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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental study report.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
The objective of this acute oral toxicity study was to assess the toxicological profile of the test item when administered to rats by a single oral gavage.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- IUPAC Name: (2E)-3-phenylprop-2-en-1-ol
- InChI: 1S/C9H10O/c10-8-4-7-9-5-2-1-3-6-9/h1-7,10H,8H2/b7-4+
- Smiles: c1(ccccc1)/C=C/CO
- Molecular formula :C9H10O
- Molecular weight :134.177 g/mol
- Substance type:Organic
- Physical state: Clear colorless liquid
- Purity as per Certificate of Analysis: 98.25%
- Lot No.: 2017101201R-253
- Manufactured date:12 October 2017
- Retest date:11 September 2018
- pH:4.05 at 24°C
- Storage conditions:Ambient (+18 to +36°C)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Geniron Biolabs Pvt. Ltd, Bengaluru
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10 to 11 Weeks
- Weight at study initiation: 176.30 to 193.98 g
- Identification:By rat accession number. Identification of individual rats was by cage card and turmeric colour body markings. The rat accession number was allotted during the course of the study. The temporary body marking during acclimatization period was done with crystal violet.
- Fasting period before study: rats were fasted overnight (16 to 18 hours).
- Housing:Rats were housed individually in standard polysulfone cages (Size: L 425 x B 266 x H 185 mm), with stainless steel top grill
- Diet (e.g. ad libitum): Hypro Rat & Mice pellet feed, ad libitum
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier, ad libitum
- Acclimation period: The animals were acclimatized six days for G1-FTS, eight days for G2-FTS and ten days for G2-STS before treatment. Animals were observed once daily during acclimatization period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 24°C
- Humidity (%): 66 to 68%
- Air changes (per hr): air conditioned with adequate fresh air supply (12.4 to 13.0 air changes/hour).
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle.

IN-LIFE DATES: From: 18 April 2018 To: 28 August 2018

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DOSAGE PREPARATION (if unusual): Undiluted test item as supplied by the sponsor was administered based on the density of the test item i.e., 1.01 g/cm3 at 27°C (as per TIDS) and the
dose volume was 1.98 and 0.30 mL/kg body weight to attain the doses of 2000 and 300 mg/kg body weight as a single oral gavage.
Doses:
G1 (FTS) - 2000 mg/kg
G2 (FTS) - 300 mg/kg
G1 (STS) - 300 mg/kg
No. of animals per sex per dose:
G1 (FTS) - 2000 mg/kg - 3
G2 (FTS) - 300 mg/kg - 3
G1 (STS) - 300 mg/kg - 3
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs and pre-terminal deaths - At each step, the animals were observed five times on test day 1 (day of administration) i.e. at 30 minutes and four times at hourly intervals and once daily during days 2 to 15 post administration. Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern. Attention was directed to the observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma and all observed clinical signs were recorded.
Body weights - The body weights were recorded on test day 1 (pre-administration), day 8 (7 days post administration) and day 15 (14 days post administration).
- Necropsy of survivors performed: yes, the rats surviving to the end of the observation period were euthanised by using isoflurane anaesthesia and subjected to detailed necropsy. Gross pathological findings were recorded and reported. Microscopic examination was not carried out as no gross pathological changes were observed.
Statistics:
not specified

Results and discussion

Preliminary study:
not specified
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
At 2000 mg/kg body weight (G1-FTS) one rat died at 4 hours post dose and the other rat was found dead on day 2.
At G2 - [300 mg/kg body weight - Treatment (FTS & STS)]: There was no mortality.
Clinical signs:
G1 - [2000 mg/kg body weight - Treatment (FTS)]: Clinical signs of recumbency and ataxia were observed in two rats at 30 minutes to 4 hours.
G2 - [300 mg/kg body weight - Treatment (FTS & STS)]: There were no clinical signs observed.
Body weight:
G1 - [2000 mg/kg body weight - Treatment (FTS and STS)]: The dead rats had lost body weight and the surviving rat gained bodyweight throughout the observation period.
G1 - [300 mg/kg body weight - Treatment (FTS and STS)]: All the rats gained bodyweight throughout the observation period.
Gross pathology:
There were no gross pathological changes at necropsy.
Other findings:
not specified

Any other information on results incl. tables

TABLE 1.      Body weight, body weight change and pre-terminal deaths

Group and

Dose

(mg/kg

body weight)

Rat

No.

