Diamminediisocyanatozinc

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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 401 (Acute Oral Toxicity)

Deviations:

not applicable

Principles of method if other than guideline:

Groups comprising 5 males and 5 females were dosed with 951, 1347 or 1901 test item/kg body weight. Five male and five female control rats were dosed with vehicle only. Animals were observed for 14 days after treatment.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

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, Margatet 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 254 g to 300 g for males and 217 g to 255 g for females.
- Housing: Rats were housed by sex for each dose level in galvanised metal all mesh cages.
- Diet (e.g. ad libitum): free access to Modified Expanded S.Q.C. Rat and Mouse Diet (3P 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.
For treatment, they were distributed into 4 groups of males and 4 groups of females each comprising 5 animals (a total of 40 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.

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 300 mg/ml
- Amount of vehicle (if gavage): 0.9 - 1.8 ml
Control animals were dosed with corn oil at a dose volume of 6 ml/kg body weight.

Prior to starting the study, the stability of the test item in corn oil was established by Analytical Development Department. There was 98% recovery of the test item after 24 hours at a concentration of 200 mg/ml.
Analysis of four 1 ml aliquots of test suspension taken at random time points during the dosing period showed that the mean content of the test item in the suspension was 102.1% of the expected value. This analysis also showed that the concentration of the test suspension was constant throughout the dosing period.

Doses:

0, 951, 1347, 1901 mg/kg

No. of animals per sex per dose:

5

Control animals:

yes

Remarks:

vehicle only

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 day of treatment (Day 1), 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 coordination and reflexes, aggression, excitability and response to soundv was assessed daily by observing interaction of the rats with the observer and with each other.
Body weights were recorded immediately prior to treatment on Day 1, on Day 8, and immediately prior to terminal necropsy on Day 15.
- Necropsy of survivors performed: yes
Surviving animals f which were killed by CO2 asphyxiation, and those found dead during the study were subjected to gross post mortem examination for external abnormalities and for abnormalities of the thoracic and abdominal viscera.

Statistics:

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). Mortality results were analysed according to Weil (Weil, C.S., Biometrics, 8, 249-263, 1952)

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 127 mg/kg bw

Based on:

test mat.

95% CL:

>= 989 - <= 1 285

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 208 mg/kg bw

Based on:

test mat.

95% CL:

>= 971 - <= 1 503

Effect levels 3

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 052 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 038 - <= 1 067

Mortality:

Deaths occurred between 18 hours and 2 days after treatment in males 9 and between 5 and 22 hours after treatment in females.

Clinical signs:

other: No symptoms were seen in control animals. The principal symptoms seen in both sexes treated with the test item included reduced activity and muscle tone, salivation, facial and urogenital soiling, hunched posture and piloerection. Also seen were urinary i

Gross pathology:

The principal findings amongst decedents of both sexes were distension of the stomach and/or intestines with fluid/gas, haemorrhagic patches on the glandular region of the stomach wall and facial and urogenital soiling. Also seen were black fluid in the intestine, pale patches on the liver, lung congestion and autolysis of internal viscera.
No abnormalities were seen at post mortem examination of survivors.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

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 of fairly low acute oral toxicity to male and female Sprague-Dawley rats.

Executive summary:

The objective of this study was to establish the acute oral toxicity of the test item in the rat. The test substance was suspended in corn oil. Groups comprising 5 males and 5 females were dosed with 951, 1347 or 1901 test item/kg body weight. Five male and five female control rats were dosed with vehicle only. Animals were observed for 14 days after treatment.

Deaths occurred between 4.5 hours and 2 days after treatment.

The principal symptoms seen were similar in both sexes and included reduced activity and muscle tone, salivation, soiling of the urogenital region and face, hunched posture and piloerection.

Onset of symptoms occurred between 1 minute and 30 hours after treatment and recovery was complete 13 days after treatment.

Body weight gains for males dosed with 951 and 1347 mg/kg body weight, and females dosed with 951 mg/kg were less than in controls over the first 7 days post treatment, but were comparable with controls over the next 7 days.

The principal gross post mortem findings amongst decedents were distension of stomach and/or intestines with fluid/gas, haemorrhagic patches on the glandular region of the stomach wall and facial and urogenital soiling. No abnormalities were seen at post mortem examination of survivors.

The acute oral LD50 values of the test item in the Sprague-Dawley rat (with 95% confidence limits) were:

Males + Females: 1127 (989-1285) mg/kg body weight.

Males: 1208 (971-1503) mg/kg body weight.

Females: 1052 (1038-1067) mg/kg body weight.

It is concluded that the test item is of fairly low acute oral toxicity to the Sprague-Dawley rat, classification as acute tox. 4 according to EU GHS is triggered.