Salicylonitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-02-05 to 2008-02-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxybenzonitrile

IUPAC Name:

2-hydroxybenzonitrile

Constituent 2

Reference substance name:

Salicylonitrile

EC Number:

210-259-3

EC Name:

Salicylonitrile

Cas Number:

611-20-1

Molecular formula:

C7H5NO

IUPAC Name:

2-hydroxybenzonitrile

Details on test material:

TEST MATERIAL
- Name of test material (as cited in study report): 2-hydroxybenzonitrile
- Substance type: pure test substance, recrystallised 2-cyanophenol
- Physical state: solid, yellowish (beige) crystalline powder
- Melting range: 95.4°C
- Stability under test conditions: not determined
- Storage condition of test material: room temperature, stable

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 170 - 190 g
- Fasting period before study: overnight, until 3 hours post application
- Housing: optimal hygienic conditions (OHC), single caging in Makrolon type III cages
- Diet: ad libitum, Ssniff R/M-H Maintenance diet for rats and mice (item V1534-3)
- Water: communal drinking water from automated watering system, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.7 (average, continuous monitoring)
- Humidity (%): 49.6% (average, continuous monitoring)
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 2008-02-05 To: 2008-02-20

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.1% aqueous solution, plus Tween 80

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 15 and 100 mg/mL, suspension
- Amount of vehicle (if gavage): 20 mL/kg body weight
- Justification for choice of vehicle: test substance insoulble in water, CMC plus Tween is a common vehicle for oral toxicity testing

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg body weight

DOSAGE PREPARATION (if unusual): suspension

CLASS METHOD
- Rationale for the selection of the starting dose: No prior information on toxicity was available. in accordance with the guideline, a starting dose of 300 mg/kg bw was chosen.

Doses:

300 and 2000 mg/kg body weight (bw)

No. of animals per sex per dose:

3, that is:
- step 1, 300 mg/kg bw: 3 females
- step 2, 300 mg/kg bw: 3 females
- step 3, 2000 mg/kg bw: 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Applicarion day: 0-0.5, 0.5-1, 1-2, 2-4, and 4-6 hours post administration
- Frequency of weighing: before administartion, day 7, day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

none, decision tree of the OECD guideline used

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD0

Effect level:

300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2 groups of 3, totally 6 animals

Effect levels 2

Sex:

female

Dose descriptor:

LD100

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 3 animals

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Reported in full study report as 300

Mortality:

300 mg/kg bw: 0/6
2000 mg/kg bw: 3/3 (within 10 - 20 minutes post application)

Clinical signs:

other: 300 mg/kg bw: signs of reduced well-being (unspecific, such as sedation, apathy, piloerection, hunched posture, or closed eyes, in single or multiple occurrence), until 6 h post application 2000 mg/kg bw: all deaths occurred before first observation

Gross pathology:

No abnormal findings in survivors (300 mg/kg bw).
Glandular stomach, mucosa: pseudomembranes in animals dying on test within 20 minutes (2000 mg/kg bw)

Other findings:

- Potential target organs: gastrointestinal tract

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The study is considered to be reliable and adequate. Comparison of the decision tree in Regulation (EC) No. 440/2008, B.1 tris, Appendix 1C, with the raw data indicated that LD50=500mg/kg bw, and not the reported range 300-500mg/kg bw.