Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
74.7 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):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
747.57 mg/m³
Explanation for the modification of the dose descriptor starting point:
The starting point was corrected according to Figure R.8-3 in chapter R.8 in the ECHA guidance document (version 2.1, November 2012). It is assumed that the inhalation absorption in human is similar to the oral absorption in rat. NOAEL(oral, rat) = 424 mg/kg bw/day => NOAEC(corrected, inhalation) = NOAEL(oral, rat) x 1/(0.38 m3/kg bw/day) x 6.7 m3/10 m3 = 747.57 mg/m3
AF for dose response relationship:
1
Justification:
There are no effects up to the limit dose.
AF for differences in duration of exposure:
2
Justification:
Default value (ECHA) for sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
rat versus human: According to table R.8-4 in chapter R.8 of the ECHA guidance document (version 2.1, November 2012) the AF of 4 is already included in the route to route extrapolation.
AF for other interspecies differences:
1
Justification:
In an evaluation by ECETOC in 2003 and 2010 it is considered that routine application of the factor 2.5 as a default factor is scientifically unjustified. The view is supported by data generated by the ERASM project (Batke et al. 2010).
AF for intraspecies differences:
5
Justification:
Default value (ECHA) for workers
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
374.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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:
10.6 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):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
424 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
On the assuption, that dermal absorption is not higher than oral absorption, the NOAEL of the oral subchronic study is used (ECHA guidance, chapter R.8, R.8.4.1)
AF for dose response relationship:
1
Justification:
There are no effects up to the limit dose
AF for differences in duration of exposure:
2
Justification:
Default value (ECHA) for sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (ECHA) for rat versus human
AF for other interspecies differences:
1
Justification:
In an evaluation by ECETOC in 2003 and 2010 it is considered that routine application of the factor 2.5 as a default factor is scientifically unjustified. The view is supported by data generated by the ERASM project (Batke et al. 2010).
AF for intraspecies differences:
5
Justification:
Default value (ECHA) for workers
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
53 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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

Known occupational exposure limit(s):

There is no occupational limit available.

 

DNEL systemic (worker)

Basis for delineation of the DNELs systemic (worker):

A repeated dose toxicity study in Wistar rats (90 day feeding study) according OECD Guideline 408 is available.

There is no long term study available using the inhalation or dermal route. Thus, as starting point for the calculation, the NOAEL of the subchronic feeding study has to be taken into account.

 

Study

Title: PBS-AM Subchronische toxikologische Untersuchungen an Ratten (Fütterungsversuch über 3 Monate)

Administration period: 90 days

Doses: 50, 200, 1000, 5000 ppm = male rats: 0, 4.17, 14.91, 84.11, 424.41 mg/kg bw/day, female rats: 0, 6.05, 12.51, 125.48, 632.65 mg/kg bw/day

 

NOAEL, Effects

NOAEL (systemic) = 424 mg/kg bw (male and female rats)

Effects: All doses were tolerated without any effects

Thus, the NOAEL is equal or higher than 5000 ppm (equivalent to about 424 mg/kg bw for male rats and 632 mg/kg bw for female rats).

 

Reference

Löser E, Kaliner G (1976), PBS-AM Subchronische toxikologische Untersuchungen an Ratten (Fütterungsversuch über 3 Monate), Bayer AG, Institut für,

 

DNEL local effects (worker)

Basis for delineation of the DNELs local (long and short term toxicity):

 

Irritation/corrosion

In the key studies for skin irritation/corrosion and eye irritation, the test substance (tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate) is not irritating to the skin and eyes.

A classification is not justified.

 

Sensitization

In a Guinea Pig maximization test (GPMT) the test substance (tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate) revealed no sensitisation potential.

A classification is therefore notjustified.

