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Administrative data

Description of key information

Acute toxicity, oral (OECD 401, No GLP: QA declaration): 1156 mg/kg bw. No acute dermal and inhalation toxicity studies were performed on the substance due to its corrosive properties.

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
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP; does not fully conform to current guidelines-no individual responses
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
pre-GLP; QA declaration
Test type:
standard acute method
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Equal numbers of male and female CFY (Sprague-Dawley origin) rats were obtained from Interfauna UK Ltd., Huntingdon, Cambridgeshire, England.
They were in a weight range of 89 to 121 g prior to dosing (Day 1) in the main study and approximately four to six weeks of age. All the rats were
acclimated to the experimental environment for a period of 5 days prior to the start of the main study.

The rats were allocated to cages within the treatment groups. They were housed in groups by sex in metal cages with wire mesh floors. A standard
laboratory rodent diet (Labsure LAD 1) and water were provided ad libitum. The batch of diet used for the study was analysed for certain chemical and
microbiological contaminants. Access to food only was prevented overnight prior to and approximately 4 hours after dosing.

The mean daily minimum and maximum temperatures of the animal room were 21°C and 22°C respectively and the mean daily relative humidity value
was 47%. The rate of air exchange was maintained at approximately 15 air changes/hour. Lighting was controlled by means of a time switch to 12
hours artificial light in each 24 hour period.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Redicote EN611 was administered, as supplied by the Sponsor, at a volume not exceeding 1.52 ml/kg (S.G. 1.05) in the main study.
Doses:
A trial test was carried out to establish a dosing regimen for the main study using groups of two male and two female rats at three dose levels of
1000, 2500 and 5000 mg/kg bodyweight.

Doses selected for the main study were 640, 1000 and 1600 mg/kg bodyweight.

No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The appropriate dose volume of the test substance was administered to each rat using a syringe and plastic catheter.

Animals were observed soon after dosing; then at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on weekdays or 11.30 hours on Saturday and Sunday. Clinical signs were recorded at each observation.

The animals on the preliminary and main studies were observed for 5 and 14 days respectively, after dosing.

Surviving animals on the main study were killed on Day 15 by cervical dislocation. All animals that died during the study and those killed on Day 15
were subjected to a macroscopic post mortem examination which consisted of opening the abdominal and thoracic cavities. The macroscopic
appearance of abnormal organs when present was recorded.
Statistics:
The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of: Finney (1971) Probit Analysis (3rd Edition)
Cambridge University Press. Separate LD 50 values for males and females were estimated by undertaking probit analysis on the mortality data by
fitting two parallel lines on the data (males only and females only) using the technique described by Finney 1978, Statistical Method in Biological
Assay, 3rd Edition, Charles Griffin, London). A chi-squared test was carried out to check that the data did not contain any evidence for
non-parallelism.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 145 mg/kg bw
95% CL:
871 - 1 543
Sex:
female
Dose descriptor:
LD50
Effect level:
1 164 mg/kg bw
95% CL:
893 - 1 506
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 156 mg/kg bw
95% CL:
956 - 1 405
Mortality:
There were deaths among male and female rats treated at 1000 (3/10) and 1600 mg/kg (9/10) from within one hour of dosing to Day 2.
Clinical signs:
Signs of reaction to treatment observed in all rats shortly after dosing were pilo-erection, abnormal body carriage (hunched posture),
abnormal gait (waddling) and increased salivation. These were accompanied by: lethargy and decreased respiration in all animals surviving
for more than one hour after treatment at 1000 or 1600 mg/kg, ptosis in one rat dosed at 640 mg/kg and in all rats surviving for more than one hour after treatment at higher doses, pallor of the extremities of one rat dosed at 640 mg/kg and in all animals given higher doses, diarrhoea in all rats
treated at 640 mg/kg. Recovery, as judged by external appearance and behaviour, was advanced by Day 3 and complete by Day 5.
Body weight:
Bodyweight losses or no change of bodyweight were recorded for rats that died.

Slightly low bodyweight gains were recorded on Day 8 for one male dosed at 1000 mg/kg and on Day 15 for one female treated at 640 mg/kg. Other
rats achieved anticipated bodyweight gains throughout the study.
Gross pathology:
Autopsy of rats that died commonly revealed renal pallor. There were no other macroscopic abnormalities.Terminal autopsy findings were normal.

Time and Number of Deaths

Sex

Dose

(mg/kg)

# deaths

Total #

animals

Day 1

Day 2

Day 3

Day 4

Day

5-15

a     b

a     b

a     b

a     b

a     b

M

640

0

5

M

1000

1

5

1

M

1600

5

5

5

F

640

0

5

F

1000

2

5

        2

F

1600

4

5

4

a = first, b = second observation

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute oral LD50 of Redicote EN611 and its 95% confidence limits were estimated to be 1156 mg/kg bodyweight (956-1405).
Executive summary:

The purpose of the study was to evaluate the acute toxicity of Redicote EN611 when administered to rats by gavage in accordance with OECD 401. Male and female rats were administered the test article at 640, 1000 or 1600 mg/kg bodyweight and observed for clinical signs of toxicity and mortality.

