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Administrative data

Description of key information

Based on the oral and dermal LD50 values available for the read across substances, Oleyl TMAC can be considered to be of moderate acute toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From 07 November, 1986 to 10 December, 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Justification for type of information:
Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Interfauna (UK) Limited, Wyton, Huntingdon, Cambridgeshire
- Age at study initiation: 5-8 wks old
- Weight at study initiation: Males weighed: 130 - 162g and females weighed: 123 - 151g
- Fasting period before study: Overnight fast immediately before dosing and for approximately two hours after dosing.
- Housing: Solid-floor polypropylene cages with sawdust bedding
- Diet and water (e.g. ad libitum): Free access to mains drinking water and food (rat and mouse expanded diet No.1, special diet services limited, with am, Essex, U.K.) was allowed throughout the study.
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23°C
- Humidity: 45-65%
- Air changes: 15/h
- Photoperiod: 12 h light/12 h dark
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Undiluted

MAIN STUDY:
Four groups of ten rats (five males and five females) were dosed at logarithmically spaced dose levels, selected using the results of the range-finding study. All animals were dosed once only at the appropriate dose level by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.


Doses:
0, 1,000, 1,260, 1,587 and 2,000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Animals were observed 1 and 4 h after dosing and subsequently once daily for 14 d. Deaths and evidence of overt toxicity were recorded at each observation. Individual bodyweights were recorded on the day of treatment (day 0), Day 7 and 14, and at death.
- Necropsy of survivors performed: Yes, all animals were subjected to gross necropsy examination for any macroscopic abnormalities
- Other observations: Clinical signs
Statistics:
Method of Weil C.S. (1952) Biometrics 8, 249 was used to calculate the acute oral median lethal dose (LD50 )and 95% confidence limits of the test substance.
Preliminary study:
The results of the range finding study based on mortality indicated an oral LD50 between 1,000 and 2,000 mg/kg bw.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 260 mg/kg bw
Based on:
test mat.
95% CL:
ca. 1 061 - ca. 1 496
Remarks on result:
other: equivalent to 630 mg a.i./kg bw
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 289 mg/kg bw
Based on:
test mat.
95% CL:
ca. 1 151 - ca. 1 444
Remarks on result:
other: equivalent to 644.5 mg a.i./kg bw
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 1 000 - <= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: equivalent to be between 500 to 1000 mg a.i./kg bw
Mortality:
The number and percentage of mortality observed at different doses were:
- At 1,000 mg/kg bw: 0/5 (M); 2/5 (F); 2/10 (total), i.e., 20%
- At 1,260 mg/kg bw: 2/5 (M); 4/5 (F); 6/10 (total), i.e., 60%
- At 1,587 mg/kg bw: 5/5 (M); 2/5 (F); 7/10 (total), i.e., 70%
- At 2,000 mg/kg bw: 5/5 (M); 4/5 (F); 9/10 (total), i.e., 90%
Clinical signs:
Major signs of toxicity noted in decedent and survlvlng animals were hunched posture, lethargy, pilo-erection, decreased respiratory rate and diarrhoea. Animals treated with 1,260 mg/kg bw and above showed additional signs including: ataxia, tip-toe gait, ptosis, pallor of the extremities, increased lacrimation, chromodacryorrhoea, diuresis, occasional body tremors, emaciation and red/brown staining around the snout.
The single survivor in the 2,000 mg/kg bw dose group showed signs of toxicity until Day 12, but all other surviving animals appeared normal three to six days
after treatment.
Body weight:
Effects on bodyweight gain (reduction) were commonly noted in animals treated with 1,260 mg/kg bw and above at Day 7, but all survivors made expected bodyweight gains during the second week.
Gross pathology:
Necropsy of decedents revealed abnormally red lungs, dark livers, haemorrhage and ulceration of the gastric mucosa and congestion of the small intestines. Surviving animals necropsied at termination showed white raised areas on the non-glandular region of the stomach or general white thickening of this region. Isolated animals from the 1,260 and 2,000 mg/kg bw dose groups showed adhesion of the stomach to the abdominal wall and/or liver.
Interpretation of results:
other: Acute Tox. 4 based on CLP criteria
Conclusions:
Based on the results of the read across study, the oral LD50 value for the test substance can also considered to be 630 mg/kg bw/day.
Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, C16-18 and C18-unsatd. TMAC (active: 50%), in Sprague Dawley rats according to OECD 402 Guideline, in compliance with GLP. Four groups of 10 fasted animals (five males and five females) were administered an oral gavage dose of the test substance (i.e., 50% active ingredient) at doses of 1,000, 1,260, 1,587 and 2,000 mg/kg bw. The animals were observed for 14 d and were then sacrificed and subjected to gross pathological examination. Mortality was observed at all doses (females: 2/5, 4/5, 2/5, 4/5; males: 0/5, 2/5, 5/5, 5/5, at each respective dose) with percentages ranging from 60-90 at ≥1,260 mg/kg bw. Major signs of toxicity noted in decedent and surviving animals were hunched posture, lethargy, pilo-erection, decreased respiratory rate and diarrhoea. All animals showed expected body weight gain during the second week of the study. Necropsy of decedents revealed abnormally red lungs, dark livers, haemorrhage and ulceration of the gastric mucosa and congestion of the small intestines. Surviving animals necropsied at termination showed white raised areas on the non-glandular region of the stomach or general white thickening of this region. Under the test conditions, the LD50 was determined to be 1,260 mg/kg bw for males/females (i.e., equivalent to 630 mg a.i./kg bw) (Jones et al., 1987). Based on the results of the read across study, the oral LD50 value for the test substance, Oleyl TMAC, can also considered to be 630 mg/kg bw/day.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
630 mg/kg bw
Quality of whole database:
Good quality study

