Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.002 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
DNEL value:
0.26 mg/m³
Explanation for the modification of the dose descriptor starting point:
0.3 x 1/0.38 x 6.7/10 x 0.5 [50% oral abs rat / 100% inhalation abs humans]
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:
1
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:
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:
0.025 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
DNEL value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
0.3 x [oral absorption rat 50%/dermal absorption human 1%]
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:
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

2,2-dioctyl-1,3,2-oxathiastannolan-5-one, is acutely toxic after oral administration, with LD50 values between 300 and 2000 mg/kg.Reading-across fromdioctyloxostannane, the substance is not acutely toxic after dermal application, as the LD50 value is higher than 2000 mg/kg bw. No data on inhalation are available however, the substance was not irritating to the delicate mucous membrane of the eye, in additionthe substance is a solid, in the form of large waxy pieces, and is therefore highly unlikely to form an inhalable dust. No local effects following inhalation are expected to occur. The substance was neither corrosive nor irritating to the skin, based on results ofin vitrostudies, and was not irritating to the eye in both in vitro and in vivo studies.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 and it is not necessary to set acute systemic DNELs for inhalation based on the physical form of the substanceand the fact Risk Management Measures are implemented in working places to assure that exposure, if any, remains below the long-term inhalation DNEL.

In a 14-d oral (dietary) range finding study conducted on dioctyloxostannane 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 studies, on 2,2-dioctyl-1,3,2-oxathiastannolan-5-one and the read across substance dioctyloxostannane is considered not to possess any genotoxic potential.

 

A 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.

Two teratogenic studies (OECD 414) in the mouse and in the rabbit, with the structural analoge DOTE (CAS 15571 -58 -1) did not result any treatment relatet effects

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0 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
DNEL value:
0.13 mg/m³
Explanation for the modification of the dose descriptor starting point:
0.3 x 1/1.15 x 0.5 [rat oral abs 50%/human inhalation abs 100%/]
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:
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:
0.013 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
DNEL value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
0.3 x [oral absorption rat 50%/dermal absorption human 1%]
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:
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:
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
DNEL value:
0.3 mg/kg bw/day
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:
DNEL (Derived No Effect Level)
Value:
0.001 mg/kg bw/day
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

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.