Ammonium sulphate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

11.167 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

18

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

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:

42.667 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

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:

no hazard identified

Additional information - workers

- Short-term exposure and local effects:

Acute/short-term DNELs were not calculated as they are covered by calculation of long-term DNELs. On the basis of the available animal and human data on acute toxicity following inhalation, there is no need for classification. Ammonium sulfate (CAS No. 7783 -20 -2 was not irritating to the skin and eyes of rabbits. In rabbits, single semiocclusive exposure for 20 hours or multiple exposures (8 h/day) on five consecutive days to the neat test substance (purity not reported) did not elicit any adverse effects on intact skin. Single exposure for 8 hours to scarified skin caused only slight redness, and slight edema. These effects were completely reversible within 8 days (BASF AG,1968). In two rabbits, single exposure of up to 20 hours to an 80 % aqueous preparation of ammonium sulfate (“chemically pure”) was not irritating to the intact skin (BASF AG, 1969). Concerning eye irritation, in two rabbits, slight edema and conjunctival redness was noted one hour after instillation of 50 mm³ of the test substance (“chemically pure”) into the conjunctival sac. No edema, but still slight redness was present at 24 hours. In the eyes treated with talcum, effects similar to the treatment with the test substance were found one and 24 hours after exposure. No effects were noted at day 8 (BASF AG, 1969). There are no data about respiratory irritation and sensitization. Considering a study using ammonium chloride as an analogous test substance, only very slight to slight edema were observed after the induction phase and 24 and 48 hours after challenge exposure using an occlusive dressing, 10 % of the animals showed a positive reaction (very slight, hardly perceptible erythema), assessed as not sensitizing due to required response of at least 15% in a non-adjuvant test. Accordingly, no sensitization effects were considered for ammonium sulfate.

 

Therefore the following DNEL(s) for local effects and short term exposure were not determined:

- Dermal DNEL for acute / short-term exposure - systemic effects

- Inhalation DNEL for acute / short-term exposure - systemic effects

- Dermal DNEL for acute / short-term exposure - local effects

- Inhalation DNEL for acute / short-term exposure - local effects

- Long-term exposure and local effects:

No local dermal or irritating effects were observed in repeated dose studies.

Therefore the following DNEL(s) for local effects and long term exposure were not determined:

- Dermal DNEL for long-term exposure - local effects

- Inhalation DNEL for long-term exposure - local effects

- Long-term exposure - systemic effects

 

- Dermal DNEL for long-term exposure - systemic effects

Based on the No-(Adverse)-Effect-Level for oral repeated-dose toxicity of ammonium sulfate (CAS No. 7783-20-2), the endpoint-specific dermal DNEL was calculated using a 52 and 104 weeks feeding study in rats. Concerning increased kidney weight at the high dose level, decreased absolute spleen weights and increased relative liver weights in high dose males a NOAEL of 256 mg/kg bw/day for males and 284 mg/kg bw/day for females was determined (Ota et al., 2006). For calculation of DNEL, the NOAEL of 256 mg/kg bw/day was taken.

The dermal absorption was assumed as 50 %. Accordingly, for dermal exposure the corrected starting point was calculated as 512 mg/kg body weight/day. Using the overall assessment factor of 12, including assessment factors for interspecies extrapolation of 4 (allometric scaling rat to human), intraspecies extrapolation of 3 for worker according to ECETOC 2003, and for exposure duration, remaining factors, dose response and quality of database of 1, respectively, the DNEL (Worker) for dermal exposure was calculated as follows:Corrected starting point of 512 mg/kg/day/ assessment factors (4*3*1*1*1*1) = DNEL (worker) of 42.667 mg/kg body weight /day.

 

- Inhalation DNEL for long-term exposure - systemic effects

DNEL calculation was based on a 14 day inhalation study on ratsexposed to ammonium sulfate(Cas No. 7783-20-2) at the only tested dose of 300 mg/m³ for 8 hours per day(Pepelko, Mattox and Cohen, 1980). Due to nohistopathological changes in the respiratory tract as well as no changes in pulmonary function and arterial blood gases aNOEL of 300 mg/m³ for toxicity to the lower respiratory tract was assessed.The conversion of the inhalatory rat NOAEC into a corrected inhalatory human NOAEC was based on the different respiratory rate during light activity at work (10 m³) and standard conditions (6.7 m³). Based on the daily exposure of 8 hours in the animal study, a correction for different exposure duration of workers was not necessary.

