Lithium bromide

Toxicological Summary

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

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:

3.8 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 (EC) No 1907/2006, Annex VIII, section 8.6.1 (see IUCLID 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, please refer to the discussion

AF for the quality of the whole database:

1

Justification:

Please refer to the discussion

AF for remaining uncertainties:

1

Justification:

Please refer to the discussion

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:

10.9 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:

10.9 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Calculations based on worst case (human data, oral route). Performance of the study was waived according to column 2 of REACH Regulation (EC) No 1907/2006, Annex VIII, section 8.6.1 (see IUCLID section 7.5.2). 

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, please refer to the discussion

AF for the quality of the whole database:

1

Justification:

Please refer to the discussion

AF for remaining uncertainties:

1

Justification:

Please refer to the discussion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low 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.

Long-term inhalation exposure

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 bromide was based on the ADI (Acceptable Daily Intake) value of bromide (1.0 mg bromide/kg bw/day) being the toxicological limiting value for lithium bromide (see IUCLID section 7.5). Thus, the NOAEC (human) calculation for lithium bromide was based on the NOAEL (human) long-term value of bromide (1 mg Br-/kg bw/day) corresponding to 70 mg Br-/person/day (70 kg/person x 1 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 3.5 mg Br-/ m³ was calculated which is equivalent to 3.8 mg LiBr/m³.

NOAEC (worker)inhalation = 70 mg Br-/person/day x (1 / 10 m³/person/day(8h)) x (50 % Abs. / 100 % Abs.) = 3.5 mg Br-/ m³ = 3.8 mg LiBr/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 bromide) which is relevant for worker and general population including sub-populations. The resulting worker DNEL long-term inhalation = 3.8 mg LiBr/m³ : 1 (AFs) = 3.8 mg LiBr/m³.

Long-term dermal exposure

The NOAEL long-term dermal (human) of 10.9 mg (LiBr)/kg bw/day was calculated from the NOAEL long-term oral (human) of 1.09 mg LiBr/kg bw/day considering a conservative 10 % absorption through the skin (ECHA document R.7c, 2012, 7.12).

NOAEL long-term dermal = 1.09 mg LiBr/kg bw/day x 100 : 10 = 10.9 mg LiBr/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 bromide) which is relevant for workers and general population. The resulting DNEL long-term dermal = 10.9 mg/kg bw/day : 1 (AFs) = 10.9 mg LiBr/ kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.63 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:

1.63 mg/m³

Explanation for the modification of the dose descriptor starting point:

Calculations based on worst case

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, please refer to the discussion.

AF for the quality of the whole database:

1

Justification:

Please refer to the discussion.

AF for remaining uncertainties:

1

Justification:

Please refer to the discussion.

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:

10.9 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:

10.9 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 (EC) No 1907/2006, Annex VIII, section 8.6.1 (see IUCLID 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, please refer to the discussion.

AF for the quality of the whole database:

1

Justification:

Please refer to the discussion.

AF for remaining uncertainties:

1

Justification:

Please refer to the discussion.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.09 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:

1.09 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation was not required as an ADI for bromide is available.

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, please refer to the discussion.

AF for the quality of the whole database:

1

Justification:

Please refer to the discussion.

AF for remaining uncertainties:

1

Justification:

Please refer to the discussion.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.27 mg/kg bw/day

Most sensitive endpoint:

repeated dose 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:

low 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.

Long-term inhalation exposure

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 bromide was based on the ADI (Acceptable Daily Intake) value of bromide (1.0 mg bromide/kg bw/day) being the toxicological limiting value for lithium bromide (see IUCLID section 7.5). Thus, the NOAEC (human) calculation for lithium bromide was based on the NOAEL (human) long-term value of bromide (1 mg Br-/kg bw/day) corresponding to 60 mg Br-/person/day (60 kg/person x 1 mg Br-/kg bw/day). This value was converted to an inhalation NOAEC (human), assuming body weight of 60 kg for general population, 100 % absorption via the lung and 50 % absorption via the oral route, breathing volume of 20 m³/day and daily exposure period of 24 hours. Accordingly, a NOAEC of 1.5 mg Br-/ m³ was calculated which is equivalent to 1.63 mg LiBr/m³.

NOAEC (general population)inhalation = 60 mg Br-/person/day x (1 / 20 m³/person/day (24h)) x (50 % Abs. / 100 % Abs.) = 1.5 mg Br-/ m³ = 1.63 mg LiBr/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 bromide) which is relevant for worker and general population including sub-populations. The resulting general population DNEL long-term inhalation = 1.63 mg LiBr/m³ : 1 (AFs) = 1.63 mg LiBr/m³.

Long-term dermal exposure

The NOAEL long-term dermal (human) of 10.9 mg (LiBr)/kg bw/day was calculated from the NOAEL long-term oral (human) of 1.09 mg LiBr/kg bw/day considering a conservative 10 % absorption through the skin (ECHA document R.7C, 2008, 7.12)

NOAEL long-term dermal = 1.09 mg LiBr/kg bw/day x 100 : 10 = 10.9 mg LiBr/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 bromide) which is relevant for workers and general population. The resulting DNEL long-term dermal = 10.9 mg/kg bw/day : 1(AFs) = 10.9 mg LiBr/ kg bw/day.

Long-term oral exposure

For calculation of the NOAEL long-term oral of lithium bromide the following (human) data was available (see IUCLID section 7. 5): The NOAEL/DNEL of lithium (1.2 mg lithium/kg bw/day) and the (smaller) ADI value (comparable to DNEL) of bromide (1.0 mg bromide/kg bw/day). The calculated NOAEL oral of lithium bromide (1.086 mg lithium bromide/kg bw/day) based on the ADI of bromide is smaller than the calculated NOAEL of lithium bromide (15.01 mg lithium bromide/kg bw/day) based on the NOAEL/ DNEL of lithium. Thus, the determined NOAEL oral of lithium bromide is 1.086 mg lithium bromide/kg bw/day (rounded to 1.09 mg lithium bromide/kg bw/day) based on the ADI value of bromide being the toxicological limiting value for lithium bromide.

As the NOAEL long-term oral of lithium bromide is based on the ADI of bromide (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 bromide) which is relevant for general population and worker. DNEL (general population) long-term oral = 1.09 mg lithium bromide/kg bw/day : 1 (AFs) = 1.09 mg lithium bromide/kg bw/day.