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Reason / purpose for cross-reference:
data waiving: supporting information
Reason / purpose for cross-reference:
data waiving: supporting information
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:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From 22 February, 1988 to 24 March, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Justification for type of information:
Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Toxic Substances Control Act (TSCA) acute dermal toxicity guideline
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Mochican Valley Rabbitry, Loidonville, Ohio
- Weight at study initiation: 2140 to 2990 g
- Housing: individual suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified rabbit chow # 5322, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Minimum 7 d

ENVIRONMENTAL CONDITIONS
- Humidity (%): 49-74%
- Photoperiod (h dark / h light): 12 h / 12 h
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Shaved intact dorsal skin
- % coverage: 20%
- Type of wrap if used: Test substance was applied under gauze binders that were secured with non-irritating tape.
Duration of exposure:
24 h
Doses:
0, 520, 1020 and 2000 mg/kg bw.
No. of animals per sex per dose:
Five animals per sex per test group, three animals per sex in control group.
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: Animals were observed at 1, 3 and 4 h post-dosing on Day 0 and twice daily for mortality and once daily for clinical observations for 14 d. Application sites were examined for erythema, oedema and other dermal findings at 30−60 min after bandage removal and daily thereafter for 13 d. Erythema and oedema were graded according to Draize method.
- Frequency of observations and weighing: Day 0, 7 and 14
- Necropsy of survivors performed: yes
Statistics:
LD50 and slopes (with 95% confidence limits) were calculated by method of Litchfield and Wilcoxon.
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 1 300 mg/kg bw
Based on:
test mat.
95% CL:
ca. 800 - ca. 1 900
Remarks on result:
other: i.e., equivalent to 429 mg a.i./kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 1 900 mg/kg bw
Based on:
test mat.
95% CL:
ca. 1 500 - ca. 2 400
Remarks on result:
other: i.e., equivalent to 627 mg a.i./kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 600 mg/kg bw
Based on:
test mat.
95% CL:
ca. 1 200 - ca. 2 100
Remarks on result:
other: i.e., equivalent to 588 mg a.i./kg bw
Mortality:
Control: 0/6 animals
520 mg/kg bw: 0/10 animals
1020 mg/kg bw: 2/5 males and 0/5 females
2000 mg/kg bw: 4/5 males and 3/5 females
Clinical signs:
Lethargy and ataxia were major clinical findings. Other findings included hypothermia, decreased respiratory rate, laboured respiration, nasal discharge, decreased defecation, emaciation, red staining around the mouth, diarrhoea.
Body weight:
Treatment-related body weight loss in one animal each at two higher doses throughout the 14 d. For other eight rabbits body weight was decreased during first wk with a subsequent recovery in the second wk and net gain in the entire 14 d study period.
Gross pathology:
Treatment-related abnormality on the application sites of all rabbits. No substance-related internal abnormalities in rabbits that died during study or terminally sacrificed.
Other findings:
Test substance induced moderate to severe erythema and oedema with other significant dermal findings such as necrosis, desquamation, scabbing, eschar, exfoliation, fissuring and blenching. Subcutaneous haemorrhage was present on the application sites of one rabbit in the 2000 mg/kg bw group that survived and all animals that died.