NOEC = 300 mg / m³ * 6.7 m³ (8h) / 10 m³ (8h) = corrected NOEC of 201.0 mg / m³.  

Using the overall assessment factor of 18, including assessment factors for intraspecies extrapolation of 3 for worker according to ECETOC 2003, exposure duration of 6 (sub-acute to chronic) and for remaining factors, dose response and quality of database of 1, respectively, the DNEL (Worker) for inhalative exposure was calculated as follows:

Corrected NOEC 201.0 mg/kg body weight/day/ assessment factors (3*6*1*1*1) = DNEL (worker) of 11.167 mg/m³.

 

Based on the facts, that in the inhalation study used for the DNEL calculation, only an exposure duration of 14 days and only one dose of 300 mg/m³ was tested which did not show any effects, an additional calculation of the endpoint specific DNEL for inhalation repeated-dose toxicity for workers was performed using the oral chronic repeated dose (feeding) study (Ota et al., 2006).

The conversion of the rat oral NOAEL of 256 mg/kg bw/day to a corrected inhalatory human NOAEL was based on the different respiratory volume of the rat (0.38 m³/kg/day and the different rate during light activity at work (10 m³) and standard conditions (6.7 m³):

NOAEL 256 mg / m³ * 1/0.38 m³/kg/day * 6.7 m³ (8h) / 10 m³ (8h) = 451.4 mg/m³ as corrected NOAEL (corrected starting point).

Using the overall assessment factor of 3, including assessment factors for intraspecies extrapolation of 3 for worker according to ECETOC 2003 and for exposure duration, remaining factors, dose response and quality of database of 1, respectively, the DNEL (Worker) for inhalative exposure was calculated as follows:

Corrected NOAEL 451.4 mg/m³/ (3*1*1*1*1) = DNEL (worker) of 150.456mg/m³.

 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.667 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

60

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:

DNEL (Derived No Effect Level)

Value:

12.8 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:

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:

DNEL (Derived No Effect Level)

Value:

6.4 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:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

- Short-term exposure and local effects:

Acute/short-term DNELs were not calculated as they are covered by calculation of long-term DNELs.

Ammonium sulfate (CAS No. 7783 -20 -2 was not irritating to the skin and eyes of rabbits. In rabbits, single semiocclusive exposure for 20 hours or multiple exposures (8 h/day) on five consecutive days to the neat test substance (purity not reported) did not elicit any adverse effects on intact skin. Single exposure for 8 hours to scarified skin caused only slight redness, and slight edema. These effects were completely reversible within 8 days (BASF AG, 1968). In two rabbits, single exposure of up to 20 hours to an 80 % aqueous preparation of ammonium sulfate (“chemically pure”) was not irritating to the intact skin (BASF AG, 1969). Concerning eye irritation, in two rabbits, slight edema and conjunctival redness was noted one hour after instillation of 50 mm³ of the test substance (“chemically pure”) into the conjunctival sac. No edema, but still slight redness was present at 24 hours. In the eyes treated with talcum, effects similar to the treatment with the test substance were found one and 24 hours after exposure. No effects were noted at day 8 (BASF AG, 1969). There are no data about respiratory irritation and sensitization. Considering a study using ammonium chloride as an analogous test substance, only very slight to slight edema were observed after the induction phase and 24 and 48 hours after challenge exposure using an occlusive dressing, 10 % of the animals showed a positive reaction (very slight, hardly perceptible erythema), assessed as not sensitizing due to required response of at least 15% in a non-adjuvant test. Accordingly, no sensitization effects were considered for ammonium sulfate.

 

Therefore the following DNEL(s) for local effects and short term exposure were not determined:

- Dermal DNEL for acute / short-term exposure - systemic effects

- Inhalation DNEL for acute / short-term exposure - systemic effects

- Dermal DNEL for acute / short-term exposure - local effects

- Inhalation DNEL for acute / short-term exposure - local effects

 

Long-term exposure and local effects:

No local dermal or irritating effects were observed in repeated dose studies.

