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Description of key information

The oral LD50 and dermal LD50 in rats is considered to be >2,000 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:
28 October 1997 - 13 November 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to international guideline and GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
not specified
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 9 weeks
- Housing: Group housing (polycarbonate cages) 3 animals per sex
- Diet (e.g. ad libitum): Free access, standard pelleted laboratory animal diet (Carfil Quality BVBA, Oud-Turnhour, Belgium).
- Water (e.g. ad libitum): Free access to tap-water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28 October 1997 To: 13 November 1997
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg


Doses:
2000 mg/kg (10 ml/kg) body weight
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality/Viability - Twice daily; Body Weight - Days 1 (pre-administration), 8 and 15; Clinical Signs - periodic intervals on day of dosing, and once daily thereafter, until day 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: Necropsy was performed at the end of the observation period and internal macroscopic abnormalities were recorded.
Statistics:
None performed
Preliminary study:
Since the 2000 mg/kg limit test resulted in no adverse effects, or mortalities in the study group, no additional dose levels were required.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other: There were no signs toxicity throughout the 15 day observation period. All male and females animals appeared normal throughout the observation period.
Gross pathology:
No abnormalities were observed at the macroscopic level for all animals necropsied at the conclusion of the 15-day observation period.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance, when administered as supplied to 3 male and 3 female Wistar rats, indicates an acute oral LD50 greater than 2000 mg/kg.
Executive summary:

The oral LD50 value of the test substance in Wistar rats was established as greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 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:
30 October 1997 - 13 November 1997
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, sulzfed, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: Males (average): 369 grams; Females (average) 235 grams
- Fasting period before study: No
- Housing: Individually in polycarbonated cages
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (Carfil Quality BVBA, OUd-Turnhout, Belgium).
- Water (e.g. ad libitum): Free access tap-water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50%
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: Back
- % coverage: 10% of total body surface
- Type of wrap if used: Gauze patch, fixed successively to aluminium foil and Coban elastic bandage; in addition micropore tape was used.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Tap-water moistened tissue
- Time after start of exposure: 24 hours after application
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males;
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality/Viability - Twice Daily; Body Weights - Day 1 (pre-administration), day 8 and day 15; Clinical Signs - periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: Internal macroscopic abnormalities
Preliminary study:
Since the 2000 mg/kg body weight limit test resulted in no adverse effects, or mortalities in the study group, no additional dose levels were required.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality reported.
Clinical signs:
other: General or focal erythema, scales and scabs on the back or flank were reported in one male and two females. By day 8 the females recovered from symptoms, however scabs persisted in the male at termination of study. Yellow staining of the skin by the test
Gross pathology:
No treatment related abnormalities were reported at the macroscopic level.
Pelvic dilation of the kidneys were found in one male, however this is a common occurrence among rats of this age and strain and was not considered toxicologically related.

Clinical Signs - Males                                    
   
Test day     1 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time after treatment Hours   0 2 4                            
   
Animal No. Signs Max Grade  
1 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
2 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1  -  -  -  -
3 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
4 Skin/Fur/Plumage/Erythema Focal (Back) 4  -  -  - 2 2 2 1 1 1 1 1 1  -  -  -  -  -
Scabs (Back) 3  -  -  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1
Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
5 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1

Clinical Signs - Females                                    
   
Test day     1 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time after treatment Hours   0 2 4                            
   
Animal No. Signs Max Grade  
6 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
7 Skin/Fur/Plumage/General Erythema (Back) 4  -  -  - 2 2 2 1 1 1  -  -  -  -  -  -  -  -
Scales (Back) 3  -  -  -  -  - 1  -  -  -  -  -  -  -  -  -  -  -
Skin Yellow (Flank Left) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
8 Skin/Fur/Plumage/General Erythema (Back) 4  -  -  - 2 2 2  -  -  -  -  -  -  -  -  -  -  -
Erythemal Focal (Flank Right) 4  -  -  -  -  -  - 2 2 1  -  -  -  -  -  -  -  -
Scales (Back) 3  -  -  -  -  - 1  -  -  -  -  -  -  -  -  -  -  -
Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1  -  -  -  -
Skin Yellow (Flank Left) 1  -  -  -  -  -  -  -  -  -  -  -  -  - 1 1 1 1
9 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
10 Skin/Fur/Plumage/Skin Yellow (Back) 1  -  -  - 1 1 1 1 1 1 1 1 1 1 1 1 1 1
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance, when administered as supplied to 5 male and female Wistar rats, appears to have an acute dermal LD50 greater than 2000 mg/kg
Executive summary:

The dermal LD50 value of the test substance in rats was established as exceeding 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
mg/kg bw

Additional information

The oral LD50 and dermal LD50 in rats is considered to be >2,000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
The oral LD50 value of the test substance in Wistar rats was established as greater than 2000 mg/kg body weight.

Justification for selection of acute toxicity – dermal endpoint
The dermal LD50 value of the test substance in rats was established as exceeding 2000 mg/kg body weight.

Justification for classification or non-classification

Epyrron is classified as not hazardous according to the Directive 67/548 EEC and Regulation (EC) 1272/2008 (CLP).