Only (systemic) pathology observed in animals sacrificed at termination were kidney abnormalities (pale, reddened, pitted) in 5/21 of the terminally sacrificed dosed rabbits. Pale kidneys were also observed for one female in the control group. The skin of the animals that died showed eschar, subcutaneous haemorrhage, blanching and thickening. Internal abnormalities included hemorrhagic thymus glands (6/9) (typical agonal change), red foci or dark red area in the stomach (3/9), brain haemorrhages (3/9) and liver soft or pale and soft (2/9). No internal abnormalities were observed among rabbits that died which could be attributed to the test substance. There were no test substance related internal changes for rabbits that were terminally sacrificed.

Considering the generally low dermal absorption of Coco TMAC (<10% in Bartnik and Wingen, 1979 study), it is likely that severe corrosive effects upon the 24 h exposure of the concentrated product were more cause to the death of the animals, than real systemic toxicity. This is supported by the relatively limited observations on internal organs upon necropsis of the animals that died. The most commonly observed internal abnormalities were hemorrhagic thymus glands (6/9), which is a typical agonal change, and likely not a specific sign of toxicity.

Interpretation of results:
other: Category 3 based on CLP criteria
Conclusions:
Based on the results of the read across study, the acute dermal LD50 value of the test substance, Oleyl TMAC, can also be considered to be 528 mg a.i./kg bw.
Executive summary:

A study was conducted to determine the acute dermal toxicity of the read across substance, Coco TMAC (active: 33%), in albino rabbits according to OECD Guideline 402, in compliance with GLP. The test substance at 0, 520, 1,020 or 2,000 mg/kg bw was applied under semi-occlusive conditions for 24 h in a single application to the shaved, intact skin of groups of 10 rabbits (five per sex). Animals were observed at 1, 3 and 4 h post-dosing. Following the 24 h exposure period, animals were observed for mortality, clinical signs and skin response for 14 d. There was no mortality in the control or 520 mg/kg bw group. Two males died in the 1,020 mg/kg bw group while 4 males and 3 females died in the 2,000 mg/kg bw group. Under the conditions of the test, the acute dermal LD50 for male and female albino rabbits was determined to be 1,600 mg/kg bw (i.e., equivalent to 528 mg a.i./kg bw) (95% confidence limits of 1,200 – 2,100 mg/kg bw). Considering the generally low dermal absorption potential of Coco TMAC (<10% in Bartnik and Wingen, 1979 study), the observed systemic effects and mortality were attributed to the severe corrosive properties of the test substance following 24 h exposure rather than real systemic toxicity. This is supported by the relatively limited observations on internal organs upon necropsis of the animals that died (Naas, 1988). Based on the results of the read across study, the acute dermal LD50 value of the test substance, Oleyl TMAC, can also be considered to be 528 mg a.i./kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
528 mg/kg bw
Quality of whole database:
Guideline and GLP compliant study

