Registration Dossier

Diss Factsheets

Administrative data

Description of key information

In an acute oral toxicity study (OECD 425) on rats, the Oral LD50 was higher than 5000 mg/kg (GLP study, Rel. K1)

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:
01 - 30 April 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted in compliance with OECD Guideline No. 425 without any deviation.
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
The Swiss GLP Monitoring Authorities (inspected on 05-09 and 26-30 November 2007 / signed on 12 November 2008)
Test type:
up-and-down procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Plant Impact plc / X25902
- Appearance: Yellow to orange liquid
- Expiration date of the lot/batch: 01 May 2009
- Purity test date: 15 May 2008

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (range of 20 ± 5 °C), light protected.
- Stability: Stable under storage conditions
Species:
rat
Strain:
other: HanRcc: WIST
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories Ltd., Laboratory Animal Services, Wölferstrasse 4, 4414 Füllinsdorf / Switzerland.
- Females - nulliparous and non-pregnant: Yes
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 179.4-205.7 g
- Fasting period before study: Overnight fasting period (approximately 17 to 19 hours) prior to intubation and approximately 3-4 hours post dose
- Housing: Animals were housed individually in Makrolon type-3 cages with standard softwood bedding (‘Lignocel’ Schill AG, 4132 Muttenz / Switzerland) during treatment and observation.
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 76/08 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland); ad libitum
- Water: Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30-70 % (values above 70 % during cleaning process possible)
- Air changes: Air-conditioned with 10-15 air changes per hour
- Photoperiod: Automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period

IN-LIFE DATES: 01 - 30 April 2009
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
Polyethylene glycol 300 (PEG 300)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION
- The dose formulations were prepared shortly before each dosing occasion using a magnetic stirrer as homogenizer. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

TEST ITEM ADMINISTRATION
- Animals received a single dose of the test item by oral gavage administration after being fasted for approximately 17 to 19 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
3 females (total)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Viability/Mortality: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (in common with the clinical signs) and twice daily during days 2-15.
Clinical signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1, depending on the occurrence of clinical signs of toxicity. Once daily during days 2-15.
Body weights: On test day -1 (prior to removal of food), on test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: Yes; all animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.
Statistics:
The statistical programme (AOT 425 Stat Pgm) version: 1.0, 2001 was used for the selection of dose levels and calculation of the LD50 values.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
The three 5000 mg/kg treated animals were observed with slightly ruffled fur, hunched posture and slight sedation between 1 hour after treatment and test days 3, 6 or 7. One animal was additionally observed with almost to completely closed eyes on test day 2. The three animals were free of any clinical signs from test days 4, 7 or 8 until the end of the study (test day 15).
Body weight:
The body weight of the animals was within the range commonly recorded for rats of this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the oral LD50 for test substance is > 5000 mg/kg bw in female rats therefore it is not classified according to the CLP Regulation (EC) N° (1272-2008).
Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 425 and in compliance with GLP, 3 female HanRcc:WIST (SPF) rats were given a single oral (gavage) dose of test substance at 5000 mg/kg bw. The test substance was formulated in PEG 300 at a concentration of 500 mg/mL and administered at a dosing volume of 10 mL/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

All animals survived until the end of the study period. Slight clinical signs including ruffled fur, hunched posture and slight sedation on the day of treatment were observed in the three animals treated at 5000 mg/kg body weight which persisted up to test day 7 at the latest. One animal was additionally observed with almost to completely closed eyes on test day 2. By day 4, 7 or 8 all the animals were free of any clinical signs until the end of the study (test day 15). The body weight of the animals was within the range commonly recorded for rats of this strain and age. No macroscopic findings were recorded at necropsy.

 

Under the test conditions, the oral LD50 for test substance is > 5000 mg/kg bw in female rats therefore it is not classified according to the CLP Regulation (EC) N° (1272-2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an acute oral toxicity study (limit test) performed according to OECD Guideline 425 and in compliance with GLP, 3 femaleHanRcc:WIST (SPF) rats were given a single oral (gavage) dose of test substance at 5000 mg/kg bw.The test substance was formulated in PEG 300 at a concentration of 500 mg/mL and administered at a dosing volume of 10 mL/kg bw.Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

All animals survived until the end of the study period. Slight clinical signs including ruffled fur, hunched posture and slight sedation on the day of treatment were observed in the three animals treated at 5000 mg/kg body weight which persisted up to test day 7 at the latest. One animal was additionally observed with almost to completely closed eyes on test day 2. By day 4, 7 or 8 all the animals were free of any clinical signs until the end of the study (test day 15). The body weight of the animals was within the range commonly recorded for rats of this strain and age. No macroscopic findings were recorded at necropsy.

 

Under the test conditions, the oral LD50 for test substance is > 5000 mg/kg bw in female rats therefore it is not classified according to the CLP Regulation (EC) N° (1272-2008).

Justification for classification or non-classification

Self classification:

Acute toxicity via Oral route:

Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 5000 mg/kg bw

Categories Display