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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 - 27 March 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Pyridine-2-carbaldehyde oxime
EC Number:
212-849-6
EC Name:
Pyridine-2-carbaldehyde oxime
Cas Number:
873-69-8
Molecular formula:
C6H6N2O
IUPAC Name:
pyridine-2-carbaldehyde oxime
Test material form:
other: crystals
Details on test material:
- Name of test material (as cited in study report): Pyridin-2-aldoxim
- Physical state : white crystals
- Analytical purity : at least 98%
- Lot/batch No. : 7054 046 172

Test animals

Species:
rat
Strain:
other: rats outbred with Wistarstock KFM:WIST (SPF HAN.)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG/ 4414 Fuellingsdorf, Switzerland
- Age at study initiation: 9-12 weeks
- Weight at study initiation: 203 - 269 g (males) and 174 - 214 g (females)
- Fasting period before study: 12 - 18 hours
- Housing: the animals were caged in groups of five in macrolon cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland). The cages were cleaned twice weekly during the test period.
- Diet (e.g. ad libitum): pelleted standard KLIBA 343/BATCH 36/85 rat maintenance diet (Klingentalmuehle AG/ 4303 Kaiseraugust/Switzerland), available ad libitum. Results of analysis for contaminants are included in the original report.
- Water (e.g. ad libitum): tap water available ad libitum. Results of analyses for contaminants are incIuded in the original report.
- Acclimation period: at least one week under laboratory conditions, after veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

IDENTIFICATION: by unique cage number and corresponding color-coded spots.

RANDOMIZATION: randomly selected at time of delivery in groups of five.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4 % solution of CMC (Carboxymethylcellulose sodium salt purum/ Fluka AG/ CH-9470 Buchs/Switzerland) in distilled water
- Amount of vehicle (if gavage): 10 mL at 100 mg/kg, 250 mg/kg, 600 mg/kg, 1000 mg/kg and 20 mL at 5000 mg/kg

MAXIMUM DOSE VOLUME APPLIED: 20 mL at 5000 mg/kg

DOSAGE PREPARATION: A weight by volume dilution of the test compound was prepared using a homogenizer (Ultra-Turrax/Janke and Kunkel/Staufen/ West-Germany) and kept homogenous during treatment using a magnetic stirrer (Auer-Bittmann/Switzerland). The preparation was made immediately prior to dosing.
Doses:
100 mg/kg bw, 250 mg/kg bw, 600 mg/kg bw, 1000 mg/kg bw and 5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- single oral intubation via gavage to animals fasted for 12 to 18 hours
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Bodyweights were recorded at the test days 1 (pre-administration), 8 and 15. / Symptoms were assessed four times at day 1 and then daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The LOGIT-Model (COX, Analysis of Binary Data, London 1977) was applied to estimate the toxicity value. Additionally, the 90, 95 and 99 % confidence intervals for the toxicity for each sex the slope of the dose response line were estimated.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
388 mg/kg bw
Based on:
test mat.
95% CL:
>= 261 - <= 577
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
350 mg/kg bw
Based on:
test mat.
95% CL:
>= 201 - <= 609
Sex:
female
Dose descriptor:
LD50
Effect level:
383 mg/kg bw
Based on:
test mat.
95% CL:
>= 180 - <= 815
Mortality:
For detailed results see Table 1 at "any other information on results incl. tables"
Clinical signs:
100 mg/kg : sedation, dyspnea, ataxia, curved body position, ruffled fur.
250 mg/kg : sedation, dyspnea, ataxia, curved body position, ruffled fur.
600 mg/kg : sedation, dyspnea, ataxia, ventral body position, latero-abdominal position, curved body position, ruffled fur.
1000 mg/kg : sedation, dyspnea, ataxia, ventral body position, latero-abdominal position, curved body position, ruffled fur.
5000 mg/kg : sedation, dyspnea, ataxia, ventral body position, latero-abdominal position, curved body position.
Body weight:
Males
mean body weight in g at day 1 / 8 / 15 :
Dose 100 mg/kg : 210 ±5.5 / 243 ±12 / 272 ±18
Dose 250 mg/kg : 205 ±2.1 / 232 ±11 / 258 ±12
Dose 600 mg/kg : 220 ±8.8 / DEAD / ---
Dose 1000 mg/kg : 254 ±11 /DEAD / ---
Dose 5000 mg/kg : 225 ±11 / DEAD / ---