Additional information

Oral

A study was conducted to determine the acute oral toxicity of the read across substance, C16-18 and C18-unsatd. TMAC (active: 50%), in Sprague Dawley rats according to OECD Guideline 401, in compliance with GLP. Four groups of 10 fasted animals (five males and five females) were administered an oral gavage dose of the test substance (i.e., 50% active ingredient) at doses of 1,000, 1,260, 1,587 and 2,000 mg/kg bw. The animals were observed for 14 d and were then sacrificed and subjected to gross pathological examination. Mortality was observed at all doses (females: 2/5, 4/5, 2/5, 4/5; males: 0/5, 2/5, 5/5, 5/5, at each respective dose) with percentages ranging from 60-90 at ≥1,260 mg/kg bw. Major signs of toxicity noted in decedent and surviving animals were hunched posture, lethargy, pilo-erection, decreased respiratory rate and diarrhoea. All animals showed expected body weight gain during the second week of the study. Necropsy of decedents revealed abnormally red lungs, dark livers, haemorrhage and ulceration of the gastric mucosa and congestion of the small intestines. Surviving animals necropsied at termination showed white raised areas on the non-glandular region of the stomach or general white thickening of this region. Under the test conditions, the LD50 was determined to be 1,260 mg/kg bw for males/females (i.e., equivalent to 630 mg a.i./kg bw) (Jones et al., 1987). Based on the results of the read across study, similar oral LD50 value is considered for the test substance, Oleyl TMAC, for acute oral toxicity.

Dermal

A study was conducted to determine the acute dermal toxicity of the read across substance, Coco TMAC (active: 33%), in albino rabbits according to OECD Guideline 402, in compliance with GLP. The test substance at 0, 520, 1,020 or 2,000 mg/kg bw was applied under semi-occlusive conditions for 24 h in a single application to the shaved, intact skin of groups of 10 rabbits (five per sex). Animals were observed at 1, 3 and 4 h post-dosing. Following the 24 h exposure period, animals were observed for mortality, clinical signs and skin response for 14 d. There was no mortality in the control or 520 mg/kg bw group. Two males died in the 1,020 mg/kg bw group while 4 males and 3 females died in the 2,000 mg/kg bw group. Under the conditions of the test, the acute dermal LD50 for male and female albino rabbits was determined to be 1,600 mg/kg bw (i.e., equivalent to 528 mg a.i./kg bw) (95% confidence limits of 1,200 – 2,100 mg/kg bw).Considering the generally low dermal absorption potential of Coco TMAC (<10% in Bartnik and Wingen, 1979 study), the observed systemic effects and mortality were attributed to the severe corrosive properties of the test substance following 24 h exposure rather than real systemic toxicity. This is supported by the relatively limited observations on internal organs upon necropsis of the animals that died(Naas, 1988). Based on the results of the read across study, similar dermal LD50 value is considered for the test substance, Oleyl TMAC, for acute dermal toxicity.

Inhalation

The substance is a slippery solid-paste with a low vapour pressure at room temperature. Due to its physical state and physical chemical properties it is unlikely that this substance will form inhalable dust, mist or fumes during normal processing and use conditions. In case inhalable forms of the substance are created under particular conditions (e.g. spraying, elevated temperature/pressure), appropriate risk management measures such as closed systems, exhaust ventilation or wearing of respirators are implemented to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation.


Justification for classification or non-classification

Based on the acute toxicity data (oral LD50 = 630 mg a.i./kg bw and dermal LD50 = 528 mg a.i./kg bw) of the read across substances, Oleyl TMAC is considered to be classified as 'Acute Tox.4, H302: harmful if swallowed' for oral route and 'Acute Tox.3, H311: toxic in contact with skin' for dermal route, according to EU CLP criteria (Regulation 1272/2008/EC).