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Diss Factsheets

Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions . High mortality in lowest dose group.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: "Appraisal of the safety of chemicals in foods , drugs and cosmetics, FDA"
Principles of method if other than guideline:
Method: in accordance with "Appraisal of the safety of chemicals in foods, drugs and cosmetics, FDA"
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3-hydroxypropiononitrile
EC Number:
203-704-8
EC Name:
3-hydroxypropiononitrile
Cas Number:
109-78-4
Molecular formula:
C3H5NO
IUPAC Name:
3-hydroxypropanenitrile
Details on test material:
- Name of test material (as cited in study report): Ethylencyanhydrin
- Substance type: aliphatic nitrile
- Physical state: liquid
-Density : 1.050 g/ml (20°C)
- Analytical purity: as supplied by producer: purity in the test report not mentioned, but probably > 98,5% ; colourless liquid
- pH 5.5

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: SPF Wistar rats, Zucht Winkelmann, Paderborn, Germany
- Age at study initiation: no data
- Weight at study initiation: 160 - 205 g
- Fasting period before study: 16 hours
- Housing: single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 45 - 55 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Maximum dose volume applied: 15.9 ml/kg
- Rationale for the selection of the starting dose: preliminary study for range finding
Doses:
6.3, 7.94, 10.0, 12.6, 15,9 ml/kg bw equals 6.615, 8.337, 10.50, 13.23 and 16.7 mg/kg bw (calculated with a density of 1.050 g/ml)
No. of animals per sex per dose:
5f/5m per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighting: 20 min, 1h, 3h, 24h, 48h, 7d, 14d
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: reflexes, emotions, consciousness, central
symptoms, autonomous functions, tone
Statistics:
Probit analysis

Results and discussion

Preliminary study:
No further information mentioned in the study report.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 6 000 mg/kg bw
Remarks on result:
other: 14 days LD50
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 229 - < 6 960 mg/kg bw
Remarks on result:
other: 14 days LD50
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 9 335 mg/kg bw
Remarks on result:
other: 24 hours LD50
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 9 345 - 10 164 mg/kg bw
Remarks on result:
other: 24 hours LD50
Mortality:
In the first an second dose group mortalities occurred within 3 days (6/10 and 7/10), in the third and the fourth dose group mortalities occurred
within 48h (9/10 and 10/10), in the highest dose group all rats died within 24h (10/10).
Clinical signs:
Hemorrhages of the intestinal and gastric mucosa

Body weight:
In the first and second dose group, rats gained ~21% of weight during 14 days of postexposure time (37,50g/175.00g =>21.4% ;
38.67g/183.00g=>21.1%), in the third dose group, gain weight in the same time was determined to only 5.4% (for the only surviving rat), for the
highest dose groupes no data were obtained.
Remark: At the end oft the post exposure period of 14 days all surviving animals showed again normal body weight gain.
Gross pathology:
Decrease in activity, reduction of pain reflexes, decreased tonus of extremities, disturbance in coordination, slight hyperemia, ptosis, piloreaction

Any other information on results incl. tables

Table (I) Mortality (mortalities occurred within 7 days p.a.)

 group   dose  24 hours (p.a.)  14 days (p.a.)
 (I)  6.3 ml/kg  2/10  6/10
 (II)  7.94 ml/kg   3/10  7/10
 (III)  10.0 ml/kg  7/10  9/10
 (IV)  12.6 ml/kg  7/10  10/10
 (V)  15.9 ml/kg  10/10  10/10

 

Table(II) Weight development

group/ number of animals   mean weight (ante application; a.a.)   mean weight (post application; p.a.) after 14days
 (I) / 5f, 5m  175.00 g  212.50 g
 (II) / 5f, 5m   183.00 g  221.67 g
 (III) / 5f, 5m   185.00 g  195.00 g
 (IV) / 5f, 5m  188.50 g    - 
 (V) / 5f, 5m  181.50 g    - 

 Remark: At the end of the  post exposure period of 14 days all surviving animals showed normal body weight gain.

After application of the test substance, animals exhibited dose-dependent decrease in activity, decreased tonus of extremities, marked disturbance in coordination, slight hyperemia and piloerection; in high dose groups ptosis was observed; symptoms occured 20 min after application of TS; 24 h after treatment the surviving rats showed usual habit again.

Survival after 14 days:  6.3 ml/kg: 4 out of 10;  7.94 ml/kg: 3 out of 10;  10.0 ml/kg: 1 out of 10; in higher dose groups, all rats died within 48 h. Acute and delayed mortalities showed by dissection intense hemorrhages of the intestinal and gastric mucosa.Those animals, which were killed humanly at the end of the study, showed by dissection no macroscopic changes in organs. 

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
According to the test result: LD50(14days) ca. 6000 mg/kg bw the test substance ethylene cyanohydrin has to be classified as nontoxic in respect of its acute oral toxicity.
Executive summary:

In an acute oral toxicity study, groups of fasted male and female SPF Wistar rats were given a single oral dose of Ethylene cyanohydrin > 98.5 % at doses of   6.615, 8.337, 10.50, 13.23 and 16.7 mg/kg bw and observed for 14 days.

 

Oral LD50 Combined = 5.71 ml/kg bw equals ca. 6000  mg/kg  bw (95% C.I. not available)

GHS Category 5 ranges from 2000 -5000 mg/kg bw and represents the lowest hazard category for classifying the acute oral toxicity of a chemical substance. ("Criteria for hazard Category 5 are intended to enable the identification of the test substancese which are of relatively low acute toxicity hazard but which, under certain circumstances may present a danger to vulnerable populations". (OECD guideline 425 annex 4)).

    

Ethylene cyanohydrin is of very low oral toxicity based on this LD50 test in males and females.