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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 May - 20 Jun 2008
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
Adopted 08 Feb 2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
The Department of Health of the Government of the United Kingdom, London, England
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Pyridine-2-carboxylic acid
EC Number:
202-719-7
EC Name:
Pyridine-2-carboxylic acid
Cas Number:
98-98-6
Molecular formula:
C6H5NO2
IUPAC Name:
pyridine-2-carboxylic acid
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
other: Sprague-Dawley CD (Crl: CD® (SD) IGS BR)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 220-245 g
- Fasting period before study: Animals were fasted overnight before, and for 3 to 4 h after dosing
- Housing: groups of up to 4 animals in suspended solid-floor polypropylene cages furnished with woodflakes, and provided environmental enrichment items
- Diet: "Certified Rat Diet," not further specified, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): ≥15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20 May 2008 To: 20 Jun 2008

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: distilled water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100%
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: the test substance was soluble in distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD:
- Rationale for the selection of the starting dose: Based on the use of available information on the toxicity of the test substance, 300 mg/kg bw was chosen as the starting dose.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
5 (300 mg/kg bw)
1 (2000 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed at 1/2, 1, 2 and 4 h after dosing and daily thereafter until necropsy, and individual body weights were determined on the day of dosing (before administration), and on days 7 and 14, or at death.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:
A single animal was dosed initially at 300 mg/kg bw and no clinical signs or mortality were observed.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
300 mg/kg bw: 0/5 females died
2000 mg/kg bw: 1/1 female died (at 4 h post-dose)
Clinical signs:
300 mg/kg bw: no clinical signs of toxicity in 5/5 animals were observed up to the end of the 14-day observation period
2000 mg/kg bw: hunched posture, lethargy, decreased respiratory rate, laboured respiration and ataxia were observed in 1/1 animals up to 4 h post-dose, followed by death
Body weight:
300 mg/kg bw: bodyweight gains were within the normal ranges in females during the whole study period
2000 mg/kg bw: since only one animal was tested at this dose level, which died shortly after treatment, no assessment on body weight change is feasible.
Gross pathology:
Necropsy examination revealed no substance-related findings

Applicant's summary and conclusion

Interpretation of results:
other: Classification as Cat 4 H302 according to CLP Regulation (EC) No. 1272/2008 is required.
Conclusions:
The acute oral LD50 of test substance in female Sprague-Dawley CD rats was estimated to be in the range of 300 - 2000 mg/kg bodyweight.
CLP: Category 4. H302: Harmful if swallowed.

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