Registration Dossier

Administrative data

Description of key information

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 - 20 November 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The acute oral toxicity study was conducted according to EU Method B.1 and OECD Guideline Method 423 without deviations and GLP practices.
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 9-10 weeks old
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Food was withheld overnight prior to dosing until approximately 3-4 hours after treatment of the test substance
- Housing: Group house of 3 animals per sex per cage in labelled polycarbonatge cages
- Diet (e.g. ad libitum): Standard pelleted laboratory diet (from Carfil Quality BVBA, Oud-Turnout, Belgium), Ad libitum
- Water (e.g. ad libitum): Tap-water, ad libitum
- Acclimation period: At least 5 days before the start of treatment under laboratory conditions

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

IN-LIFE DATES: From: Not documented in the report To: Not documented in the report
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
DOSAGE PREPARATION (if unusual): The formulations (w/w) were prepared immediately prior to dosing. Adjustment was made for specific gravity of the vehicle. The concentration of the test sustance in vehile was varied to allow constant dosage volume in terms of ml/kg body weight. Homogeneity was accomplished to a visually acceptable level.
Doses:
2000 mg/kg bw, 200 mg/kg bw, and 25 mg/kg bw
No. of animals per sex per dose:
3/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability was observed twice daily; body weights were recorded on Day 1 (pre-administration, 8 and 15 and at death (if found dead after Day 1); Clinical signs were periodically observed on the day of dosing (Day 1) and once daily thereafter, until Day 15 (the time of onset, degree and duration were recorded and the symptoms graded according to fixed scales: Max grade 4= drading slight (1) to very severe (4), Max grade 3= drading slight (1) to severe (3), Max grade 1= presence is scored (1)).
- Necropsy of survivors performed: yes, at the end of the observation period, all animals were sacrificed by asphyxiation using a oxygen/carbon dioxide procedure and subject to necropsy.
Statistics:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
25 - 200 mg/kg bw
Based on:
test mat.
Mortality:
All animals dosed at 2000 or at 200 mg/kg were found dead on day 2 or day 3, respectively. The surviving animals had recovered from the symptoms by day 2.
Clinical signs:
Clinical signs observed during the study period were as follows:
25 mg/kg: Uncoordinated movements (females only)
200 mg/kg: Lethargy, hunched posture, uncoordinated movements and piloerection.
2000 mg/kg: Lethargy, tremors, uncoordinated movements and ptosis of the eyes.
Body weight:
Body weight gain shown by the animals over the study period was considered to be normal.
Gross pathology:
Yellowish discoloration of all adipose tissue and reddish watery fluid in the thoracic and/or abdominal cavity were found in the 200 mg/kg treated animals at macroscopic post mortem examination. No abnormalities were found in the other dose groups.

Inadvertently, no animals observations were performed on Day 11 (males) and on Day 13 (females) of the 25 mg/kg dose group. Based on the previous observation, it was considered that this evernt has not adversely effected the study integrity.

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Oral LD50 value of Epyrrol in Wistar rats was established to be within the range of 25-200 mg/kg body weight.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50

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)
Rationale for reliability incl. deficiencies:
other: This study was conducted according to OECD guideline 402 and EU Method B.3 (Acute Dermal Toxicity Test) without deviations and GLP practices. .
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
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 9-10 weeks old
- Weight at study initiation: 298 g (male mean) and 226 g (female mean)
- Fasting period before study: Food was withheld overnight prior to dosing until approximately 3-4 hours after treatment of the test substance
- Housing: Group house of 3 animals per sex per cage in labelled polycarbonatge cages
- Diet (e.g. ad libitum): Standard pelleted laboratory diet (from Carfil Quality BVBA, Oud-Turnout, Belgium), Ad libitum
- Water (e.g. ad libitum): Tap-water, ad libitum
- Acclimation period: At least 5 days before the start of treatment under laboratory conditions

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

IN-LIFE DATES: From: Not documented in the report To: Not documented in the report
Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and or flank
- % coverage: 10% of total body surface (25 cm3 for males and 18 cm3 for females (5X5 cm and 3.5X5 cm, respectively))
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressings were removed and residual test substance was removed using a tissue moistened with tap water.
- Time after start of exposure: 24 hours after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg
- Concentration (if solution): No data
- Constant volume or concentration used: yes
Duration of exposure:
Single dose
Doses:
2000 mg/kg (10ml/kg) body weight
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability observed twice daily; Body weight observed on Days 1, 8 and 15; Clinical signs observed periodically on Days 1 and once daily thereafter, until Day 15 (the time of onset, degree and duration were recorded and the symptoms graded according to fixed scales).
- Necropsy of survivors performed: Yes, at the end of the observation period, all animals were sacrificed by asphyxiation using a oxygen/carbon dioxide procedure.
Statistics:
No statistical analysis was performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture was noted in one male, between days 5-7. Focal erythema, scales, and scabs on the back and/or flank were noted in the majority of animals from day 3-5 onwards. The animals had recoved from the symptoms between days 7 and 14, although scabs persisted in two males at termination.
Body weight:
Body weight gain during the observation period was within the range expected for rats used in this type of study.
Gross pathology:
No abnormalities were found in the animals at macroscopic post mortem examination.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 for rats treated with a single dermal application was established as exceeding 2000 mg/kg bw as no mortalities were observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
Oral LD50 value of Epyrrol in Wistar rats was established to be within the range of 25-200 mg/kg body weight.

Justification for selection of acute toxicity – dermal endpoint
The dermal LD50 for rats treated with a single dermal application was established as exceeding 2000 mg/kg bw as no mortalities were observed.

Justification for classification or non-classification