Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
70.5 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
1 763.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
using bioavailability of 10% for the oral and 10% for the inhalation route and assuming that rat oral and inhalation absorptions are equal to human oral and inhalation absorption, a NOAEC corr of 1000 mg/kg/day / 0.38 m³/kg * 6.7/10 * 10/10 = 1763.2 mg/m³ is used.
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL/NOAEC
AF for differences in duration of exposure:
2
Justification:
due to subchronic study data used
AF for interspecies differences (allometric scaling):
1
Justification:
not required due to route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
for worker, a default AF of 5 is to be used
AF for the quality of the whole database:
1
Justification:
not required, as supporting studies for the oral NOAEL are available
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
10 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
using bioavailability of 10% for the oral and 10% for the dermal route and assuming that rat oral and dermal absorptions are equal to human oral and dermal absorption, thus the corrected dermal NOAEL is 1000 mg/kg/day based on the oral NOAEL of 1000 mg/kg bw/d derived from subchronic studies.
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
due to subchronic study data used
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
for worker, a default AF of 5 is to be used
AF for the quality of the whole database:
1
Justification:
not required, as supporting studies for the oral NOAEL are available
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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

Several subchronic toxicity studies are available, all with oral exposure.

Whereas Donaubauer 1984 reported a NOAEL of 1000 mg/kg bw/d (929 mg/kg bw/d for males and 1004 mg/kg bw/d for females) in a feeding study with 90 days exposure period, Gupta et al. 1979 reported a NOEL of 500 mg/kg bw/d for ammonium sulphamate which was the highest dose tested in this study. Ambrose et al. 1943 investigated sulphamic acid in a feeding study with 105 days of exposure and the NOAEL was set to 600 mg/kg bw/d with effects only on growth rate seen at 1500 mg/kg bw/d. When dosing ammonium sulphamate rather than sulfamic acid, similar effects but to a lesser extent were seen at the same doses (calculated as sulfamic acid).

In a 2-week range finding study with female rats up to 1000 mg/kg bw/d dosed, one animal in the 1000 mg/kg bw/d dose was found dead. This study was gavage dosed and gastro-intestinal lesions were observed as well as hepatic changes (liver partly pale). This may have occurred due to a dosing injury effect by gavage as no other effects were seen and the other two animals of the dose group had shown no such effects. Thus, the NOAEL of 300 mg/kg bw/d in this study should be seen with caution and is disregarded here.

Although in the OECD 414 study slight growth reduction was observed at 600 mg/kg bw/d in parental animals when dosed for 14 days (GD 6-19) such effects were also observed in the subchronic studies at higher doses only.

Considering all studies in a weight of evidence, the subchronic NOAEL of 1000 mg/kg bw/d from the key study (Donaubauer, 1984) appears best suited to derive DNELs for long-term exposure, considering exposure time and reliability of the study and also considering consistency with the remaining supportive studies.

Although sulfamic acid is a very strong acid (negative pKa) it was shown not to be corrosive to skin. When tested in vivo only mild skin and eye irritation was observed. Only when tested to abraded skin stronger irritation response was observed. Thus, the skin barrier seems to be efficient and stable towards sulfamic acid and absorption via skin is low.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.4 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
869.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
using bioavailability of 10% for the oral and 10% for the inhalation route and assuming that rat oral and inhalation absorptions are equal to human oral and inhalation absorption, a NOAEC corr of 1000 mg/kg/day / 1.15 m³/kg * 10/10 = 869.6 mg/m³ is used.
AF for dose response relationship:
1
Justification:
not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
due to subchronic study data used
AF for interspecies differences (allometric scaling):
1
Justification:
not required due to route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
for consumer, a default AF of 10 is to be used
AF for the quality of the whole database:
1
Justification:
not required, as supporting studies for the oral NOAEL are available
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
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
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
using bioavailability of 10% for the oral and 10% for the dermal route and assuming that rat oral and dermal absorptions are equal to human oral and dermal absorption, thus the corrected dermal NOAEL is 1000 mg/kg/day based on the oral NOAEL of 1000 mg/kg bw/d derived from subchronic studies.
AF for dose response relationship:
1
Justification:
not required as NOAEL is used
AF for differences in duration of exposure:
2
Justification:
due to subchronic study data used
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
for consumer, a default AF of 10 is to be used
AF for the quality of the whole database:
1
Justification:
not required, as supporting studies for the oral NOAEL are available
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
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
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation applied
AF for dose response relationship:
1
Justification:
not required as NOAEL is used
AF for differences in duration of exposure:
2
Justification:
due to subchronic study data used
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling factor rat-human
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
for consumer, a default AF of 10 is to be used
AF for the quality of the whole database:
1
Justification:
not required, as supporting studies for the oral NOAEL are available
AF for remaining uncertainties:
1
Justification:
not required
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

Several subchronic toxicity studies are available, all with oral exposure.

Whereas Donaubauer 1984 reported a NOAEL of 1000 mg/kg bw/d (929 mg/kg bw/d for males and 1004 mg/kg bw/d for females) in a feeding study with 90 days exposure period, Gupta et al. 1979 reported a NOEL of 500 mg/kg bw/d for ammonium sulphamate which was the highest dose tested in this study. Ambrose et al. 1943 investigated sulphamic acid in a feeding study with 105 days of exposure and the NOAEL was set to 600 mg/kg bw/d with effects on growth rate seen at 1500 mg/kg bw/d. When dosing ammonium sulphamate rather than sulfamic acid, similar effects but to a lesser extent were seen at the same doses (calculated as sulfamic acid).

In a 2-week range finding study with female rats up to 1000 mg/kg bw/d dosed, one animal in the 1000 mg/kg bw/d dose was found dead. This study was gavage dosed and gastro-intestinal lesions were observed as well as hepatic changes (liver partly pale). This may have occurred due to a dosing injury effect by gavage as no other effects were seen and the other two animals of the dose group had shown no such effects. Thus, the NOAEL of 300 mg/kg bw/d in this study should be seen with caution and is disregarded here.

Although in the OECD 414 study slight growth reduction was observed at 600 mg/kg bw/d in parental animals when dosed for 14 days (GD 6-19) such effects were also observed in the subchronic studies at higher doses only.

Considering all studies in a weight of evidence, the subchronic NOAEL of 1000 mg/kg bw/d from the key study (Donaubauer, 1984) appears best suited to derive DNELs for long-term exposure, considering exposure time and reliability of the study and also considering consistency with the remaining supportive studies.

Although sulfamic acid is a very strong acid (negative pKa) it was shown not to be corrosive to skin. When tested in vivo only mild skin and eye irritation was observed. Only when tested to abraded skin stronger irritation response was observed. Thus, the skin barrier seems to be efficient and stable towards sulfamic acid and absorption via skin is low.