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Description of key information

The oral LD50 value of the test substance was determined to be 699 mg a.i./kg bw in rats, suggesting a moderate acute toxicity potential.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From June 27, 1984 to August 02, 1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Kastengrund
- Weight at study initiation: 176-201 g for males; 181-219 g for females
- Fasting period before study: 16 h
- Housing: up to 5 animals per cage in Macrolon cages
- Diet : Altromin 1324 (Altromin GmbH, Lage/Lippe) ad libitum
- Water : Tap water ad libitum
- Acclimation period: min 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 45 - 65
Route of administration:
oral: gavage
Vehicle:
water
Doses:
630, 1000, 1600, 2500, 3150 and 4000 mg/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of weighing: Days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs, body weight and gross pathological examination
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 410 mg/kg bw
Based on:
test mat.
Remarks on result:
other: equivalent to 699 mg a.i./kg bw
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 2 970 mg/kg bw
Based on:
test mat.
Remarks on result:
other: equivalent to 861 mg a.i./kg bw
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 1 550 mg/kg bw
Based on:
test mat.
Remarks on result:
other: equivalent to 450 mg a.i./kg bw
Mortality:
Mortalities occured from Day 1 to Day 13 of the study.
Clinical signs:
Clinical signs observed in the first days in male and female rats included: quiet behaviour, hunched posture, closed eyelids, retracted flanks, rough fur, paleness, noisy unregular breathing, myosis and slimy feces.
Body weight:
Reduced bodyweight compared to the other groups was seen in individual animals at most dosage groups, in particular after 7 days.
Gross pathology:
Animals dying during the study showed the following symptoms:
- Bleeding in the mucous membrane of the stomach, swollen stomach, stomach filled with liquid, slime or feed, glassy appearence of the small intestine, reddened small intestine mucous membrane, small intestine filled with yellowish-clear mass
- Darkened adrenal glands, very full bladder
- Bleeding in the lungs

Animals sacrificed at the end of the study did not present any significant macroscopic changes.

For result tables, kindly refer to the attached background material section of the IUCLID.

Interpretation of results:
other: Category 4 based on CLP criteria
Conclusions:
Under the study conditions, the acute oral LD50 was determined to be 2,410 mg/kg bw for males/females combined, 2,970 mg/kg bw for males and 1,550 mg/kg bw for females (equivalent to 699, 861 and 450 mg a.i./kg bw, respectively).
Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance, C16 TMAC (29% active in water) in Wistar rats according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. A group of 10 fasted animals (five males and five females) were administered a single oral dose of the test substance at nominal doses of 630, 1,000, 1,600, 2,500, 3,150 and 4,000 mg/kg bw. The animals were observed for 14 days following exposure. The animals were then sacrificed and subjected to gross pathological examination. The animals responded with squatting position and retracted flanks; the breathing was affected. At autopsy the animals were observed to have hamorrhagia and irritation of the stomach and intestinal mucosa. Under the study conditions, the acute oral LD50 was determined to be 2,410 mg/kg bw for males/females combined, 2,970 mg/kg bw for males and 1,550 mg/kg bw for females (equivalent to 699, 861 and 450 mg a.i./kg bw, respectively) (Rüpprich and Weigand, 1984).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 31 March, 1990 to 14 April, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP not specified
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substances Control Act, 16 CFR 1500.3
Deviations:
no
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hilltop lab animals, Scottdale, PA
- Weight at study initiation: 228-295 g
- Fasting period before study: 18 h
- Housing: Individually in suspended stainless steel caging with mesh floors
- Diet : Pelleted Purina rat chow # 5012, ad libitum
- Water : Tap water supplied by automatic water system, ad libitum
- Acclimation period: 25 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
5,000 mg/kg bw of 5% active substance
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 1 and 2 h after dosing and subsequently once daily for 14 days
- Frequency of weighing: Day 0 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs, body weight and gross pathological examination
Preliminary study:
One animal died on day 2. No other deaths up to day 14.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: equivalent to >250 mg a.i./kg bw
Mortality:
One animal died on day 2. Signs prior to death were lethargy, anogenital staining and hunched posture.
Clinical signs:
During the first 3 d post-dosing, transient diarrhoea, soft faeces and ano-genital staining were observed in several animals. From Day 4 all animals appeared active and healthy. There were no further signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.
Body weight:
All of the surviving males gained weight. One surviving female lost 2 g by test termination.
Gross pathology:
Necropsy of the decedent revealed discolouration of the lungs, liver, kidney and spleen and accumulation of fluid and distention of the gastro-intestinal tract.
Interpretation of results:
other: not used for classification
Conclusions:
Under the study conditions, the acute oral LD50 of test substance was considered to be greater than 5,000 mg/kg bw (i.e., equivalent to 250 mg a.i./kg bw).
Executive summary:

