Pyridine-2-carbaldehyde

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983-05-25 to 1983-06-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted May 12, 1981

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Pyridine-2-carbaldehyde

EC Number:

214-333-6

EC Name:

Pyridine-2-carbaldehyde

Cas Number:

1121-60-4

Molecular formula:

C6H5NO

IUPAC Name:

pyridine-2-carbaldehyde

Test material form:

liquid

Test animals

Species:

rat

Strain:

other: outbred WISTARSTOCK , kfm: WIST (SPF Han.)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: males : 7 weeks , females : 8 weeks
- Weight at study initiation: males : 178-216 g , females : 164-190g
- Fasting period before study: 12-18 hours (overnight) before treatment , approximately 1 hour after treatment
- Housing: animals were caged in groups of five in Macrolon cages type 3 with wire mesh lids and standardized granulated soft wood bedding
- Diet (e.g. ad libitum): pelleted standard Kliba 343 , Batch 74/83 and 77/83 rat maintenance diet ad libitum
- Water (e.g. ad libitum): tap water , ad libitum
- Acclimation period: 1 week under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2% solution of CMC in distilled water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage):
10ml at 400 mg/kg
10ml at 700 mg/kg
10ml at 1000 mg/kg

Doses:

- 400 mg/kg
- 700 mg/kg
- 1000 mg/kg

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:
Mortality : Five times during the first day , daily thereafter
Body weight : Body weights were recorded on the day of administration and days 8 and 15 of the test
Symptoms : Five times at day 1 , daily thereafter for the nature , onset , severity and duration of all gross or visible toxic or pharmacologic effects or time of death
- Necropsy of survivors performed:
yes , all test animals were subjected to a complete gross necropsy . All animals surviving to termination were killed by exsanguination after pentobarbital anestesia . All organ abnormalities were recorded .

- Other examinations performed: other: The animals were checked daily for the symptoms listed below .
General behaviour : aggressive,crying,restlessness/excitement,nervousness,fear,sedation,somnolence,sleep,coma
Respiration : apnea,dyspnea
Eye : chromodacryorrhea,exophthalmos,miosis,mydriasis,whitish discharge,lid adhesion
Nose : rhinorrhea,epistaxis
Motility : akinesia,ataxia,drooped head,hyperkinesia,hypokinesia,paralysis flaccid,paralysis spatic,paddling movements,stiff movements,rolling movements,hunched posture
Body position : ventral body position,latero-abdominal position,curved body position
Skin : erythema,edema,necrosis
Motor susceptibility : spasms,tonic muscle spasms,clonic muscle spasms,opisthotonus,saltatory spasms,trismus,retching,"Straub" phenomenon,tremor,muscle -twitching
Various : loss of weight,emaciation,nagative corneal reflex,diarrhea,ruffled fur,necrosis of tissue of application area,salivation,pallor,cyanosis

Statistics:

The LOGIT Model (COX , Analysis of Binary Data , London 1977) was applied to estimate the LD50 value . Additionally , the 90 , 95 and 99% confidence intervals for the LD50 for each sex and the slope of the concentration response line was estimated .

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

603 mg/kg bw

Based on:

test mat.

95% CL:

>= 407 - <= 773

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

566 mg/kg bw

Based on:

test mat.

95% CL:

>= 359 - <= 728

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

585 mg/kg bw

Based on:

test mat.

95% CL:

>= 463 - <= 686

Mortality:

Males :
Dose 400 mg/kg : no animal died
Dose 700 mg/kg : 1 animal died 5 h after application , 3 more animals died 24 h after application
Dose : 1000 mg/kg : 5 animals died 24 h after application

Females :
Dose 400 mg/kg : no animal died
Dose 700 mg/kg : 2 animals died 5 h after application , 3 more animals died 24 h after application
Dose : 1000 mg/kg : 5 animals died 24 h after application

Clinical signs:

other: The following symptoms were observed : 400 mg/kg : sedation,dyspnea,chromodacryorrhea,rhinorrhea,ataxia,curved body position,loss of weight,ruffled fur 700 mg/kg : sedation,dyspnea,ataxia,curved body position,saltatory spasms,loss of weight,ruffled fur,cy

Gross pathology:

Mottled lungs were observed in seven killed rats of the 400 mg/kg group and in 9 rats which died in the 700 mg/kg group . In addition reddened colon was observed in 5 , and mottled liver in 2 rats of the 700 mg/kg group .
All rats of the 1000 mg/kg group showed mottled lungs as well as a reddened and mottled stomach and a reddened colon with red contents .

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

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. The test material did induce mortality and treatment-related clinical signs in the dose group of 1000 mg/kg bw (100 % mortality) and in dose group 700 mg/kg bw (90 % mortality). In the dose group 400 mg/kg bw treatment-related clinical signs were observed too (0% mortality). The LD50 was identified to be 585 mg/kg bw for rats of both sexes with a 95% confidence interval of 463 – 686 mg/kg bw.

Executive summary:

The acute oral toxicity of the test material was investigated in rats of both sexes. The test was conducted according to OECD TG401. As doses 400, 700 and 1000 mg/kg bw of the test substance were administered via gavage to the rats. Observations were made for a period of 14 days. The following symptoms were observed :

- 400 mg/kg bw : sedation, dyspnea, chromodacryorrhea, rhinorrhea, ataxia, curved body position, loss of weight, ruffled fur.

- 700 mg/kg bw : sedation, dyspnea, ataxia, curved body position, salutatory spasms, loss of weight, ruffled fur, cyanosis

- 1000 mg/kg bw : crying, ataxia, sedation, dyspnea, ventral-, abdominal and curved body position, spasms, salutatory spasms.

The above symptoms increased in intensity with higher dose levels.

All animals in the highest dose group died within 24 hours. In the 700 mg/kg bw dose group 3 animals died within 5 hours and another 6 within the following 24 hours. No animals died in the lowest dose group. The gross pathology performed after sacrifice reveals the following findings : Mottled lungs were observed in seven killed rats of the 400 mg/kg group and in 9 rats which died in the 700 mg/kg group . In addition reddened colon was observed in 5 , and mottled liver in 2 rats of the 700 mg/kg group . All rats of the 1000 mg/kg group showed mottled lungs as well as a reddened and mottled stomach and a reddened colon with red contents .

An oral LD50 was identified to be 585 mg/kg bw for rats of both sexes with a 95% confidence interval of 463 – 686 mg/kg bw.

LD50 (males) : 603 mg/kg bw with a 95% Confidence interval of 407 - 773 mg/kg bw

LD50 (females) : 566 mg/kg bw with a 95% Confidence interval of 359 - 728 mg/kg bw