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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.41 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):
24
Modified dose descriptor starting point:
NOAEC
DNEL value:
250 mg/m³
Explanation for the modification of the dose descriptor starting point:
no inhalation study available, long term local effects not expected
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
3
Justification:
This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003). A lower factor of 3 (i.e. closer to the 90th percentile of the distribution of the variability for these datasets) is proposed for the more homogeneous worker population. In the worker population, the more susceptible groups are typically excluded and/or may be protected from specific exposures. Thus, and in consideration of normal hygiene practices at the workplace, a lower value for the assessment factor is considered appropriate for workers.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
5.91 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):
24
Modified dose descriptor starting point:
NOAEL
DNEL value:
142 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no dermal study available
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
3
Justification:
This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003). A lower factor of 3 (i.e. closer to the 90th percentile of the distribution of the variability for these datasets) is proposed for the more homogeneous worker population. In the worker population, the more susceptible groups are typically excluded and/or may be protected from specific exposures. Thus, and in consideration of normal hygiene practices at the workplace, a lower value for the assessment factor is considered appropriate for workers.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
low hazard (no threshold derived)

Additional information - workers

Read-across concept (human health) for tin bis(tetrafluoroborate):

Substance-specific toxicity data for the substance tin bis(tetrafluoroborate) (water solubility >50 % w/w) are not available. However, since upon dissolution in water, full dissociation of the highly water-soluble tin bis(tetrafluoroborate) to (i) Sn2+cations and (ii) tetrafluoroborate anions occurs, read-across to (i) inorganic tin(II) substances and (ii) inorganic salts of tetrafluoroboric acid is made, respectively.

This read-across is considered fully justified in view of the comparable water solubilities of the similarly soluble read-across substances, such as (i) tin(II)chloride, water solubility 178 g/L at 20°C, and (ii) potassium tetrafluoroborate, water solubility 5.4 g/L at 22°C.

 

Whereas it is noted that upon dilution of aqueous solutions, “clouding” and precipitation of basic tin salts occurs , which can be described by the following equation:

 

SnX2+ H2O <--> "SnXOH"(s) + HX

 

this Sn2+-specific behaviour is not considered to restrict the read-cross since oral bioavailability of inorganic tin(II) substances is generally very low.

 

Potassium tetrafluoroborate is currently not classified according to the criteria specified by Directive 67/548/EEC and subsequent regulations, and is correspondingly considered not to require classification according to the criteria set forth by EC Regulation No. 1272/2008 and subsequent regulations, neither for HH or ENV hazards.

 

Any toxicological or ecotoxicological hazards (if any) are therefore assumed to be related to Sn2+only.

 

Estimation of DNELs for Sn(CH3SO3)2,Sn(BF4)2and Sn2+:

A 90-day oral toxicity study with tin(II)methanesulfonate in rats was selected as the point-of-departure, because it is considered the most appropriate for read-across purposes (i.e., maximum solubility with respect to tin(II) cations) and also the most reliable repeated dose toxicity study with a treatment duration of 90 days. Under consideration of all observed effects, the no-observed-effect level (NOEL) for systemic effects was 50 mg/kg bw/day. However, since there were no effects on organ weights and no pathological/histopathological correlate to the findings in mid-dose female animals, the findings observed were regarded as incidental and not adverse, and thus a NOAEL can be established at the mid-dose level of 150 mg/kg bw/d.

The following assessment factors were used, reproduced from Chapter R-8 of technical guidance with some adaptation according to a position paper by ECETOC:

 

Allometric scaling, rat to human           

4

Remaining differences                   

1

Correction for workers                            

5(3)*

Sub-chronic to chronic (90 day oral)      

2

Dose response and quality, default       

1

 *ECETOC 

 

The total factor is therefore 24 for chronic exposure in consideration of the ECETOC AF.

 

Units and route to route estimations

A route-to-route extrapolation was performed on a 1:1 basis based on the sub-chronic oral toxicity NOAEL of 150 mg/kg/day, thus equates to a dermal NOAEL of 150 mg/kg/day or inhalation at 150 mg/kg/day. 

 

A dose of 150 mg to be inhaled by a rat over 8 hours would require an airborne concentration of 150/0.38 mg/m3= approximately 400 mg/m3

 

Table. Default physiological parameters for inhalation

  

Rat

Human

Human

Body weight

250 g

Per kg

70 kg

6 h exposure

8 h exposure

24 h exposure

0.29 m3/kg bw

0.38 m3/kg bw

1.15 m3/kg bw

0.07 m3/ kg

0.1 m3/ kg

0.3 m3/ kg

5 m3/person

6.7 m3/person

20 m3/person

Respiratory volume light activity for worker (wRV)

8 h exposure

10 m3/person

 

The starting points for each endpoint described above were used to calculate the respective DNELs using the allometric scaling factor for rat to human and the remaining factors as described above. The inhalation and chronic dermal values were derived via route-to-route extrapolation from oral administration, using the table above and noting that inhalation DNELs are expressed as ‘per kg’ and need recalculation to match a 70kg human.

 

Estimated DNELs for workers:

Due to the fact that the intended uses of the substance definitely preclude any exposure of the general population and consumers whatsoever, DNELs for these groups were not derived.

 

 

Substance

Molecular weight [g/mol]

NOAEL RDT* [mg/kg]

DNELdermal systemic workers[mg/kg]

Corrected starting point NOAEC (inhalation) [mg/m3]

DNELinhalation systemic worker[mg/m3]

 

 

 

old

new$

old

new#

old

New$

Sn(CH3SO3)2

308.9

150

3.75

6.25

394.7 (400)

264.5

10

11

Sn

118.6

57.7

1.44

2.40

151.8

101.7

3.85

4.23

Sn(BF4)2

292.3

141.9

3.55

5.91

373.4

250.2

9.46

10.41

*starting point for DNELdermal systemic
$ in consideration of the ECETOC assessment factor (AF) of 3 (instead of 5),
resulting in an overall AF of 24 (instead of 40)
# in consideration of light activity for workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
no hazard identified
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

No anticipated exposure to the general population.