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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018/09/24 - 2018/10/12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
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:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS s.r.l., San Pietro al Natisone (UD), Italy
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 6 - 7 weeks
- Weight range at arrival: 159.0-163.5 g
- Weight at study initiation: 185.6 - 212.2 g
- Fasting period before study: Food was removed fromthe cages overnight prior to dosing (Day -1) and was made available approximately 4 hours after dosing
- Housing: Polisulfone solid bottomed cages measuring 59.5×38×20 cm with nesting material provided into suitable bedding bags
- Animals per cage: 3 during the study; up to 5 during acclimatisation
- Diet (e.g. ad libitum): 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy), ad libitum
- Water (e.g. ad libitum): Drinking water supplied to each cage via a water bottle, ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2 °C
- Humidity (%): 55±15%
- Air changes (per hr): Approximately 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
0.5% aqueous solution of carboxymethylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10mL/kg
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:

Throughout the study all animals were checked for morbidity and mortality twice daily.

Animals were observed for clinical signs as indicated below:
-Day of dosing
· Session 1: on dosing
· Session 2: approximately 0.5 hour after dosing
· Session 3: approximately 2 hours after dosing
· Session 4: approximately 4 hours after dosing
-Daily thereafter for a total of 14 days (Session 1).

All animals were weighed at allocation to the study (Day -1), on the day of dosing (Day 1) and on Days 2, 8 and 15.

- Necropsy of survivors performed: yes, Necropsy was carried out on all animals (gross necropsy examination for both external and internal abnormalities, with particular attention to the gastro-intestinal tract).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in the 6 animals following dosing at 2000 mg/kg.
Clinical signs:
No signs of toxicity were observed in the 6 animals following dosing at 2000 mg/kg.
Body weight:
Changes in body weight observed during the study were within the expected range for this strain and age of animals.
Gross pathology:
No abnormalities were seen at necropsy examination performed on all animals dosed at 2000mg/kg (Groups 2 and 4) at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
These results indicate that the test item did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the acute toxicity estimate (ATE) to be greater than 2000 mg/kg body weight.
Executive summary:

The acute toxicity of TP1740 was investigated following OECD 429 (Class method) and GLP. A single oral administration to the Sprague Dawley rat was followed by a 14-day observation period. A first group of 3 female animals was initially dosed at 2000 mg/kg (Step 1). No mortality occurred and no clinical signs were observed. A second group of 3 female animals was then dosed at the same dose level (Step 2). No death occurred and no clinical signs were noted. Body weight changes recorded during the study were within the expected range for this strain and age of animals. No abnormalities were seen at necropsy examination performed at the end of the observation period on animals of both groups. These results indicate that the test item did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the acute toxicity estimate (ATE) to be greater than 2000 mg/kg body weight.