Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.003 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
0.46 mg/m³
Explanation for the modification of the dose descriptor starting point:
0.3 × 1/0.38 × 6.7/10 × 0.5 [50% oral abs rat / 100% inhalation abs hum] × 1.75 [ratio of MW to the read across substance]
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:
6
Justification:
Extrapolation from subacute 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:
2
Justification:
Limited information on chronic, reproductive and developmental toxicity. (OECD 422 study on highly similar read across substance only)
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:
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:
DNEL (Derived No Effect Level)
Value:
0.044 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
Modified dose descriptor starting point:
NOAEL
Value:
26.25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
0.3 × 50 [oral absorption rat 50%/dermal absorption human 1%] × 1.75 [ratio of MW to the read across substance]
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:
6
Justification:
Extrapolation from subacute 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 safety assessment
AF for the quality of the whole database:
2
Justification:
Limited information on chronic, reproductive and developmental toxicity. (OECD 422 study on highly similar read across substance only)
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:
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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Dioctyltin bis-(ethylmaleate) is not acutely toxic after oral administration, as the LD50 values are higher than 2000 mg/kg bw, and as high as 6000 mg/kg. Dioctyltin bis-(ethylmaleate) did show irritating properties to both skin and eye when tested in vivo, but there is no dose response data. The read across substance dioctyloxostannane did not produce any sensitisation when tested in a Local Lymph Node Assay in mice. Therefore acute DNELs for systemic effects or acute and long-term DNELs for local effects are not possible to define.

In a 14-d oral (dietary) range finding study females treated at 500 mg/kg in the diet showed body weight loss during the first 3 days of treatment. Compared to the 4 control animals which gained a mean of 8 g, the treated 4 females had a mean loss of 3.57 g/ Examination of food consumption data revealed that these animals ate approximately 43 % less food than controls (in terms of g/animal/day). On this basis, it cannot be excluded that the effect on body weight was due to palatability of the treated diet instead of acute toxicity. This is supported by the fact that effects on body weight and/or food consumption at the highest tested dosage of 250 ppm were observed only later in the main study. Therefore, no acute DNELs for acute systemic effects are considered necessary.

Based on results of in vitro and in vivo studies, on Dioctyltin bis-(ethylmaleate) and the read across substance dioctyloxostannane is considered not to possess any genotoxic potential.

 

A single repeat-dose combined reproductive/developmental toxicity study on the read across substance dioctyloxostannane was available, performed in rats. As the only suitable study available Waalkens-Berendsen DH (2004) was used as the starting point for DNELs setting.

 

An additional safety factor of 2 has been applied, because even though the majority of the data are new high quality studies performed in line with good laboratory practices and current standardised guidelines the data was on the read across substance dioctyloxostannane.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.001 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):
300
Modified dose descriptor starting point:
NOAEC
Value:
0.23 mg/m³
Explanation for the modification of the dose descriptor starting point:
0.3 × 1/1.15 × 0.5 [rat oral abs 50%/human inhalation abs 100%] × 1.75 [ratio of MW to the read across substance]
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:
6
Justification:
Extrapolation from subacute 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:
2
Justification:
Limited information on chronic, reproductive and developmental toxicity. (OECD 422 study on highly similar read across substance only)
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:
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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.022 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):
1 200
Modified dose descriptor starting point:
NOAEL
Value:
26.25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
0.3 × 50 [oral absorption rat 50%/dermal absorption human 1%] × 1.75 [ratio of MW to the read across substance]
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:
6
Justification:
Extrapolation from subacute 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:
2
Justification:
Limited information on chronic, reproductive and developmental toxicity. (OECD 422 study on highly similar read across substance only)
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:
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)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0 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):
1 200
Modified dose descriptor starting point:
NOAEL
Value:
0.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
0.3 × 1.75 [ratio of MW to the read across substance]
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:
6
Justification:
Extrapolation from subacute 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:
2
Justification:
Limited information on chronic, reproductive and developmental toxicity. (OECD 422 study on highly similar read across substance only)
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:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

The same endpoint used for workers was selected for setting the long-term DNELs for the general population. The larger assessment factor for intraspecies sensitivity was considered adequately protective for the more sensitive population.