Therefore the following DNEL(s) for local effects and long term exposure were not determined:

- Dermal DNEL for long-term exposure - local effects

- Inhalation DNEL for long-term exposure - local effects

 

Long-term exposure - systemic effects

Based on the No-(Adverse)-Effect-Level for oral repeated-dose toxicity ofammonium sulfate (CAS No. 7783-20-2)the endpoint-specific oral DNEL was calculated using a52 and 104 weeks feedingstudy in rats with increased kidney weight at the high dose level in both sexes, decreased absolute spleen weights and increased relative liver weights in high dose males. Therefore, a NOAEL of256 mg/kg bw/day for males and 284 mg/kg bw/dayfor females was determined (Ota et al., 2006). For calculation of DNEL, the NOAEL of 256 mg/kg bw/day was taken. Using an over all assessment factor of 40, including the assessment factors for interspecies extrapolation of 4 (allometric scaling rat to human), intraspecies extrapolation of 10 for general population, and for exposure duration, remaining factors, dose response and quality of database of 1, respectively, the DNEL (general population) for oral exposure was calculated as follows:

NOAEL of 256 mg/kg/day/ (4*10*1*1*1*1) = DNEL (general population) of 6.400 mg/kg body weight /day.

 

- Dermal DNEL for long-term exposure - systemic effects

For the determination of the dermal DNEL, the NOAEL of 256 mg/kg bw/day of the same rat oral chronic repeated dose study (Ota et al., 2006) was used.

The dermal absorption was assumed as 50 %. Accordingly, for dermal exposure the corrected starting point was calculated as 512 mg/kg body weight/day. Using the overall assessment factor of 40, including assessment factors for interspecies extrapolation of 4 (allometric scaling rat to human), intraspecies extrapolation of 10 for general population, and for exposure duration, remaining factors, dose response and quality of database of 1, respectively, the DNEL (general population) for dermal exposure was calculated as follows:Corrected starting point of 512 mg/kg/day/ (4*10*1*1*1*1) = DNEL (general population) of 12.800 mg/kg body weight /day.

 

- Inhalation DNEL for long-term exposure - systemic effects

DNEL calculation was based on a 14 day inhalation study on rats exposed to300 mg/m³ ammonium sulfate(Cas No. 7783-20-2), the only tested dose, for 8 hours per day(Pepelko, Mattox and Cohen, 1980). Due to nohistopathological changes in the respiratory tract as well as no changes in pulmonary function and arterial blood gases aNOEC of 300 mg/m³ for toxicity to the lower respiratory tract was assessed.The conversion of the inhalatory rat NOEC into a corrected inhalatory human NOEC was based on the different exposure duration of the general population (24 hours) compared to the animal study (8 hours).

NOEC = 300 mg / m³ * 8h per day / 24h per day * = corrected NOEC of 100.0 mg / m³.  

Using the overall assessment factor of 60, including assessment factors for intraspecies extrapolation of 10 for general population, exposure duration of 6 (sub-acute to chronic) and for remaining factors, dose response and quality of database of 1, respectively, the DNEL (general popluation) for inhalative exposure was calculated as follows:

Corrected NOEC100.0 mg/kg body weight/day/ (10*6*1*1*1) = DNEL (general population) of 1.667 mg/m³.

 

Based on the facts, that in the inhalation study used for the DNEL calculation, only an exposure duration of 14 days and only one dose of 300 mg/m³ was tested, an additional calculation of the endpoint specific DNEL for inhalation repeated-dose toxicity for workers was performed using the oral chronic repeated dose (feeding) study (Ota et al., 2006).

The conversion of the rat oral NOAEL of 256 mg/kg bw/day to a corrected inhalatory human NOAEL was based on the respiratory volume of the rat due to 24 hour exposure (1.15 m³/kg/day):

NOAEL 256 mg / m³ * 1/1.15 m³/kg/day = 222.6 mg/m³ as correctedNOAEL (corrected starting point).

Using the overall assessment factor of 10 based on intraspecies extrapolation for general population, and for exposure duration, remaining factors, dose response and quality of database of 1, respectively, the DNEL (general population) for inhalative exposure was calculated as follows:

Corrected NOAEL 222.6 mg/m³/ (10*1*1*1*1) = DNEL (general population) of 22.261mg/m³.