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Administrative data

Description of key information

Acute oral toxicity

One reliable acute toxicity study via the oral route is available. After a single exposure to rats of 2000 mg/kg, the LD50 was established as greater than 2000 mg/kg bw (TalviOja, 2006). Based on these results, the test substance is considered not classified as an acute oral toxicant.

Acute toxicity via inhalation

No study was available for this endpoint. Therefore the endpoint has been waived:

In addition to the oral route of exposure, for substances other than gases, the information mentioned under REACH section 8.5.2 to 8.5.3 shall be provided for at least one other exposure route (REACH Regulation, column 2 adaptation of Annex VIII). For this substance, a key study is available for the dermal route of exposure. Therefore, an acute inhalation toxicity study should not be performed.

Acute dermal toxicity

One reliable acute toxicity study via the dermal route was available.After single dermal administration to rats of both sexes, observed over a period of 14 days, the LD50 was found to be greater than 2000 mg/kg body weight (Ott, 2006). Based on these results, the test substance is considered not classified as an dermal toxicant.

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:
2006-03-07 to 2006-03-30
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 (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): TIC2782 (T002907)
- Substance type: white solid
- Physical state: solid
- Analytical purity: 99.9%
- Lot/batch No.: 00467090 (= Charge 05C0836)
- Expiration date of the lot/batch: 2006-05-04
- Stability of test item: stable under storage conditions
- Stability under test conditions: Unknown in PEG 300
- Storage condition of test material: At room temperature (range of 17-23°C),away from direct sunlight.
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HanRcc:WIST (SPF) from RCC Ltd., Laboratory Animal Services, CH-4414 Füllinsdorf / Switzerland
- Age when treated: 12 weeks
- Weight at day 1 treatment: 181.9-191.4g
- Fasting period before study: yes, for approximately 18 to 19 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.
- Housing: Standard laboratory conditions, in groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet: ad libitum, Pelleted standard Provimi Kliba 3433 rat/mouse mainte-nance diet
- Water: ad libitum, community tap water from Füllinsdorf
- Acclimation period: 6 days, 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
- Photoperiod (hrs dark / hrs light): 12/12
- Other: music during daytime light period

IN-LIFE DATES: 2006-04-14 (group 1); 2006-04-16 (group 2)
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2g/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: PEG 300 was found to be a suitable vehicle. The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
- Lot/batch no. (if required): 120471944705164
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/ KG BODY WEIGHT;

