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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
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:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Acute dermal toxicity of test chemical in Wistar Albino rats
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Sorbitan monostearate, ethoxylated
Cas Number:
9005-67-8
Molecular formula:
C64H126O26
IUPAC Name:
Sorbitan monostearate, ethoxylated
Test material form:
solid
Details on test material:
IUPAC name: Sorbitan monostearate, ethoxylated
Smiles: CCCCCCCCCCCCCCCCCC(=O)OCCOC[C@H]([C@@H]1[C@H]([C@@H](CO1)OCCO)OCCO)OCCO
InChI: 1S/C32H62O10/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-30(36)40-25-24-37-26-28(38-21-18-33)32-31(41-23-20-35)29(27-42-32)39-22-19-34/h28-29,31-35H,2-27H2,1H3/t28-,29-,31+,32-/m1/s1

Test animals

Species:
rat
Strain:
other: Wistar albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Institute for Industrial Research and Toxicology
Ghaziabad
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 180±40 g
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25oC
- Humidity (%): humidity 40-
60%
- Air changes (per hr): Air conditioned rooms with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial
fluorescent light and 12 hours dark


IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: Distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure: Back skin
- % coverage: 10%
- Type of wrap if used: Impervious dressing secured with adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washing done with lukewarm water
- Time after start of exposure:24 hrs

TEST MATERIAL
- Amount(s) applied : 2000 mg/kg bw:
- Constant volume or concentration used: yes
- For solids, paste formed: yes
Duration of exposure:
24 hrs
Doses:
Group-I 2000 mg/kg b. wt : limit test
Group-II 2000 mg/kg b. wt: Confirmatory test
No. of animals per sex per dose:
10(5/sex)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:all the animals was observed weekly on day 0 (pre
treatment), 7th and 14th (post treatment).
- Necropsy of survivors performed: yes
- Other examinations performed:
clinical signs:The treated animals were closely observed for clinical signs of intoxication, first
4 hours and thereafter for every 1 hrs interval for 24 hrs after dosing and twice
a day for 14 days
body weight:The body weight of all the animals was observed weekly on day 0 (pre
treatment), 7th and 14th (post treatment).
histopathology:Necropsy was carried out on all the animals that died during the study or
surviving animals were sacrificed at the end of the study to observe any gross
pathological changes.
Statistics:
not specified

Results and discussion

Effect levels
Key result
Sex:
male/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 was recorded in Wistar albino rats after administration of test compound at the dose level of 2000 mg/kg b.wt. throughout the observation period of 14 days
Clinical signs:
other: Wistar albino rats treated with the test compound at the dose level of 2000 mg/kg b.wt. did not elicit any clinical sign of toxicity throughout the observation period of 14 days.
Gross pathology:
No gross pathological changes obsered during necropsy of the test animal.
Other findings:
No abnormality observed

Any other information on results incl. tables

TABLE 1:SUMMARY OF BODY WEIGHT (GM)

Group

Animal ID

Day 0

Day 7

%

Gain/loss

Day 14

%

Gain/loss

Group-I

2000 mg/kg bw

201315-1

200.7

205.02

2.12

213.21

6.20

 

201315-2

199.36

204.98

2.81

212.05

6.36

 

201315-3

182.13

191.8

5.30

202.3

11.07

 

201315-4

204.9

209.6

2.29

217.5

6.14

 

201315-5

202.2

208.4

3.06

215.6

6.62

 

201315-6

201.4

206.2

2.38

211.4

4.96

 

201315-7

190.8

197.2

3.35

212.3

11.2

 

201315-8

204.9

209.6

2.29

217.5

6.14

 

201315-9

202.2

208.4

3.06

215.6

6.62

 

201315-10

201.39

206.56

2.56

215.89

7.19

Group-II

2000 mg/kg bw

201315-11

202.89

207.25

2.14

215.99

6.45

 

201315-12

195.34

201.00

2.98

208.99

6.98

 

201315-13

200.56

205.66

.54

213.45

6.42

 

201315-14

199.86

204.52

2.33

212.71

6.42

 

201315-15

203.58

207.81

2.07

215.27

5.74

 

201315-16

201.69

206.54

2.40

214.63

6.41

 

201315-17

202.84

208.11

2.59

215.69

6.33

 

201315-18

199.64

205.43

2.95

213.73

7.05

 

201315-19

203.64

207.39

1.84

216.57

6.34

 

201315-20

200.56

205.66

2.54

213.45

6.42

TABLE 2: CLINICAL SIGNS AND MORTALITY

Group-I Limit test     2000 mg/kg

Parameters

Incidence of clinical signs observed after dosing on

Mortality

Day 0

 

DAY

Min

Hour

 

30

1

2

4

6

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total

%

Mortality (total)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/10

0

Clinical signs-local

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Redness

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Pain

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Swelling

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Systemic signs

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

- = OBSERVED AFTER 24 HOURS

0 = NO CLINICAL SIGNS

+ =MILD

++ = MODERATE

+++ =HIGH

++++=SEVERE

TABLE 3:

GROUP :II CONFIRMATORY TEST     Dose: 2000 mg/kg b.wt

Parameters

Incidence of clinical signs observed after dosing on

Mortality

Day 0

 

DAY

Min

Hour

 

30

1

2

4

6

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total

%

Mortality (total)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/10

0

Clinical signs-local

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Redness

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Pain

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Swelling

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Systemic signs

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

- = OBSERVED AFTER 24 HOURS

0 = NO CLINICAL SIGNS

+ =MILD

++ = MODERATE

+++ =HIGH

++++=SEVERE

Table 4 :SUMMARY OF NECROPSY FINDINGS

 

S. NO.

FATE

WISTAR ALBINO RATS

DOSE (mg/kg b.wt)

2000

(limit test)

2000

(confirmatory test)

1.

Terminal ssacrifice

10/10

10/10

2.

Found dead

0/10

0/10

3.

Abnormalities detected

0/10

0/10

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
The LD50 value is reported to be 2000 mg/kg bw.Based on the results obtained from present investigation, it can be concluded that the test compound is non toxic to Wistar albino rats under test condition.
Executive summary:

Acute dermal toxicity test was performed on 10 wistar male and female rats to determine the LD50 value of test chemical. Ten healthy Wistar albino rats of both sex (ranging bw 180±40 gm) were selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test chemical was applied dermally at the dose level of 2000 mg/kg b.wt for each animal. The treated animals were closely observed for clinical signs of intoxication during first four hours of test compound administration. Thereafter, all the animals were observed periodically at one hour interval for 24 hrs and twice daily for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all animals at the termination of the study. Rats were free from any systematic and local clinical signs when observed after 24 hours of patch removal. After 14 days observation no mortality was observed. No body weight change was observed.

Necropsy was conducted at the end of the observation on all the animals (day 15th), did not reveal any significant gross pathological changes related to compound toxicity. Skin- Skin and hair coat was observed wet, All external and internal orifices were observed to be normal.  

The LD50 value is reported to be >2000 mg/kg bw. Based on the results obtained from present investigation, it can be concluded that the test compound is non toxic to Wistar albino rats under test condition.

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