absorption via the lung, 50 % absorption via the oral route and a daily exposure period of 24 hours during light activity (corresponding to breathing volume of 20 m³/day (8 h). Accordingly, a NOAEC of 5.55 mg nitrate/ m³ was calculated which is equivalent to 6.12 mg lithium nitrate/m³.

NOAEC (general population)inhalation = 222 mg nitrate/person/day x (1 / 20 m³/person/day(24h)) x (50 % Abs. / 100 % Abs.) = 5.55 mg nitrate/m³ = 6.12 mg lithium nitrate/m³.

An AF for exposure duration was not applicable as data covered long-term chronic exposure. Interspecies AFs were not applicable as the relevant NOAEL was derived from very reliable and relevant high quality human data. Intraspecies differences were considered not applicable as the NOAEL was based on a toxicological value (ADI of nitrate) which is relevant for worker and general population including sub-populations. The resulting general population DNEL long-term inhalation = 6.12 mg LiNO3/m³ : 1 (AFs) = 6.12 mg LiNO3/m³.

DNEL long-term dermal, systemic effects

The NOAEL long-term dermal of 41.1 mg (LiNO3)/kg bw/day was calculated from the NOAEL long-term oral of 4.11 mg (LiNO3)/kg bw/day considering a conservative 10 % absorption through the skin (ECHA document R.7c, 2012, 7.12).

NOAEL long-term dermal = 4.11 mg/kg bw/day x 100 : 10 = 41.1 mg/kg bw/day.

An AF for exposure duration was not applicable as data covered long-term chronic exposure. Interspecies AFs were not applicable as the relevant NOAEL was derived from very reliable and relevant high quality human data. Intraspecies differences were considered not applicable as the NOAEL was based on a toxicological value (ADI of nitrate) which is relevant for workers and general population.

The resulting DNEL long-term dermal = 41.1 mg LiNO3/ kg bw/day : 1 (AFs) = 41.1 mg LiNO3/ kg bw/day.

DNEL long-term oral, systemic effects

For calculation of the NOAEL long-term oral of lithium nitrate the following (human) data was available (see IUCLID section 7. 5): The ADI value of nitrate (3.7 mg nitrate/kg bw/day) and the NOAEL/DNEL of lithium (1.2 mg lithium/kg bw/day). The calculated NOAEL oral of lithium nitrate (4.11 mg lithium nitrate/kg bw/day) based on the ADI of nitrate is smaller than the calculated NOAEL of lithium nitrate (11.92 mg lithium nitrate/kg bw/day) based on the NOAEL/ DNEL of lithium. Thus, the determined NOAEL oral of lithium nitrate is 4.11 mg lithium nitrate/kg bw/day based on the ADI value of nitrate being the toxicological limiting value for lithium nitrate.

As the NOAEL long-term oral of lithium nitrate is based on the ADI of nitrate (comparable to DNEL), it can be assumed that the AFs were already included. Thus, no AFs were considered (AF = 1). It can also be explained and detailed as following: An AF for exposure duration was not applicable, as data available covered long-term chronic exposure. Interspecies AFs were not applicable as the relevant NOAEL was derived from reliable and relevant high quality human data. Intraspecies differences were considered not applicable as the NOAEL was based on a toxicological value (ADI nitrate) which is relevant for general population and worker. DNEL (general population) long-term oral = 4.11 mg lithium nitrate/kg bw/day : 1 (AFs) = 4.11 mg lithium nitrate/kg bw/day.