Sex

Body weight (g)

Day of Death

 (Time of Death)

No. dead/

 No. tested

Pre-terminal deaths

(%)

Initial

(Day 1)

8thday

Weight change

(day 8 – Initial)

15thday

Weight change          

(day 15 – Initial)

At Death

G1

(FTS)

2000

 

Rm9115

F

193.98

-

-

-

-

186.75

2 (8.55 AM)

2/3

66.66

Rm9116

F

182.88

-

-

-

-

177.78

1 (2.38 PM)

Rm9117

F

189.56

216.22

26.66

220.87

31.31

-

-

G2

(FTS)

300

 

Rm9118

F

190.53

197.13

6.6

199.87

9.34

-

-

0/3

0

Rm9119

F

187.80

191.75

3.95

198.35

10.55

-

-

Rm9120

F

189.20

198.65

9.45

207.10

17.9

-

-

G2

(STS)

300

 

Rm9121

F

181.96

203.94

21.98

207.53

25.57

-

-

0/3

0

Rm9122

F

176.30

198.66

22.36

202.16

25.86

-

-

Rm9123

F

186.62

188.08

1.46

191.57

4.95

-

-

F: Female        FTS: First Treatment Step            STS: Second Treatment Step             - : Nil         

 

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results of the present study, The LD50 of the given test chemical is 2000 mg/kg. Thus, the test item is classified “Category 4” (300 mg/kg < Acute Toxicity Estimates ≤ 2000 mg/kg) as per Globally Harmonized Classification system of Annex 2d of the Guideline, OECD 423 as there was two mortalities observed at 2000 mg/kg body weight.
Executive summary:

The acute oral toxicity study was conducted to assess the toxicological profile of the test chemical in Wistar rats.

Undiluted test chemical was administered based on the density of the test item i.e., 1.01 g/cm3 at 27°C (as per TIDS) and the dose volume was 1.98 and 0.30 mL/kg to attain the doses of 2000 and 300 mg/kg body weight respectively.

The test item was administered as a single oral gavage to overnight fasted (16 to 18 hours) three female rats (G1-FTS) at the dose of 2000 mg/kg body weight. Clinical signs of Recumbency and ataxia were observed in two rats at 30 minutes to 4 hours, one rat died at 4 hours post dose and the other rat was found dead on day 2. The third rat was normal from day one till end of observation.

Hence as per Annex 2d, three female rats were tested at the next lower dose of 300 mg/kg body weight (G2-FTS). There were no clinical signs and there was no pre-terminal deaths observed. As per annex 2d of the guideline the treatment was continued with three additional rats at the same dose of 300 mg/kg bodyweight (0.30 mL/kg body weight) – G2-STS. There were no clinical signs and there was no pre-terminal deaths observed, as per the scheme – the Annex 2d of the guideline OECD 423, the dosing was stopped.

The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded prior to dosing on day 1 and again on days 8 and 15. Necropsy was performed for all the rats at termination. All survived rats gained weight during experimental period. There were no gross pathological changes at necropsy.

Based on the results of the present study, The LD50 of the given test chemical is 2000 mg/kg. Thus, the test item is classified “Category 4” (300 mg/kg < Acute Toxicity Estimates ≤ 2000 mg/kg) as per Globally Harmonized Classification system of Annex 2d of the Guideline, OECD 423 as there was two mortalities observed at 2000 mg/kg body weight.