potassium (oxido-NNO-azoxy)cyclohexane; cyclohexylhydroxydiazene 1-oxide, potassium salt; [K-HDO]

Acute Toxicity: oral

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

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

Test material information

Constituent 1

Reference substance name:

Cyclohexylhydroxydiazene 1-oxide, potassium salt

EC Number:

613-953-8

Cas Number:

66603-10-9

Molecular formula:

C6H11KN2O2

IUPAC Name:

Cyclohexylhydroxydiazene 1-oxide, potassium salt

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 or test system 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- Fasting period before study: Food was withdrawn about 16 h before administration.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 levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

150 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

122 mg/kg bw

Based on:

test mat.

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

136 mg/kg bw

Based on:

test mat.

Mortality:

see table below

Clinical signs:

other: see table below

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