Registration Dossier

Administrative data

Description of key information

There are no data available concerning the skin sensitation potential of ammonium sulfate. A read across from an analogous substance was used. Thereby, in an in vivo study, a guinea pig maximization test, for the structural analogue ammonium chloride no skin sensitizing potential was reported (Hoechst AG, 1986).


There are no animal studies available concerning the respiratory sensitation. In a study on humans, both healthy, "sensitive" and asthmatic adult men were exposed to ammonium sulfate, ammonium bisulfate, and sulfuric acid (Alvol E.L. et al., 1979). In a second study, pulmonary function and bronchial reactivity to metacholine was studied after exposure to an ammonium sulfate aerosol (Kulle et al., 1984). In a third study, thirteen male healthy volunteers were exposed to ammonium sulfate (Stacy R.W. et al. 1983). In a forth study a panel of 16 laboratory workers inhaled ammonium sulfate (Utell M.J. et al. 1982). No sensitizing effect was observed in all studies after exposure to ammonium sulfate.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: EPA 540/9-82-025
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The Guinea Pig Maximazitation Test met the previous requirements before the entry into force of REACH. The GPMT is suitable and reliable to cover this endpoint. For this reason and for animal welfare reasons, no further in vivo study (LLNA test) needs to be performed.
Species:
guinea pig
Strain:
other: Pirbright-White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeder
- Age at study initiation: about 8 weeks
- Mean weight at study initiation: 240 g

ENVIRONMENTAL CONDITIONS: not reported

Route:
other: 1st: intracutaneous, 2nd: occlusive epicutaneous
Vehicle:
other: 0.9% NaCl solution
Concentration / amount:
1st Induction: 5%, 2nd Induction 25 %, 3rd: Challenge: 10 %.
Route:
epicutaneous, occlusive
Vehicle:
other: 0.9% NaCl solution
Concentration / amount:
1st Induction: 5%, 2nd Induction 25 %, 3rd: Challenge: 10 %.
No. of animals per dose:
20
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
1st application: Induction 5 % intracutaneous
2nd application: Induction 25 % occlusive epicutaneous

B. CHALLENGE EXPOSURE
3rd application: Challenge 10 % occlusive epicutaneous

METHOD
Day 1 : Intradermal induction exposure (Injection): The injection sites were not covered.
Day 1-7: The application area was investigated.
Day 9 : Dermal induction exposure: 0.5ml of the test substance preparation were applied to a cellulose patch of 2x4 cm. This patch covered
the area of the intradermal injection sites. An occlusive dressing with impermeable foil and an elastic bandage sealed the application site for 48 hours.
Day 11 : Removal of the occlusive dressing. Recording of the irritation.
Day 22 : Dermal challenge exposure. 0.5ml of test substance preparation were applied to a cellulose patch and placed onto the clipped skin of the flank. An occlusive dressing with impermeable foil and an elastic bandage sealed the application site for 24 hours.
Day 23 : Removal of the occlusive dressing.
Day 24-25: Assessment of the skin.
Key result
Reading:
other: 1st and 2nd reading
Group:
test chemical
Dose level:
ca. 76.5 mg
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
24 and 48 hours after removal of the occlusive dressing, very slight, hardly perceptible erythema
Remarks on result:
other: see Remark
Remarks:
Reading: other: 1st and 2nd reading. Group: test group. Dose level: ca. 76.5 mg. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: 24 and 48 hours after removal of the occlusive dressing, very slight, hardly perceptible erythema .

1) The treated animals did not show any signs of toxicity throughout the study period.
2) Induction: Very slight to slight edema were observed in the treatment group.
3) Challenge: 24 and 48 hours after removal of the occlusive dressing, a total of 2 animals (in 20) of the treatment group showed

very slight, hardly perceptible erythema.
Ten percent of the animals of treatment group demonstrated a positive reaction after the challenge exposure

(the criteria: the limit value of 30 percent).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Animal Data

In a guinea pig maximization test (Hoechst AG, 1986) conducted with the analogous substance ammonium chloride according GLP and according to EPA 540/9-82-025, a test group of 20 animals received 5% ammonium chloride in vehicle (physiological saline) for intracutaneous induction, followed by epicutaneous induction with 0.5 ml 25% ammonium chloride in vehicle under occlusive dressing for 48 hours. For challenge, 0.5 ml of a 10% solution in vehicle was applied to the intact clipped skin with a 24 hour covered patch (occlusive). Ten percent of the animals demonstrated a positive reaction after the challenge exposure (below the limit value of 30 percent). The study showed that the substance had no sensitizing potential.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Human data

In a study on humans, both healthy, "sensitive" and asthmatic adult men were exposed to nominal (100 µg/m³) concentrations of ammonium sulfate, ammonium bisulfate, and sulfuric acid with a mass median aerodynamic diameter (MMAD) of 0.3-0.6 µm and a relative humidity ranging between 40 and 85% (Alvol et al., 1979). The study showed no evidence of an adverse health effect on healthy, sensitive and asthmatic adult men.

In the second study (Kulle et al., 1984), pulmonary function and bronchial reactivity to metacholine was studied in 20 non-smoking subjects after a 4 -hour exposure to an ammonium sulfate aerosol (528 +/- 39 µg/m³, mass median diameter: 0.97 +/- 0.05 µm) and was shown not to be affected.

In a third study (Stacy et al., 1983), thirteen male healthy volunteers were exposed to ammonium sulfate (0.133 mg/m³) with a MMAD for the chemical specimen of 0.55 µm for 4 hours including 15 min treadmill exercise at 30°C and 60% relative humidity. Exposure to ammonium sulfate caused no significant effects on any pulmonary function of healthy men.

In a forth study (Utell et al., 1982), 16 normal (mean age 27 years) subjects inhaled a control NaCl aerosol followed by ammonium sulfate (particles with an average MMAD of approximately 0.5-1.0 µm and concentrations of 0.1 and 1 mg/m³). At 1 mg/m³ quite small changes in flow on the maximum expiratory flow-volume (MEFV) and partial expiratory flow-volume (PEFV) curves was observed, which may be based on improved flow rates caused by sodium chloride inhalation resulting in statistical significance, despite the relatively small reduction in flow.

For details see Section 7.10.5 Exposure related observations in humans.


Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The substance is not considered to be classified for skin sensitisation under Regulation (EC) No 1272/2008, as amended for the ninth time in Regulation (EU) No 2016/1179. Based on the human data, classification concerning respiratory sensitisation is not warranted.