Sorbitan monostearate, ethoxylated

Acute Toxicity: dermal

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

Test material information

Constituent 1

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.