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

Endpoint summary

Description of key information

The oral LD50 was determined to be >2000 mg/kg bw.

The dermal LD50 was determined to be >2500 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Remarks:

RCC Ltd. Toxicology Division, CH-4452 Itingen/Switzerland

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Name of the test material: JODOSEPT L- Batch No. ZK 1055/175-2- ZHT no: 98/429-1- Storage: In the original container at room temperature, away from direct sunlight

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wölferstrasse 4, CH-4414 Füllinsdorf/Switzerland- Age at study initiation: males 8 weeks, females 10 weeks- Weight at study initiation: males 209.5 – 220.5 g, females 167.9 – 182.8 g- Fasting period before study: overnight prior to intubation (approx. 17 h)- Housing: in groups of three in Makrolon type-4 cages with standard softwood bedding (“Lignocel”, Schill AG, CH-4132 Muttenz)- Diet: Pelleted standard Kliba 3433, batch no. 28/98, rat maintenance diet (Kliba Mühlen AG, CH-4301 Kaiseraugst) available ad libitum- Water: community tap water from Itingen, ad libitum ENVIRONMENTAL CONDITIONS - Temperature (°C): 22 ± 3 - Humidity (%): 40 - 70 - Air changes (per hr): 10 - 15 - Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

bi-distilled

Details on oral exposure:

VEHICLE - Concentration in vehicle: 20% (w/v) - Amount of vehicle (if gavage): 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days- Frequency of observations and check for viability: four times during test day 1 and once daily for surviving animals during days 2-15.- Frequency of weighing: On test day 1 (pre-administration), 8 and 15 for surviving animals.- Necropsy of survivors performed: yes- Other examinations performed: clinical signs were checked once daily.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured during the study.

Clinical signs:

No clinical signs were observed during the study period.

Body weight:

The body weight of the animals was within the range of physiological variability known for rats of this strain and age.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

Ten Sprague-Dawley rats per sex were exposed to 2500 mg/kg bw of the test substance for 24 hours. The substance was applied to the dorsal shaved skin. After an observation period of 14 days animals were necropsied.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of the test material: PVP-Jod CE 5041- Purity: 92%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: WIGA, Sulzfeld- Weight at study initiation: mean males 137 g, mean females 126 g- Diet: ad libitum, Altromin R (Altromin GmbH, Lage/Lippe)- Water: ad libitum

Type of coverage:

not specified

Vehicle:

water

Details on dermal exposure:

TEST SITE - Area of exposure: 50 cm2 shaved dorsal skin TEST MATERIAL- Concentration (if solution): 50%

Duration of exposure:

24 hours

Doses:

2500 mg/kg as 50% aq. solution

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days - Necropsy of survivors performed: yes- Other examinations performed: clinical signs and local irritation

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

No clinical signs were observed.

Gross pathology:

The investigation revealed no pathological abnormalities.

Other findings:

No local signs of irritation were observed.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 500 mg/kg bw

Additional information

Acute oral toxicity

There are seven acute toxicity studies available, which are all performed with rats.

In a GLP compliant study (1999), performed according to OECD guideline 423, three Wistar rats per sex were exposed to the test substance via oral gavage. The animals were exposed to 2000 mg/kg bw dissolved in water. After an observation period of 14 days animals were necropsied. No mortality was observed. No clinical signs or macroscopic findings during necropsy were observed. The body weight of the animals was within the range of physiological variability. The LD50 was determined to be >2000 mg/kg bw.

In a second study (1977) ten Sprague-Dawley rats per sex per dose were exposed to the test substance via oral gavage. Animals were exposed to 3830, 4640, 5620 or 6810 mg/kg bw dissolved in water. After an observation period of 14 days animals were necropsied. Diarrhea, dyspnea, apathy, brown colored feces and urine, a poor general state, staggering, and a spastic gait were observed. Upon necropsy in the animals that died acute dilatation and congestive hyperemia of the heart was observed. Liver consisted of broadened peripheral lobules, was general yellowish discolored and of soft consistence indicating degeneration. Also atonic bowels, containing diarrhea were observed. No gross pathology effects were observed in the sacrificed animals. The LD50 was determined to be 6800, 4600 - 5600, and 5990 mg/kg bw, for males, females and males/females, respectively.