Females :
mean body weight in g at day 1 / 8 / 15 :
Dose 100 mg/kg : 188 ±5.2 / 198 ±5.7 / 208 ±6.5
Dose 250 mg/kg : 185 ±7.3 / 189 / 196
Dose 600 mg/kg : 191 ±4.4 / DEAD / ---
Dose 1000 mg/kg : 199 ±9.6 /203 / 216
Dose 5000 mg/kg : 196 ±8.3 / DEAD / ---

Gross pathology:
100 mg/kg:
-Killed - Lung: mottled, dark-red (1); mottled, slight (2); No pathologic changes (7).

250 mg/kg:
-Dead
Lung: mottled, slight (1)
Stomach: filled, severe (1)
Intestines: partly reddened, with reddish contents (1)
Urinary bladder: filled with reddish contents (1)
-Killed
Lung: dark-red mottled (3.); mottled slight (2); No pathologic changes (4)

600 mg/kg:
-Dead
Lung: mottled (7), slight (2), dark-red (4)
Liver: dark-red mottled (1)
Stomach/Intestines: reddened, with reddish contents (2); reddened, mottled, dark-red, partial severe (3); with reddish partial severe dark-red contents (2); with orange to red, partial severe dark-red contents (1); reddened, severe, with dark-red contents (1)
Stomach: slightly reddened, with reddish contents (3) reddened, with red contents (1)
Intestines: severe reddened, with dark-red contents (3); reddened, with dark-red contents (1)
Urinary bladder: filled with reddish contents (5); reddened, with reddish contents (1)

1000 mg/kg:
-Dead
Lung: dark-red (1), dark-red mottled (6)
Liver: mottled, dark-red (4)
Stomach/Intestines: reddened (2), slight (1), red contents (1)
Stomach: reddened (2), slight (3), with reddish contents (6), filled (1)
Intestines: reddened severe (3), dark-red, severe (2), contents, red (1), dark-red (3), severe (2)
Urinary bladder: reddened, slight (2), filled with reddish contents (1), filled with dark-red contents (2); filled, severe, with reddish contents (1).
-Killed
No pathologic changes (1)

5000 mg/kg:
-Dead
Stomach/Intestines: reddened, slight (10).
Other findings:
No other findings were reported.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
EU implementation
Conclusions:
LD50 : 388 mg/kg (male/females)
LD50 : 350 mg/kg (male)
LD50 : 383 mg/kg (females)
The study was performed according to the OECD TG401 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled.
Executive summary:

The acute oral toxicity of the test material was investigated in rats according to OECD TG401. The test substance Pyridin-2 -aldoxim was administered to rats of both sexes by oral gavage, at doses from 100 to 5000 mg/kg. The following death rate was observed :

0 % at 100 mg/kg *

10 % at 250 mg/kg *

100 % at 600 mg/kg *

90 % at 1000 mg/kg *

100 % at 5000 mg/kg

* Selected for the LOGIT-Estimation

Based on these observations, the LOGIT-ESTIMATION for the acute oral toxicity of Pyridin-2 -aldoxim in rats observed for a period of 15 days is:

LD50 : 388 mg/kg (male/females)

LD50 : 350 mg/kg (male)

LD50 : 383 mg/kg (females)

with a 95% confidence interval of :

Males/Females : 261 - 577 mg/kg

Males : 201 - 609 mg/kg

Females : 180 - 815 mg/kg