Lithium bis(trifluoromethylsulfonyl)imide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.24 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):

75

Modified dose descriptor starting point:

NOAEC

Value:

17.6 mg/m³

AF for dose response relationship:

1

Justification:

Not required, starting point is NOAEC

AF for differences in duration of exposure:

6

Justification:

Extrapolation from sub-acute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not necessary for the inhalation route

AF for other interspecies differences:

2.5

Justification:

Default factor for remaining differences

AF for intraspecies differences:

5

Justification:

Default factor for workers

AF for the quality of the whole database:

1

Justification:

Database of appropriate quality

AF for remaining uncertainties:

1

Justification:

No remaining uncertainty identified

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:

low hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

A DNEL value was derived for systemic effects after long-term exposure in workers by inhalation. The key study for DNEL derivation was identified as a repeated dose oral study according to OECD 407 (Edwards, 1993). In this study TFSILi was adminstered by daily oral gavage followed by a 14 -day recovery period to male and femlae Sprague-Dawley rats at dose levels of 1.67, 10 and 60 mg/kg/day. Based on the results the liver was identified as a principal target organ at 60 mg/kg/day, the high dose. The effects of treatment at 10 mg/kg/day were considered minor in nature and for this reason this dose level is considered to be the NOAEL.

The DNEL for chronic systemic toxicity for the inhalation is derived via route-to-route extrapolation based on the repeated dose oral toxicity study.

No data on toxicokinetics, metabolism and distribution are available for TFSILi. Based on its high water-solubility, moderate molecular weight and the effects observed in rats upon (sub)acute oral exposure and acute dermal exposure, the substance is expected to be well absorbed by the gastro-intestinal and respiratory tracts and through the skin. Therefore the absorption value is assumed to be 100% for all routes.

Worker DNELs

Long-term inhalation, systemic effects

As inhalation repeated dose toxicity studies with TFSILi are not available, route to route extrapolation was applied to derive a DNEL for the inhalation route, based on the results of an oral OECD 407 study in rat (Edwards, 1993) where an NOAEL of 10 mg/kg bw/day was derived.

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 10 mg/kg bw/day	In a repeated dose toxicity study according to OECD 407, TFSILi was adminstered by daily oral gavage followed by a 14-day recovery period to male and female Sprague-Dawley rats at dose levels of 1.67, 10 and 60 mg/kg/day. Based on the results the liver was identified as a principal target organ at 60 mg/kg/day, the high dose. The effects of treatment at 10 mg/kg/day were considered minor in nature and for this reason this dose level is considered to be the NOAEL.
Step 2) Modification of starting point	1               0.38 m^3/kg bw         6.7 m^3/10 m^3	Based on the moderate molecular weight (287.08 g/mol), the high water solubility, and the low log Pow (< -1) it is assumed that oral absorption of the test substance is high. Consequently, a default factor of 1 is included for route-to-route extrapolation, which means that 100% absorption is assumed for oral and inhalation route.     Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2).   Correction for activity driven differences of respiratory volumes in workers compared to workers in rest.
Modified dose-descriptor	10 / 1 / 0.38 x (6.7/10) = 17.6 mg/m3
Step 3) Assessment factors
Interspecies	2.5	No factor for allometric scaling is needed in case of inhalation exposure.A default factor of 2.5 for remaining uncertainties is used.
Intraspecies	5	Default AF for workers
Exposure duration	6	Extrapolation to chronic exposure based on a sub-acute toxicity study
Dose response	1
Quality of database	1
DNEL	Value
Step 4) Calculate DNEL	17.6 / (2.5 x 5 x 6 x 1 x 1) = 0.235 mg/m3

   

General Population - Hazard via inhalation 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

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:

DNEL (Derived No Effect Level)

Value:

0.017 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):

600

Dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation was performed.

AF for dose response relationship:

1

Justification:

Not required, starting point is NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Extrapolation rat to human

AF for other interspecies differences:

2.5

Justification:

remaining differences

AF for intraspecies differences:

10

Justification:

general population

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not required

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

As there is no consumer use for Bis trifluoromethanesulfonimide Lithium (TFSILi), no inhalation and dermal DNELs for the general population were calculated. However, the deposition of TFSILi onto soil or vegetation may lead to exposure of the general public, therefore, a long-term oral DNEL for the general population was calculated. No route-to-route extrapolation had to be performed since the DNEL has been derived from a NOAEL observed in a sub-acute oral toxicity study.

Long-term – oral, systemic effects (based on sub-acute oral toxicity study with rats)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 10 mg/kg bw/day	In a repeated dose toxicity study according to OECD 407, TFSILi was administered by daily oral gavage followed by a 14-day recovery period to male and female Sprague-Dawley rats at dose levels of 1.67, 10 and 60 mg/kg/day. Based on the results the liver was identified as a principal target organ at 60 mg/kg/day, the high dose. The effects at 10 mg/kg/day were considered minor in nature and for this reason this dose level is considered to be the NOAEL.
Step 2) Modification of starting point	-
Step 3) Assessment factors
Interspecies	4 x 2.5	Default assessment factors for allometric scaling and remaining interspecies differences.
Intraspecies	10	Default assessment factor for general population
Exposure duration	6	Extrapolation to chronic exposure based on a sub-acute toxicity study.
Dose response	1
Quality of database	1
DNEL	Value
	10 / (4 x 2.5 x 10 x 6 x 1 x 1) = 10/600 = 0.017 mg/kg bw/day