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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

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.