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Description of key information

The substance is of low acute toxicity in mammals by both the oral and dermal routes. The acute oral LD50 is > 2350 mg/kg (based on active ingredient) while the acute dermal LD50 is > 2000 mg/kg (based on test material). The acute dermal toxicity has been addressed by use of read-across from a structurally related substance (methyl trimethyl-3-[(1-oxododecyl)amino]propylammonium sulphate; CAS No.10595-49-0).Testing by the inhalation route is not scientifically justified.


Key value for chemical safety assessment

Acute toxicity: via oral route

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Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
GLP compliance:
not specified
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
- Age at study initiation: no data
- Weight at study initiation: m: 125 - 135g; f: 110 - 125g
- Fasting period before study: over night
- Housing: single caging, cage type: Macrolon type IlI./max. 5
- Diet: ad libitum; rat diet (R 4 Alleindiät für Ratten), Ssniff Spezialdiäten GmbH, 4770 Soest/Westfalen
- Water: ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23
- Humidity (%): 40 - 70
- Air changes (per hr): 10 per hour
- Photoperiod (hrs dark / hrs light): 12 hours daily
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg bw

The test substance was weighed out in a glass, then was filled with Aqua destillata up to the desired volume, was shaken well and afterwards labeled. The formulated test substance was a clear solution.
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
The group of 5 female and 5 male rats were were given a single oral dose 5000 mg/kg of the test substance by gavage.

- Duration of observation period following administration: 14 d
- Body weights were recorded before treatment (day -1), at the treatment day (day 0), and on days 7 and 14 after treatment
- Clinical observation: Animals were observed 1/4 h, 1/2 h, 1 h, 2 h, 4 h after dosing and thereafter once daily up to day 14.
- Necropsy of the survivors performed: yes
Statistics:
As none of the test animals died a calculation of the LD50 was not possible.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: based on product; mortality 0/10
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 350 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: based on a.i.; mortality 0/10
Mortality:
There were no mortalities
Clinical signs:
Except of ruffled fur on the day of treatment, the animals were free of clinical-/toxicological symptoms during the entire observation period of 14 days.
Body weight:
Body weight changes during the observation period showed a normal weight gain.
Gross pathology:
Necropsies were performed on all animals at the end of the 14-day observation period. In one animal a slight thickening of the stomach mucosa could be observed. Necropsies of all other animals showed no test compound-related macroscopic findings in the cranial-, thoracic- and abdominal cavity.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity of the test material was >5000 mg/kg bw (47% a.i.), equivalent to LD50 > 2350 mg/kg bw (100% a.i.)
Executive summary:

In an acute oral toxicity study similar to OECD Guideline 401 (1981) 5 male and 5 female Sprague-Dawley rats were given a single dose of the substance (a.i. 47 %) at a dose of 5000 mg/kg bw (limit test). The test item was formulated in water and applied in a volume of 10 mL/kg bw. Animals were subsequently observed for 14 consecutive days.There were no deaths following a single oral dose of the substance. Except of ruffled fur on the day of treatment, the animals were free of clinical/ toxicological signs during the entire observation period of 14 days. Necropsies were performed on all animals at the end of the 14-day observation period. In one animal a slight thickening of the stomach mucosa could be observed. Necropsies of all other animals showed no test compound-related macroscopic findings in the cranial-, thoracic- and abdominal cavity.

Oral LD50Combined: > 2350 mg/kg bw (active ingredient)

LD50 > 5000 mg/kg bw determined in the study report refers to the test substance as delivered by the sponsor. Amount of active ingredient in test substance is 47 % according to the sponsor information. Therefore the calculated oral LD50 combined referring to 100 % active substance is 2350 mg/kg bw. The substance is practically nontoxic based on LD50 in males and females.

                            

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 350 mg/kg bw
Quality of whole database:
Sufficient to meet data requirements. The study is Klimisch 2.

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not 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
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
An acute inhalation toxicity study is scientifically unjustified and is not in the interests of animal welfare. Acute studies are available by the oral and dermal routes.

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 May 2012 and 30 May 2012.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Recently conducted guideline study to GLP
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Number: Five male and five female
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: at least 200g. The weight variation did not exceed ±20% of the mean weight for each sex.
- Housing: suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-Hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet and Water: Free access to mains drinking water and food (2014C Teklad Global Rodent diet) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: surgical guaze with self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water
- Time after start of exposure: 24 hour
Duration of exposure:
24 hours
Doses:
- Dose level: 2000 mg/kg bodyweight
- Dose Volume: 1.97 ml/kg (based on specific gravity of the test substance of 1.016)
No. of animals per sex per dose:
5 male, 5 female
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: ½, 1, 2 and 4 hours after dosing and subsequently once daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test item was made.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
Animals showed expected gains in bodyweight, except for one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Signs of dermal irritation noted were very slight to well-defined erythema, very slight to slight oedema, haemorrhage of dermal capillaries, blanching of the skin, light brown discolouration of the epidermis, loss of skin elasticity, crust formation, small superficial scattered scabs, scab lifting at edges to reveal dried blood and scab lifting to reveal glossy skin.

Dermal Reactions

 Animal Erythema  Oedema 
 1-0 Male   2 - reversible by day 7  2 - reversible by day 5
 1-1 Male   2 - reversible by day 10  1 - reversible by day 6
 1-2 Male   2 - reversible by day 8  1 - reversible by day 5 
 1-3 Male   2 - reversible by day 11  1 - reversible by day 6 
 1-4 Male   2 - reversible by day 9  2 - reversible by day 6 
 2-0 Female   2 - reversible by day 9  2 - reversible by day 9 
 2-1 Female   2 - reversible by day 7  2 - reversible by day 5 
 2-2 Female   2 - reversible by day 10  2 - reversible by day 5 
 2-3 Female   2 - reversible by day 10  2 - reversible by day 7 
 2-4 Female   2 - reversible by day 7  1 - reversible by day 5 

Erythema

2 - Well-defined erythema

Oedema

2 - Slight oedema (edges of area well-defined by definite raising)

1 - Very slight oedema (barely perceptible)

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 was >2000 mg/kg bodyweight.
Executive summary:

The acute dermal toxicity of CAS#10595 -49 -0 was assessed in the Wistar strain rat. The method was designed to be compatible with OECD 402 and Method B3 Acute Toxicity (Dermal) of EC No. 440/2008.

A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths. There were no signs of systemic toxicity. Signs of dermal irritation noted were very slight to well-defined erythema, very slight to slight oedema, haemorrhage of dermal capillaries, blanching of the skin, light brown discolouration of the epidermis, loss of skin elasticity, crust formation, small superficial scattered scabs and scab lifting to reveal dried blood or glossy skin.

Animals showed expected gains in bodyweight, except for one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week. No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Sufficient to meet data requirements. The study is Klimisch 1 (or Klimisch 2 allowing for read-across).

Additional information

Justification for classification or non-classification

Based on the available acute toxicity data, classification for acute toxicity is not justified.