Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
62.5 mg/m³
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
160.7 mg/m³
DNEL related information
Overall assessment factor (AF):
1

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
62.5 mg/m³
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
160.7 mg/m³
DNEL related information
Overall assessment factor (AF):
1

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
57 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Ammonium hydrogencarbonate is a naturally occurring substance, which rapidly dissociates in biological fluids to yield ammonium ions (NH4+) and hydrogencarbonate ions (HCO3-), which further disintegrate to NH3, CO2and H2O depending on the temperature. Ammonia and ammonium ions are integral components of normal metabolic processes and play an essential role in the physiology of man and other species.

Ammonium hydrogencarbonate as a human food ingredient is generally recognized as safe (GRAS) by the US FDA. It is also widely used in industrial uses (in cooling baths, in fire extinguishers, in the manufacture of porous plastics and ceramics, dyes, and pigments, in catalyst system for the stiffening of tobacco), in therapeutic and agricultural uses.

A national exposure survey conducted in 1983 including 18 industries with 2082 facilities counted 38228 employees to come in contact with ammonium hydrogencarbonate.

 

Therefore, long-term dermal and inhalative intakes are the possible exposure routes for worker, whereas oral, dermal and inhalative intakes are the possible exposure routes for consumer. Together with the fact that no substance-related local effects could be determined, only the DNELs for long-term systemic effects are derived since they have greater toxicological significance:

 

The DNELs for dermal long-term exposure are derived from the no observed effect level obtained in an oral repeated dose toxicity study with ammonium chloride. The ammonium ion, which is the cation in both ammonium chloride and ammonium hydrogencarbonate is relevant for the acute oral toxicity of both substances as well as repeated dose toxicity. Therefore, the available data for ammonium chloride can be used to assess the repeated dose toxicity of ammonium hydrogencarbonate.

Since no substance-related effects were noted, a NOAEL of 684 mg/kg bw/day was estimated after treatment for 70 days with ammonium chloride (Arnold, 1997). Results reported by Lina et. al. (2004) indicate an even higher NOAEL for ammonium chloride but the NOAEL of 684 mg/kg bw/day was chosen as worst case assumption due to the read across from ammonium hydrogencarbonate to ammonium chloride.

The DNEL for long-term exposure via inhalation for the worker is derived from the European limit value - eight hours for ammonia of 14 mg/m3. Ammonium hydrogencarbonate has a vapor pressure of 78.5 hPa at 25.4 °C and disintegrates to NH3, CO2and H2O depending on the temperature. Therefore the limit value for ammonia can be used and corrected as follows: Ammonia has a molar mass of 17.03 g/mol and ammonium hydorgencarbonate of 76.06 g/mol. The European limit value - eight hours for ammonia of 14 mg/m3 can therefore be corrected by a factor of (76.06/17.03) leading to a limit value - eight hour for ammonium hydrogencarobate of 62.5 mg/m3 for the worker. The respective European short term limit value for ammonia of 36 mg/m3 can be modified accordingly leading to a short term limit value for ammonium hydrogencarbonate of 160.7 mg/m3 for the worker. These DNELs cover both systemic and local effects.

 

For the DNEL of systemic dermal effects a correction of the starting point is not required, since the observed no effect level of 684 mg/kg bw/day (oral) was derived in 70-day repeated dose toxicity study (Arnold, 1997).

Subsequently, following assessment factors are taken into account for the final DNEL calculation: interspecies differences (4), remaining differences (1), intraspecies differences (3), exposure duration (2). These assessment factors are sufficient as outlined in the technical report Nr. 86 of ECETOC in 2003.

An additional assessment factor (0.5) was used to consider the different absorption properties of the skin and after oral intake.

As a consequence, the resulting DNEL for long-term dermal systemic effects is 57 mg/kg bw/d for workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.33 mg/m³
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
143.91 mg/m³
DNEL related information
Overall assessment factor (AF):
1

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.33 mg/m³
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
143.91 mg/m³
DNEL related information
Overall assessment factor (AF):
1

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
34.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
34.05 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Additional information - General Population

Ammonium hydrogencarbonate is a naturally occurring substance, which rapidly dissociates in biological fluids to yield ammonium ions (NH4+) and hydrogencarbonate ions (HCO3-), which further disintegrate to NH3, CO2and H2O depending on the temperature. Ammonia and ammonium ions are integral components of normal metabolic processes and play an essential role in the physiology of man and other species.

