Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species:Rat (Rattus norvegicus)Strain:Wistar Sex:Male and FemaleNumber of Animals:10 (Five per sex)Supplier/Source:In-House Bred Health Status:Healthy young adult animals were used for the study. Females were nulliparous and non pregnantBody weight of animals:Male:Minimum: 249 g and Maximum: 276 g (Prior to Treatment) Female:Minimum: 236 g and Maximum: 254 g Acclimatisation :All animals were acclimatized to the test conditions for 6 days prior to administration of the test itemIdentification:During Acclimatization, animals were temporarily marked by permanent marker, on their tails. After acclimatization, the animals were marked bytoe pad micro tattooing and cage cards. Individual cage cards were labelled with study no., study type, test system, group, dose, sex, animal number experimental start and completion date.Randomization :Animals were selected manually. No computer generated randomization program was used.Diet:All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum. Batch No 400010 and 400011.Bedding:All cages were provided with corn cobs Water:Aqua guard filtered tap water was provided ad libitum via drinking bottles. Husbandry:The animals were housed individually in polycarbonate cages.Room Sanitation :The experimental room floor and work tops were swept and mopped with disinfectant solution every day. Cages and water bottle:All the cages and water bottles were changed at least twice every weekTemperature:Minimum: 20.00 °C Maximum: 22.30 °CRelative humidity :Minimum: 49.10% Maximum: 67.30%Light-dark-rhythm:12 hour light and 12 hour darkAir Changes:More than 12 changes per hour

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test item was applied uniformly over clipped dorsal area of rat skin. Individual rat was applied with a volume of test item, calculated based on the density (0.93237) and latest body weight. Test item was held in contact with the skin with a porous gauze dressing (Approx. 10% of body surface area of rat) and non-irritating tape throughout a 24-hour exposure period. It was ensured that the animals cannot ingest the test item.At the end of the exposure period, residual test item was removed by using distilled water
Duration of exposure:
The test item was applied uniformly over clipped dorsal area of rat skin. Individual rat was applied with a volume of test item, calculated based on the density (0.93237) and latest body weight. Test item was held in contact with the skin with a porous gauze dressing (Approx. 10% of body surface area of rat) and non-irritating tape throughout a 24-hour exposure period. It was ensured that the animals cannot ingest the test item. At the end of the exposure period, residual test item was removed by using distilled water. The animals were dosed between 12:06 to 12:13 p.m
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 male & 5 female
Control animals:
yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: not specified
Mortality:
No mortality was observed at limit dose of 2000 mg/kg body weight during the 14 day observation period
Clinical signs:
At 2000 mg/kg, all the animals were observed normal at 1, 2, 3 and 4 hours post dosing. Animal nos. 1, 4, 7, 8 and 9 were observed with erythema on day 1 and scale formation from day 2 to 8 followed by normal clinical sign till day 14. Animal nos. 5 and 6 were observed with erythema on day 1 and scale formation from day 1 to 6 followed by normal clinical sign till day 14. Animal nos. 2, 3 and 10 were observed with erythema on day 1 and scale formation from day 2 to 7 followed by normal clinical sign till day 14.
Body weight:
Decrease in mean body weight was observed on day 7 and increase in mean body weight was observed on day 14 in male rats whereas in female rats decrease in mean body weight was observed on day 7 and 14 when compared to day 0 mean body weight
Gross pathology:
The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality

Any other information on results incl. tables

TABLES

Table 1: Dose Volume, Individual Animal Body Weight (g) andBody Weight Changes(%)

 

Dose:2000 mg/ kg bodyweight                                                                            Density:0.93237

Animal No.

Sex

Dose Volume* (ml)

Body Weight (gram)

Body Weight Change (%)

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

1

Male

0.56

261

257

278

-1.53

6.51

2

0.59

276

275

276

-0.36

0.00

3

0.53

249

248

276

-0.40

10.84

4

0.59

275

269

312

-2.18

13.45

5

0.55

255

257

316

0.78

23.92

6

Female

0.54

254

239

239

-5.91

-5.91

7

0.52

243

229

230

-5.76

-5.35

8

0.54

251

226

236

-9.96

-5.98

9

0.51

236

228

235

-3.39

-0.42

10

0.54

252

241

248

-4.37

-1.59

Keys: * = based on the test item density and day 0 body weight


Table 2: Individual Animal Clinical Signs and Symptoms

 

Dose:2000 mg/kg body weight

 

Animal

No.

