Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
13rd April 2017 - 23rd May 2017
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The complete read-across justification is detailed in section 13; source study has reliability 1.
Justification for type of information:
The complete read-across justification is detailed in section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

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: first batch: 7 weeks old; second batch: 6-7 weeks old
-Weight at study initiation: first batch: 158-161 g; second batch: 168.3-189.3 g
-Fasting period before study: food was removed from the cages overnight prior to dosing (Day -1) and was made available approximately 4 hours after dosing
-Housing: 3 animals during the study; up to 5 animals during acclimatisation in Polisulphone solid bottomed cages measuring 59.5 × 38 × 20 cm with nesting material provided into suitable bedding bags
-Diet: 4 RF; 18 ad libitum
-Water: drinking water supplied to each cage via a water bottle; ad libitum
-Acclimation period: at least 5 days
-Veterinary health check: during acclimatisation period

ENVIRONMENTAL CONDITIONS
-Temperature: 22 °C ± 2 °C
-Humidity: 55 % ± 15 %
-Air changes: Approximately 15 to 20 air changes per hour
-Photoperiod: 12 hours cycle dark/light with artificial fluorescent tube

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Softened
Details on oral exposure:
-Dosing method: the formulated test item was administered at a dose volume of 10mL/kg using a plastic feeding tube attached to a graded syringe.
Doses:
300 and 2000 mg/kg b.w.
No. of animals per sex per dose:
Three females per group; two groups per dose
Control animals:
no
Details on study design:
-Frequency of treatment: once only on Day 1
-Duration of observation period following administration: 14 days
-Mortality and morbidity: throughout the study, all animals were checked twice daily
-Frequency of observations: on the day of dosing, animals were observed for clinical signs as indicated below, after which they were dosed daily for a total of 14 days (Session 1):
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
-Frequency of weighing: 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

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
-In the first group dosed at 300 mg /kg, one animal was found dead on Day 2 of the observation period.
-In the second group dosed at the same dose level, no death occurred.
-Both in the third and in the fourth groups dosed at 2000 mg/kg, no death occurred.
Clinical signs:
-In both groups dosed at 300 mg /kg, no clinical signs were observed.
-In the third group dosed at 2000 mg/kg no clinical signs were observed.
-In the fourth group at the same dose level, only black staining on the tail of all animals was observed for the entire observation period.
Body weight:
-Changes in body weight observed during the study were within the expected range for this strain and age of animals.
Gross pathology:
-Abnormalities observed during the necropsy of the early decedent animal consisted of: abnormal colour (dark red) of lungs, brain, thymus, heart and thoracic cavity. In addition, abnormal content (dark fluid) in the thoracic cavity was recorded.
-No abnormalities were observed at necropsy examination performed at the end of the observation period on the surviving animals treated at either 300 or 2000 mg/kg.
-Only two animals (Step 4) showed dark staining on the tail.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified according to the CLP Regulation (EC 1272/2008)
Conclusions:
The acute toxicity expected (ATE) was found to be greater than 2000 mg/kg body weight
Executive summary:

The acute toxicity was investigated following a single oral administration to the Sprague Dawley rat, followed by a 14-day observation period. The test was performed according to the OECD Guideline 423 (2001). Two groups, each of 3 female animals, were initially dosed at 300 mg /kg. A third group, similarly composed, was dosed at 2000 mg/kg. A fourth group of 3 female animals was administered at the same dose level.

No mortality occurred at any dose levels, excepting one animal found dead on Day 2 of the observation period in the first group dosed at 300 mg /kg. No clinical signs were observed in any dose levels, excepting only black staining on the tail of all animals in the fourth group dosed at 2000 mg/kg was observed for the entire observation period. Body weight changes recorded during the study were within the expected range for this strain and age of animals.

No abnormalities were observed at necropsy examination performed at the end of the observation period on the surviving animals treated at 300 mg/kg and in animals treated at 2000 mg/kg. Only two animals in the fourth group dosed at 2000 mg/kg showed dark staining on the tail. In the early decedent animal consisted in abnormal colour (dark red) of lungs, brain, thymus, heart and thoracic cavity; in addition abnormal content (dark fluid) in the thoracic cavity was recorded.

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 expected (ATE) to be greater than 2000 mg/kg body weight.