2'-acetonaphthone

Acute Toxicity: oral

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

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

Test material information

Constituent 1

Reference substance name:

2'-acetonaphthone

EC Number:

202-216-2

EC Name:

2'-acetonaphthone

Cas Number:

93-08-3

Molecular formula:

C12H10O

IUPAC Name:

1-(naphthalen-2-yl)ethan-1-one

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 or test system 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: 10 mL/kg body weight

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:

other: G1/Step-1 to G6/Step-6: There were no clinical sings and pre-terminal deaths.

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 median lethal dose 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".