Sex

Hour(s) - Day 0

Day

1

2

3

4

1

2

3

4

5

6

7

1

Male

1

1

1

1

65+

147+

147++

147++

147++

147++

147+

2

1

1

1

1

65+

147+

147++

147++

147++

147+

147+

3

1

1

1

1

65+

147+

147++

147++

147++

147+

147+

4

1

1

1

1

65+

147+

147++

147++

147++

147+

147+

5

1

1

1

1

65+

147++

147++

147++

147+

147+

1

6

Female

1

1

1

1

65+

147+

147++

147+

147+

147+

1

7

1

1

1

1

65+

147+

147++

147++

147++

147++

147+

8

1

1

1

1

65+

147+

147++

147++

147++

147++

147+

9

1

1

1

1

65+

147+

147++

147++

147++

147+

147+

10

1

1

1

1

65+

147+

147+

147+

147+

147+

147+

 

Animal

No.

Sex

Day

8

9

10

11

12

13

14

1

Male

147+

1

1

1

1

1

1

2

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

4

147+

1

1

1

1

1

1

5

1

1

1

1

1

1

1

6

Female

1

1

1

1

1

1

1

7

147+

1

1

1

1

1

1

8

147+

1

1

1

1

1

1

9

147+

1

1

1

1

1

1

10

1

1

1

1

1

1

1

Key: 1 = Normal, 65 =Erythema, 147 = Scale, + = Mild (slight), ++ = Moderate


Table 3: Individual Animal Mortality Record

 

Dose:2000 mg/kg body weight

       Animal No.

Sex

Days of Observation (0 to 14)

Morning Observations

Evening Observations

1

Male

No mortality and morbidity

No mortality and morbidity

2

No mortality and morbidity

No mortality and morbidity

3

No mortality and morbidity

No mortality and morbidity

4

No mortality and morbidity

No mortality and morbidity

5

No mortality and morbidity

No mortality and morbidity

6

Female

No mortality and morbidity

No mortality and morbidity

7

No mortality and morbidity

No mortality and morbidity

8

No mortality and morbidity

No mortality and morbidity

9

No mortality and morbidity

No mortality and morbidity

10

No mortality and morbidity

No mortality and morbidity

Table 4:Summaryof Animal Body Weight (g) and Body Weight Changes (%)

 

Dose:2000 mg/kg body weight

Sex

Body Weight (gram)

Body Weight Changes (%)

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

Male

Mean

263.20

261.20

291.60

-0.74

10.95

SD

12.01

10.73

20.51

1.15

8.86

n

5

5

5

5

5

Female

Mean

247.20

232.60

237.60

-5.88

-3.85

SD

7.53

6.88

6.66

2.51

2.64

n

5

5

5

5

5

Keys:SD= Standard deviation, n = Number of animals

Applicant's summary and conclusion

Interpretation of results:
not classified
Conclusions:
The acute dermal median lethal dose of “Reaction mass of Cardanol diene and Cardanol monoene and Cardanol triene  (CAS No. – 37330-39-5)” was > 2000 mg/kg body weight.
Executive summary:

Acute Dermal Toxicity Study of“ Reaction mass of Cardanol diene and Cardanol monoene and Cardanol triene  (CAS No. – 37330-39-5)”in Wistar Rats This study was performed as per OECD No. 402.

Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Ratsfree from injury and irritation of skin were selected for the study. .

At 2000 mg/kg, all the animals were observed normal at 1, 2, 3 and 4 hours post dosing. Animal nos. 1, 4, 7, 8 and 9 were observed with erythema on day 1 and scale formation from day 2 to 8 followed by normal clinical sign till day 14. Animal nos. 5 and 6 were observed with erythema on day 1 and scale formation from day 1 to 6 followed by normal clinical sign till day 14. Animal nos. 2, 3 and 10 were observed with erythema on day 1 and scale formation from day 2 to 7 followed by normal clinical sign till day 14.

The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.

The acute dermal median lethal dose of Reaction mass of Cardanol diene and Cardanol monoene and Cardanol triene  (CAS No. – 37330-39-5)”was> 2000 mg/kg body weight.thus based on above results we can conclude that the test substance Cardanol does not exhibit the acute toxcity (Dermal route) as per CLP criteria set by EU.