Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
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 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 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The objective of this acute dermal toxicity study was to assess the toxicological profile of the test item on application as a single semi-occlusive dermal application to rats.
GLP compliance:
yes
Test type:
fixed dose 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 10 weeks
- Weight at study initiation: 200.06 to 238.66 g
- Fasting period before study:
- Housing: Animals 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
enrichment objects 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): Hypro Rat & Mice pellet feed, manufactured by Krishna Valley Agro Tech, was provided to animals.
- 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 , India, was provided to animals in polycarbonate bottles with stainless steel sipper tubes
- Acclimation period: After physical examination for good health and suitability for experiment, the rats were acclimatized for seven days for G1DRF, eleven days for G2DRF, fifteen days for G3DRF, eighteen days for G3 Main group before treatment under standard laboratory conditions. Animals were observed once daily during acclimatization period. Females were nulliparous and non-pregnant

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 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:31.08.2018-02.10.2018

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: Milli-Q water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsolateral thoracic surface of the skin
- % coverage: 10 %
- Type of wrap if used: adhesive tape and cotton gauge

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with deionized water and wiped
dry using clean towel
- Time after start of exposure:24 hrs

TEST MATERIAL
- Amount(s) applied :200, 1000 and 2000 mg/kg bw
- Concentration (if solution):
- Constant volume or concentration used: no
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit):10 mg/l
Duration of exposure:
24 hours
Doses:
G1: 200 mg/kg bw
G2: 1000 mg/kg bw
G3: 2000 mg/kg bw
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:The animals were observed for clinical signs and pre-terminal deaths (mortality) once during first 30 minutes after application, and at hourly intervals for 6 hours after application on the day of treatment (day 1) and once daily during Days 2 to 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:treatment site was observed 24, 48 and 72 hours after removal of test chemical using the Draize criteria (Refer Annexure 4 of this report). All rats were observed for 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 observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Statistics:
Not specified

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
No mortality observed
Mortality:
No mortality observed
Clinical signs:
There were no clinical signs and pre-terminal deaths (mortality) observed during the study. There were no skin reactions at the site of application at 24, 48 and 72 hours after test patch removal (as per draize method).
Body weight:
All rats gained body weight throughout the observation period
Gross pathology:
No abnormality was detected at necropsy

Any other information on results incl. tables

Table 3: Individual body weight, body weight changes and pre-terminal deaths

Group and Dose

(mg/kg body weight)

Rat No.

Sex

Body weight (g)

Pre-terminal deaths

Initial deaths

(Day 1 - at

treatment)

8thday

Weight change

(day 8 – Initial)

15thday

Weight change

(day 15 – Initial)

G1and200DRF

Rw991

F

238.66

243.39

4.73

246.84

8.18

0

G2and1000DRF

Rw992

F

209.41

213.09

3.68

222.64

13.23

0

G3and2000DRF

Rw993

F

207.43

210.56

3.13

215.41

7.98

0

G3and2000Mainstudy

Rw994

F

201.54

204.86

3.32

209.47

7.93

0

Rw995

F

200.06

202.45

2.39

205.79

5.73

0

DRF: Dose Range Finding    F: Female

Table 4: Individual test item application, clinical signs, skin reaction and necropsy findings

Dose range finding study

 

Group &

Dose

(mg/kg

body weight)

Date and time

of application

Rat

Number

Sex

Initial

Bwt

(g)

Quantity

(mg)

applied

Observation and skin reaction

Days

1

2

3

4

5

30 min

1h

2h

3h

4h

5h

6h

*

Er@

Ed@

*

Er@

Ed@

*

Er@

Ed@

G1 and 200

7 September

2018

and

11.07 AM

Rw991

F

238.66

47.73

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

 

 

Group & Dose

(mg/kg

body weight)

Animal

Number

Sex

Observation

Necropsy findings

Days

6

7

8

9

10

11

12

13

14

15

G1 and 200

Rw991

F

N

N

N

N

N

N

N

N

N

N

NAD

 

 