A study was performed to determine the acute oral toxicity of the test substance C16 TMAC (5% active in water) in Sprague-Dawley rats, according to Federal Hazardous Substances Control Act, 16 CFR 1500.3. A group of 10 fasted animals (five males and five females) were administered a single oral dose of 5,000 mg/kg bw of the test substance (5% active ingredient). The animals were observed for 14 days post-exposure and then sacrificed and subjected to gross pathological examination. One animal died on Day 2. The signs prior to death were lethargy, anogenital staining and hunched posture. During the first 3 days post-dosing, transient diarrhea, soft feces and ano-genital staining were observed in several animals. From Day 4 through the balance of the study all animals appeared active and healthy. There were no further signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. All the surviving males gained weight. One surviving female lost 2 g by test termination. Therefore, under the study conditions, the acute oral LD50 of was considered to be greater than 5,000 mg/kg bw (i.e., equivalent to >250 mg a.i./kg bw) (Shapiro, 1990).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
699 mg/kg bw
Quality of whole database:
Guideline compliant 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:
the study does not need to be conducted because the substance is classified as corrosive to the skin
other:
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
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as corrosive to the skin
Reason / purpose for cross-reference:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral  

Study 1:A study was conducted to determine the acute oral toxicity of the test substance, C16 TMAC (29% active in water) in Wistar rats according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. A group of 10 fasted animals (five males and five females) were administered a single oral dose of the test substance at nominal doses of 630, 1,000, 1,600, 2,500, 3,150 and 4,000 mg/kg bw. The animals were observed for 14 days following exposure. The animals were then sacrificed and subjected to gross pathological examination. The animals responded with squatting position and retracted flanks; the breathing was affected. At autopsy the animals were observed to have hamorrhagia and irritation of the stomach and intestinal mucosa. Under the conditions of the study, the acute oral LD50 was determined to be 2,410 mg/kg bw for males/females combined, 2,970 mg/kg bw for males and 1,550 mg/kg bw for females. This is equivalent to 699, 861 and 450 mg a.i./kg bw, respectively (Rüpprich and Weigand, 1984).

 

Study 2:A study was performed to determine the acute oral toxicity of the test substance C16 TMAC (5% active in water) in Sprague-Dawley rats, according to Federal Hazardous Substances Control Act, 16 CFR 1500.3. A group of 10 fasted animals (five males and five females) were administered a single oral dose of 5,000 mg/kg bw of the test substance (5% active ingredient). The animals were observed for 14 days post-exposure and then sacrificed and subjected to gross pathological examination. One animal died on Day 2. The signs prior to death were lethargy, anogenital staining and hunched posture. During the first 3 days post-dosing, transient diarrhea, soft feces and ano-genital staining were observed in several animals. From Day 4 through the balance of the study all animals appeared active and healthy. There were no further signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. All the surviving males gained weight. One surviving female lost 2 g by test termination. Therefore, under the study conditions, the acute oral LD50 of was considered to be greater than 5,000 mg/kg bw (i.e., equivalent to >250 mg a.i./kg bw) (Shapiro, 1990).

 

Inhalation: 

In accordance with Annex VII, Section 8.5, Column 2, additional acute toxicity study for inhalation route does not need to be conducted because the substance is classified as corrosive to the skin. Further, the substance has a low vapour pressure (VP = 0.0058 Pa at 25°C), which is below the cut-off of 0.01 Pa set for defining low volatility substances, as per the ECHA Guidance R.7a. Therefore, due to the physical state and low VP, it is unlikely that it will form inhalable dust, mist or fumes when handled and used in solid form. 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. 

Dermal:  

In accordance with Annex VII, Section 8.5, Column 2, additional acute toxicity study for dermal route does not need to be conducted because the substance is classified as corrosive to the skin.  

Justification for classification or non-classification

Based on the oral LD50 value, the test substance warrants an ‘Acute Tox. 4; H302: harmful if swallowed’ classification according to EU CLP criteria (Regulation EC 1272/2008).In addition for the inhalation route, although C16 TMAC is classified to be corrosive (see section 5.3) and this drives its mechanism of action of toxicity, its inherent low vapour pressure prohibits the occurrence of respiratory irritation or corrosion by vapour. Therefore, it does not warrant an additional labelling as: EUH071 — ‘Corrosive to the respiratory tract’ according to EU CLP criteria (Regulation EC 1272/2008).

Further, the available data does not show indication that classification for STOT-SE cat 1 or 2 is indicated. For STOT-SE Cat 3: C16 TMAC or QAS substances are not narcotic.