3,4-dimethoxyphenylacetonitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study. Non-GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

BASF Test

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

veratrylcyanid

IUPAC Name:

veratrylcyanid

Constituent 2

Reference substance name:

78/834

IUPAC Name:

78/834

Details on test material:

Veratrylcyanid; no data on purity given in the report

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- diet: Herilan MRH-Haltung; H. Eggersmann KG

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

- way of application: oral (not further specified)
- form of application: suspension
- formulation in: ß.5% aqueous carboxymethyl cellulose
- fasting before application: 15 - 20 h
- observation period: 14 days
- max. volume applied: 10 mL/kg bw.
- range of concentration: 1.00-5.64 % (g/v)

Doses:

100, 147, 215, 316, 464 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not described in the protocol
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

230 mg/kg bw

Mortality:

Mortality in male rats after 1 hour/1 day/2 days/7 days/14 days:
- 464 mg/kg bw dose level: 3/5/5/5/5
- 316 mg/kg bw dose level: 0/4/4/4/4
- 215 mg/kg bw dose level: 0/3/3/3/3
- 147 mg/kg bw dose level: 0/0/0/0/0
- 100 mg/kg bw dose level: 0/0/0/0/0

Mortality in female rats after 1 hour/1 day/2 days/7 days/14 days:
- 464 mg/kg bw dose level: 1/5/5/5/5
- 316 mg/kg bw dose level: 0/4/4/4/4
- 215 mg/kg bw dose level: 0/2/2/2/2
- 147 mg/kg bw dose level: 0/0/0/0/0
- 100 mg/kg bw dose level: 0/0/0/0/0

Clinical signs:

- 464 mg/kg bw dose level: dyspnoe, apathy, abnormal position, staggering, atonia, no reflex on pain, tremor, poor general state, salivation, dermal erythema, convulsions.
- 316 mg/kg bw dose level: dyspnoe, apathy, aggressivness, abnormal position, staggering, tremor, convulsions, dermal erythema, poor general state, salivation.
- 215 mg/kg bw dose level: dyspnoe, apathy, abnormal position, staggering, no reflex on pain, convulsion, piloerection, dermal erythema, exsiccosis, salivation, poor general state.
- 147 mg/kg bw dose level: dyspnoe, apathy, staggering, tremor, piloerection, dermal erythema, poor general state.
- 100 mg/kg bw dose level: dyspnoe, apathy, staggering, dermal erythema, poor general state.

Body weight:

Mean body weight [g] in male rats before application/2-4 days after appl./7 days after appl./13 days after appl.
- 464 mg/kg bw dose level:----
- 316 mg/kg bw dose level: 200/213/246/247
- 215 mg/kg bw dose level: 160/193/233/271
- 147 mg/kg bw dose level: 210/231/257/290
- 100 mg/kg bw dose level: 210/218/253/293

Mean body weight [g] in female rats before application/2-4 days after appl./7 days after appl./13 days after appl.
- 464 mg/kg bw dose level:----
- 316 mg/kg bw dose level: 170/169/182/211
- 215 mg/kg bw dose level: 170/185/204/201
- 147 mg/kg bw dose level: 170/175/198/182
- 100 mg/kg bw dose level: 170/183/197/210

Any other information on results incl. tables

Mortality was 5/10, 8/10 and 10/10 in the groups administered 215, 316 and 464
 mg/kg bw, respectively. Deaths were approximately equally divided by sex and
 occurred within the first day after dosing.
Signs of toxicity were observed at all dose levels and included dyspnea, apathy,
 aggressive behavior, anomal position, staggering, atony, loss of pain reflex,
 narcotic-like state, tremor, spastic gait, tonus with bending, tonic 
convulsion, tonic-clonic convulsion, piloerection, skin redness, exsiccosis, 
salivation and poor general state. Body weight gains were within the expected 
range.
Post-mortem examination of the decedents revealed changes of the heart (acute 
ventricular dilatation, acute congestive hyperemia), brightened liver and slight
 acute distention of the lungs. No pathological findings were observed in 
survivors sacrificed at the end of the observation period.

Applicant's summary and conclusion

Conclusions:

Based on the results of this study, the test substance veratrylcyanid has to be classified "Acute oral Tox Cat. 3" and R22 according to Regulation (EU) No. 1272/2008 and Directive 67/548/EEC, respectively.