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Description of key information

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:
From January 03, 1996 to February 21, 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- Product code: 06 FHFR555
- pH: Approximately 5 (10 g/L)
- Appearence: Light yellowish scales
- Melting point: 60-70⁰C
- Solubility: >10 g/L in water, ethanol, isopropanol
- Batch number: 1061969521
- Storage conditions: Darkness at room temperature in a fume cupboard
-Active ingredient 79.8%
Species:
rat
Strain:
other: Hoe: WISKf (SPF71)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst aktiengesellschaft, Kastengrund, SPF breeding colony
- Age at study initiation: Approximately 7 wk (m) and 8 wk (f)
- Weight at study initiation: Mean: 185g (m) and 171g (f)
- Fasting period before study: Yes
- Housing: In fully air-conditioned rooms in macrolon cages on soft wood granulate in group of 5 animals
- Diet: Ssniff R/M-H (V 1534), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: Atleast one day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ± 20%

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Deionized
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 6.3, 8, 12.5 and 20% in deionised water
- Justification for choice of vehicle: Test substance is soluble in water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Dose range finding study
Doses:
800 and 2,000 mg/kg bw for males and 630, 800, 1,250 and 2,000 mg/kg bw
No. of animals per sex per dose:
5 per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14d
- Frequency of observations and weighing: Symptoms and lethality were recorded twice every day, on weekends and public holiday only once. weighing was done weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
The LD50 and the equation of the probit line were established in female animals on the basis of the lethality rates by probit analysis.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
702.5 mg/kg bw
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 800 - < 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD100
Effect level:
1 250 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD100
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
Yes, although in males there was no mortality at 800 mg/kg bw, all animals died at 2,000 mg/kg bw. In females, only 2 and 3 animals survived at 630 and 800 mg/kg bw, respectively. At 1,250 and 2,000 mg/kg bw, all females died.
Clinical signs:
Decreased spontaneous activity, squatting posture, narrowed palpebrae fissures and irregular respiration. Also, stupor was observed only in the animals of the 2,000 mg/kg bw group. One female animal of the 800 mg/kg bw group showed blood encrusted lid margin on Day 6 of the study. All clinical signs were reversible at Day 8 of the study.
Body weight:
No effects
Gross pathology:
Macroscopic examination of the dead animals:
Stomach: Full of clear fluid, full of gas, detachment of the mucosa, petechial bleeding
Intestinal tract: Full of yellowish mucous, full of clear fluid, detachment of the mucosa, full of reddish mucosa

The animals killed at the end of the observation period showed macroscopically visible changes.
Conclusions:
Under the study conditions, the LD50 for the female Wistar rats was found to be 702.5 mg test substance/kg bw (i.e., 560.5 mg a.i./kg bw). Male animals did not show a higher sensitivity to the test substance.
Executive summary:

A study was conducted to determine the oral acute toxicity of the test substance (purity 79.8%) according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. The experiment was performed in Wistar rats. The test substance was administered as a single dose to 5 female rats per group at 630, 800, 1250 and 2000 mg/kg bw (equivalent to 503, 638, 998 and 1596 mg a.i./kg bw) and to 5 males rats per group at doses of 800 and 2000 mg/kg bw (equivalent to 638 and 1596 mg a.i./kg bw, after which animals were examined for 14 days. Examinations performed were mortality, body weights, clinical signs and gross necropsy for any macroscopic abnormalities. In males, there was no mortality at 800 mg/kg bw, however all animals died at 2000 mg/kg bw. In females, only 2 and 3 animals survived at 630 and 800 mg/kg bw respectively. At 1250 and 2000 mg/kg bw, all females died. Females, therefore, appeared to be more susceptible to the effects of treatment than males. Decreased spontaneous activity, squatting posture, narrowed palpebrae fissures and irregular respiration were recorded. Also, stupor was observed only in the animals of the 2000 mg/kg bw group. One female animal of the 800 mg/kg bw group showed blood encrusted lid margin on Day 6 of the study. All clinical signs were reversible at Day 8 of the study. No effects were seen on the body weight. The animals killed at the end of the observation period showed macroscopically visible changes. Under the study conditions, the LD50 for the female Wistar rats was found to be 702.5 mg test substance/kg bw (i.e. 560.5 mg a.i./kg bw) (Jensch, 1996).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
560.5 mg/kg bw
Quality of whole database:
One reliable OECD guidelines as well as GLP compliant acute oral toxicity study available, meeting the tonnage information requirements.

