Iodine

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Published literature study, guideline-comparable with limitations: - No positive control used - Sampling time was not at recommended by current OECD guideline - Lack of well documented rationale to confirm toxicity/availability in the target tissue - No data on mitotic index. - Based on a similar mode action, release of iodine (I2), data from the iodine, iodine tincture and PVP-I is considered interchangeable

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

GLP compliance:

no

Type of assay:

mammalian bone marrow chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Povidone-iodene USP

IUPAC Name:

Povidone-iodene USP

Details on test material:

No further details reported.

Test animals

Species:

hamster, Chinese

Strain:

other: Gricetulus griseus

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Thomae Co., Biberach, Federal Republic of Germany
- Age at study initiation: Not reported
- Weight at study initiation: Not reported
- Assigned to test groups randomly: Not reported
- Fasting period before study: Not reported
- Housing: Plastic (polycarbonate) cages
- Diet: Standardized feed (Altromin R supplied by Altromin Co. Lage/Lippe, Federal Republic of Germany or Ssniff H supplied by Intermast GmbH, Boeckum-Hoevel, Federal Republic of Germany), Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 55 ± 5
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Solvent used: water

Duration of treatment / exposure:

Experiment 1: Single intraperitoneal administration (2 different doses: 38.3 or 82.5 mg/kg)
Experiment 2: Five intraperitoneal injections of one dose level 38.3 mg/kg

Frequency of treatment:

In experiment 2, the intraperitoneal injections were administered in a 24-h interval

Post exposure period:

Experiment 1: Animals were sacrificed at 6, 24 and 48 after the single application
Experiment 2: Animals were sacrificed 6 hours after last application

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

38.3 mg/kg bw/day (actual dose received)

Remarks:

Single or five applications

Doses / concentrations 2

Dose / conc.:

82.5 mg/kg bw/day (actual dose received)

Remarks:

Single application

No. of animals per sex per dose:

6 male and 6 female per group

Control animals:

yes, concurrent no treatment

yes, concurrent vehicle

Positive control(s):

No positive control was used

Examinations

Tissues and cell types examined:

Metaphases from bone marrow

Details of tissue and slide preparation:

No further details reported

Evaluation criteria:

Statistical comparison to control

Statistics:

Significant differences were checked using chi-square or U test

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

repeated application caused the animals to show signs of pain lasting for ~1 min.

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

not examined

Any other information on results incl. tables

There was no increase in the percentage of aberrant metaphases when the substance was administered singly (Table 1) or repeatedly (Table 2). The animals tolerated povidone-iodine with no symptoms when administered in a single dose, but repeated application caused the animals show signs of pain lasting for approximately 1 min.

Table 1: Testing povidone-iodine in the bone marrow test on Chinese Hamster with single intraperitoneal injection

Dose	Untreated			10 mL of saline/kg			38.3 mg/kg			82.5 mg/kg
Put to death (h)	6	24	48	6	24	48	6	24	48	6	24	48
No of animals	12	11	12	12	12	12	12	11	12	12	12	12
Analyzed metaphases	1200	1100	1200	1200	1200	1200	1200	1100	1200	1200	1200	1200
Animals with aberrant metaphases	8	8	9	7	9	6	9	8	8	6	9	9
Metaphases with aberrations
Including gaps	16	12	18	11	22	11	18	23	15	12	20	21
Excluding gaps	3	4	2	2	2	2	4	5	2	2	2	5
Gaps (chromatide)	9	8	14	7	15	9	10	15	10	7	12	16
Gaps (isochromatide)	4	0	2	2	5	0	4	3	3	3	6	0
Breaks (chromatide)	0	2	1	1	0	2	2	2	2	1	0	2
Breaks (isochromatide)	0	0	0	0	1	0	0	0	0	0	0	0
Acentric fragments	3	1	1	0	1	0	2	3	0	1	1	3
Multiple aberrations	0	1	0	1	0	0	0	0	0	0	1	0

Table 2: Testing povidone-iodine in the bone marrow test on Chinese Hamster with five intraperitoneal injection

Dose	Untreated	5 x 10 mL of saline/kg	5 x 38.3 mg/kg
No of animals	12	11	11
Analyzed metaphases	1200	1100	1100
Animals with aberrant metaphases	7	8	7
Metaphases with aberrations
Including gaps	10	25	13
Excluding gaps	2	7	2
Gaps (chromatide)	8	17	8
Gaps (isochromatide)	0	1	3
Breaks (chromatide)	1	6	2
Breaks (isochromatide)	0	0	0
Acentric fragments	0	1	0
Multiple aberrations	1	0	0

Applicant's summary and conclusion

Conclusions:

Povidone-iodine USP was tested for genotoxic potential in Chinese Hamsters by the in vivo chromosome aberrations assay in the bone marrow in a study design similar to OECD testing guideline 475. Under testing conditions, povidone-iodine did not induce chromosome aberrations in the bone marrow of Chinese Hamster.

Executive summary:

Povidone-iodine USP was tested for genotoxic potential in Chinese Hamsters by the in vivo chromosome aberrations assay in the bone marrow in a study design similar to OECD testing guideline 475.

To assess this potential, two experiments were carried out. In the first one, male and female hamsters were administered by single peritoneal injection with test compound, distilled water and a third group remained untreated. Animals were sacrificed after 6, 24 and 48 h post administration. In a second experiment, male and female hamsters were injected five times with a daily interval and sacrificed 6 hours after the last application. 100 metaphases per animal were examined for gaps, breaks and fragments.

There was no increase in the percentage of aberrant metaphases when the substance was administered singly or repeatedly. In conclusion, povidone-iodine did not induce chromosome aberrations in the bone marrow of Chinese Hamster, under testing conditions.