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Description of key information

The acute oral and dermal studies returned results of LD50 > 2000 mg/kg bw.

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:
19th July - 2nd August 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Ltd, Bicester, Oxon, England
- Age at study initiation: approximately 4 to 7 weeks
- Weight at study initiation: 97 to 114 g
- Fasting period before study: overnight prior to and approximately 4 hours after dosing
- Housing: Housed in groups of up to 5 rats of the same sex in metal cages with win mesh floors
- Diet (e.g. ad libitum): standard laboratory rodent diet (SDS LAD 1) ad libitum
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): Relative humidity was not controlled but was anticipated to be in the range 30-70% RH
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period

IN-LIFE DATES: From: To: 19 July and 2 August 1995
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose level was chosen in compliance with the guideline.
Doses:
2.0 g/kg bodyweight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Mortality: Checked at least twice daily for any mortalities
- Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of six hours). Thereafter animals were observed twice daily (with the exception of Day 15- morning only).
- Bodyweight: The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination
Preliminary study:
No prelimunary study undertaken.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Piloerection was observed in all rats within five minutes of dosing, accompanied at this time by increased salivation in two males only. In addition, hunched posture, waddling gait and pallor of the extremities were seen in all rats at later intervals on Day 1. There were no other clinical signs and recovery, as judged by external appearance and behaviour, was complete by either Day 3 (males) or by Day 4 (females).
Body weight:
All rats achieved satisfactory bodyweight gains throughout the study (see table 2 of the attached report).
Gross pathology:
Macroscopic examination on Day 15 revealed no abnormalities.

A study was performed to assess the acute oral toxicity of New Eporva 800 to the rat.

A group of ten fasted rats (five males and five females) was given a single dose by oral gavage of the test substance, as supplied, at a dose level of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no deaths. Clinical signs of reaction to pregnant were confined to piloerection, hunched posture, waddling gait, and pallor of the extremities, seen in all rats with increased salivation seen in two males only. Recovery was complete in all instances by Day 4.

All rats achieved satisfactory bodyweight gains throughout the study.

Macroscopic examination on Day 15 revealed no abnormalities.

The acute lethal oral dose to rats of New Eporva 800 was found to be greater than 2.0 g/kg bodyweight.


According to GHS criteria, New Eporva 800 should be classified as “category 5” or “not classified” with regard to acute oral toxicity.

Interpretation of results:
practically nontoxic
Conclusions:
The acute lethal oral dose to rats of New Eporva 800 was found to be greater than 2.0 g/kg bodyweight.

According to GHS criteria, New Eporva 800 should be classified as “category 5” or “not classified” with regard to acute oral toxicity.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Klimisch 1

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3 March 2014 to 5 June 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animal Breeding Facility, JRF
- Age at study initiation: 9-15 weeks
- Weight at study initiation (g): Males: Min. 281.3 and Max. 297.8; Females: Min. 234.7 and Max. 249.6
- Housing: Polypropylene rat cages with stainless steel grid tops. Bedding was autoclaved clean rice husk. Rats were group-housed during acclimatisation, and individually housed following test item application. After patch removal following 24 hrs exposure, rats were housed 2 to 3 rats/cage, according to group and sex. Animal room was cleaned daily.
- Diet (e.g. ad libitum): Teklad certified Global High Fiber Rat/Mice Feed manufactured by Harlan, U.S.A.
- Water (e.g. ad libitum): UV sterilized water filtered through Kent Reverse Osmosis water filtration system.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23
- Humidity (%): 65 to 67 (relative humidity)
- Air changes (per hr): Minimum 15
- Photoperiod (hrs dark / hrs light): 12/12 (light hours: 06:00 h - 18:00 h)

IN-LIFE DATES: From: 20 March 2014 to 10 April 2014
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Approximately 7x5 cm body surface area
- % coverage: >10% body surface was clipped 24 hours prior to test substance application
-Type of wrap: Porous gauze dressing and non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test item was removed using cotton soaked in distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg body weight (undiluted)
Duration of exposure:
24 hour
Doses:
Limit dose of 2000 mg/kg body weight (undiluted)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Toxicity and mortality were observed 1, 2, 3 and 5h post-dermal application on day 0. Morbidity and mortality were observed twice daily for 14 days
- Clinical signs were recorded once daily
- Individual body weight: Prior to dermal application on day 0 and on days 7 and 14 post-application.
- Necropsy of survivors performed: Yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
Erythema was observed in a single male and all females
Body weight:
No biologically relevant body weight change observed
Gross pathology:
- Necropsy (Macroscopic Findings): External examination of male and female rats revealed no abnormality of pathological significance. Internal visceral examination of male and female rats reveal no abnormal lesions.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose, LD50 of reaction products of N-(2-aminoethyl)-N’-{2-[(2-aminoethyl)amino]ethyl}ethane-1,2-diamine, N-(2-aminoethyl)-N’-[2-(piperazin-1-yl)ethyl]ethane-1,2-diamine,N-{2-[4-(2-aminoethyl)piperazin-1-yl]ethyl}ethane-1,2-diamine,N,N,N’-tris(2-aminoethyl) ethane-1,2-diamine, carbon disulphide and sodium hydroxide in Wistar rats was found to be greater than 2000 mg/kg body weight.

Based on the results, an indication of the classification is Category 5 or Unclassified.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

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

Justification for selection of acute toxicity – dermal endpoint
Only study available.

Justification for classification or non-classification

The acute oral and dermal studies returned results of LD50 > 2000 mg/kg bw. Therefore this substance will not be classified as toxic, at this level.