Reaction mass of iodine and 2-Pyrrolidinone, 1-ethenyl-, homopolymer

Genetic toxicity: in vivo

Administrative data

Endpoint:

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

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Reference 2

Reference Type:

publication

Title:

Absence of Povidone -Iodine -Induced Mutagenicity in Mice and Hamsters

Author:

Merkle J., Zeller H.,

Year:

1979

Bibliographic source:

J. Pharm. Sc., Vol. 68(1), 100-102, 1979

Materials and methods

Principles of method if other than guideline:

The test substance was tested for mutagenic effects on Chinese hamsters when applied once and five times intraperitoneally, using the bone marrow test (chromosome aberration assay).

GLP compliance:

no

Remarks:

Study pre-dates GLP regulations

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of iodine and 2-Pyrrolidinone, 1-ethenyl-, homopolymer

EC Number:

913-404-5

Molecular formula:

Unspecified

IUPAC Name:

Reaction mass of iodine and 2-Pyrrolidinone, 1-ethenyl-, homopolymer

Details on test material:

- Purity: ≥ 92%- pH: ≥ 1 - ≤ 5 (aqueous preparation)

Specific details on test material used for the study:

- Name of the test substance: PVPJod CE 5o41 - Polyvinylpyrrolidone-Iodine- Purity: 92%, remainder H2O

Test animals

Species:

hamster, Chinese

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS - Source: Tierzuchtinstitut der Universität Zürich und Firma THOMAE, Biberach - Weight at study initiation: 25 to 33 g - Housing: Makrolon cages, Type M 2 - Diet: Standardised pelletted feed SSNIFF-H produced by Intermast GmbH, Bockum-Hovel,; ad libitum - Water: Drinking water from bottles; ad libitum ENVIRONMENTAL CONDITIONS - Temperature (°C): 22 ± 2 - Humidity (%): 55 ± 5 - Air changes (per hr): Air conditioned rooms - Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: Distilled water

Details on exposure:

The test involved 15 groups of six male and six female Chinese hamsters each. This test was used for direct analysis of induced structural and numerical chromosome aberrations in somatic cells. Three groups of animals received a single 38.3 mg/kg (one-quarter LD50) or 82.5 mg/kg (one-half LD50) dose of povidone-iodine or 10 mL of saline solution/kg. Three groups remained untreated. Two other groups received five applications of 38.3 mg of povidone-iodine/kg or five 10 mL/kg applications of saline solution on 5 successive days. Another group of animals remained untreated.

Duration of treatment / exposure:

The animals were sacrificed 6, 24, or 48 hr after the single application or 6 hr after the fifth application

Frequency of treatment:

The animals were treated once or five times (daily) by intraperitoneal application

Post exposure period:

6 to 48 hours

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

38.3 mg/kg bw/day

Remarks:

Single application

Doses / concentrations 2

Dose / conc.:

82.5 mg/kg bw/day

Remarks:

Single application

Doses / concentrations 3

Dose / conc.:

38.3 mg/kg bw/day

Remarks:

Five applications

No. of animals per sex per dose:

6

Control animals:

yes, concurrent no treatment

yes, concurrent vehicle

Examinations

Tissues and cell types examined:

Clinical symptoms: The animals were checked for externally recognizable toxic symptoms after administration of the substance.Mortality: A daily check was made in this respect.Dissection of the animals on completion of testing: On completion of the particular series of tests, the animals were put to death, the femur prepared and the hamsters were examined macroscopically for pathological changes in the internal organs.

Details of tissue and slide preparation:

Preparation of the bone marrow: After the animals were put to death, the femurs were removed, the epiphyses taken out and the diaphyse rinsed with a hypotonic solution (0.56 % KCl) (approximately 2 ml/bone). The suspension was placed in a waterbath at 37 °C for approximately 30 minutes, following which it was centrifuged for 10 minutes at 1000 r.p.m. The liquid on top was extracted by suction and the sediment mixed with a solution of glacial acetic acid and methanol (1 + 2.5). After 5 minutes this fixation solution was replaced by fresh material. The liquid on top was then again extracted by suction and the suspension places on a slide. Preparation of smears and air-drying of the slides in addition to staining of the slides with orcein.

Evaluation criteria:

From each animal, 100 metaphases were counted out and evaluated. Where only individual metaphases were found in the smears, evaluation was not carried out.

Statistics:

Using the figures for the number of aberrant metaphases including gaps and excluding gaps, the chi²-test and the U-test were carried out.The asymptotic U-test according to Mann-Whitney with binding correction according to Walter and, if necessary, the constancy correction according to Yates were used. As a criterion for determining the order, the number or relative occurrence of metaphases was used with the property to be tested per 100 metaphases.

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

After the second administration 38.3 mg, signs of being in pain and assumed a curled-up position

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

other: PVP-Iodine did not result in an increase in the number of aberrant metaphases following single or repeated application. No changes as compared with the control animals were to be seen.

