Phenylacetonitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: 2.e: study sufficiently documented, based on a good principle. Confusion on a meaning of lethal dose but quality of overall investigation good.

Data source

Reference

Reference Type:

publication

Title:

Toxicity of benzyl cyanide in the rat

Author:

Guest A., Jackson J.R. and James S.P.

Year:

1982

Bibliographic source:

Toxicology letters, 10, 265-272.

Materials and methods

Principles of method if other than guideline:

Three different doses of benzyl cyanide were administered orally to Wistar rats (three male) and their mortality, behaviour and excretion of cyanide and thiocyanide were followed to estimate lethal oral doses.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phenylacetonitrile

EC Number:

205-410-5

EC Name:

Phenylacetonitrile

Cas Number:

140-29-4

Molecular formula:

C8H7N

IUPAC Name:

2-phenylacetonitrile

Details on test material:

- Name of test material (as cited in study report): benzyl cyanide
- Physical state: liquid
- Analytical purity:99.5 %
No further information

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Birmingham Wistar rat
- Housing: individual housing
- Diet (e.g. ad libitum):Heygates oxoid powdered diet ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): constant
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): normal light cycle

no further data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

mazola

Details on oral exposure:

No further information

Doses:

58, 152, 210 and 304 mg/Kg bw

No. of animals per sex per dose:

Three

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 3 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights
No further information

Statistics:

None reported

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

210 mg/kg bw

Based on:

test mat.

Remarks on result:

other: lethal oral dose is assumed to be related to LD50 since the authors compares it to a median lethal dose

Effect levels 2

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

304 mg/kg bw

Based on:

test mat.

Remarks on result:

other: lethal oral dose is assumed to be related to LD50 since the authors compares it to a median lethal dose

Clinical signs:

other: Initial phase of immobility lasting 10-15 min followed by an increase in activity and irritability. Then uncoordinated movements appeared and some animals exhibited hind limb paralysis. Nasal haemorrhage before death

Gross pathology:

No data

Other findings:

No further data

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The authors tested the acute toxicity potential of benzyl cyanide after oral administration in rats. in the test conditions, the authors found lethal oral doses of 210 and 304 mg/Kg bw for female and male rats respectively.
Based on the CLP criteria, benzyl cyanide should then be considered as an acute oral toxicity category 3.

Executive summary:

The authors of this study investigated the acute oral potential of benzyl cyanide (CAS n° 140 -29 -4) on male and female Wistar rats. The metabolism and the most likely route of elimination of benzyl cyanide was also investigated. The study ambitionned to delineate the toxicity mehcanisms of benzyl cyanide. Hence four groups of three rats were exposed orally to 58, 152, 210 and 304 mg/Kg bw respectively formulated in corn oil. Urinary volume, excretion of metabolites, distribution of cyanide in the body, main clinical signs and mortality was monitored to establish oral lethal dose. Survivals if any were sacrificed for the metabolism experiment to collect organs and tissue for cyanide dosage.

In the test conditions, the authors found that benzyl cyanide has lethal oral doses of 210 and 304 mg/Kg bw for female and male rats respectively. Animals exhibited an initial phase of immobility lasting 10-15 min followed by an increase in activity and irritability. Then uncoordinated movements appeared and some animals showed hind limb paralysis. Nasal haemorrhage occured before death.

This study is quite well documented and based on a good principle. There is a little confusion on the proper meaning of lethal doses but provided the overall quality of the investigation, this study is considered as reliable with restrictions, a Klimisch 2.e.