Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.8 mg/m³
Most sensitive endpoint:
effect on fertility
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:
882 mg/m³
Explanation for the modification of the dose descriptor starting point:
Dose descriptor There are no data available in humans or laboratory animals relating to fertility effects following repeated inhalation exposure to SLMI or read across material. There is however an oral screening study performed to OECD 421 on SCI that achieved a NOAEL. Therefore, the NOAEL of 1000 mg/kg bw/day on from this screening study on SCI will be used for the calculation of the inhalation DNEL (fertility ). Mode-of-action SCI is considered to have only threshold effects, as the weight-of-evidence indicates that it does not possess genotoxic potential.
AF for dose response relationship:
1
Justification:
Default ECHA AF; human health relevant NOAEL from well-conducted 28day screening study
AF for differences in duration of exposure:
6
Justification:
Default ECHA AF for Screening study (sub acute) exposure
AF for interspecies differences (allometric scaling):
1
Justification:
A health precautionary approach is to assume 100% absorption following inhalation exposure. Therefore, the starting point has been corrected to reflect 50% oral absorption and 100% inhalation absorption. Thus, 1000mg/kg bw/day / (100/50) = 500 mg/kg bw/day. Workers are assumed to be exposed for 8 h/day. The oral dose for the rat is converted to the corresponding air concentration, using a standard breathing volume for the rat, of 0.38 m3/kg bw for 8 h/day (exposure of workers). To account for the presumed light activity of workers, this value has been corrected for an increase in breathing volume. Thus (500 mg/kg bw/day / 0.38 m3/kg bw/day) x 0.67 m3 = 882 mg/m3(8-h exposure of workers, light activity).
AF for other interspecies differences:
2.5
Justification:
Default ECHA AF for remaining toxicokinetic differences (not related to metabolic rate) and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
Default ECHA AF for (healthy) worker
AF for the quality of the whole database:
1
Justification:
Default ECHA AF; the health effects data are reliable and consistent, the available information meets the tonnage driven data requirements, and confidence in the database is high
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
DNEL (Derived No Effect Level)
Value:
3.3 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dose descriptor There are no data available in humans relating to repeated dermal exposure which are suitable as the basis from which to calculate a dermal DNEL for fertility There is however an oral screening study performed to OECD 421 on SCI that achieved a NOAEL. Therefore, the NOAEL of 1000 mg/kg bw/day on from this screening study on SCI will be used for the calculation of the dermal DNEL (fertility). Mode-of-action SCI is considered to have only threshold effects, as the weight-of-evidence indicates that they do not possess genotoxic potential. Modification of starting point In the absence of any data to the contrary, the same bioavailability is assumed for humans and laboratory animals. As no relevant study data on effects of repeated dermal exposure to SCI in humans or laboratory animals are available, route-to-route extrapolation to calculate a dermal DN(M)EL from repeated dose oral toxicity studies was considered a suitable alternative. In the absence of route-specific information on absorption the end route (dermal), a conservative assumption equal to the oral absorption will be made. Therefore, the starting point is 1000 mg/kg/bw/day. Workers are assumed to be exposed for 8 h/day.
AF for dose response relationship:
1
Justification:
Default ECHA AF; human health relevant NOAEL from well-conducted 28day screening study
AF for differences in duration of exposure:
6
Justification:
Default ECHA AF for screening study (sub acute) exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA AF for rat for toxicokinetic differences in metabolic rate (allometric scaling)
AF for other interspecies differences:
2.5
Justification:
Default ECHA AF for remaining toxicokinetic differences (not related to metabolic rate) and toxicodynamic differences
AF for intraspecies differences:
5
Justification:
Default ECHA AF for (healthy) worker
AF for the quality of the whole database:
1
Justification:
Default ECHA AF; the health effects data are reliable and consistent, the available information meets the tonnage driven data requirements, and confidence in the database is high
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Toxicity studies on SCI and reproductive / developmental toxicity screening studies on SLI predict that SLMI is of low toxicity following acute or repeated dose exposure. There was no evidence of genotoxicity or effects on reproductive performance and development of offspring. SLMI is predicted to cause slight skin irritation and reversible eye irritation. SLMI is not expected to cause skin sensitisation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.9 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Value:
882 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of any data to the contrary, the same bioavailability is assumed for humans and laboratory animals. Route-to-route extrapolation to calculate an inhalation DNEL (fertility) from oral studies was considered suitable. A health precautionary approach is to assume 100% absorption following inhalation exposure. Therefore, the starting point has been corrected to reflect 50% oral absorption and 100% inhalation absorption. Thus, 1000mg/kg bw/day / (100/50) = 500 mg/kg bw/day. General populations are assumed to be exposed for 8 h/day. The oral dose for the rat is converted to the corresponding air concentration, using a standard breathing volume for the rat, of 0.38 m3/kg bw for 8 h/day (exposure of general populations). To account for the presumed light activity of general populations, this value has been corrected for an increase in breathing volume. Thus (500 mg/kg bw/day / 0.38 m3/kg bw/day) x 0.67 m3 = 882 mg/m3(8-h exposure of general populations, light activity).
