Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-01-03 - 1985-01-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report) : Pyridin-2-ethanol
- Physical state : liquid
- Analytical purity : 98%
- Lot/batch No. : CH 5/1

Test animals

Species:
rat
Strain:
other: KFM-Han. Wistar (outbred, SPF-Quality)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG/ 4414 Fuellingsdorf, Switzerland
- Age at study initiation: 8 to 11 weeks
- Weight at study initiation: 176 - 241 g (males) and 162 - 183 g (females)
- Fasting period before study: fasting for 12 to 18 hours before receiving the test article
- Housing: the animals were caged in groups of five in macrolon type-3 cages with standard softwood bedding (Lignocel/Schill AG/Switzerland).
- Diet : pelleted standard KLIBA 343/BATCH 15/84 rat maintenance diet (Klingentalmuehle AG/Switzerland), ad libitum.
- Water : tap water ad libitum.
- Acclimation period: 1 week under laboratory conditions after veterinary examination .

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr) : 10 - 15
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

IDENTIFICATION: by unique cage number and corresponding colour-coded spots
RANDOMIZATION: in order to set up a fully randomized experiment/animals were assigned to the different groups by means of a computer-generated random algorithm.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 % solution of CMC (Carboxymethylcellulose Natriumsalt purum, visc. 100 CPS, Fluka AG, CH 9470 Buchs, Switzerland) in distilled water
- Amount of vehicle (if gavage): 10 mL at 2000 mg/kg , 20 mL at 5000 mg/kg and 20 mL at 8000 mg/kg

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

DOSAGE PREPARATION: A dilution (w/w) of the test compound was prepared using a homogenizer (Ultra-Turrax/Janke and Kunkel/Staufen/
Germany) and kept homogenous during treatment using a magnetic stirrer (Auer-Bittmann/Switzerland).The preparations were made immediately prior to each dosing.
Doses:
2000 mg/kg bw , 5000 mg/kg bw and 8000 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 before treatment
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Bodyweights were recorded at the day of administration and days 8 and 15 after the administration / 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 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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
6 061 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
3 842 mg/kg bw
Based on:
test mat.
95% CL:
2 129 - 5 599
Sex:
male/female
Dose descriptor:
LD0
Effect level:
4 878 mg/kg bw
Based on:
test mat.
95% CL:
3 608 - 6 513
Mortality:
Males :
Dose : 2000 mg/kg : no animal died
Dose : 5000 mg/kg : 1 animal died 24 h after application
Dose : 8000 mg/kg : 3 animals died 1 h after application, 1 more animal died 2 h after application

Females :
Dose : 2000 mg/kg : no animal died
Dose : 5000 mg/kg : 2 animals died 3 h after application , 1 animal died 24 h after application and 1 more animal died at day 3 after application
Dose : 8000 mg/kg : 3 animals died 1 h after application , 1 animal died 2 h after application and 1 more animal died 3 h after after application
Clinical signs:
The following symptoms were observed:
2000 mg/kg : sedation, dyspnea, curved body position, ruffled fur
5000 mg/kg : sedation, somnolence, coma (females), dyspnea, ataxia, ventral body position, latero-abdominal position, curved body position, spasms (females), ruffled fur.
8000 mg/kg : sedation, somnolence, dyspnea, ataxia (males), latero-abdominal position, curved body position (males), ruffled fur (males).

The above symptoms were more pronounced in the higher dose groups. The surviving rats had recovered within 2 to 7 observation days.

For detailed results see Tables 1 ,2 and 3
Body weight:
Males :
Dose 2000 mg/kg : mean body weight at day 1,8,15 : 226g +/-5.9 , 260g +/- 12 , 275g +/- 14
Dose 5000 mg/kg : mean body weight at day 1,8,15 : 199g +/-13 , 250g , 282g
Dose 8000 mg/kg : mean body weight at day 1,8,15 : 232g +/-6.4 , 258g , 278g

Females :
Dose 2000 mg/kg : mean body weight at day 1,8,15 : 174g +/-7.8 , 192g +/- 11 , 198g +/- 11
Dose 5000 mg/kg : mean body weight at day 1,8,15 : 171g +/-5.9 , 186g , 189g
Dose 8000 mg/kg : mean body weight at day 1,8,15 : 176g +/-8.4 , Dead
Gross pathology:
GROUP 1 : 2000 mg/kg :
KILLED AT TERMINATION
male No. 11-15 : No pathoIogic changes.
female No. 16-20 : No pathologic changes.

