Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017-05-03 to 2017-05-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(N,N-dimethylpropane-1,3-diamine-N)[29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]cobalt(1+) chloride
EC Number:
284-943-5
EC Name:
Bis(N,N-dimethylpropane-1,3-diamine-N)[29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]cobalt(1+) chloride
Cas Number:
84989-53-7
Molecular formula:
C42H44CoN12.Cl
IUPAC Name:
hydroxylamine
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Remarks:
WI(Han)
Sex:
female
Details on test animals or test system and environmental conditions:
Housing and Feeding Conditions
- Full barrier in an air-conditioned room
- Temperature: 22 ± 3 °C
- Relative humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich
- Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test item was administered at a single dose by gavage using a feeding tube in the morning. The test item (at concentration of 0.2 mg/mL) was administered at a dose volume of 10 mL/kg body weight.
Doses:
- step 1 and 2: 2000 mg/kg body weight
No. of animals per sex per dose:
- steps 1 and 2: 3 females each dose
Control animals:
no
Details on study design:
Preparation of the Animals
The animals were marked for individual identification by tail painting. Prior to the administration a detailed clinical observation was made of all animals. Only healthy animals were used.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.

Observation Period
The surviving animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.

Weight Assessment
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.

Clinical Examination
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Pathology
At the end of the observation period the animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally at a dosage of 250-400 mg/kg bw. All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. In the absence of gross pathological changes no tissues were preserved for a possible histopathological evaluation.

Evaluation of Results
Results were interpreted according to OECD Guideline 423, Annex 2 and GHS. Individual reactions of each animal were recorded at each time of observation. Toxic response data were recorded by dose level. Nature, severity and duration of clinical observations were described. The body weight changes were summarised in a tabular form. Necropsy findings were described.
Statistics:
n.a.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test item showed no mortality but acute oral toxicity characteristics after a single dose administration.
Clinical signs:
At a concentration of 2000 mg/kg all animals showed moderate toxic effects which recovered within 2 days post-dose.
The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced and increased spontaneous activity, piloerection, half eyelid closure, hunched posture, slow movements and prone position.
Body weight:
None of the animals showed weight loss during the observation period.
Gross pathology:
No specific gross pathological changes were recorded for any animal.

Any other information on results incl. tables

LD50 Cut-Off

Starting Dose (mg/kg bw) Number of animals Number of intercurrent deaths LD50 Cut-Off (mg/kg bw)
2000 6 0 > 2000

bw = body weight

Absolute Body Weights in g and Body Weight Gain in %

Step/
Dose (mg/kg)

Animal no. / sex

 

Days after dosing

 

Body weight change in comparison to day 1 (%)

 

1

8

15

15

Step 1 /
2000

1 /female

161

191

203

26

2 /female

158

177

195

23

3 /female

158

178

184

16

Step 2 /

2000

4 /female

170

188

193

14

5 /female

188

216

217

15

6 /female

167

181

196

17

bw = body weight

Applicant's summary and conclusion

Interpretation of results:
other:
Remarks:
Not classified according to CLP
Conclusions:
A single oral application of the test item to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity but not mortality.The median lethal dose of the test substance, after a single oral administration to female rats, observed over a period of 14 days, is: LD50cut-off (rat): > 2000 mg/ kg bw.
Executive summary:

The purpose of this study was to assess the toxicity of the test article when administered to rats after a single oral dose. The study was carried out in accordance with OECD TG 423 and in compliance to GLP.

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was suspended with corn oil at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.

All animals used in the study after their entrance at the test facility were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study showing signs of toxicity. The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced and increased spontaneous activity, piloerection, half eyelid closure, hunched posture, slow movements and prone position. All symptoms recovered within 2 days post-dose. Throughout the 14-day observation period, the weight gain of the animals was within the normal range of variation for this strain. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

Under the conditions of the present study, a single oral application of the test item to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity but no mortality. The median lethal dose after a single oral administration to female rats, observed over a period of 14 days is: LD50cut-off (rat): > 2000 mg/ kg bw.