DOSAGE PREPARATION (if unusual): dose levels are in terms of the test item as supplied. The dose formulations were made shortly before each dosing occasion using a magnetic stirrer, a spatula and an Ultra-Turraw as homogenizers. 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.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Doses:
Single dosing
2000 mg/kg (2 groups)
No. of animals per sex per dose:
3 females/group
6 females in total
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Moratility / 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 the clinical signs) and twice daily during days 2-15. Clinical observations: 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.
- Necropsy of survivors performed: yes, All surviving animals were killed at the end of the observation period by an intraperitoneal injection of Vetanarcol at a dose of at least 2.0 mL/kg body weight (equivalent to at least 324 mg sodium pentobarbitone/kg body weight) and discarded after macroscopic examina-tions were performed. No organs or tissues were retained.
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:
Slightly ruffled fur was observed in 5 of the treated animals on the day of testing from 30 minutes to 3 hours after dosing or 2−3 hours or 5 hours after dosing. A hunched posture was observed in two of the animals 3 hours after the treatment and persisted in one of the animals at the 5-hour reading. For the remaining days of the study no clinical signs were observed. One of the animals was absent of clinical signs thourhgout the study.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age with the exception of animal No. 3 in which a very minor (1.3%) body weight loss was observed during the second week of observation.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose of TIC2782 (T002907) 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. Therefore T002907 is not classified based on CLP Regulation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
2005-10-12 to 2005-11-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline 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)
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): TIC2782 (T002907)
- Substance type: White solid
- Physical state: solid
- Analytical purity: 99.9 %
- Purity test date: No data
- Lot/batch No.: 00467090 (= charge 05C0836)
- Expiration date of the lot/batch: 2006-05-04
- stability of test item dilution: unknown in PEG300
- Stability of test item: stable under storage conditions
- Storage condition of test material: At room temperature (range of 20 +/- 5 °C), light protected.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HanRcc:WIST (SPF) from RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf / Switzerland
- Age when treated: Males: 8 - 9 weeks; Females: 12 -13 weeks.
- Weight at first day of treatment: Males: 236.9 - 246.4; Females: 188.3 - 205.4g.
- Fasting period before study: unknown
- Housing: Standard laboratory conditions; during acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation.
- Diet: Ad libitum, pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet.
- Water: Ad libitum, community tap water from Füllinsdorf
- Acclimation period: at least 6 days, 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 (values above 70% during cleaning process possible)
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12
- Other: Music during the daytime light period.
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
PEG300
Details on dermal exposure:
TEST SITE
- Area of exposure: backs of the animals
- % coverage: 10% of the total body surface
- Type of wrap if used: gauze patch which was applied to the intact skin with a syring and sovered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm tapwater and dried with disposable paper towels.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/kg
- Concentration (if solution): 0.5g/mL
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE (PEG300)
- Amount(s) applied (volume or weight with unit): 4 mL/kg
- Lot/batch no.: 1157790 51105271
- Purity: no data
- justification: the vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males, 5 females all 2000 mg/kg body weight (total 10 animals)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Moratilty / Viability: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 ours after adminstration on test day 1 (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 ours after adminstration on test day 1 and once daily during days 2-15. Body weights: on test days 1 (prior to administration), 8 and 15; other: local signs: Once dailing 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.
Statistics:
No statistical analysis were used.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occured during the study.
Clinical signs:
No systemic or local signs of toxicity were observed during the study period.
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 observed at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose of TIC2782 (T002907) after single dermal administration to rats of both sexes, observed over a period of 14 days is: LD50 (rat): greater than 2000 mg/kg body weight. Therefore T002907 is not classified based on CLP regulation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute oral toxicity

One reliable acute toxicity study via oral administration is available.

In this study, 5 male and 5 female Sprague-Dawley rats were dosed on a single occasion with the test substance in polyethylene glycol (PEG 300) at 2000 mg/kg bw (according to OECD guideline 423 and GLP; TalviOja, 2006). During the subsequent 14-day observation period, no deaths or significant toxicity-related clinical signs were observed. The slightly ruffled fur and hunched posture that was seen resolved in about 5 hours. Body weight gain showed only minor deviations in one animal (1.3% loss), and macroscopic examination at necropsy demonstrated no deviations.

The LD50 was higher than 2000 mg/kg bw. No signs of toxicity were observed at this dose. Based on these results, the test substance is considered not classified as an acute oral toxicant.

Acute inhalation toxicity

There was no reliable acute inhalation study available. Therefore the study has been waived:

In addition to the oral route of exposure, for substances other than gases, the information mentioned under REACH section 8.5.2 to 8.5.3 shall be provided for at least one other exposure route (REACH Regulation, column 2 adaptation of Annex VIII). For this substance, a key study is available for the dermal route of exposure. Therefore, an acute inhalation toxicity study should not be performed.

Acute dermal toxicity

In this study, 5 male and 5 female Sprague-Dawley rats were dosed on a single occasion with the test substance in polyethylene glycol (PEG 300) (according to OECD 402 guideline and GLP; Ott, 2006). 0.5 g/mL of the test substance was applied to the backs of the animals (10% of total body surface), and covered with a semi-occlusive dressing. 24 hours after dosing, the dressing was removed and the area washed with lukewarm tap water. Observations at 1, 2, 3 and 5 hours after administration on test day 1, and twice daily during days 2-15 showed no test-item related mortality, clinical signs or body weight effects. Based on these results, the test substance is considered not classified as an acute dermal toxicant.

Justification for classification or non-classification

Acute oral toxicity

The LD50 is greater than 2000 mg/kg bw and therefore the test substance is considered not classified as an acute oral toxicant according to the CLP Regulation.

Acute inhalation toxicity

There was no reliable acute inhalation study available. Therefore no classification can be derived for acute inhalation toxicity.

Acute dermal toxicity

The LD50 is greater than 2000 mg/kg bw, and therefore the test substance is considered not classified as an acute dermal toxicant according to the CLP Regulation.