GROUP 2 : 5000 mg/kg :
DEAD DAY 1
females No. 8, 10 : Intestines : reddened, slight; with reddish contents.
DEAD DAY 2
male No. 1 : Lung marmorated ; Intestines : reddened, with reddish contents.
female No. 6 : Lung/liver: marmorated.
DEAD DAY 3
female No. 7 : Lung : marmorated ; Intestines : with reddish contents.
KILLED AT TERMINATION
male No. 2-5 : No pathoIogic changes.
female No. 9 : No pathologic changes.

GROUP 3 : 8000 mg/kg :
DEAD DAY 1
males No. 22-25 : Intestines : reddened, slight; with reddish contents.
females No. 26-30 : Intestines : reddened, slight; with reddish contents.
KILLED AT TERMINATION
male No. 21 : No pathoIogic changes.
Other findings:
No other findings were reported.

Any other information on results incl. tables

Table 1 : Signs and symptoms (Dose 2000 mg/kg)

Males No. 11-15                                    
Test day        10  11 12  13  14  15 
hrs. after start exp.  24                           
sedation  0 0
dyspnea 
curved body position  -

ruffled fur 

Females No. 16-20                                    
Test day        10  11 12  13  14  15 
hrs. after start exp.  24                           
sedation  0 0
dyspnea 
curved body position  -

ruffled fur 

0

Table 2 : Signs and symptoms (Dose 5000 mg/kg)

Males No. 1-5                                    
Test day        10  11 12  13  14  15 
hrs. after start exp.  24                           
sedation  0 0
somnolence 
dyspnea 
ataxia 
ventral body position 
latero-abdominal position  -
curved body position  -

ruffled fur 

Females No. 6 -10                                    
Test day        10  11 12  13  14  15 
hrs. after start exp.  24                           
sedation  0 0
somnolence 
coma 
dyspnea 
ataxia 
ventral body position  -
latero-abdominal position  -

curved body position 

spasms 
ruffled fur 

Table 3 : Signs and symptoms (Dose 8000 mg/kg)

Males No. 21-25                                    
Test day        10  11 12  13  14  15 
hrs. after start exp.  24                           
sedation  0 0
somnolence 
dyspnea 
ataxia 
latero-abdominal position  -
curved body position  -

ruffled fur 

Females No. 26-30                                    
Test day        10  11 12  13  14  15 
hrs. after start exp.  24                           
sedation 
somnolence 
dyspnea  DEAD 
latero-abdominal position 

Key : 0/-=none , 1=slight , 2=moderate , 3=severe , X=observed

LOGIT-Estimation (LD50) :

No. of dose groups : 3

Species : rats both sexes

 Dose (mg/kg) No. of animals  No. of responses  % of responses 
2000  10 
5000  10  50 
8000  10  90 

LD50 estimate : 4878 mg/kg

90% confidence limits (3848 - 6137 mg/kg)

95% confidence limits (3608 - 6513 mg/kg)

99% confidence limits (3009 - 7666 mg/kg)

LOGIT-Estimation (LD50) :

No. of dose groups : 3

Species : rats males

 Dose (mg/kg) No. of animals  No. of responses  % of responses 
2000 
5000  20 
8000  80 

LD50 estimate : 6061 mg/kg

90% confidence limits (4075 - 14400 mg/kg)

95% confidence limits (3630 - 33220 mg/kg)

LOGIT-Estimation (LD50) :

No. of dose groups : 3

Species : rats females

 Dose (mg/kg) No. of animals  No. of responses  % of responses 
2000 
5000  80 
8000  100 

LD50 estimate : 3842 mg/kg

90% confidence limits (2513 - 5194 mg/kg)

95% confidence limits (2129 - 5599 mg/kg)

99% confidence limits (930.5 - 7000 mg/kg)

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 TG401 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled. On the basis of the test result the test material was considered to be not classified.
Executive summary:

The test article PYRIDIN-2-ETHANOL was administered to rats of both sexes by oral gavage, at doses from 2000 to 8000 mg/kg. The following death rate was observed:

0 % at 2000 mg/kg

50 % at 5000 mg/kg

90 % at 8000 mg/kg

Based on these observations, the LOGIT-ESTIMATION for the acute oral LD50 of. PYRIDIN-2-ETHANOL in rats of both sexes observed for a period of 15 days is : 4878 mg/kg

For males: 6061 mg/kg

For females: 3842 mg/kg

WITH A 95 % CONFIDENCE INTERVAL

Males/Females : 3608 - 6513 mg/kg

Females : 2129 - 5599 mg/kg