Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.26 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):
25
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
882 mg/m³
Explanation for the modification of the dose descriptor starting point:
Key 90-day oral toxicity study available; no repeated dose inhalation toxicity study available. In
absence of kinetic data, inhalation absorption is considered 2x oral absorption as conservative approach.
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (90 day study)
AF for interspecies differences (allometric scaling):
1
Justification:
Factor already taken into account in route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
226 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):
37.5
Dose descriptor starting point:
NOAEC
DNEL value:
5 020 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
8 475 mg/m³
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation, but correction for workers respiratory rate and duration of exposure
(see justification & comments)
AF for dose response relationship:
3
Justification:
Safety factor for laboured respiration and respiratory rate increase at limit dose
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not applicable to concentrations (ECHA R8 p 26)
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
226 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
37.5
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
3
Justification:
Safety factor for laboured respiration and respiratory rate increase at limit dose
AF for interspecies differences (allometric scaling):
1
Justification:
Allometiric scaling not applicable to local effects (ECHA R8 p 26)
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 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):
100
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Key 90-day oral toxicity study available; no repeated dose dermal toxicity study available. In absence
of kinetic data, dermal absorption is considered equal to oral absorption as conservative approach.
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (90 day study)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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

Source information for DNEL derivation:

A key inhalation toxicity study was performed in Wistar rats (sighting exposure using 2 males and 2 females, followed by main study 5 males and 5 females) at target dust aerosol concentration of 5 mg/L Tin disulfide (Nagy, 2012). The animals were exposed for 4 hours using a nose-only exposure system, followed by a 14 day observation period. In the main study, the mean achieved atmosphere concentration was 5.02 mg/L. The MMAD was 3.91 µm ± 2.13 (GSD). Significant clinical signs were recorded on the day of exposure including laboured respiration and respiratory rate increase. All animals recovered by Day 2. Normal bodyweight gain was recorded, with the exception of one female where a slight bodyweight loss was recorded during the first three days of the observation period. No gross macroscopic observations were apparent at necropsy. LC50 > 5 mg/L.

A key 90- day repeated dose toxicity study in rats daily dosed with Tin sulfide was available (Slais, 2010). Four groups of rats (male/female Wistar rats) were daily administered with the test item suspension in 0.5% Carboxymethylcellulose (CMC) orally by gavage for 90 days.Three treated groups were administered with doses of 100, 300 and 1000 mg/kg bw per day. Dosing resulted in a slight increase in food consumption, associated with slight increases in body weight and serum glucose concentrations in females dosed at 1000 mg/kg. These were however not considered as adverse effects. Slight dose dependent decreases in serum Na and Cl, varying within physiological range, were observed. Except for the above mentioned changes, tin sulfide did not cause any negative effect on body weight, food consumption, ophthalmoscopy, hematology and clinical chemistry parameters and organ weights. Tin sulfide further did not cause any organ weight changes nor gross or histopathological changes in the liver, kidneys, gastrointestinal tract or other organs of survived animals indicative of a toxic effect. Under the test conditions used, 90 - day administration of the test item Tin sulfide to rats was safe and well tolerated up to the dose of 1000 mg/kg bw/day. The NOAEL was defined at 1000mg/kg and the NOEL at 300 mg/kg.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.7 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):
50
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
435 mg/m³
Explanation for the modification of the dose descriptor starting point:
Key 90-day oral toxicity study available; no repeated dose inhalation toxicity study available. In
absence of kinetic data, inhalation absorption is considered 2x oral absorption as conservative approach
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (90-day study)
AF for interspecies differences (allometric scaling):
1
Justification:
Factor already taken into account in route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
169 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):
75
Dose descriptor starting point:
NOAEC
DNEL value:
5 020 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
12 650 mg/m³
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation, but correction for workers respiratory rate and duration of exposure (see justification & comments)
AF for dose response relationship:
3
Justification:
Safety factor for laboured respiration and respiratory rate increase at limit dose
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not applicable to concentrations (ECHA R8 p 26)
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
169 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEC
DNEL value:
5 020 mg/m³
AF for dose response relationship:
3
Justification:
Safety factor for laboured respiration and respiratory rate increase at limit dose
AF for interspecies differences (allometric scaling):
1
Justification:
Allometiric scaling not applicable to local effects (ECHA R8 p 26)
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 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):
200
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Key 90-day oral toxicity study available; no repeated dose dermal toxicity study available. In absence
of kinetic data, dermal absorption is considered equal to oral absorption as conservative approach.       
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (90-day study)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
5 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):
200
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not applicable
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
ECHA default (90-day study)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed
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

Source information for DNEL derivation:

A key inhalation toxicity study was performed in Wistar rats (sighting exposure using 2 males and 2 females, followed by main study 5 males and 5 females) at target dust aerosol concentration of 5 mg/L Tin disulfide (Nagy, 2012). The animals were exposed for 4 hours using a nose-only exposure system, followed by a 14 day observation period. In the main study, the mean achieved atmosphere concentration was 5.02 mg/L. The MMAD was 3.91 µm ± 2.13 (GSD). Significant clinical signs were recorded on the day of exposure including laboured respiration and respiratory rate increase. All animals recovered by Day 2. Normal body weight gain was recorded, with the exception of one female where a slight body weight loss was recorded during the first three days of the observation period. No gross macroscopic observations were apparent at necropsy. LC50 > 5 mg/L.

A key 90- day repeated dose toxicity study in rats daily dosed with Tin sulfide was available (Slais, 2010). Four groups of rats (male/female wistar rats) were daily administered with the test item suspension in 0.5% Carboxymethylcellulose (CMC) orally by gavage for 90 days.Three treated groups were administered with doses of 100, 300 and 1000 mg/kg bw per day. Dosing resulted in a slight increase in food consumption, associated with slight increases in body weight and serum glucose concentrations in females dosed at 1000 mg/kg. These were however not considered as adverse effects. Slight dose dependent decreases in serum Na and Cl, varying within physiological range, were observed. Except for the above mentioned changes, tin sulfide did not cause any negative effect on body weight, food consumption, ophthalmoscopy, hematology and clinical chemistry parameters and organ weights. Tin sulfide further did not cause any organ weight changes nor gross or histopathological changes in the liver, kidneys, gastrointestinal tract or other organs of survived animals indicative of a toxic effect. Under the test conditions used, 90 - day administration of the test item Tin sulfide to rats was safe and well tolerated up to the dose of 1000 mg/kg bw/day. The NOAEL was defined at 1000mg/kg and the NOEL at 300 mg/kg.