Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.017 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
DNEL value:
0.44 mg/m³
Explanation for the modification of the dose descriptor starting point:
0.5 mg/kg bw/day x [1/0.38 x 50/100 x 6.7/10]
AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
Differences in species addressed in calculation of dose descriptor starting point
Justification:
Differences in species addressed in calculation of dose descriptor starting point
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for the quality of the whole database:
1
Justification:
Good quality data available on dimethyltin dichloride
AF for remaining uncertainties:
2.5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
NOAEC
DNEL value:
0.29 mg/m³
Explanation for the modification of the dose descriptor starting point:
0.33 mg/kg/day x [1/0.38 x 50/100 x 6.7/10]
AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
Differences in species addressed in calculation of dose descriptor starting point
Justification:
Differences in species addressed in calculation of dose descriptor starting point
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for the quality of the whole database:
1
Justification:
Good quality data available on dimethyltin dichloride
AF for remaining uncertainties:
2.5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment

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)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.01 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
DNEL value:
1.25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
0.5 mg/kg/day x [50%/20%]
AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
Differences in species addressed in calculation of dose descriptor starting point
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical sa
AF for the quality of the whole database:
1
Justification:
Good quality data available on dimethyltin dichloride
AF for remaining uncertainties:
2.5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
DNEL value:
0.825 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
0.33 mg/kg/day x [50%/20%]
AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
Differences in species addressed in calculation of dose descriptor starting point
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical sa
AF for the quality of the whole database:
1
Justification:
Good quality data available on dimethyltin dichloride
AF for remaining uncertainties:
2.5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 µg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
30
Dose descriptor:
other: NOAEC
AF for dose response relationship:
1
Justification:
Vehicle or matrix effects
AF for differences in duration of exposure:
6
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
No interspecies differences
Justification:
No interspecies differences
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical sa
AF for the quality of the whole database:
1
Justification:
Good quality data available on dimethyltin dichloride
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties. Same mode of action in human and rat skin
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.8 µg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor starting point:
other: NOAEC
AF for dose response relationship:
1
Justification:
Vehicle or matrix effects
Justification:
No interspecies differences
Justification:
No interspecies differences
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical sa
AF for the quality of the whole database:
1
Justification:
Good quality data available on dimethyltin dichloride
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties. Same mode of action in human and rat skin.

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Results of acute studies indicate that the registered substance should be classified as toxic if swallowed, toxic in contact with skin and fatal if inhaled. These studies, however, provide only information on lethality. Nonetheless, neurotoxicity/developmental neurotoxicity represents the main concern for the registered substance, and repeated exposures of women of child bearing age cannot be excluded, hence there is potential for damage to the unborn child. On these bases the NOAEL of 3 ppm, (0.33 mg/kg/day during pregnancy) obtained in the key study from Ehman et al. (2007) has been considered an appropriate dose descriptor for acute exposure (there is no evidence to exclude the occurrence developmental effects after single exposure events). Within this paper there are 2 experiments/studies. In the first experiment, females were treated 2 weeks before mating and throughout gestation and lactation. Male offspring were then tested for neurotoxicity and neuropathology. Average weighed intake at 3 ppm was 0.4 mg/kg/day. In the second experiment, females were treated from day 6 of pregnancy to weaning and then offspring were tested.The second study in which female rats were exposed from day 6 of pregnancy through to weaning of pups was considered more suitable for acute effects than the first study in which females were treated 2 weeks before mating, during gestation and until weaning of pups.Intake during pregnancy at 3 ppm was 0.33 mg/kg/day, and this value was considered the more appropriate starting point for setting the acute systemic DNELs.

 

The registered substance is corrosive and causes serious damage to eyes. However, from the in-vitro dermal absorption study Ward, R.J. (1999) a NOAEC concentration of 53.5 µg tin/cm2for skin damage was determined. The report indicates100 µg/cm² as the non corrosive concentration. As the tested substance was a mixture of MMTTC and the registered substance (89%), consistently with the approach taken for the oral studies, a NOAEC of 89 µg/cm² has been used as the starting point for deriving dermal DNELs for local effects.

 

In contrast to other organotin compounds, the registered substance has no immunotoxic properties as evidenced by the NOAELs obtained in specific studies investigating these endpoints, which are considerably higher than the NOAELs obtained in repeat-dose and pre-natal developmental studies. The main toxic effect for the registered substance is neurotoxicity, both in the adult animals and in offspring pre-natal exposed. The subchronic key study Beyrouty, P. (1997a), chosen on the basis that the tested mixture contains 90% of the registered substance and that it was fully GLP compliant, resulted in a LOAEL of 1.6 mg/kg/day (25 ppm in drinking water) because of neuropathological findings. The supportive study from Appel (2000) supports the key study and gives a NOAEL of 0.98 mg/kg bw/day (15 ppm in the diet), again based on neurological effects, but the purity of the tested mixture was 33.5% MMTTC and 66.5% registered substance. Considering the content in terms of the registered substance only, and applying an assessment factor of 3 for extrapolating from a LOAEL to a NOAEL, the resulting consistent NOAEL for repeat-dose toxicity is approximately 0.5-0.6 mg/kg/day. This value is also consistent with the NOAEL of 3 ppm obtained for neurodevelopmental effects in the 1st experiment from Ehman et al. (2007), when an average weighted intake is calculated for the entire treatment period of approximately 9 weeks i.e. pre-mating, mating, pregnancy and lactation to weaning (ca. 0.4 mg/kg/day). The value of 0.5 mg/kg/day, used as the starting point for setting the long-term systemic DNELs, is an estimate considering all together the NOAEL from the 1st experiment reported in Ehman et al. (2007) (3 ppm = 0.4 mg/kg/day) + the LOAEL from Beyrouty, P. (1997a) (25 ppm in drinking water = 1.6/3 = 0.5-0.6 mg/kg/day) + NOAEL from Appel (2000) (15 ppm in diet = 0.98 mg/kg/day x 66.5% DMTC = 0.6517 mg/kg/day).

 

Oral absorption: 50%

Dermal absorption (humans): 20%

Inhalation absorption: 100%

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.009 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
0.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
0.5 mg/kg/day x [1/1.15]
AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
Differences in species addressed in calculation of dose descriptor starting point
Justification:
Differences in species addressed in calculation of dose descriptor starting point
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for the quality of the whole database:
1
Justification:
Good quality data available on dimethyltin dichloride
AF for remaining uncertainties:
2.5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.003 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
DNEL value:
0.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Same oral absorption in rat and human
AF for dose response relationship:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
Differences in species addressed in calculation of dose descriptor starting point
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for the quality of the whole database:
1
Justification:
Good quality data available on dimethyltin dichloride
AF for remaining uncertainties:
2.5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The same endpoints as used for workers, were selected for setting the DNELs for the general population. The larger assessment factor for intraspecies sensitivity was considered adequately protective for the more sensitive population. As no consumer uses are being supported, only DNELs for systemic oral and inhalation exposure are required (for secondary poisoning).