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Administrative data

Description of key information

Acute oral toxicity of hydrazine monohydrate was determined in male and female rats according to OECD TG 401 and GLP (MHLW 2003). Assuming that hydrazine monohydrate solution contains 64 % hydrazine the respective results for hydrazine LD50 (rat, oral): 173 mg/kg bw for males and ranges between 108 and 141 mg/kg bw for females. Rats were exposed to 400 -800 ppm hydrazine for 4 hours and resulted in a LC50 (male rat) of 570 ppm (759 mg/m³, Jacobson 1955). Hydrazine is classified as corrosive. Thus, a dermal acute toxicity study needs not to be available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study, GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Species:
rat
Strain:
other: Crj:CD(SD)IGS
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: young adult
- Weight at study initiation: males 151-176 g; females: 126-145 g
- Fasting period before study: yes
- Housing: group-caged by sex
- Acclimation period: 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 30-70

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
single oral application by gavage and a 14-day observation period
Doses:
0, 100, 130, 169, 220, 286 mg/kg bw hydrazine monohydrate (corresponds to 0, 64-183 mg/kg bw hydrazine)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: no data
-necropsy of the dead animals: yes
Other examinations performed: clinical signs, body weight, histopathology,
Statistics:
Method of Bliss 1938, Litchfield and Wilcoxon 1949, Finney1971, Weil 1952 Thompson1947, Miller and Tainter1944
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 262 mg/kg bw
95% CL:
>= 165 - <= 903
Remarks on result:
other: corresponding to 173 mg/kg bw hydrazine
Sex:
female
Dose descriptor:
LD50
Effect level:
> 165 - < 220 mg/kg bw
Remarks on result:
other: corresponding to 108-141 mg/kg bw hydrazine
Mortality:
169 mg/kg bw 2 males and 2 females
220 mg/kg bw 1 male and 5 females
286 mg/kg bw 3 males and 5 females
Clinical signs:
in all treatment groups:
hypoactivity, abnormal gait, salivation, adoption of a prone or lateral position, hair soiling amd wasting
Body weight:
body weight developmental data not given
Gross pathology:
red patches/zones in the lungs, nasal hemorrhage and black patches/zones in the glandular stomach
Other findings:
no further details reported

No mortality males,females: 100 mg/kg bw group and 130 mg/kg bw-group.

Mortality occurred in the
169 mg/kg bw group: 2/5 males and 2/5 females
220 mg/kg bw group: 1/5 male and 5/5 females
286 mg/kg bw group: 3/5 males and 5/5 females
These animals died within 24 hours after treatment.
Clinical signs in all treatment groups:
hypoactivity, abnormal gait, salivation, adoption of a prone or lateral position, hair soiling and waisting.

LD50 (males) 262 mg/kg bw.
LD50 (females) 169-220 mg/kg bw.

Interpretation of results:
Category 3 based on GHS criteria
Executive summary:

Acute oral toxicity was tested with hydrazine monohydrate in male and female rats according to OECD TG 401 (gavage, 100-286 mg/kg bw) and resulted in the death of some animals within 24 hours after treatment. All animals displayed clinical signs including hypoactivity, abnormal gait, salivation, adoption of a prone or lateral position, hair soiling amd wasting. LD50(male) : 269 mg/kg bw and LD50(female): 169 -220 mg/kg bw (MHLW 2003). Assuming that hydrazine monohydrate solution contains 64 % hydrazine unaqueous, the respective LD50 (rat, oral) is 173 mg/kg bw for males and ranges between 108 and 141 mg/kg bw for females.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
108 mg/kg bw
Quality of whole database:
This rat study is performed according to OECD TG 401 and under GLP conditions. Therefore it is evaluated with Klimisch score 1.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: description sufferes from deficiencies because no individual animal data were given.
Principles of method if other than guideline:
Method: 5 concentrations tested; 10 animals per group; 14 days post exposure observation period.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
no further data
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: other
Details on inhalation exposure:
Chamber concentration were established by passing dry nitrogen through a bubbbler containing the liquid agent.The vapour was mixed with air in a glass premixing bowl, and this mixture was then drawn into a constant flow gassing chamber. A 0.4m³ chamber operated at an air flow of 0.10 to 0.115 m³ per minute. Samples of chamber air were drawn into Vigreaux-type bubblers containing water acidified with a drop of concentrated hydrochloric acid. Analyses of hydrazine was performed by potentiometric bromate titration.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
400 - 800 ppm
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
5 concentrations tested;
10 animals per group;
14 days post exposure observation period;
one group of rats at each concentration was killed periodically
after exposure for a study of pathological changes. The other
group was observed for development of toxic signs during
exposure and for 14 days thereafter.
Statistics:
method of Bliss as described by Finney
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
570 ppm
95% CL:
504 - 649
Exp. duration:
4 h
Remarks on result:
other: corresponding to 759 mg/m³
Mortality:
Individual data are not given, only a graphic: range between 20 and 90 %.
Clinical signs:
other: Restlessness, dyspnea, clonic convulsions with exophthalmos.
Body weight:
no data
Gross pathology:
no data
Other findings:
no data