Ammonium hydrogencarbonate as a human food ingredient is generally recognized as safe (GRAS) by the US FDA. It is also widely used in industrial uses (in cooling baths, in fire extinguishers, in the manufacture of porous plastics and ceramics, dyes, and pigments, in catalyst system for the stiffening of tobacco), in therapeutic and agricultural uses.

A national exposure survey conducted in 1983 including 18 industries with 2082 facilities counted 38228 employees to come in contact with ammonium hydrogencarbonate.

 

Therefore, long-term dermal and inhalative intakes are the possible exposure routes for worker, whereas oral, dermal and inhalative intakes are the possible exposure routes for consumer. Together with the fact that no substance-related local effects could be determined, only the DNELs for long-term systemic effects are derived since they have greater toxicological significance:

 

The DNEL for oral and dermal long-term exposure are derived from the no observed effect level obtained in an oral repeated dose toxicity study with ammonium chloride. The ammonium ion, which is the cation in both ammonium chloride and ammonium hydrogencarbonate is relevant for the acute oral toxicity of both substances as well as repeated dose toxicity. Therefore, the available data for ammonium chloride can be used to assess the repeated dose toxicity of ammonium hydrogencarbonate.

Since no substance-related effects were noted, a NOAEL of 684 mg/kg bw/day was estimated after treatment for 70 days with ammonium chloride (Arnold, 1997). Results reported by Lina et. al. (2004) indicate an even higher NOAEL for ammonium chloride but the NOAEL of 684 mg/kg bw/day was chosen as worst case assumption due to the read across from ammonium hydrogencarbonate to ammonium chloride.

The short-term acute oral DNEL for systemic effects was derived based on an acute toxicity study (BASF AG,1989). At a dose level of 681 mg/kg bw., no mortality and no clinical signs were observed. This value was therefore considered as the NOAEL for short-term acute systemic toxicity. A safety factor of 5 for the general population (intraspecies) and an interspecies factor of 4 (rat to human) was used to derive a DNEL of 34.05 mg/kg bw for short-term acute systemic toxicity by the oral route.

 

The DNEL for long-term exposure via inhalation for consumers is derived from the limit value - eight hour for ammonium hydrogencarobate of 62.5 mg/m3 for the worker. This limit value has to be corrected for the reduced breathing volume of 6.7 m3 (consumer) instead of 10 m3 (worker), the prolonged exposure duration of 24 hours (consumers) instead of 8 hours (worker) and 7 days (consumer) instead of 5 days (worker) as well as an intraspecies factor (3/5). The inhalation DNEL for the consumer is calculated as follows: 62.5 mg/m3 x (10/6.7) x (8/24) x (5/7) x (3/5) = 13.33 mg/m3. The respective short term DNEL for the consumer is calculated from the short term DNEL for the worker of 160.7 mg/m3 correcting for the inhalation volume (10 m3/6.7 m3) and an additional safety factor of (5/3) (worker to general population) leading to a short term inhalative consumer DNEL of 143.91 mg/m3. These DNELs cover both systemic and local effects.

 

For the DNEL of systemic oral and dermal effects a correction of the starting point is not required, since the observed no effect level of 684 mg/kg bw/day (oral) was derived in 70-day repeated dose toxicity study (Arnold, 1997).

Subsequently, following assessment factors are taken into account for the final DNEL calculation for the oral route: interspecies differences (4), remaining differences (1), intraspecies differences (5), exposure duration (2). These assessment factors are sufficient as outlined in the technical report Nr. 86 of ECETOC in 2003.

As a consequence, the resulting DNEL for long-term oral systemic effects is 17.1 mg/kg bw/d for the general population.

 

 The following assessment factors are taken into account for the final DNEL calculation for the dermal route: interspecies differences (4), remaining differences (1), intraspecies differences (5), exposure duration (2). These assessment factors are sufficient as outlined in the technical report Nr. 86 of ECETOC in 2003.

An additional assessment factor (0.5) was used to consider the different absorption properties of the skin and after oral intake.

As a consequence, the resulting DNEL for long-term dermal systemic effects is 34.2 mg/kg bw/d for the general population.