Copper(2+), bis[N-[amino(imino-.kappa.N)methyl]urea-.kappa.O]-, nitrate (1:2)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-12-04 to 2013-03-04

Reliability:

1 (reliable without restriction)

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

copper(2+) bis(carbamimidoylurea) dinitrate

EC Number:

800-038-5

Cas Number:

1071838-81-7

Molecular formula:

Cu(C2H6N4O)2 (NO3)2

IUPAC Name:

copper(2+) bis(carbamimidoylurea) dinitrate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CHARLES RIVERS breeder, Domaine des Oncins BP 109, 69592 L’Arbresle Cedex, FRANCE
- Weight at study initiation: 238 g (female) and 246 g (male)
- Fasting period before study: no fasting period
- Housing: polycarbonate cages (Makrolon) containing autoclaved dust-free bedding (sawdust + chips), one rat per cage
- Diet: ad libitum rat/mice Altromin 1320 (Genestil, 1 rue du mesnil, 60420 ROYAUCOURT, FRANCE)
- Water: ad libitum filtered tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 40%-70%
- Air changes (per hr): 15 to 20 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: december 4 2012 To: december 18 2012

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10%
- Type of wrap if used: A 35 cm2-gauze dressing, corresponding to the 10% of the body surface, was placed on a saran-wrap. The test item was applied uniformly as a powder over the gauze dressing area. The test item is put in contact with the skin by applying the gauze to the area stripped of the animal. The animal was wrapped with non-irritating bandage. Care was taken to ensure bandages do not interfere with respiration and to minimize interference with animal’s movements.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, the site of treatment was rinsed and wiped delicately with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 488 ± 12 mg of test item per rat
- For solids, paste formed: no

Duration of exposure:

24 hours

Doses:

rats were treated with 2025 ± 30 mg/kg of body weight and with 2007 ± 10 mg/kg of body weight respectively for the male and the female.

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: on the day of treatment (D0): 30 minutes after the end of application, 2 times during the following 4 hours, and once thereafter. At D1, after removal of the bandage and rinsing of the skin, the site of treatment were observed carefully. Daily from D2 to D14 (once per day).
- Frequency of weighing: on day 0, before treatment and daily from D1 to D14.
- Necropsy of survivors performed: yes
- Necropsy observations: external examination (skin, especially the treatment site, eyes, nose), thoracic area (respiratory tracts, the trachea-bronchial lymph nodes, heart, and esophagus), Abdominal area (liver, spleen, the pancreas, the digestive tract, the adrenal glands, the kidneys, the bladder, the liver and kidneys lymphatic ganglia, the lumbar aortic lymphatic ganglia and female reproductive organs).

Statistics:

no statistical tests

Results and discussion

Preliminary study:

no preliminary study

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no mortality.
All animals were euthanized on day 14, at the end of the study.

Clinical signs:

other: No clinical sign was observed in any of the rats during the 14 days of in-life observations.

Gross pathology:

No macroscopic abnormality was observed in animals except a partial growth back of the fur in 3 males and in the 5 females. In absence of control data, we could not conclude of any interaction between the fur growth and CuGUN application.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Under the experimental conditions of this study, the test item, CuGUN (lot No.40) at a dose of 2,000 mg/kg, did not cause any acute toxicity by contact with skin. Therefore, according to the regulation 1272/2008/EEC, the classification of the test item is "not classified".

Executive summary:

The objective of this study was to evaluate the acute dermal toxicity of the test item Copper Guanylurea Nitrate (CuGUN), in rat. The study design was based on OECD Guideline No. 402.

Acute dermal toxicity was determined by a limit test at one dose level of at least 2,000 mg per kg bodyweight. Because of test item related mortality was not produced, a full study was not considered.

Method

Five males and five nulliparous and non gravid female WISTAR rats were treated with test item. Test item wasapplied as a powder to the shaven skin of the animal, on a surface corresponding to 10% of the body surface. The animal was wrapped with non-irritating bandage.The test item was left in place during 24 hours. At the end of the treatment, the bandage and all dressings were removed delicately and the site of treatment was rinsed and wiped delicately with water, to ensure elimination of potential residual test item.

Each animal was observed at least once a day for mortality, clinical signs and body weight, during 15 days. On completion of the observation period, a necropsy including macroscopic examination was realized on animals after scheduled death.

Results

Rats were treated with 2,026 ± 30 mg/kg and 2,009 ± 10 mg/kg respectively for the male and the female.

No unscheduled deaths, no clinical signs and no macroscopic changes considered to be related to the treatment of CuGUN were observed on rats treated, during the observation period.

Conclusion

Under the experimental conditions of this study, the test item, CuGUN (lot No.40) at a dose of 2,000 mg/kg, did not cause any acute toxicity by contact with skin. Therefore, according to the regulation 1272/2008/EEC, the classification of the test item is "not classified".