Isonicotinaldehyde

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 - 18 February 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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Directive 93/21/EEC for classification

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

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 approx. 4°C , in the dark , under nitrogen

Test animals

Species:

rat

Strain:

other: CRL : CD (SD) BR SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source : Charles River Wiga , D-97633 Sulzfeld
- Age at study initiation : approx. 8 weeks (males) and 12 weeks (females) at the time of administation
- Weight at study initiation : 270 - 284 g (males) and 246 - 254 g (females)
- Fasting period before study : no
- Housing : single caging in Makrolon cages type III (39 x 23 x 18 cm) . Wire mesh lids . Sanitation of cages once a week .
- Diet : Altromin 1324 forte (Producer : Altromin GmbH , D-32791 Lage) , gamma irradiated with 25 kGy 60Co , ad libitum
- Water : Tap water , offered in Makrolon bottles with stainless steel canules , ad libitum
- Acclimation period : 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C) : average of 21°C (continuous control and recording)
- Humidity (%) : average of 60% (continuous control and recording)
- Air changes (per hr) : 12
- Photoperiod (hrs dark / hrs light) : 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure : Test site on the dorsal thoracal region , clipped with an electrical hair clipper
- % coverage : 10
- Type of wrap if used : non-irritating tape (Blenderm Wundpflaster , 3M) , covered semi-occlusively by a dressing (Fixomull Stretch , Fa. Beiersdorf)

REMOVAL OF TEST SUBSTANCE
- Washing (if done) : Residual test substance was wipped off using wet cellulose tissue
- Time after start of exposure :24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit) : 2000 mg/kg bw
- Constant volume or concentration used : yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

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 :
Observations were performed 0-0,5 , >0,5-1 , >1-2 , >2-4 and >4-6 hours after administration of the test substance (p.a.) and then at least once a day . Observations included but were not limited to changes in skin , fur , eyes , the occurrence of secretions and excretions , autonomic activity , changes in gait , posture and the presence of convulsions .
Body weights were determined before administration , 7 days p.a. and 14 days p.a.
- Necropsy of survivors performed : yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the scheduled termination of the study

Clinical signs:

other: 1/5 females were affected 1 d p.a. . The finding 1 d after the administration was : chromodacryorrhoea Chromodacryorrhoea is attributed to the discomfort produced by the dressing and is not necessarily considered to be a toxic affect .

Gross pathology:

All animals were normal at terminal necropsy .

Other findings:

Observations of the skin condition : Slight yellow staining of the skin at the application site was noted from 1 d p.a. until 2 d p.a. . This discoloration is directly attributed to a staining property of the test substance and not considered to be a toxic effect . Except for this , the exposed skin was not found to be altered by the test substance .

No noteworthy sex difference in the response to the test substance was derived from clinical observations or post-mortem findings .

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 TG402 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1).The validity criteria of the test system was fulfilled. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rat was found to be greater than 2000 mg/kg bodyweight. The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU labelling regulations Commission Directive 93/21/EEC.

Executive summary:

The acute dermal toxicity of the test material was investigated in rats. The test was conducted according to OECD TG402 and EU Method B. 3. 2000 mg/kg bw of the test substance was applied semiocclusive to the shaved skin of rats. After 24 h the animals were unwrapped and observations were made for a period of 14 days. No mortalities occured during the study. There were no signs of systemic toxicity reported. Signs of dermal irritation noted during the study were slight yellow staining of the skin at the application site from 1 d p.a. until 2 d p.a. . This discoloration is directly attributed to a staining property of the test substance and not considered to be a toxic effect . Except for this , the exposed skin was not found to be altered by the test substance. Body weights and body weight gain were unremarkable during the entire study in all males. A slight body weight loss was noted in 2/5 females in the first week. This might be due to the discomfort, caused by the dressing and was not considered to be toxicologically significant. Body weights and body weight gain were unremarkable in the second week in all females. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU labelling regulations Commission Directive 93/21/EEC.