Potassium nitrite

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

The objective of the study was to assess the dermal toxicity of test chemical after single dose application by dermal route in rats and an observation period of 14 days.

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Potassium iodide

EC Number:

231-659-4

EC Name:

Potassium iodide

Cas Number:

7681-11-0

Molecular formula:

IK

IUPAC Name:

potassium iodide

Test material form:

solid

Details on test material:

- Name of test material : Potassium iodide
- Molecular formula : KI
- Molecular weight : 165.998g/mol
- Smiles notation : [K+].[I-]
- InChl : 1S/HI.K/h1H;/q;+1/p-1
- Substance type : Organic
- Physical state : Solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species:Rat (Rattus norvegicus)
Strain:Wistar
Sex:Male and Female
Number 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 pregnant
Body weight of animals:
-Male:Minimum: 273 g and Maximum: 280 g (Prior to Treatment)
-Female:Minimum: 236 g and Maximum: 250 g
Acclimatisation:All animals were acclimatized to the test conditions for 8 days prior to test item application.
Identification:During Acclimatization, animals were marked temporary by permanent marker, on their tails. After acclimatization, the animals were marked by toe 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.
Husbandry ConditionsDiet:All animals were provided conventional laboratory rodent diet 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 week.
Experimental Room Condition:
Temperature:Minimum: 19.60 °C Maximum: 21.40 °C
Relative humidity:Minimum: 47.40% Maximum: 58.60%
Light-dark-rhythm:12:12
Air Changes:More than 12 changes per hour

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Preparation of Application SiteApproximately 24 h prior to treatment, the fur of dorsal area of the trunk (greater than 10% body surface area) of rats was clipped by using clipperTest Item Application ProcedureThe test item was applied uniformly over clipped dorsal area of rat skin. Individual rat was applied with an amount of test item moistened with 0.2 ml distilled water. 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 12:45 to 12:58 p.m.Limit TestFive male and five female wistar rats were treated with test item by a single dermal application at the dose level of 2000 mg/kg body weight.Since no test item related mortality was observed, the study was terminated with limit test only.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 per sex (male and female)-2000 mg/kg bw

Control animals:

not required

Details on study design:

Preparation of Application Site:Approximately 24 h prior to treatment, the fur of dorsal area of the trunk (approximately 10% body surface area) of rats was clipped by using clipper.
Test Item Application Procedure:The test item was applied uniformly over clipped dorsal area of rat skin. Individual rat was applied with an amount of test item, calculated based on the density (1.0898) 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 11:19 to 11:32 a.m.Limit TestFive male and five female wistar rats were treated with test item by a single dermal application at the dose level of 2000 mg/kg body weight.Since no test item related mortality was observed, the study was terminated with limit test only.

Statistics:

No statistical analysis was performed since the study was terminated with limit test

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: At 2000 mg/kg, all the animals were normal throughout the experimental period.

Mortality:

No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period (refer table 3).

Clinical signs:

other: At 2000 mg/kg, all the animals were observed normal throughout the experimental period (refer table 2).

Gross pathology:

The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality (refer table 5).

Any other information on results incl. tables

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

Dose:2000 mg/ kg bodyweight                                                                                                         

Animal No.	Sex	Body Weight (gram)			Body Weight Change (%)
		Day 0	Day 7	Day 14	Day 0-7	Day 0-14
1	Male	277	282	289	1.81	4.33
2		274	295	315	7.66	14.96
3		280	296	319	5.71	13.93
4		273	286	312	4.76	14.29
5		277	292	309	5.42	11.55
6	Female	236	238	241	0.85	2.12
7		241	245	248	1.66	2.90
8		236	238	241	0.85	2.12
9		237	241	242	1.69	2.11
10		250	256	258	2.40	3.20

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	1	1	1	1	1	1	1
2		1	1	1	1	1	1	1	1	1	1	1
3		1	1	1	1	1	1	1	1	1	1	1
4		1	1	1	1	1	1	1	1	1	1	1
5		1	1	1	1	1	1	1	1	1	1	1
6	Female	1	1	1	1	1	1	1	1	1	1	1
7		1	1	1	1	1	1	1	1	1	1	1
8		1	1	1	1	1	1	1	1	1	1	1
9		1	1	1	1	1	1	1	1	1	1	1
10		1	1	1	1	1	1	1	1	1	1	1

 

Animal No.	Sex	Day
		8	9	10	11	12	13	14
1	Male	1	1	1	1	1	1	1
2		1	1	1	1	1	1	1
3		1	1	1	1	1	1	1
4		1	1	1	1	1	1	1
5		1	1	1	1	1	1	1
6	Female	1	1	1	1	1	1	1
7		1	1	1	1	1	1	1
8		1	1	1	1	1	1	1
9		1	1	1	1	1	1	1
10		1	1	1	1	1	1	1

Key: 1 = Normal

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	276.20	290.20	308.80	5.07	11.81
	SD	2.77	6.02	11.67	2.12	4.37
	n	5	5	5	5	5
Female	Mean	240.00	243.60	246.00	1.49	2.49
	SD	5.96	7.50	7.31	0.66	0.52
	n	5	5	5	5	5

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

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Conclusions:

Under the condition of study; acute dermal toxicity dose (LD50) value for given test chemical was considered to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibit acute dermal toxicity i.e it is acutely non toxic to animals.

Executive summary:

Acute Dermal Toxicity Study of test chemicalinWistar Rats 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. Approximately, twenty four hours prior to dermal application of test item, greater than 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment. On test day 0, anamount oftestitem moistened with 0.2 ml distilled water was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area.This porous gauze dressing was covered with a non-irritating tape.After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water.The skin reactions were assessed.The animals were observed daily for mortality and clinical signs, during the acclimatization period and post dosing till the termination. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically.No mortality was observed in any animal till the end of the experimental period.At 2000 mg/kg, all the animals were normal throughout the experimental period.Mean body weight of male and female animals was observed with gain on day 7 and 14 as compared to day 0 The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.

Under the conditions of the study,the acute dermal median lethal dose oftest chemicalwas> 2000 mg/kgbody weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibit acute dermal toxicity i.e it is acutely non toxic to animals.