Diamminediisocyanatozinc

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

until 1985-09-30

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 Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Noakes, D.N. and Sanderson, D.M. "A method for determining, the dermal toxicity of pesticides", Brit. J. Ind. Ned., 1969

Deviations:

not applicable

Principles of method if other than guideline:

The test item at a concentration of 300 mg/ml in corn oil was applied at a dose level of 2100 mg/kg body weight for 24 hours under occlusion, to the shaved backs of a group of 5 male and 5 female rats and the animals observed for 14 days after treatment.
Treatment was carried out according to the procedure described by Noakes and Sanderson (Noakes, D.N. and Sanderson, D.M. "A method for determining, the dermal toxicity of pesticides", Brit. J. Ind. Ned., 1969)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diamminediisocyanatozinc

EC Number:

401-610-3

EC Name:

Diamminediisocyanatozinc

Cas Number:

122012-52-6

Molecular formula:

C2H6N4O2Zn

IUPAC Name:

copper(2+) bis(carbonylazanide) diamine

Test material form:

solid: particulate/powder

Remarks:

white powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Charles River COBS CD Sprague-Dawley rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd. Manston Road, Margate, Kent
- Age at study initiation: 56-day old male and 76-day old female rats
- Weight at study initiation: On the day of treatment (Day 1) body weights ranged from 277 g to 304 g for males and 229 g to 252 g for females.
- Fasting period before study: no
- Housing: Rats were housed by sex for each dose level in galvanised metal, all mesh cages. For treatment, they were distributed into 2 groups each comprising 5 males and 5 females (a total of 20 animals) using a randomised block design based upon body weight to give groups of similar mean body weight for each sex and similar weight distribution.
- Diet (e.g. ad libitum): free access to Modified Expanded S.Q.C. Rat and Mouse Diet (BP SDS Ltd., Stepfield, Witham, Essex)
- Water (e.g. ad libitum): tap water ad libitum
Contaminants in diet and water were monitored in accordance with the standard operating procedures used within the Toxicology Department and were found to be within acceptable limits.
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature in the animal room ranged from 19°C to 23°C.
- Humidity (%): Relative humidity in the animal room ranged from 45% to 62%.
- Photoperiod (hrs dark / hrs light): There was a 12 hour artificial light photo-period from 7 am to 7 pm.

IN-LIFE DATES: From: 10th July 1985 To: 1st August 1985

Administration / exposure

Type of coverage:

occlusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: An area approximately 6 cm x 10 cm on the back of each rat was shaved on the day prior to dosing.
- Type of wrap if used: The treatment site was covered with aluminium foil which was held in place by an encircling band of waterproof plaster.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 24 hours the plaster and foil were removed, the treated skin washed with soap and water to remove residual test material, rinsed with water and dried.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2100 mg/kg body weight
- Concentration (if solution): The test material was suspended in corn oil at a concentration of 300 mg/ml
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 7 ml/kg
- Concentration (if solution): 300 mg/ml

Duration of exposure:

24 h

Doses:

0, 2100 mg/kg

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were made for 14 days after treatment. Animals were observed frequently on the days of treatment (Day 1) and decontamination (Day 2), at least once each morning and late afternoon on working days thereafter and at least once each other day. Behaviour, as assessed by changes in general activity including co-ordination and reflexes t aggression r excitability and response to sound, was assessed daily by observing interaction of the rats with the observer and with each other. After plaster removal skin treatment sites were examined daily for evidence of skin irritation.
Body weights were recorded immediately prior bo treatment on Day 1, on Day 8, and immediately prior to necropsy on Day 15.
- Necropsy of survivors performed: yes
Surviving animals were killed by CO2 asphyxiation and subjected to gross post mortem examination for external abnormalities and for abnormalities of the thoracic and abdominal viscera.
- Other examinations performed: clinical signs, body weight

Statistics:

DATA ANALYSIS: The significance of differences between body weight gains of control and test groups were estimated by the two sample test of Wilcoxon (Wilcoxon, F., Biometrics Bulletin, 1, 80-83, 1945).

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 100 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 100 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured in either male or female rats.

Clinical signs:

other: No clinical signs were detected and no deaths occured in either male or female rats dosed with the test item. Administration of 2100 mg/kg body weight to the shaved backs of rats resulted in very slight to slight erythema, dry, flaking skin and very sligh

Gross pathology:

One female rat was found to have very slight scabbing and dry skin formation of the treatment site at post mortem examination. No abnormal findings were noted in the other females or in male rats.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

not classified

Conclusions:

Given data allows the conclusion that the test was well performed and that the results are reliable. It is concluded that the test item is low acute toxicity when administered dermally to male and female Sprague-Dawley rats. The study was performed as a limit test (at least alike). A single dose of 2100 mg/kg was administered, which is above the classification limit according to EU GHS.

Executive summary:

The purpose of this study was to establish the acute dermal toxicity of the test item in the rat. The test item at a concentration of 300 mg/ml in corn oil was applied at a dose level of 2100 mg/kg body weight for 24 hours under occlusion, to the shaved backs of a group of 5 male and 5 female rats and the animals observed for 14 days after treatment. A group of 5 male and 5 female control rats were similarly treated, except that vehicle only was applied.

No deaths occured during the study.

No clinical signs or adverse effects on body weight were noted during the 14 day observation period. In rats of both sexes the test item caused irritation comprising slight erythema leading to dry, flaking skin and slight to moderate scab formation.

No abnormality was seen at gost mortem examination apart from very slightly dry skin and scabbing of the treatment site in one female.

In both sexes the acute dermal LD50 value was greater than 2100 mg/kg body weight. It is concluded that the test item is of low acute dermal toxicity to male and female Sprague-Dawley rats, no classification acc. EU GHS is triggered.