Registration Dossier

Administrative data

Description of key information

Acute toxicity: Oral

An acute oral toxicity study was performed on female Wistar rats, following the acute toxic class method in accordance with the OECD Guideline 423, the LD50 was established to be greater than 2000 mg/kg, observed over a period of 14 days (Giannini 2008). The study has been performed in compliance with GLP principles.

Acute toxicity: inhalation

No study is available. This endpoint is waived based on following justification: According to the REACH Regulation, for substances other than gasses, only one additional route of exposure should be tested other than the oral route of exposure for acute toxicity (column 2, Annex VIII, section 8.5). Therefore, it is not necessary to perform an acute toxicity study via the inhalation route of exposure.

Acute toxicity: dermal

No study is available. The study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (skin irritation, skin sensitisation).

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:
from 2008-09-03 to 2008-09-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (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:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HanRcc:WIST (SPF) rat from RCC Ltd
- Age when treated: 11 weeks
- Weight when treated: 178.4 g - 205.5 g
- Fasting period before study: animals were fasted 17 to 18.5 hours prior to dosing, food was provided again approximately 3 hours after dosing
- Housing: standard laboratory conditions, in groups of 3 in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): ad libitum, pelleted standard diet
- Water (e.g. ad libitum): ad libitum, community tap water
- Acclimation period: under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark, automatically controlled, music during the daytime light period

IN-LIFE DATES: From: 2008-09-03 To: 2008-09-26
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG300
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: vehicle was chosen after a non-GLP solubility trial which was performed before the study inititation date
- Lot/batch no. (if required): 1349048
- Purity:no data

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusual): Dose levels are in terms of the test item as supplied by the sponsor. The dose formulations were made shortly before each dosing occasion using a magnetic stirrer and a spatula as homogenizers. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 females per group (6 femals in total)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: mortality/viability: 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 (with clinical signs) and twice daily during days 2-15
- 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.
- Other examinations performed:
-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. Once daily during days 2-15. All abnormalities were recorded.
-body weight: on test days 1 (prior to administration), 8 and 15
Statistics:
No statistical analysis was used
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study
Clinical signs:
No clinical signs were observed during the course of the study.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Interpretation of results:
not classified
Conclusions:
The median lethal dose of RT003066 after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat) 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

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

The study aimed to assess the acute oral toxicity of test substance to the rat using the acute toxic class method in female Wistar rat, according to the OECD guideline 423 and EU method B.1 tris (EC 440/2008) (Giannini, 2008). The study has been performed in compliance with GLP. The substance was administered by oral gavage at a dosage of 2000 mg/kg bw to female rats, in a dosing volume of 10 mL/kg. The substance was formulated in PEG300. Two groups of 3 female rats each received a single oral dose of test item, and were observed during 14 days following administration. The animals were examined daily during the acclimatization period and mortality, viability, and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approx 1, 2, 3 and 5 hours after treatment on day 1 and once daily during the test days 2 to 15. Mortality/viability was recorded at approx 30 minutes, 1, 2, 3 and 5 hours after administration on day 1 (with clinical signs) and twice daily during days 2 -15. Body weight was recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period. No clinical signs were observed during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. The LD50 of T003066 after single oral administration to female rats, observed over a period of 14 days is greater than 2000 mg/kg body weight.

Acute toxicity: inhalation

A key study is available for the oral route of exposure. According to the REACH Regulation, for substances other than gasses, only one additional route of exposure should be tested other than the oral route of exposure for acute toxicity (column 2, annex VIII, section 8.5). Therefore, it is not necessary to perform an acute toxicity study via the inhalation route of exposure.

Acute dermal toxicity

The study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (skin irritation, skin sensitisation).

Justification for classification or non-classification

Based on the results showing an oral LD50 exceeding 2000 mg/kg bw and according to the criteria laid down in regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, T003066 does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the criteria laid down in Reulation (EC) No 1272/2008.

No data were available to decide on the classification for the inhalation route.

No data were available to decide on the classification for the dermal route.