Registration Dossier

Administrative data

Description of key information

1. Acute oral toxicity (1985), GLP, OECD 401, rats, gavage, 2000 mg/kg, 5000 mg/kg, 8000 mg/kg, LD50 4878 mg/kg bw.
2. Acute dermal toxicity (2001), GLP, OECD 402, rats, occlusive, 2000 mg/kg, LD50 > 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
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.
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.
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.

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)

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

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
4 878 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001-02-23 - 2001-10-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well-documented GLP study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Monitoring Authority
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.

No signs of systemic toxicity have been observed during 4 h of exposure and 14 days after initiation of exposure:

Mortality Data - There were no deaths.

Clinical Observations - There were no signs of systemic toxicity.

Dermal Reactions - Crust formation was noted at the treatment sites of all females two and three days after dosing. No other signs of dermal irritation were noted during the study.

Bodyweight - All animals showed expected gains in bodyweight over the study period.

Necropsy - No abnormalities were noted at necropsy.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Acute oral toxicity:

The acute oral toxicity of the test material was investigated in rats (Ullmann and Sacher, 1985). The test was conducted according to OECD TG401 without deviations and according to good laboratory practice principles and therefore considered to be of the highest reliability (Klimisch 1). 2000, 5000 and 8000 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:

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.

All female rats in the highest dose group died within 3 hours, 4 male rats died within 2 hours, 1 male rat survived to the end of the observation period. In the 5000 mg/kg bw dose group 4 animals died within 24 hours and another one within the following 3 days. No animals died in the lowest dose group. Therefore the oral toxicity can be characterised by a LD50 value in rats of both sexes of 4878 mg/kg bw .

Acute dermal toxicity:

The acute dermal toxicity of the test material was investigated in rats (Driscoll, 2001). The test was conducted according to OECD TG402 and EU Method B. 3. 2000 mg/kg bw of the test substance was applied occlusive 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, signs of systemic toxicity, treatment-related body weight changes or pathological abnormalities were reported. Crust formation was noted at the treatment sites of all females two and three days after dosing. No other signs of dermal irritation were noted during the study.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.

Justification for classification or non-classification

Acute oral Toxicity:

The test material does not meet the criteria for classification and will not require labelling for oral toxicity in accordance with European regulation (EC) No. 1272/2008.

 

Acute dermal Toxicity:

The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with European regulation (EC) No. 1272/2008.