Isonicotinaldehyde

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 March - 23 April 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Isonicotinaldehyde

EC Number:

212-832-3

EC Name:

Isonicotinaldehyde

Cas Number:

872-85-5

Molecular formula:

C6H5NO

IUPAC Name:

pyridine-4-carbaldehyde

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report) : Pyridine-4-aldehyde
- Physical state : clear yellowish liquid
- Analytical purity : 98,7% (GC)
- Lot/batch No. : 1120126/001
- Storage condition of test material : Refrigerator at ca. 4°C , in the dark , under nitrogen

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR , Sprague Dawley , SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source : Charles River Deutschland GmbH , Germany
- Age at study initiation : approx. 9 weeks
- Weight at study initiation : 305 - 318 g (male) ; 146 - 150 g (female)
- Fasting period before study : no
- Housing : animals were house individually in Makrolon cages type III (39x23x18cm;Bedding material: Aspen wood chips) with mesh lids
- Diet (e.g. ad libitum) : Altromin diet No. 1324forte , ad libitum (Reduction of micro-organisms by 25 kGy 60Co-gamma irradiation)
- Water (e.g. ad libitum) : Tap water from an automatic watering system , ad libitum
- Acclimation period : 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C) : Average of 22,0°C (range 21,6 to 22,4°C)
- Humidity (%) : Average of 44% (range 33 to 46%)
- Air changes (per hr) : about 12
- Photoperiod (hrs dark / hrs light) : 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus : "nose-only" inhalation apparatus (TSE , Technical&Scientific Equipment GmbH , Kronberg , Germany ; article no. 504101)
- Exposure chamber volume : 19 litres
- Method of holding animals in test chamber : no data
- Source and rate of air : obtained from a central pressure pump , 700 l/h (37 air exchanges per hour)
- Method of conditioning air : The relative humidity was reduced to about 10% . The air was filtered oil-free .
- System of generating particulates/aerosols : The test substance was transported by an infusion pump to a nozzle and was nebulized with pressurised air . Larger droplets of the aerosol were caught in the inner chamber by sedimentation and impaction . Small droplets reached the outer chamber and the inhalation tubes .
- Method of particle size determination : The size of the aerosol particles was analysed with a cascade impactor (Berner-Impaktor Type LPI4/0,06/2 from Hauke KG , A-4810 Gmunden , Austria)
- Treatment of exhaust air : The inhalation chamber was situated in a fume cupboard
- Temperature, humidity, pressure in air chamber : Temperature was measured with a glass-mercury thermometer ; the humidity was measured with a hygrometer (Hygrotest serie 55 , type 0555 6020 , Testotherm GmbH , Vienna , Austria) , the air flow was measured by a rotameter .

TEST ATMOSPHERE
- Brief description of analytical method used : Test substance was collected in an impinger filled with isopropanol and determined photometrically .
- Samples taken from breathing zone : yes


TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.) : MMAD : 3,93µm / GSD : 1,84

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

The mean concentration in the breathing zone was 5,14 mg of the test substance per litre .

No. of animals per sex per dose:

5 male / 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration : 14 days
- Frequency of observations and weighing : Behaviour , reactions and physical signs of each of the animals were observed 1, 2, 3, 4, 5 and 6 hours after the start of esposure and then at least once a day . The individual body mass was determined before administration , 7 d and 14 days p.a. . Body mass gain was calculated for each week of the study .
- Necropsy of survivors performed : yes

Statistics:

No LC50 value and its 95% confidence limits could be calculated because a limit test was performed .

Results and discussion

Preliminary study:

In preliminary experiments during the determination of the relation between nominal and actual concentrations 4 rats were exposed to various concentrations of the test substance . The highest exposed rat , exposed for nearly 4 hours to concentrations of 2 to 4 mg/l , did not show any signs of toxicity . It was therefore likely , that in the main study no mortalities will occur .

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

> 5.14 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

> 5.14 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

All animals survived until the scheduled termination 14 days after the exposure .

Clinical signs:

other: Parts of the fur of the animals were stained yellowish after the exposure : This is attributed to a staining property of the test substance and is not thought as a toxic sign . Respiratory murmur and dyspnoea , noted in 6 animals up to 4 days p.a. , are a

Body weight:

The mass gain in the first week after the exposure was clearly smaller than in the second week ; two females even lost mass in the first week . This is a sign of reduced wellbeing after the exposure .

Gross pathology:

All animals were normal at the necropsy 14 days p.a.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The study was performed according to the OECD TG403 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled. The acute inhalation median lethal concentration (LC50) of Pyridine-4-aldehyde in the Sprague-Dawley Crl:CD® (SD) IGS BR strain rat, were estimated to be : > 5.14 mg/L for rats of both sexes .

Executive summary:

The acute inhalation toxicity of the test material was investigated in rats of both sexes. The test was conducted according to OECD Guidelines for Testing of Chemicals (1981) No. 403 “Acute InhalationToxicity”" referenced as Method B2 in Commission Directive 92/69/EEC “Acute Toxicity-Inhalation” (which constitutes Annex V of Council Directive 67/548/EEC). Groups of ten Sprague-Dawley Crl:CD® (SD) IGS BR strain rats (five males and five females) were exposed to an aerosol atmosphere. The animals were exposed for four hours using a nose only exposure system at an actual mean concentration of 5.14 mg per litre air, followed by a fourteen day observation period. All animals survived until the scheduled termination 14 days after the exposure. The body mass gain in the first week after the exposure was clearly smaller than in the second week; two females even lost mass in the first week. This is a sign of reduced wellbeing after the exposure. Parts of the fur of the animals were stained yellowish after the exposure. This is attributed to a staining property of the test substance and is not thought as a toxic sign. Respiratory murmur and dyspnoea, noted in 6 animals up to 4 days p.a., are attributed to the action of the test substance. Closed eyes in one case immediately after the exposure, and chromodacryorrhoea, noted up to 4 days in two animals, are signs of general malaise. Three animals were normal during the whole observation period. All animals were normal at the necropsy 14 d p.a.

The LC50 per inhalation, four hours exposure, of pyridine-4 -aldehyde is greater than 5.14 mg/L for rats of both sexes.

No classification for pyridine-4-aldehyde is derived from the results of this study according to guideline 2001/59/EC from 6 August 2001.