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Description of key information

The acute oral toxicity study indicate that the substance is of low toxicity if swallowed (rat LD0 > or = 2000 mg/kg bw).

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:
8 august 2017 - 23 august 2017
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 December 2001
Deviations:
yes
Remarks:
Due to technical reason, temperature values (maximum of 25.6°C) out of the target range 19-25°C were observed.These minor differences in the environmental parameter were considered not to adversely affect the study.
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: breeder: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 182 – 193 g
- Fasting period before study: yes, during the night before treatment
- Housing: the animals were housed by three from the same group in Type II polypropylene/polycarbonate cages
- Diet: SSNIFF SM R/M; ssniff Spezialdiäten GmbH, D-59494 Soest, Germany(free access)
- Water: tap water filtered from the municipal supply (free access)
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.8 – 25.6°C
- Humidity (%): 34 – 70%
- Air changes (per hr): approximately 15 - 20 air exchanges /hour
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 3 august 2017 to 23 august 2017
Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
Lot number: A0384372, Producers: Acros Organics, Belgium
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: the test substance is an ester which hydrolyses in aqueous media, therefore corn oil was used as a vehicle during the study.. A homogenous suspension was obtained in corn oil at the concentration of 200 mg/mL.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw.

DOSAGE PREPARATION (if unusual): Dose formulations were prepared based on weight on the day of administration and kept under magnetic stirring up to the end of dose administration procedure.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: Limit dose of 2000 mg/kg bw was selected as a starting dose as it was the dose which was most likely to produce mortality in some of the dosed animals.
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
3 females per treatment step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter.
- Body weight: just before treatment, then on day of treatment (day 0) and on days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
no
Preliminary study:
Not applicable
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed at dose level of 2000 mg/kg bw.
Clinical signs:
other: All animals showed decreased activity (score 1 or 2, Day 0), hunched back (Day 0 and 1) and incoordination (score 1 or 2, Day 0). In addition, piloerection was observed in 1 out of 6 animals on Day 0. From Day 2 all animals were symptom-free.
Gross pathology:
The test item administration did not induce any macroscopic findings at necropsy.

Other findings:
no

Table 7.2.2/1: Signs associated with dosing -Individual observations on Days 1and 2

Cage number

Animal number

Observations

Observation days

0

1

2

30’

1h

2h

3h

4h

6h

 

 

1

368

Symptom Free

+

-

-

-

-

-

-

+

Activity decreased

-

-

1

1

1

2

-

-

Hunched back

-

+

+

+

+

+

+

-

Incoordination

-

-

-

-

2

2

-

-

369

Symptom Free

+

-

-

-

-

-

-

+

Activity decreased

-

-

1

1

1

2

-

-

Hunched back

-

+

+

+

+

+

+

-

Incoordination

-

-

-

-

1

1

-

-

370

Symptom Free

+

-

-

-

-

-

-

+

Activity decreased

-

-

1

1

1

1

-

-

Hunched back

-

+

+

+

+

+

+

-

Incoordination

-

-

-

-

1

1

-

-

2

371

Symptom Free

+

+

-

-

-

-

-

+

Activity decreased

-

-

-

1

1

1

-

-

Hunched back

-

-

+

+

+

+

+

-

Incoordination

-

-

-

1

1

1

-

-

372

Symptom Free

+

-

-

-

-

-

-

+

Activity decreased

-

-

-

1

1

2

-

-

Hunched back

-

+

+

+

+

+

+

-

Incoordination

-

-

1

1

2

2

-

-

Piloerection

-

-

-

-

-

+

-

-

373

Symptom Free

+

-

-

-

-

-

-

+

Activity decreased

-

-

-

1

1

2

-

-

Hunched back

-

+

+

+

+

+

+

-

Incoordination

-

-

-

1

1

2

-

-

 + = present                             - = absent

h = hours                                ‘ = minutes

Severities : 1 = slight/small/few, 2= moderate/medium, 3= marked, large, many

 

 

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
No mortalities were observed in rats receiving 2000 mg/kg b.w. but significant reversible clinical signs of toxicity occured.
The substance is not classified according to Regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures.
According to the Globally Harmonized Classification System (GHS; UNITED NATIONS), the substance is classified as Category 5.
Executive summary:

The substance was tested for acute oral toxicity according to OECD 423 guideline and in compliance with Good Laboratory Practices.

The test item was administered once by gavage to 2 groups of 3 fasted female rats under a dosage-volume of 10 mL/kg. Initially, 3 females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group of 3 females was treated at the same dose level. As no mortality was observed in the confirmatory group, no further testing was done.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was recorded before treatment then on day 0, 7 and 14. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination.

No unscheduled deaths occurred during the study. On the day of administration (day 0), All animals showed slight or moderate decreased activity, slight or moderate incoordination and hunched posture , this latter being present up to day 1. In addition, piloerection was observed in 1 out of 6 animals. From Day 2 all animals were symptom-free.

Body weight and body weight gain were unaffected by the test item treatment and no macroscopic findings were found at necropsy.

The acute oral LD0 of the test item was equal or higher than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Study complete and sufficient to fulfill the endpoint requirements.

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

Oral route:

The substance was tested for acute oral toxicity according to OECD 423 guideline and in compliance with Good Laboratory Practices.

The test item was administered once by gavage to 2 groups of 3 fasted female rats under a dosage-volume of 10 mL/kg. Initially, 3 females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group of 3 females was treated at the same dose level. As no mortality was observed in the confirmatory group, no further testing was done.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was recorded before treatment then on day 0, 7 and 14. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination.

No unscheduled deaths occurred during the study. On the day of administration (day 0), All animals showed slight or moderate decreased activity, slight or moderate incoordination and hunched posture , this latter being present up to day 1. In addition, piloerection was observed in 1 out of 6 animals. From Day 2 all animals were symptom-free.

Body weight and body weight gain were unaffected by the test item treatment and no macroscopic findings were found at necropsy.

The acute oral LD0 of the test item was equal or higher than 2000 mg/kg bw.

Justification for classification or non-classification

No mortalities were noted in rats after treatment by oral route with a single dose of 2000 mg/kg body weight.

On the basis of this result and according to regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures, no classification is warranted with respect to acute oral toxicity.

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