Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.01 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.07 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
12.5

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Additional information - workers

For the organotins as a group, SCPFC/EFSA (2004) have concluded a group NOAEL for organotins at 0.025 mg/kg bw based on immunological changes in a chronic study of tributyltin oxide (TBTO). SCPFC/EFSA comment: "Short term experiments however demonstrate that TBT-induced thymus atrophy and hepatotoxicity is preferentially generated by its metabolite DBT with a lower activity of TBT itself. From this it is concluded that DBT is at least as potent as TBT. In addition in comparative toxicity studies investigating the structure activity relationship regarding thymus toxicity in the rat, DBT and DOT (dioctyltin) were the most potent dialkyltin compounds producing dose-related thymus atrophy in similar extents". It therefore follows that a robust study of DBT is entirely appropriate for DNEL setting. SCPFC/EFSA identified no NOAEL, but a LEL for DBT-Cl, at 2.5 mg/kg bw/day based on a 2-week study; these data remain consistent with data used to derive DNELs in this CSR. An in vitro study simulating gastric condition indicate that DBT-Cl is an appropriate anchor compound when exposure occurs by the oral route, because the substance quickly hydrolised to DBT-Cl. A critical study, not included in the SCPFC/EFSA review, is the OECD 421 study with DBT-Cl (Waalkens-Berendsen, 2003) with a NOAEL at 0.3 mg/kg bw/day for thymus effects in female rats following dietary exposure. The thymus effects are critical toassessment of organotin toxicity; this study evaluates the critical effect in an appropriate study design. The OECD 421 NOAEL is supported by results of a teratogenicity study in rats (Osterburg 1993), and by studies of immune function showing an absence of effect at doses up to 2.5 mg/kg bw/day in adult rats and in pups exposed in utero and throughout lactation (DeWitt 2005, 2006) also not included in the EFSA/SPCFC review. As proposed classification for Annex I inclusion included Xn; R22, acute systemic DNELs have been derived on the basis of the maternal NOAEL of 1 mg/kg bw/day, obtained in a teratogenicity study in rats (Osterburg 1993) in which thymus weight was included among the evaluated parameters. These data for DBT-Cl are more robust (longer duration, more informative dose levels, more modern and GLP-compliant) than the data on which EFSA/SPCFC conclusions are based, and considered sufficiently robust that they can be used for the substance in preference to the SPCFC/EFSA group NOAEL for organotins. The NOAEL of the OECD 421 study by Waalkens et al (2003) is supported by the results of a subchronic study, and is therefore considered as a subchronic (not subacute) NOAEL for purposes of assessment factors used for deriving chronic DNELs. Consequences of exceeding the DNEL: The DNELs calculated in this CSR compare to published occupational hygiene limits for the organotins, expressed at OEL, TLV or STELs, at 0.2 mg/m3 (for very short term exposures equivalent to “acute” in this CSR) or 0.1 mg/m3 for longer-term exposures. Exceedance of DNELs by as much as 10-fold would remain within acceptable limits in most jurisdictions. At higher concentrations, workplace complaints of irritancy to the respiratory tract have been reported. Irritancy to the respiratory system is likely to be the most sensitive endpoint for the organotins, and likely to occur at levels below those at risk of causing systemic toxicities (e.g. immunotoxicity). Since affected workers are likely to adopt behaviour to reduce unpleasant irritancy, e.g. to remove themselves from the workplace, minor exceedances of the DNEL are unlikely to be cause for significant concern.

General Population - 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
DNEL related information
Overall assessment factor (AF):
50
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
25

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
1 500
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.002 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.01 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Additional information - General Population

The same toxicological endpoints chosen for setting the DNELs for workers have been used for setting DNELs for the general population. The increased assessment factor for interspecies sensitivity is considered sufficiently protective.