Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

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 study repport

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 425 (Acute Oral Toxicity: Up-and-Down Procedure)
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:
up-and-down procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
IUPAC name: 1-(2-naphthalenyl)-ethanone
Smiles: c12c(ccc(c1)C(C)=O)cccc2
InChI
1S/C12H10O/c1-9(13)11-7-6-10-4-2-3-5-12(10)8-11/h2-8H,1H3

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Invivo Biosciences, Bengaluru
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 11 Weeks
- Weight at study initiation: 199.46 g to 224.12 g
- Fasting period before study: overnight fasted (16 to 18 hours)
- Housing: Rats were housed individually in standard polysulfone cages
(Size: approximately L 425 x B 266 x H 185 mm), with stainless steel top
grill having facilities for pelleted food and drinking water in polycarbonate
bottle. Additionally, polycarbonate rat huts were placed inside the cage as an
enrichment object and were changed along with the cage at least once a week.
Bedding: steam sterilized corn cob was used and changed at least once a
week along with the cage.
- Diet (e.g. ad libitum): Rat & Mice pellet feed, manufactured by Krishna Valley Agro Tech LLP
- 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 manufactured by
Eureka Forbes Ltd, Mumbai
- Acclimation period: After physical examination for good health and
suitability for experiment, the animals were
acclimatized six to twenty two days prior to
treatment. Animals were observed once daily during
acclimatization period. Females were nulliparous
and non-pregnant.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 64 to 66%,
- Air changes (per hr): 13.2-13.8 air changes/hour.
- Photoperiod (hrs dark / hrs light): 12 hours light and
12 hours dark cycle.

IN-LIFE DATES: From: To:31.08.2018 to 06.10.2018

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% w/v Sodium carboxy methyl cellulose in Milli-Q water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 550, 730, 970, 1290,1750 and 2300 mg/kg
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Based on solubility test, the test item forms a suspension in 0.5% sodium
carboxy methyl cellulose (NaCMC) in Milli-Q water and used to prepare the
dose formulations.
- Lot/batch no. (if required): SLBR1692V

MAXIMUM DOSE VOLUME APPLIED: 2300 mg/kg

DOSAGE PREPARATION (if unusual):A required quantity (g) of test item was weighed in an aluminum foil and transferred into clean mortar and gently triturated using pestle to obtain fine powder. Small volume of vehicle was added gradually to the mortar with continuous trituration until a uniform suspension was obtained. The mixture was quantitatively transferred to a measuring cylinder. Further, a small volume of vehicle was added to the mortar and rinsed with the vehicle, all the rinsing was quantitatively transferred into the measuring cylinder. The final volume was made up to the mark with vehicle to get the desired test item concentration (mg/mL). The prepared dose formulation was transferred to the dedicated labeled beaker. Preparation were made prior to dosing.Homogeneity of the test item in the vehicle was maintained during treatment by constant stirring using a magnetic stirrer.
Doses:
G1A/ 1-550 mg/kg
G2/2- 730 mg/kg
G3/3- 970 mg/kg
G4/4- 1290 mg/kg
G5/5- 1750 mg/kg
G6/6- 2300 mg/kg
No. of animals per sex per dose:
1 female per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Clinical signs: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
The rats surviving to the end of the observation period were euthanized 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.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 300 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
No mortality observed
Mortality:
No mortality observed
Clinical signs:
G1/Step-1 to G6/Step-6: There were no clinical sings and pre-terminal
deaths.
Body weight:
G1/Step-1 to G6/Step-6: The body weights of all the rats increased
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 3:Body weight, body weight change and pre-terminal deaths

 

Group/Step and Dose (mg/kg

body weight)

Rat No.

Sex

Body weight (g)

Day of Death(Time of

Death)

No. dead/

No.

tested

Preterminal deaths (%)

 

Initial

(Day 1)

8th day

Weight

change

(day 8 –

Initial)

15th day

 

Weight

change

(day 15

– Initial)

At Death

G1/Step 1/550

Rw979

F

221.37

225.61

4.24

230.26

8.89

NA

NA

NIL

-

G1A/Step 1/550

Rw980

F

224.12

226.76

2.64

231.79

7.67

NA

NA

NIL

-

G2/Step 2/730

Rw981

F

210.84

213.26

2.42

221.12

10.28

NA

NA

NIL

-

G3/Step 3/970

Rw982

F

209.16

214.03

4.87

220.24

11.08

NA

NA

NIL

-

G4/Step 4/1290

Rw983

F

201.90

214.17

12.27

219.38

17.48

NA

NA

NIL

-

G5/Step 5/1750

Rw984

F

206.64

210.32

3.68

214.96

8.32

NA

NA

NIL

-

G6/Step 6/2300

Rw985

F

199.46

203.61

4.15

208.52

9.06

NA

NA

NIL

-

F: Female NA: Not Applicable mg: milligram kg: kilogram g: gram

Note: G1/Step 1 was not considered for results and assessment of toxicity as the food was provided before dosing

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
Based on the results of the present study, the LD50 for test chemical is greater than 2000 mg/kg body weight
Executive summary:

The acute oral toxicity study was conducted to assess the toxicological profile of the test item as per OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure) in Wistar rats.

The dose formulation was prepared by using Milli-Q water and administered as a single oral gavage to overnight fasted (16 to 18 hours) female rats at each step. There were no clinical signs of toxicity and pre-terminal deaths.

The stopping criteria met as 3 consecutive animals survive at the upper bound. Hence, the further dosing was stopped as per AOT 425 Stat program result (version: 1.0). There were no clinical signs of toxicity and pre-terminal deaths.

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 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 value of the given test chemical is >2000 mg/kg bw. Thus, the test item is not classified for acute oral toxicity. CLP criteria "Not Classified".