Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
71 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
Modified dose descriptor starting point:
NOAEC
Explanation for the modification of the dose descriptor starting point:

1000 mg/kg bw/d * (1/0.38 * 0.004%/0.004% * 6.7/10) = 1763 mg/m3

AF for dose response relationship:
1
Justification:
A clear NOAEL was derived from the study. No correction is required for dose reponse.
AF for differences in duration of exposure:
2
Justification:
Default factor when extrapolating from the equivalent of a subchronic NOAEL to a chronic NOAEL
AF for interspecies differences (allometric scaling):
1
Justification:
Not required when correcting for inhalation starting point.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
Default factor for workers.
AF for the quality of the whole database:
1
Justification:
Data is complete and of acceptable quality.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
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 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
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

1000 x (0.004/0.004) = 1000 mg/kg bw/day

AF for dose response relationship:
1
Justification:
A clear NOAEL was derived from the study. No correction is required for dose reponse.
AF for differences in duration of exposure:
2
Justification:
A chronic study is used to set a chronic DNEL. No correction required.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric factor when extrapolating from rat to man.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
Default factor for workers.
AF for the quality of the whole database:
1
Justification:
Data is complete and of acceptable quality.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
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:
no hazard identified

Additional information - workers

Tin metal has no practical bioavailability via any route, and is not acutely toxic via the oral, dermal or inhalation route. It was not genotoxic in a satisfactory battery of in vitro tests. The subchronic NOAEL was set on the basis of no practical absorption, and was based on the absence of any effects in a 28 day oral study in rats upto the limit dose of 1000 mg/kg bw/day (a waiver for the 90 day study was written and the NOAEL from the 28 day study adopted as the 90 day end point). There were also no effects in an OECD 414 developmental toxicity study in rats up to the limit dose of 1000 mg/kg bw day. On the basis of the properties of tin and the absence of any toxicity seen in the studies conducted so far, a second species developmental toxicity study and EOGRTS studies are waved, and chronic toxicity and carcinogenicity studies are not triggered.

Available human data also rules out any long term toxicological effects. Robertson J (1960) studied stannosis (tin oxide induced pneumoconiosis) in workers from a tin smelting works. Even with positive X-ray findings, workers with many years of exposure suffered no health effects, deposition of the dust in the lungs did not lead to a fibrous response, indicating no cellular interaction. Observations were performed on workers exposed later in the production line, such as ingot casters exposed to pure molten tin, which reports that there is little dust or fume exposure during this process and changes were not observed in these workers. Though the working conditions are not comparable to today’s practices (much improved), it gives a worst case scenario of exposure during various points of the lifecycle of the registered substance. Dietary studies examining the effects of tin migrated from packaging, like the available animal studies demonstrate rapid excretion (Calloway DH & McMullen JJ (1966) and a lack of toxicological effects (Boogard PH et al, 2003).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
870 mg/m³
Explanation for the modification of the dose descriptor starting point:

1000 mg/kg bw/d * (1/1.15 * 0.004%/0.004% ) = 870 mg/m3

AF for dose response relationship:
1
Justification:
A clear NOAEL was derived from the study. No correction is required for dose reponse.
AF for differences in duration of exposure:
2
Justification:
Default factor when extrapolating from the equivalent of a subchronic NOAEL to a chronic NOAEL
AF for interspecies differences (allometric scaling):
1
Justification:
Not required when correcting for inhalation starting point.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
Default factor for the general population.
AF for the quality of the whole database:
1
Justification:
Data is complete and of acceptable quality.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
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:
80 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):
12.5
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

1000 mg/kg bw/day x (0.004/0.004) = 1000 mg/kg bw/day

AF for dose response relationship:
1
Justification:
A clear NOAEL was derived from the study. No correction is required for dose reponse.
AF for differences in duration of exposure:
2
Justification:
Default factor when extrapolating from the equivalent of a subchronic NOAEL to a chronic NOAEL
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric factor when extrapolating from rat to man.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
Default facotr for the general population.
AF for the quality of the whole database:
1
Justification:
Data is complete and of acceptable quality.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
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:
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
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
A clear NOAEL was derived from the study. No correction is required for dose reponse.
AF for differences in duration of exposure:
2
Justification:
Default factor when extrapolating from the equivalent of a subchronic NOAEL to a chronic NOAEL
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric factor when extrapolating from rat to man.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
Default factor for the general population.
AF for the quality of the whole database:
1
Justification:
Data is complete and of acceptable quality.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties.
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

Tin metal has no practical bioavailability via any route, and is not acutely toxic via the oral, dermal or inhalation route. It was not genotoxic in a satisfactory battery of in vitro tests. The subchronic NOAEL was set on the basis of no practical absorption, and was based on the absence of any effects in a 28 day oral study in rats upto the limit dose of 1000 mg/kg bw/day (a waiver for the 90 day study was written and the NOAEL from the 28 day study adopted as the 90 day end point). There were also no effects in an OECD 414 developmental toxicity study in rats up to the limit dose of 1000 mg/kg bw day. On the basis of the properties of tin and the absence of any toxicity seen in the studies conducted so far, a second species developmental toxicity study and EOGRTS studies are waved, and chronic toxicity and carcinogenicity studies are not triggered.

Human data:Some biological effects monitoring data was available and relevant for assessment. Robertson J (1960) studied stannosis (tin oxide induced pneumoconiosis) in workers from a tin smelting works. Even with positive X-ray findings, workers with many years of exposure suffered no health effects, deposition of the dust in the lungs did not lead to a fibrous response, indicating no cellular interaction. Observations were performed on workers exposed later in the production line, such as ingot casters exposed to pure molten tin, which reports that there is little dust or fume exposure during this process and changes were not observed in these workers. Though the working conditions are not comparable to today’s practices, it gives a worst case scenario of exposure during various points of the lifecycle of the registered substance. Dietary studies examining the effects of tin migrated from packaging, like the available animal studies, demonstrate rapid excretion (Calloway DH & McMullen JJ (1966) and a lack of toxicological effects (Boogard PH et al, 2003).