Salicylonitrile

Endpoint summary

Description of key information

Oral: LD50=500 mg/kg bw, female, rat, OECD 423, Wolf 2008

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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

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

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

Sex:

female

Dose descriptor:

LD100

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 3 animals

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Only a single acute oral toxicity study conducted according to method B.1 tris (OECD guideline 423) and under GLP was available. No deaths were reported at 300mg/kg bw, whereas there were no survivors reported at 2000mg/kg bw. Shock from gastrointestinal lesions was proposed to be the cause of death. The LD₅₀in female rats was reported as between 300 and 500 mg/kg bw, however, 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. This has no effect on classification and labelling, nor risk assessment.

The study is considered to be relevant, reliable (Klimisch 1) and adequate for the purposes of risk assessment, classification and labelling.

Justification for selection of acute toxicity – oral endpoint
Valid study in compliance with OECD testing guideline and GLP

Justification for classification or non-classification

The key value selected for the acute oral toxicity, LD₅₀=500 mg/kg bw leads to classification of the substance as Category 4, H302, Harmful if swallowed, according to the criteria in Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.1.2.