Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Principles of method if other than guideline:
The acute oral toxicity of K-HDO in Sprague-Dawley rats has been determined. For this purpose, the product was administered once by gavage as 0.562 - 2.61 % w/v aqueous solutions in doses of 56.2, 68.1, 82.5, 100, 121, 147, 178, 215 and 261 mg/kg.
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was performed, however the conditions of good laboratory practice have always been observed.
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Test item: (N-Cyclohexyl-diazeniumdioxy)-potassium
IUPAC name: Cyclohexylhydroxydiazene 1-oxide, potassium salt
Chemical name: Cyclohexylhydroxydiazene 1-oxide, potassium salt; synonyma: (N-Cyclohexyl-diazeniumdioxy)-potassium, K-HDO, K-NCH, Xyligen K powder, Xyligen K
Molecular formula: C6 H11 K N2 O2
Molecular mass: 182.27
Specific details on test material used for the study:
Chemical name: N-Cyclohexyldiazeniumdioxy potassium
Test substance number: XXV/210
Degree of purity: analytical grade

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: WIGA, Sulzfeld, FRG
- Sex: male / female
- Weight at study initiation: male: 203 g; female: 163 g
- Fasting period before study: Food was withdrawn about 16 h before administration.
- Diet / water (e.g. ad libitum): The animals received Altromin R 1324 supplied by ALTROMIN GmbH, Lage/Lippe, FRG and water ad libitum.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: aqueous solution
Details on oral exposure:
The product was administered once by gavage in various doses as 0.562 - 2.61 % w/v aqueous solutions.
Doses:
Test doses: 56.2, 68.1, 82.5, 100, 121, 147, 178, 215, 261 mg/kg
Test concentrations: 2.61, 2.15, 1.78, 1.47, 1.21, 1, 0.825, 0.681, 0.562 % w/v
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 1, 24 and 48 hours and 7 and 14 days
- Examinations performed: signs of toxicity and necropsy of the animals which died and those which were sacrificed with carbon dioxide at the end of the observation period.
Statistics:
Determination of the median Lethal dose (LD 50), calculated by FINNEY'S Probit analysis for a Log-normal distribution.

Results and discussion

Preliminary study:
no preliminary study performed
Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
150 mg/kg bw
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
122 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
136 mg/kg bw
Based on:
test mat.
Mortality:
see table below
Clinical signs:
see table below
Body weight:
not given in the report
Gross pathology:
Results of necropsy are given in the table below.
Other findings:
All findings are summarized in the tables below.

Any other information on results incl. tables

Mortality:

Dose

(mg/kg)

Cone.

(%)

Number of animals

died within

1 h

24 h

48 h

7 days

14 days

261

2.61

10 m

10 f

1/10

0/10

6/10

3/10

6/10

4/10

8/10

7/10

8/10

9/10

215

2.15

10 m

10 f

3/10

0/10

7/10

7/10

8/10

7/10

8/10

8/10

8/10

9/10

178

1.78

10 m

10 f

1/10

1/10

6/10

1/10

8/10

2/10

8/10

2/10

8/10

3/10

147

1.47

10 m

10 f

2/10

2/10

4/10

3/10

4/10

3/10

5/10

4/10

5/10

5/10

121

1.21

10 m

10 f

1/10

1/10

3/10

1/10

3/10

2/10

8/10

2/10

8/10

2/10

100

1

10 m

10 f

0/10

1/10

1/10

1/10

1/10

2/10

2/10

2/10

2/10

3/10

82.5

0.825

10 m

10 f

2/10

1/10

2/10

2/10

2/10

2/10

4/10

2/10

4/10

2/10

68.1

0.681

10 m

10 f

0/10

1/10

0/10

1/10

1/10

1/10

1/10

1/10

1/10

1/10

56.2

0.562

10 m

10 f

0/10

0/10

0/10

0/10

0/10

0/10

1/10

0/10

1/10

0/10

Applicant's summary and conclusion

Conclusions:
The determined LD50 value of male and female rats for acute oral toxicity amounts to 136 mg K-HDO/kg bw corresponding to 452 mg (30% w/w K-HDO)/kg bw
Executive summary:

The median lethal dose (LD50), calculated by FINNEY's probit analysis for a log-normal distribution, determined in this study was:

for male and female animals after 14d:       136 (117 - 161) mg/kg

for male animals after 14d:                        122 (92 - 161) mg/kg

for female animals after 14d:                     150 (120 - 202) mg/kg

Clinical signs (summary):

Immediately after administration strong neurological effects were observed; At the low dose group clonic spasms, twitching, dyspnoea and poor general condition. With increasing doses also tremor, tonic spasms, saltatory spasms, salivation, staggering, spastic gate, lateral position, apathy and agitation were observed.

The determined LD50value of male and female rats for acute oral toxicity amounts to 136 mg K-HDO/kg bw corresponding to 452 mg (30% w/w K-HDO)/kg bw