The combined LD50 of Redicote EN611 was 1156 mg/kg (956 -1405).

As Redicute EN611 contains 30-40% active substance, this equals 350-450 mg a.s./kg;

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
350 mg/kg bw
Quality of whole database:
OECD 401 guideline study performed pre-GLP, but with QA declaration included. The report does not include complete analytical verification of substance, and the LD50 value of 350 mg/kg is a worst case value based on lowest possible active substance content in tested product.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute Oral Toxicity:

A study is available to evaluate the acute oral toxicity of N,N,N',N',N'-Pentamethyl-N-C16-18(even numbered) C18 unsatured-alkyl-1,3 propanediammonium chloride to rats by gavage in accordance with OECD 401. Male and female rats were administered test substance Redicote EN611 at 640, 1000 or 1600 mg/kg bodyweight and observed for clinical signs of toxicity and mortality. The combined LD50 for both sexes was 1156 mg/kg (956 -1405). As tested product Redicote EN611 contains 30-40% active substance, this represents a LD50 for Diamine quaternised C16-18, C18 unsaturated, of 350-450 mg/kg.

Overall the study is considered reliable although it does not include complete analytical verification of substance. Reliability is further increased with the observed consistency of the results with the reported LD50 from literature for N,N,N,N',N'-Pentamethyl-N'-octadecyl-N,N'-trimethylenediammonium dichloride (CAS 7392-72-5) indicating an LD50 in mouse of 1000 mg/kg bw, and for rat almost 1000 mg/kg bw (94 mL/kg bw) (NTIS).

 

Acute dermal and inhalation toxicity:

The substance is classified as corrosive to skin and testing for acute toxicity is therefore not needed according to REACH regulation (EC) 1907/2006 (Annex VII, point 8.5, column 2).


Justification for selection of acute toxicity – oral endpoint
Only available study of appropriate riliability.

Justification for selection of acute toxicity – inhalation endpoint
There is no study on inhalation toxicity available for Diamine quaternised C16-18, C18 unsaturated, and testing is not scientifically justified for animal welfare reasons. The substance is classified as corrosive and no acute toxicity testing should normally be conducted. Upon inhalation of corrosive substances, symptoms of local respiratory irritation are expected, which should limit the systemic uptake of amount needed for systemic toxicity considering the relatively low acute oral toxicity.
Furthermore, exposure of humans to Diamine quaternised C16-18, C18 unsaturated, via inhalation is not likely taking into account the low vapour pressure of the substance (fatty acid ammonium electrolyte << 1.5 x 10-3 Pa at 20 °C) as well as low possibility of exposure to aerosols or droplets of an inhalable size.

Justification for selection of acute toxicity – dermal endpoint
In accordance with column 2 of REACH Annex VIII, the acute dermal toxicity study does not need to be conducted as the substance is classified as corrosive to the skin.
There is no dermal LD 50 value for acute skin toxicity of Diamine quaternised C16-18, C18 unsaturated, and due to the corrosive nature of the substance it is not ethical to carry out this animal study. The corrosive classification of the substance requires risk management methods which eliminate the potential for skin contact. The lack of a dermal LD50 will therefore not affect the safe handling of the substance.

Justification for classification or non-classification

Oral route:

According to the criteria laid down in EU regulation (EC) n° 1272/2008/EC (CLP), the substance should be classified in category 4 of toxicity with the hazard statement H302.

 

Dermal route: Acute oral toxicity testing indicates a relatively low acute systemic toxicity, and effects observed are attributable to its corrosive properties in the GI-tract. Following its severe corrosive properties, systemic toxicity following acute dermal exposure is not likely to occur. Therefore no classification is warranted.

 

Inhalation route: No data is available on inhalation toxicity. The combination of very low vp, low likelihood of exposures aerosols and the severe corrosive local effects expected for this substance makes further acute toxicity testing by inhalation with the substance itself ethically not justified.

Based on its physical appearance as paste, there is no need for classification for aspiration hazard.

 

The available data does not show indication that classification for STOT-SE cat 1 or 2 is indicated.

For STOT-SE Cat 3: There is no indication for possible narcotic effects. Although the substance is corrosive, the very low vapour pressure prohibits occurrence of respiratory irritation by vapour. The classification of corrosive is already considered to implicitly cover the potential of RTI and additional Cat.3 is considered to be superfluous (Guidance CLP Ch. 3.8.2.5)