AF for dose response relationship:
1
Justification:
Default ECHA AF; human health relevant NOAEL from well-conducted 28day screening study
AF for differences in duration of exposure:
6
Justification:
Default ECHA AF for Screening study (sub acute) exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling already considered in correcting starting point above
AF for other interspecies differences:
2.5
Justification:
Default ECHA AF for remaining toxicokinetic differences (not related to metabolic rate) and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
Default ECHA AF for (healthy) general population
AF for the quality of the whole database:
1
Justification:
Default ECHA AF; the health effects data are reliable and consistent, the available information meets the tonnage driven data requirements, and confidence in the database is high
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Modification of starting point In the absence of any data to the contrary, the same bioavailability is assumed for humans and laboratory animals. As no relevant study data on effects of repeated dermal exposure to SCI in humans or laboratory animals are available, route-to-route extrapolation to calculate a dermal DN(M)EL from repeated dose oral toxicity studies was considered a suitable alternative. In the absence of route-specific information on absorption the end route (dermal), a conservative assumption equal to the oral absorption will be made. Therefore, the starting point is 1000 mg/kg/bw/day. General populations are assumed to be exposed for 8 h/day
AF for dose response relationship:
1
Justification:
Default ECHA AF; human health relevant NOAEL from well-conducted 28day screening study
AF for differences in duration of exposure:
6
Justification:
Default ECHA AF for screening study (sub acute) exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA AF for rat for toxicokinetic differences in metabolic rate (allometric scaling)
AF for other interspecies differences:
2.5
Justification:
Default ECHA AF for remaining toxicokinetic differences (not related to metabolic rate) and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
Default ECHA AF for (healthy) general population
AF for the quality of the whole database:
1
Justification:
Default ECHA AF; the health effects data are reliable and consistent, the available information meets the tonnage driven data requirements, and confidence in the database is high
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
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)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.78 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
465 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Mode-of-action SCI is considered to have only threshold effects, as the weight-of-evidence indicates that it does not possess genotoxic potential. Modification of starting point In the absence of any data to the contrary, the same bioavailability is assumed for humans and laboratory animals. The starting point of SI must be corrected for the change in MW for SLMI So, 200 mg/kg/bw/d*(344.44/148.11) = 465mg/kg/bw/day General populations are assumed to be exposed for 24 h/day
AF for dose response relationship:
1
Justification:
Default ECHA AF; human health relevant NOAEL from well-conducted 28day screening study
AF for differences in duration of exposure:
6
Justification:
Default ECHA AF for Screening study (sub acute) exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA AF for rat for toxicokinetic differences in metabolic rate (allometric scaling)
AF for other interspecies differences:
2.5
Justification:
Default ECHA AF for remaining toxicokinetic differences (not related to metabolic rate) and toxicodynamic differences
AF for intraspecies differences:
10
Justification:
Default ECHA AF for (healthy) general population
AF for the quality of the whole database:
1
Justification:
Default ECHA AF; the health effects data are reliable and consistent, the available information meets the tonnage driven data requirements, and confidence in the database is high
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:
medium hazard (no threshold derived)

Additional information - General Population

Toxicity studies on SCI and reproductive / developmental toxicity screening studies on SLI predict that SLMI is of low toxicity following acute or repeated dose exposure. There was no evidence of genotoxicity or effects on reproductive performance and development of offspring. SLMI is predicted to cause slight skin irritation and reversible eye irritation. SLMI is not expected to cause skin sensitisation.