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Administrative data

Description of key information

The available data on C12-14 ADMAES indicates potential for acute oral toxicity (LD50 = 570 mg a.i./kg bw). Data on the read-across substance C12-18 TMAC indicates potential for acute dermal toxicity (LD50 = 528 mg a.i./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:
July 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD Guilenine 401 in compliance with GLP.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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
Sex:
male/female
Dose descriptor:
LD50
Effect level:
600 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 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:
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

Males:
- 600 mg/kg: sedation, hypoactivity, piloerection, dyspnea, bloating, rhinorrhea, soft faeces.
Body weight:
Normal
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the acute oral median lethal dose (LD50) of the test substance in male/female rats was found to be >600 mg/kg bw.
Executive summary:

A study was conducted to assess the acute oral toxicity of C12-14 ADMAES (active ingredient > 95%) in Sprague-Dawley rats according to OECD guideline 401. Groups of five Sprague-Dawley rats (5/dose) received a single oral (gavage) dose of 600 mg/kg bw of the test substance. Parameters evaluated included survival, clinical observations, body weight and necropsy findings in all animals after a 14 or 21 day observation period in females and males, respectively. Mortality was observed at 500, 750 and 1,000 mg/kg in females and 600 mg/kg in males. Under the test conditions, the acute oral median lethal dose (LD50) of the test substance in male/female rats was found to be >600 mg/kg bw (i.e., 570 mg a.i./kg bw).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
570 mg/kg bw
Quality of whole database:
A reliable good quality study.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
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:
migrated 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:
other: Study was conducted according to the OECD guideline 402 and EPA OPP 81-2 as well as in compliance with GLP.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Toxic Substances Control Act (TSCA) acute dermal toxicity guideline
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals 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:
1 300 mg/kg bw
Based on:
test mat.
95% CL:
800 - 1 900
Sex:
female
Dose descriptor:
LD50
Effect level:
1 900 mg/kg bw
Based on:
test mat.
95% CL:
1 500 - 2 400
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 600 mg/kg bw
Based on:
test mat.
95% CL:
1 200 - 2 100
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 429 mg/kg bw
Based on:
act. ingr.
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 627 mg/kg bw
Based on:
act. ingr.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 528 mg/kg bw
Based on:
act. ingr.
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.
Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the acute dermal LD50 of the test substance for male and female albino rabbits was found to be 1600 mg/kg bw (95% confidence limits of 1200 − 2100 mg/kg bw) or 528 mg a.i./kg bw.
Executive summary:

An OECD 402 study was conducted to determine the acute dermal toxicity of C12-18 TMAC (active ingredient 33%) in male or female albino rabbits. The test substance was applied (single application) to groups of 10 rabbits (five per sex) at dose levels of 0, 520, 1,020 and 2,000 mg/kg bw to shaved, intact skin under semi-occlusive conditions for 24 h. 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 found to be 1,600 mg/kg bw (i.e., 528 mg a.i./kg bw) (95% confidence limits of 1,200 – 2,100 mg/kg bw).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
528 mg/kg bw
Quality of whole database:
Guideline equivalent study with Klimisch score 2, meeting the tonnage information requirements.

Additional information

Oral

 

A study was conducted to assess the acute oral toxicity of C12-14 ADMAES (active ingredient > 95%) in Sprague-Dawley rats according to OECD guideline 401. Groups of five Sprague-Dawley rats (5/dose) received a single oral (gavage) dose of 600 mg/kg bw of the test substance. Parameters evaluated included survival, clinical observations, body weight and necropsy findings in all animals after a 14 or 21 day observation period in females and males, respectively. Mortality was observed at 500, 750 and 1,000 mg/kg in females and 600 mg/kg in males. Under the test conditions, the acute oral median lethal dose (LD50) of the test substance in male/female rats was found to be >600 mg/kg bw (i.e., 570 mg a.i./kg bw) (Molinier B, 1995).

Dermal

An OECD 402 study was conducted to determine the acute dermal toxicity of C12-18 TMAC (active ingredient 33%) in male or female albino rabbits. The test substance was applied (single application) to groups of 10 rabbits (five per sex) at dose levels of 0, 520, 1,020 and 2,000 mg/kg bw to shaved, intact skin under semi-occlusive conditions for 24 h. 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 found to be 1,600 mg/kg bw (i.e., 528 mg a.i./kg bw) (95% confidence limits of 1,200 – 2,100 mg/kg bw) (Naas DJ, 1988).


Justification for selection of acute toxicity – oral endpoint
Only one guideline-compliant study available.

Justification for selection of acute toxicity – dermal endpoint
Reliable guideline study available on read-across substance.

Justification for classification or non-classification

Oral

Based on the oral LD50 value of 570 mg a.i./kg bw from a guideline study, Xn; R22 (harmful if swallowed) classification is warranted according to Directive 67/548/EEC and Acute Tox.4; H302: harmful if swallowed according to Regulation EC 1272/2008.

Dermal

Based on the dermal LD50 value of 528 mg a.i./kg bw from a guideline study, Xn; R21 (harmful in contact with skin) classification is warranted according to Directive 67/548/EEC and Acute Tox.3; H311: toxic in contact with skin.