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Description of key information

The oral LD50 of Etherdiamine C13i/acetate is around 500 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2 February 1990 - 20 February 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The test was performed according to guideline and under GLP. No deviations. Test substance is without acetate.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bantin & Kingman Ltd., England
- Age at study initiation: 5-8 weeks
- Weight at study initiation: males: 120-146g and females 129-140g
- Fasting period before study: overnight
- Housing: animals were housed in groups of up to six by sex in solid-floor polypropylene cages with sawdust bedding.
- Diet (e.g.ad libitum ): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 44-60
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 2 February 1990 To: 20 February 1990
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: depends on dose level between 2.5 and 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusual): For the purpose of this study the test material was freshly prepared, as required, at the appropriate concentration as a solution in arachis oil B.P
Doses:
range finding study:
2000, 200 and 25 mg/kg bw

main study:
200 mg/kg bw
No. of animals per sex per dose:
Range finding:
2

Main study:
5
Control animals:
no
Details on study design:
range finding:
- Duration of observation period following administration: 5 days
- Frequency of observations and weighing: on the day of dosing animals were weighed
- Necropsy of survivors performed: no
- Other examinations performed: none

Main study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. Deaths and evidence of overt toxicity were recorded at each observation. Individual bodyweights were recorded on the day of treatment (day 0) and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: none
Statistics:
none
Preliminary study:
In the range finding study all rats died at 2000 mg/kg bw on day 1 and one male animals died on day 4.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Mortality:
In the main study a limit test was performed with doses of 200 mg/kg bw none of the animals died.
Clinical signs:
Signs of toxicity were confined to hunched posture and pilo-erection.
Body weight:
All animals showed expected gain in bodyweight during the study period.
Gross pathology:
No abnormalities were noted at necropsy of animals killed at the end of the study.
Other findings:
none
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute oral median lethal dose (LD50) o f the test material, LILAFLOT D817, to the Sprague-Dawley strain rat was found to be greater than 200 mg/kg but less than 2000 mg/kg bodyweight. At 200 mg/kg bw 1/14 animals died. LD50 is expected to be > 300 mg/kg: The classification under GHS is Toxicity Category IV.
Executive summary:

A study was performed, according to OECD 401 and under GLP, to determine the acute oral median lethal dose (LD50) of the test material, administered as a solution in arachis oil B.P. in the Sprague-Dawley strain rat . In a range-finding study (2000, 200 and 25 mg/kg bw, 2 animals sex dose) all animals were found dead the next day at 2000 mg/kg bw and one animal died at 200 mg/kg bw at day 4. Following these results a group of ten fasted animals (five males and five females) was given a single oral dose of test material preparation at a dose level of 200 mg/kg bodyweight. There were no deaths. Signs of toxicity were confined to hunched posture and pilo-erection observed 4 hrs after dosing in all animals and on day one in one male. All animals showed expected gain in bodyweight during the study period. No abnormalities were noted at necropsy of animals killed at the end of the study . The acute oral median lethal dose (LD50) o f the test material, LILAFLOT D817, to the Sprague-Dawley strain rat was found to be greater than 200 mg/kg but less than 2000 mg/kg bodyweight. Formal classification under GHS is not possible, but LD50 is expected >= 300 mg/kg, using a LD50 cut-off level of 500 mg/kgbw seems appropriate.

Endpoint conclusion
Dose descriptor:
LD50
500 mg/kg bw
Quality of whole database:
Two adequate studies resulting both to a similar LD50 level

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:

There are two studies available on the etherdiamine product without acetate:

The first study involves the evaluation of the acute oral toxicity of etherdiamine C13i in a OECD 401-like study, under GLP. The test material was administered as a solution in arachis oil. In a range-finding study (2000, 200 and 25 mg/kg bw, 2 animals per sex per dose) all animals were found dead the next day at 2000 mg/kg bw and one animal died at 200 mg/kg bw at day 4. In the final study, 10 animals were dosed with 200 mg/kg bw which resulted to no mortality.

The study therefore concluded to a LD50 between 200 and 2000 mg/kg bw. Formal classification under GHS is not possible, but LD50 is expected >= 300 mg/kg, and using a LD50 cut-off level of 500 mg/kgbw seems appropriate.

 

These results are supported by a second available study where acute oral toxicity was evaluated following a OECD 401 study outline. This study resulted to a LD50 of 518 mg/kg bw (c.i.: 442-606 mg/kg) for Etherdiamine C13i. Gross pathology of deceased animals showed blood stained stomach and intestinal contents, probably caused by the corrosive nature of the test material.

 

Both studies indicate a similar level of toxicity for the etherdiamine. Although both studies have been performed on etherdiamine C13i without acetate, they are considered to be relevant for the evaluation of etherdiamine C13i with acetate as well. Dermal corrosion studies have shown that the presence of acetate does not impact the corrosive properties of the compound. Additionally, the conversion of about half of the etherdiamine to etherdiamine-acetate salt, as is the case for theEtherdiamine /acetate product mixture,is not considered to have a large impact as it will probably be dissociated again in stomach and intestinal fluids.

 

Acute dermal toxicity:

Etherdiamine C13i/acetate is corrosive to the skin. Testing for acute dermal toxicity is therefore not justified. Toxicity following dermal exposure is characterised by local tissue damage, rather than the result of percutaneously absorbed material. For corrosive substances, the use of protective gloves and other equipment, such as face shields, aprons and good work practices are mandatory. Consequently, the occurrence of substantial dermal exposure of amounts comparable to the levels for acute oral toxicity is unlikely.

 

Acute inhalation toxicity:

There is no study on inhalation toxicity available on Etherdiamine C13i.

REACH stipulates that testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. REACH guidance R.7.a, chapter. 7.4 Acute toxicity, indicates that in principle no inhalation studies are needed when vp < 0.1 Pa at 20°C or particle size > 100 µm. Etherdiamine C13i is a liquid with a vapour pressure of 0.005 Pa at 25°C. Also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur, and no acute inhalation test was performed.

Justification for selection of acute toxicity – oral endpoint
Appropriate study of the highest quality and validity

Justification for selection of acute toxicity – inhalation endpoint
There is no study on inhalation toxicity available on Etherdiamine C13i.
REACH stipulates that testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. REACH guidance R.7.a, chapter. 7.4 Acute toxicity, indicates that in principle no inhalation studies are needed when vp < 0.1 Pa at 20°C or particle size > 100 µm. Etherdiamine C13i is a liquid with a vapour pressure of 0.005 Pa at 25°C. Also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur, and no acute inhalation test was performed.

Justification for selection of acute toxicity – dermal endpoint
Etherdiamine C13i/acetate is corrosive to the skin. Testing for acute dermal toxicity is therefore not justified.

Justification for classification or non-classification

LD50 is expected >= 300 mg/kg, and using a LD50 cut-off level of 500 mg/kgbw seems appropriate.

The substance therefore needs to be classified for acute toxicity according to GHS as Cat.4 with hazard statement H302 “harmful if swallowed”, and as Harmful, R22 “harmful if swallowed” for DSD.

Acute dermal testing with corrosive materials is not justified. As a consequence no classification can be made for acute dermal toxicity. Effects will be characterised by local tissue damage. Systemic uptake via skin is likely to be very limited.

No classification for acute dermal toxicity is therefore indicated.

 

For acute inhalation toxicity the information for classification is lacking, and testing is not justified.

 

Etherdiamine C13i/acetate is not a pure aliphatic, alicyclic and aromatic hydrocarbons and has a relatively high viscosity (Kinematic viscosity 377 mm2/s at 20 °C) and so do not indicate an immediate concern for aspiration hazard.