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
the study need not 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
Reason / purpose:
data waiving: supporting information
Related information:
Composition 1
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

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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 February 22, 1988 to March 24, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
RA study
Justification for type of information:
Refer to the section 13 for details on the read across justification. The dermal acute toxicity study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reference:
Composition 1
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
Specific details on test material used for the study:
- Physical state: Clear yellow liquid
- Analytical purity: 33%
- Lot/batch No.: 1735305
- Storage condition of test material: Sealed container at room temperature
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 2990g
- 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 7d

ENVIRONMENTAL CONDITIONS
- Humidity (%): 49-74%
- Photoperiod (h dark / h light): 12h / 12h
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:
24h
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 4h post-dosing on Day 0 and twice daily for mortality and once daily for clinical observations for 14d. 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
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 900 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 500 - <= 2 400
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
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 429 mg/kg bw
Based on:
act. ingr.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 627 mg/kg bw
Based on:
act. ingr.
Key result
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 the 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 14d observation peirod. For the 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:
The 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.
Conclusions:
Based on the results of the read across study, 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:

A study was conducted to determine the dermal acute toxicity of the read across substance,quaternary ammonium compounds, C12-C18 (even numbered) alkyltrimethyl chloride (C12-18 TMAC), according to OECD Guideline 402 and US EPA OPP 81 -2, in compliance with GLP. The test substance (0, 520, 1020 or 2000 mg/kg bw) was applied to male and female albino rabbits under semi-occlusive conditions for 24 h. The experiment consisted of 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 1020 mg/kg bw group while 4 males and 3 females died in the 2000 mg/kg bw group.Lethargy and ataxia were the major clinical findings. Other findings included hypothermia, decreased respiratory rate, laboured respiration, nasal discharge, decreased defecation, emaciation, red staining around the mouth, diarrhoea. Treatment-related body weight loss was recorded in one animal each at two higher doses throughout the 14 d observation period. For the other eight rabbits, body weight was decreased during first week with a subsequent recovery in the second week and net gain in the entire 14 d study period. Moreover, the 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. Based on the results of the read across study, 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 (Naas, 1988).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
528 mg/kg bw
Quality of whole database:
The acute dermal toxicity study conducted with structurally similar substance C12-C18 TMAC.

Additional information

Oral:

A study was conducted to determine the oral acute toxicity of the test substance (purity 79.8%) according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. The experiment was performed in Wistar rats. The test substance was administered as a single dose to 5 female rats per group at 630, 800, 1250 and 2000 mg/kg bw (equivalent to 503, 638, 998 and 1596 mg a.i./kg bw) and to 5 males rats per group at doses of 800 and 2,000 mg/kg bw (equivalent to 638 and 1596 mg a.i./kg bw, after which animals were examined for 14 days. Examinations performed were mortality, body weights, clinical signs and gross necropsy for any macroscopic abnormalities. In males, there was no mortality at 800 mg/kg bw, however all animals died at 2000 mg/kg bw. In females, only 2 and 3 animals survived at 630 and 800 mg/kg bw respectively. At 1250 and 2000 mg/kg bw, all females died. Females, therefore, appeared to be more susceptible to the effects of treatment than males.Decreased spontaneous activity, squatting posture, narrowed palpebrae fissures and irregular respiration were recorded. Also, stupor was observed only in the animals of the 2000 mg/kg bw group. One female animal of the 800 mg/kg bw group showed blood encrusted lid margin on Day 6 of the study. All clinical signs were reversible at Day 8 of the study. No effects were seen on the body weight. The animals killed at the end of the observation period showed macroscopically visible changes. Under the study conditions, the LD50 for the female Wistar rats was found to be 702.5 mg test substance/kg bw (i.e. 560.5 mg a.i./kg bw) (Jensch, 1996).

Dermal:

A study was conducted to determine the dermal acute toxicity of the read across substance,quaternary ammonium compounds, C12-C18 (even numbered) alkyltrimethyl chloride (C12-18 TMAC), according to OECD Guideline 402 and US EPA OPP 81 -2, in compliance with GLP. The test substance (0, 520, 1020 or 2000 mg/kg bw) was applied to male and female albino rabbits under semi-occlusive conditions for 24 h. The experiment consisted of 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 1020 mg/kg bw group while 4 males and 3 females died in the 2000 mg/kg bw group.Lethargy and ataxia were the major clinical findings. Other findings included hypothermia, decreased respiratory rate, laboured respiration, nasal discharge, decreased defecation, emaciation, red staining around the mouth, diarrhoea. Treatment-related body weight loss was recorded in one animal each at two higher doses throughout the 14 d observation period. For the other eight rabbits, body weight was decreased during first week with a subsequent recovery in the second week and net gain in the entire 14 d study period. Moreover, the 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. Based on the results of the read across study, 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 (Naas, 1988).

Justification for classification or non-classification

The acute toxicity data (oral and dermal LD50 of 560.5 and 528 mg a.i./kg bw, respectively) indicates that the test substance should be classified as follows: R22 (harmful if swallowed) and R21 (harmful in contact with skin), according to Directive 67/548/EEC and Acute Tox. 4 - H302: harmful if swallowed and Acute Tox. 3 - H311: toxic in contact with skin classification, according to Regulation (EC) 1272/2008.