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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Limited documentation

Data source

Reference
Reference Type:
publication
Title:
A case of fatal intoxication with ammonium sulfate and a toxicological study using rabbits.
Author:
Sato A et al.
Year:
1999
Bibliographic source:
Forensic Science International101: 141-149.

Materials and methods

Objective of study:
distribution
Principles of method if other than guideline:
no data
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Ammonium sulphate
EC Number:
231-984-1
EC Name:
Ammonium sulphate
Cas Number:
7783-20-2
Molecular formula:
H3N.1/2H2O4S
IUPAC Name:
Monochloramine generated from ammonium sulphate and a chlorine source
Test material form:
solid: crystalline
Radiolabelling:
no

Test animals

Species:
rabbit
Strain:
other: Japanese white
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
Japanese white rabbits
- Weight at study initiation: 3.4 - 3.8 kg
no further data

ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:
other: gastric tube
Vehicle:
physiological saline
Duration and frequency of treatment / exposure:
single dose
Doses / concentrations
Dose / conc.:
1 500 other: mg/kg/bw
No. of animals per sex per dose / concentration:
3 (test group);
2 (control group)
Control animals:
yes, concurrent vehicle
Positive control reference chemical:
no

Results and discussion

Any other information on results incl. tables

General findings

The three rabbits used in this experiment showed similar symptoms. Mydriasis and slight irregular respiratory rhythms appeared at 10 to 20 min after ingestion of the ammonium sulfate solution. Local convulsions persisting for 5 to 10 min in the face or in the extremities starting 15 to 25 min after ingestion and soon after it spread to every part of the body, at which time they exhibited opisthotonus lasting for 1 0 to 20 s which repeated itself several times.

After the general convulsions, heart rates decreased suddenly (N=1) or gradually (N=2) depending on the rabbit and the pneumonic respiration became quiet and weak. In 60 to 70 min after the ingestion, all the rabbits fell into breathlessness along with cardiac arrest.

Blood examination

Blood gas analysis:

The value of pH, HCO3 and Base Excess decreased promptly. On the other hand, PO2 and PCO2 did not show remarkable changes during the experiment until the animals died. These results show that severe metabolic acidosis developed after ingestion of the test substance.

Ammonium and sulfate ion concentration:

The concentration of ammonium in serum had already increased remarkably 5 min after ingestion (1095 +/- 535 µg/dl , mean +/- SD), until it reached 11000 +/- 1200 µg/dl after 60 min

Inorganic sulfate ion concentration started to increase at 10 min after ingestion and its level continued to increase linearly to 20 +/- 4.9 mEq/l after 60 min

Biochemical analysis:

Electrolytes of Na+, K+, Cl - and Ca2 + did not show any significant change during the experiment except for a moderate increase in K+ just before cardiac arrest. Concentration of released enzymes such as AST, ALT and LDH remained constant and normal levels were maintained throughout the experiment. Also, the values of BUN and creatinine were always within a normal range.

Histological observation

Brain, heart, lung, spleen, kidney, liver and stomach were observed microscopically, but no pathological changes such as hemorrhage, degeneration or necrosis of tissue were found.

In control group of rabbit ingesting saline, there was no significant finding on physiological monitoring, blood examination, histological observation.

Applicant's summary and conclusion