 

Result:

For local effects no hazard is identified.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.4 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):
20
Modified dose descriptor starting point:
NOAEC
DNEL value:
368.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
The starting point was corrected according to Figure R.8-3 in chapter R.8 in the ECHA guidance document (version 2.1, November 2012). It is assumed that the inhalation absorption in human is similar to the oral absorption in rat. NOAEL(oral, rat) = 424 mg/kg bw/day => NOAEC(corrected, inhalation) = NOAEL(oral, rat) x 1/(1.15 m3/kg bw/day) = 368.7 mg/m3
AF for dose response relationship:
1
Justification:
There are no effects up to the limit dose
AF for differences in duration of exposure:
2
Justification:
Default value (ECHA) for sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
rat versus human: According to table R.8-4 in chapter R.8 of the ECHA guidance document (version 2.1, November 2012) the AF of 4 is already included in the route to route extrapolation.
AF for other interspecies differences:
1
Justification:
In an evaluation by ECETOC in 2003 and 2010 it is considered that routine application of the factor 2.5 as a default factor is scientifically unjustified. The view is supported by data generated by the ERASM project (Batke et al. 2010).
AF for intraspecies differences:
10
Justification:
Default value (ECHA) for general population
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
92 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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:
5.3 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):
80
Modified dose descriptor starting point:
NOAEL
DNEL value:
424 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
On the assuption, that dermal absorption is not higher than oral absorption, the NOAEL of the oral subchronic study is used (ECHA guidance, chapter R.8, R.8.4.1)
AF for dose response relationship:
1
Justification:
There are no effects up to the limit dose
AF for differences in duration of exposure:
2
Justification:
Default value (ECHA) for sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (ECHA) for rat versus human
AF for other interspecies differences:
1
Justification:
In an evaluation by ECETOC in 2003 and 2010 it is considered that routine application of the factor 2.5 as a default factor is scientifically unjustified. The view is supported by data generated by the ERASM project (Batke et al. 2010).
AF for intraspecies differences:
10
Justification:
Default value (ECHA) for general population
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
26.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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:
5.3 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):
80
Modified dose descriptor starting point:
NOAEL
DNEL value:
424 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not applicable
AF for dose response relationship:
1
Justification:
There are no effects up to the limit dose
AF for differences in duration of exposure:
2
Justification:
Default value (ECHA) for sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (ECHA) for rat versus human
AF for other interspecies differences:
1
Justification:
In an evaluation by ECETOC in 2003 and 2010 it is considered that routine application of the factor 2.5 as a default factor is scientifically unjustified. The view is supported by data generated by the ERASM project (Batke et al. 2010).
AF for intraspecies differences:
10
Justification:
Default value (ECHA) for general population
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
26.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
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

DNEL systemic (general population)

Basis for delineation of the DNELs systemic (general population):

A repeated dose toxicity study in Wistar rats (90 day feeding study) according OECD Guideline 408 is available.

There is no long term study available using the inhalation or dermal route. Thus, as starting point for the calculation, the NOAEL of the subchronic feeding study has to be taken into account.

 

Study

Title: PBS-AM Subchronische toxikologische Untersuchungen an Ratten (Fütterungsversuch über 3 Monate)

Administration period: 90 days

Doses: 50, 200, 1000, 5000 ppm = male rats: 0, 4.17, 14.91, 84.11, 424.41 mg/kg bw/day, female rats: 0, 6.05, 12.51, 125.48, 632.65 mg/kg bw/day

 

NOAEL, Effects

NOAEL (systemic) = 424 mg/kg bw (male and female rats)

Effects: All doses were tolerated without any effects

Thus, the NOAEL is equal or higher than 5000 ppm (equivalent to about 424 mg/kg bw for male rats and 632 mg/kg bw for female rats).

 

Reference

Löser E, Kaliner G (1976), PBS-AM Subchronische toxikologische Untersuchungen an Ratten (Fütterungsversuch über 3 Monate), Bayer AG, Institut für,

 

DNEL local effects (general population)

Basis for delineation of the DNELs local (long and short term toxicity):

 

Irritation/corrosion

In the key studies for skin irritation/corrosion and eye irritation, the test substance (tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate) is not irritating to the skin and eyes.

A classification is not justified.

 

Sensitization

In a Guinea Pig maximization test (GPMT) the test substance (tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate) revealed no sensitisation potential.

A classification is therefore notjustified.

 

Result:

For local effects no hazard is identified.