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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018-05-21 to 2018-06-29
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
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
sodium 2-chloroprop-2-enoate
EC Number:
608-818-5
Cas Number:
32997-86-7
Molecular formula:
C3H2ClO2.Na
IUPAC Name:
sodium 2-chloroprop-2-enoate
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: in house bred
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 160 - 180 g
- Housing: max. 3 animals per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 30 - 70 %
- Air changes: 12 to 15 per hr
- Photoperiod: 12 / 12 hrs dark / hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: water is the recommended vehicle by the guideline

CLASS METHOD
- Rationale for the selection of the starting dose: no information are available about the acute oral toxicity of the test item. Due to precautionary reasons it is classified as acutely toxic cat 4 according to CLP.
Doses:
300 mg/kg bw
No. of animals per sex per dose:
3 females in the first run
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All the animals were observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 hr (±10 min), 2 hrs (±10 min), 3 hrs (±10 min) and 4 hrs (±10 min) post dosing on Day 1 and at least once daily thereafter for clinical signs of toxicity throughout the experimental period. Individual animal body weight was recorded at receipt, on day 1 before test item administration and on day 8 and 15 during the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All the three animals dosed with 2000 mg/kg bw/d were found dead by day 2 observation. No mortality was observed at 300 mg/kg bw/d.
Clinical signs:
In Step-I and Step-I confirmation:
The animals were dosed with 300 mg/kg body weight. No clinical signs of toxicity and mortality were observed.
In Step-II, the animals were dosed with 2000 mg/kg body weight. No clinical signs were observed at 30 to 40 minutes. At 1st and 2nd hour clinical signs like lethargy were seen, 3rd hour lethargy and soft stool and at 4th hour recumbency was observed. All the three animals were found dead by day 2 observation.
Body weight:
No changes were observed in body weight and percent change in body weight with respect to day 1 at 300 mg/kg bw. However, decrease in body weight was observed in dead animals of the 2000 mg/kg bw dose group.
Gross pathology:
No gross pathological changes were observed in any of the animals dosed at 300 mg/kg and 2000 mg/kg body weight.
Other findings:
- Organ weights: not examined
- Histopathology: not examined

Any other information on results incl. tables

Table 1 Individual animal data on clinical signs of toxicity and mortality

Study Steps

&

Dose

(mg/kg body weight)

Animal No.

Sex

Clinical Signs of Toxicity and Mortality on

Day 1

Clinical Signs of Toxicity and Mortality on Day

30 to 40

min

1 hr

(±10 min)

2hrs

(±10 min)

3hrs

(±10

min)

4hrs

(±10

min)

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Step-I

&

300

Rc9524

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rc9525

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rc9526

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Step-I

Confirmation &

300

Rc9527

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rc9528

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rc9529

F

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Step-II

&

2000

Rc9530

F

N

1

1

1, 29

42

All the three animals were found dead by day 2 observation

Rc9531

F

N

1

1

1, 29

42

Rc9532

F

N

1

1

1, 29

42

N: Normal; F: Female; min/mins: minutes; hr/hrs: Hour/Hours, 1: Lethargy; 29: Soft stool; 42: Recumbency

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results of this study it is concluded that the LD50 of the test item is 300 < LD50 < 2000 mg/kg bw when administered as a single dose by oral gavage to female Sprague Dawley rats according to OECD 423.
Executive summary:

The test item was evaluated for acute oral toxicity in Sprague Dawley rats as per OECD Guideline No. 423. A starting dose of 300 mg/kg body weight was selected as there was no available information on the LD50 of the test item.

A total of 9 females (3 females each per Step-I, Step-I confirmation and Step-II) were used. All the animals of Step-I and Step-I confirmation were administered with 300 mg/kg body weight of the test item and Step II were administered with 2000 mg/kg body weight of the test item by oral route (gavage).

All the animals were observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 hr (±10 mins), 2 hrs (±10 mins), 3 hrs (±10 mins) and 4 hrs (±10 mins) post dosing on day 1 and once daily thereafter for clinical signs of toxicity and twice daily for mortality during the 14 days observation period. Body weight was recorded on day 1 before test item administration and on day 8 and 15 during the observation period. At the end of observation period, all the surviving animals were sacrificed under carbon dioxide anaesthesia, subjected to necropsy and gross pathological examination.

In Step-I and Step-I confirmation, the animals dosed with 300 mg/kg body weight did not reveal any clinical signs of toxicity or mortality.

In Step-II, the animals dosed with 2000 mg/kg body weight revealed clinical signs like lethargy, soft faeces and recumbency. All the animals were found dead by day 2 observation. No changes were observed in body weight and percent change in body weight with respect to day 1 at 300 mg/kg bw. All the surviving animals revealed physiologically normal increase in the body weight.No gross pathological changes were observed in any of the animals dosed at 300 mg/kg and 2000 mg/kg body weight.

Based on the findings of this study the acute oral LD50 of the test item in rats is considered to be 300 < LD50 < 2000 mg/kg bw.

 

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