Table 5:Dose range finding study

 

Group &

Dose

(mg/kg

body weight)

Date and time

of application

Rat

Number

Sex

Initial

Bwt

(g)

Quantity

(mg)

applied

Observation and skin reaction

Days

1

2

3

4

5

30 min

1h

2h

3h

4h

5h

6h

*

Er@

Ed@

*

Er@

Ed@

*

Er@

Ed@

G2 and 1000

11 September

2018

and

11.54 AM

Rw992

F

209.41

209

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

 

 

Group & Dose

(mg/kg

body weight)

Animal

Number

Sex

Observation

Necropsy findings

Days

6

7

8

9

10

11

12

13

14

15

G2 and 1000

Rw992

F

N

N

N

N

N

N

N

N

N

N

NAD

 

 Table 6:Dose range finding study

 

Group &

Dose

(mg/kg

body weight)

Date and time

of application

Rat

Number

Sex

Initial

Bwt

(g)

Quantity

(mg)

applied

Observation and skin reaction

Days

1

2

3

4

5

30 min

1h

2h

3h

4h

5h

6h

*

Er@

Ed@

*

Er@

Ed@

*

Er@

Ed@

G3 and 2000

14 September

2018

and

11.18 AM

Rw993

F

207.43

415

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

 

 

Group & Dose

(mg/kg

body weight)

Animal

Number

Sex

Observation

Necropsy findings

Days

6

7

8

9

10

11

12

13

14

15

G3 and 2000

Rw993

F

N

N

N

N

N

N

N

N

N

N

NAD

 

 

Table 7:Main study

 

Group &

Dose

(mg/kg

body weight)

Date and time

of application

Rat

Number

Sex

Initial

Bwt

(g)

Quantity

(mg)

applied

Observation and skin reaction

Days

1

2

3

4

5

30 min

1h

2h

3h

4h

5h

6h

*

Er@

Ed@

*

Er@

Ed@

*

Er@

Ed@

G3 and 2000

18 September

2018

and

10.1 AM and 10.4 AM

Rw994

F

201.54

403

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

Rw995

F

200.06

400

N

N

N

N

N

N

N

N

N

0

0

N

0

0

N

0

0

 

 

Group & Dose

(mg/kg

body weight)

Animal

Number

Sex

Observation

Necropsy findings

Days

6

7

8

9

10

11

12

13

14

15

G3 and 2000

Rw994

F

N

N

N

N

N

N

N

N

N

N

NAD

 

Rw995

F

N

N

N

N

N

N

N

N

N

N

NAD

F: Female

N: Normal

h: hour

min: minutes

NAD: No abnormality detected

Er: Erythema

Ed: Edema Score

0: No Erythema / Edema

*: Clinical signs; @: Skin scoring as per Draize method (approximately 24, 48 and 72 hours) after test patch removal

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
Based on the present study results, the acute dermal LD50 of test chemical is more than 2000 mg/kg body weight in female Wistar rats.
Executive summary:

The acute dermal toxicity study was conducted to assess the toxicological profile of the test item as per OECD Guideline 402 (Acute Dermal Toxicity) in Wistar rats.

The test item at the dose of 200, 1000 and 2000 mg/kg body weight was transferred on to the cotton gauze and applied directly (semi-occlusive) to the clipped skin of the animal to cover about 10% of the body surface of the rat It was secured in position by adhesive tape wound around the torso. The test item contact period with the skin was for 24 hours. There were no clinical signs of toxicity and pre-terminal deaths.

All the rats were observed for clinical signs of toxicity and mortality for 14 days post application. In addition, the treatment site was observed for skin reactions at 24, 48 and 72 hours after removal of test item using the Draize criteria. There were no clinical signs of toxicity and mortality observed. There was no skin reaction observed at test item applied area. Body weight was measured on days 1, 8 and 15 and all rats gained weight during experimental period. At the end of observation period, all surviving animals were euthanized and subjected to necropsy. There were no abnormalities detected at the 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 dermal toxicity. CLP criteria "Not Classified".