In a third study (1977) ten Sprague-Dawley rats per sex per dose were exposed to the test substance via oral gavage. Animals were exposed to 4640, 5620, 6810, 8250 or 10000 mg/kg bw dissolved in water. After an observation period of 14 days animals were necropsied. Symptoms observed included dyspnea, apathy, diarrhea, tumbling, spastic gait, red discoloration of the skin, slight exsiccation and partly poor general state. In animals that died during the experiment diffuse redness of the glandular stomach, diarrhetic contents in the bowel, acute dilatation and congestive hyperemia of the heart, broadened peripherical lobules and grey discoloration of the liver, and sometimes hydrothorax were observed upon necropsy. No pathological abnormalities were observed in the sacrificed animals. The LD50 was determined to be 7220, 6970, and 7090 mg/kg bw for males, females, and males/females, respectively.

In a fourth study (1977) ten Sprague-Dawley rats per sex per dose were exposed to the test substance via oral gavage. Animals were exposed to 3160, 3830, 4640, 5620, 6810 mg/kg bw dissolved in water. After an observation period of 14 days animals were necropsied. Symptoms observed included dyspnea, diarrhea and brownish feces, increasing apathy and tumbling, convulsions, brownish urine, abdominal side position and exsiccation. In animals that died pathological investigation showed acute dilatation and congestive hyperemia of the heart, broadened peripherical lobules and grey discoloration of the liver that became soft (indicating degeneration), ulceration of the stomach, and bloody and diarrhetic contents of the bowel. No pathological abnormalities were observed upon necropsy of the sacrificed animals. The LD50 was determined to be 4930, 4070, and 4470 mg/kg bw for males, females, and males/females, respectively.

In a fifth study (1985) five Wistar rats per sex per dose were exposed to the test substance via oral gavage. Animals were exposed to 2610, 3830 or 5000 mg/kg bw dissolved in olive oil. After an observation period of 14 days animals were necropsied. One male and one female of the highest dose group died. No mortality observed in any of the other tested groups. Clinical symptoms were observed in highest dose group and included dyspnea, apathy, staggering, piloerection and a poor general state (symptom-free after 2 days). No abnormalities were detected upon necropsy in the sacrificed animals and in the female that died during the study. Diagnosis was not possible for the male that died because of autolysis. The LD50 was determined to be >5000 mg/kg bw for both males and females.

In the sixth study (1979) Sprague-Dawley rats were exposed to the test substances via oral gavage. Ten males per dose were exposed to 4680 or 6810 mg/kg bw. Ten females per dose were exposed to 3160, 4640 or 6810 mg/kg bw, and an additional 5 females were exposed to 1000 mg/kg bw. Animals were observed for 14 days. Ruffled fur, incoordination and tremor observed in animals exposed to 6810 mg/kg bw. The LD50 was determined to be 5695.37 and >6810 mg/kg bw for females and males, respectively.

In the seventh study (1979) ten male Wistar rats per dose were exposed to the test substance via oral gavage. After an observation period of 14 days animals were necropsied. Light, moderate or strong sedation and a ruffled fur were observed. Strong gas accumulations were observed in the stomach and intestinal tract, in animals that died and sacrificed animals. Additionally, intestinal inflammation was observed in animals exposed to high concentrations. The LD50 was determined to be 6420 mg/kg bw.

Acute dermal toxicity

Ten Sprague-Dawley rats per sex were exposed to 2500 mg/kg bw of the test substance for 24 hours. The substance was applied to the dorsal shaved skin. After an observation period of 14 days animals were necropsied. No mortality was observed. No clinical signs or pathological abnormalities upon necropsy were observed. The LD50 was determined to be >2500 mg/kg bw for both males and females.

Justification for classification or non-classification

As the oral LD50 was determined to be >2000 mg/kg bw and the dermal LD50 was determined to be >2500 mg/kg bw, classification for oral and dermal acute toxicity is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.

Based on the available information classification for acute inhalation toxicity is not possible in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.