Quaternary ammonium compounds, C12-14-alkyltrimethyl, Me sulfates

Endpoint summary

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 from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

July 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Refer to section 13 for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Crédo, 69210 L'arbresle, France
- Age at study initiation: ca. 6 weeks
- Weight at study initiation: 178 +/- 7 g for males, 159 +/- 8 g for females
- Fasting period before study: 1 day
- Housing: housed in groups by sex
- Diet (e.g. ad libitum): "Rats et Souris entretien référence A04C" (U.A.R., 9160 Villemoisson-sur-Orge, Fance)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12/h
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light

Route of administration:

oral: gavage

Vehicle:

water

Doses:

Males:
- 600 mg/kg (10 mL/kg)

Females:
- 200 mg/kg (10 ml/kg)
- 500 mg/kg (10 ml/kg)
- 750 mg/kg (15 ml/kg)
- 1,000 mg/kg (20 ml/kg)

No. of animals per sex per dose:

5 animals

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 d for females and 21 d for males
- Frequency of observations and weighing: Animals observed for clinical signs and mortality at frequent intervals on Day 1 and twice daily thereafter; body weight measured on Day 1, 8, 15 and 22.
- Necropsy of survivors performed: yes, animals were sacrificed by CO2.
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

600 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

570 mg/kg bw

Based on:

act. ingr.

Mortality:

Females: No mortality observed at 200 mg/kg. 20, 80 and 100% mortality observed at 500, 750 and 1,000 mg/kg bw, respectively.
Males: 20% mortality observed at 600 mg/kg bw.

Clinical signs:

other: Females: - 200 and 500 mg/kg: hypoactivity on 4/5 animals on the day of administration. - 750 mg/kg: sedation, hypoactivity, lateral decubitus, dyspnoea, piloerection - 1,000 mg/kg: sedation, hypoactivity, piloerection, contaminated uro-vaginal area Mal

Interpretation of results:

other: Acute Tox. 4 based on CLP criteria

Conclusions:

Based on the results of the read across study, the acute oral median lethal dose (LD50) of the test substance in male/female rats can be considered to be >600 mg/kg bw (i.e., 570 mg a.i./kg bw).

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, C12-14 ADMAES (purity: >95%), in Sprague-Dawley rats according to OECD Guideline 401. Male Sprague-Dawley rats received a single oral (gavage) dose of 0 and 600 mg/kg bw and females received oral (gavage) doses of 0, 200, 500, 750 and 1000 mg/kg bw of the test substance. Parameters evaluated included survival, clinical observations, body weight and necropsy findings in all animals after 14 or 21 days observation period in females and males, respectively. Mortality was observed at 500, 750 and 1,000 mg/kg bw in females and 600 mg/kg bw in males. Under the study conditions, the acute oral LD50 of the test substance in male/female rats was found to be >600 mg/kg bw (equivalent to 570 mg a.i./kg bw) (Molinier, 1995).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

570 mg/kg bw

Quality of whole database:

Good quality

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 from supporting substance (structural analogue or surrogate)

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 section 13 for details on the read-across justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across source

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.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 300 mg/kg bw

Based on:

test mat.

95% CL:

>= 800 - <= 1 900

Remarks on result:

other: equivalent to 429 mg a.i./kg bw

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 900 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 500 - <= 2 400

Remarks on result:

other: equivalent to 627 mg a.i./kg bw

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 600 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 200 - <= 2 100

Remarks on result:

other: 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:

other: 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.

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, C12-14 TMAC, can also be considered to be 528 mg a.i./kg bw (429-627 mg a.i./kg bw for males and females).

Executive summary:

A study was conducted to determine the acute dermal toxicity of the read across substance, Coco TMAC (active ingredient 33%), in albino rabbits according to OECD Guieline 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 study conditions, the acute dermal LD50 for male and female albino rabbits were determined to be 1,300 mg/kg bw (equivalent to 429 mg a.i./kg bw) and 1,900 mg/kg bw (equivalent to 627 mg a.i./kg bw) respectively, and the combined dermal LD50 value for males and females was determined to be 1,600 mg/kg bw (equivalent to 528 mg a.i./kg bw)(Naas, 1988).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

528 mg/kg bw

Quality of whole database:

Good quality

Additional information

Acute oral:

A study was conducted to determine the acute oral toxicity of the read across substance, C12-14 ADMAES (purity: >95%), in Sprague-Dawley rats according to OECD Guideline 401. Male Sprague-Dawley rats received a single oral (gavage) dose of 0 and 600 mg/kg bw and females received oral (gavage) doses of 0, 200, 500, 750 and 1000 mg/kg bw of the test substance. Parameters evaluated included survival, clinical observations, body weight and necropsy findings in all animals after 14 or 21 days observation period in females and males, respectively. Mortality was observed at 500, 750 and 1,000 mg/kg bw in females and 600 mg/kg bw in males. Under the study conditions, the acute oral LD50 of the test substance in male/female rats was found to be >600 mg/kg bw (equivalent to 570 mg a.i./kg bw) (Molinier, 1995).

Acute dermal:

A study was conducted to determine the acute dermal toxicity of the read across substance, Coco TMAC (active ingredient 33%), in albino rabbits according to OECD Guieline 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 study conditions, the acute dermal LD50 for male and female albino rabbits were determined to be 1,300 mg/kg bw (equivalent to 429 mg a.i./kg bw) and 1,900 mg/kg bw (equivalent to 627 mg a.i./kg bw) respectively, and the combined dermal LD50 value for males and females was determined to be 1,600 mg/kg bw (equivalent to 528 mg a.i./kg bw) (Naas, 1988).

Justification for classification or non-classification

Based on the results of the read across studies, the test substance, Quaternary ammonium compounds, C12-14 alkyltrimethyl, Me sulfates warrants classification for acute oral and dermal toxicity as 'Acute tox. 4 (H302: Harmful if swallowed) and 'Acute tox. 3 (H311: Toxic in contact with skin)' according to EU CLP (1272/2008/EC) criteria.