LC50: 0.759 mg/l; 95% confidence limits 504-649 ppm.
Clinical signs: restlessness, dyspnea, convulsions.

Interpretation of results:
Category 2 based on GHS criteria
Executive summary:

10 male rats/group were exposed to 400 -800 ppm for 4 hours and displayed restlessness, dyspnea and convulsions, and resulted in a LC 50 (male rat) of 570 ppm (759 mg/m³, Jacobson 1955).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
759 mg/m³
Quality of whole database:
Although reported in brief in the available publication the study complies with the requiements of today. therefore the the study is evaluated with Klimisch score 2.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral:

Acute oral toxicity of hydrazine monohydrate was determined in male and female rats according to OECD TG 401 and GLP and resulted in the death of some animals within 24 hours after treatment. All animals displayed clinical signs including hypoactivity, abnormal gait, salivation, adoption of a prone or lateral position, hair soiling amd wasting. LD50(male) : 269 mg/kg bw and LD50(female): 169 -220 mg/kg bw (MHLW 2003). Assuming that hydrazine monohydrate solution contains 64 % hydrazine unaqueous, the respective LD50 (rat, oral) is 173 mg/kg bw for males and ranges between 108 and 141 mg/kg bw for females.

Acute inhalation:

In an old study with limited documentation 10 male rats/group were exposed to 400-800 ppm hydrazine for 4 hours and displayed restlessness, dyspnea and convulsions and resulted in a LC 50 (male rat) of 570 ppm (759 mg/m³, Jacobson, 1955)

AQcute dermal:

Hydrazine is classified as corrosive. Thus, a dermal acute toxicity study needs not to be available.


Justification for selection of acute toxicity – oral endpoint
This rat study is performed according to OECD TG 401 and under GLP conditions. Therefore it is evaluated with Klimisch score 1

Justification for selection of acute toxicity – inhalation endpoint
Although reported in brief in the available publication the study complies with the requiements of today. Therefore the the study is evaluated with Klimisch score 2

Justification for selection of acute toxicity – dermal endpoint
Hydrazine is classified as corrosive. Thus, a dermal acute toxicity study needs not to be available.

Justification for classification or non-classification

Under Regulation No. 1272/2008 (GHS) hydrazine is classified with H 331 (Toxic if inhaled; acute toxicity 3*), H311 (Toxic in contact with skin, acute toxicity 3*), and H301 (Toxic if swallowed; acute toxicity 3*), in the “List of harmonised classification and labelling of hazardous substances in this regulation”.

The Asterix (*) in the list indicates that the proposed classification is a minimum classification based on the transfer from the DSD classification.

Taking into account the available limited data for acute inhalation toxicity, a LC50 = 759 mg/m³ (Jacobson, 1955) will be considered as the most relevant data for classification and, consequently, it is proposed to change the minimum classification.

It is proposed to classify hydrazine with H330 (Fatal if inhaled; acute toxicity category 2). Based on the available data it is not proposed to change classification for oral and dermal acute toxicity.