Additional information on results:

Clinical symptoms: Animals which had received one single intraperitoneal administration of PVP-Iodine in dosages of 38.3 or 82.5 mg/kg body weight displayed no clinical toxic symptoms. Hamsters which received five intraperitoneal applications of 38 3 mg PVP-Iodine per kg body weight displayed from the 2nd treatment signs of pain and the posture was crooked . Although these symptoms receded after approximately one minute, they were to be seen following each further application.Mortality: No animal died during the test period.Dissection of the animals on completion of testing: With all animals put to death, it was not possible to detect any pathological changes in the internal organs caused by the administered substance, on macroscopic examination. Killing of the animals 6 hours post application: - Of the examined metaphases of untreated animals, in 16 (1.33 %) displayed aberrations incl. gaps. 3 metaphases (0.25%) aberrations excl. gaps were found. In 1 case a fragment was found, in another case acentric fragments and in a further case a fragment and gap were found. With 8 of the 12 animals examined, aberrant metaphases (incl. gaps) were found.- In the case of hamsters receiving physiological salt solution intraperitoneally, in 11 methaphases aberrations incl. gaps were found (0.92%). Two metaphases (0.17%) displayed other types of aberration. In 1 case break, and in another case multiple aberration were found in a metaphase. Seven of 12 animals displayed metaphases with aberrations incl. gaps.- Following 1 single intraperitoneal application of 38.3 mg PVP-Iodine/kg body weight, in 18 metaphases aberrations incl. gaps were found (1.50 %). In 4 metaphases (0.33%) other aberrations were diagnosed . In one case break, in another case break and gap, and in two cases a fragment was found. Nine of the 12 animals examined displayed metaphases with aberrations including gaps. No difference as compared with the control groups was ascertained.- With the animals receiving 82.5 mg PVP-Iodine/kg body weight applied intraperitoneally, in 12 metaphases aberrations including gaps were found (1.00%). Metaphases with aberrations excluding gaps were seen twice (0.17%). One break and one fragment were found. Six animals displayed metaphases with aberrations including gaps . No difference as compared with the two control groups was ascertained.Killing of the animals 24 hours post application: - With one untreated animal, because of the very few metaphases, evaluation was impossible. Of the 11 animals examined, in 8 animals metaphases with aberrations were found. A total of 12 metaphases (1.09%) displayed aberrations including gaps. Four metaphases (0.36%) displayed other aberrations. In-detail, the following were found : in one case break, one case break and gap, one case a fragment and one case a multiple aberration.- Animals which received one single intraperitoneal application of physiological common salt solution displayed aberrations including gaps in 22 metaphases (1.83%). In two metaphases (0.17%) an isochromatide break was found, and in one case a fragment. Aberrations occurred in metaphases of 9 of the 12 animals used. - Following administration of 38.3 mg PVP-Iodine/kq body weight, only 11 animals could be subjected to analysis. With these 11 animals, 23 metaphases (2.09%) displayed aberrations including gaps, In 5 metaphases (0.45%) there was in one case break, in one case 3 breaks, in one case 2 fragments and in one case a fragment and a gap . Eight of the 11 animals examined displayed metaphases with aberrations.- Following one single intraperitoneal application of 82.5 mg PVP-Iodine/kg body weight, aberrations including gaps were found in 20 metaphases (1.67%) In two metaphases (0.17%) in one case there was an acentric fragment and in one case multiple aberrations. Nine of the 12 animals displayed metaphases with aberrations.- No difference could be found between the test animals using PVP-Iodine and those which were untreated or which received physiological common salt solution.Killing of the animals 48 hours post application: - With the untreated animals aberrations were found in 18 metaphases (1.50% including gaps). In two metaphases (0.17%) one break and one fragment were found. A total of 9 of the 12 animals examined displayed aberrant metaphases. - Following intraperitoneal administration of 10 mL physiological common salt solution, aberrations including gaps were found in 11of the examined, metaphases (0.92%). Two metaphases (0.17%) each displayed one break. Six of the 12 animals examined had metaphases with aberrations. - In the case of animals receiving one single intraperitoneal application of 38.3 mg PVP-Iodine/kg body weight, 15 displayed aberrations (1.25% including gaps). In two metaphases (0.17%) each displayed one break. Eight of the animals examined displayed metaphases with aberrations.- With animals receiving one single intraperitoneal application of 82.5 mg PVP-Iodine/kg body weight, 21 of the metaphases examined (1.75% including gaps) displayed aberrations. In metaphases (0.42%) the following were found: one break, one break and gap, one fragment, one acentric fragment and in one case a fragment and a gap. Nine of the animals examined displayed aberrant metaphases.- No difference was found between the test animals using PVP-Iodine and those which were untreated or which received physiological common salt solution.Killing of the animals 6 hours after the 5th application:- With the untreated animals, aberrations including gaps were found in 10 metaphases (0.83%). Two metaphases (0.17%) displayed in 1 case a break and in one case multiple aberrations. Seven of the animals examined displayed metaphases with aberrations.- Following five intraperitoneal applications of physiological common salt solution, only 11 animals could be examined. These 11 animals had aberrations in 25 metaphases (2.27% including gaps). With 7 metaphases (0.64%) the following were found: four breaks, one break and gap, one break and two gaps, and in one case a fragment. Eight of the 11 animals examined displayed metaphases with aberrations.- Where the animals received five intraperitoneal applications of 38.3 mg PVP-Iodine/kg body weight, aberrations including gaps (1.18%) were found in 13 metaphases. In two metaphases (0.18%), each had one break. Seven of the animals examined displayed aberrant metaphases.- No difference was found between the test animals using PVP-Iodine and those which were untreated or which received physiological common salt solution.Under these test conditions, PVP-Iodine did not result in an increase in the number of aberrant metaphases following single or repeated intraperitoneal application. No changes as compared with the control animals were to be seen, either in the type of aberrations or in the percentual occurrence.