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Diss Factsheets

Administrative data

Description of key information

Oral (similar to OECD 401), rat (m, f): LD50 = 31.6 mg/kg bw (males)

Inhalation (similar to OECD 403), rat (m, f): LC50 = 7.7 mg/L air (nominal, males)

Dermal (similar to OECD 402), rabbit (m, f): LD50 = > 6.95 - < 15 mg/kg bw (males)

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Housing: individually
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12


Route of administration:
oral: gavage
Vehicle:
other: tragacanth (0.5%)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 11.2; 13.6; 15; 16.5; 18.1 mg/L
- Amount of vehicle (if gavage): 2.15 ml/kg
- Justification for choice of vehicle: test substance not soluble in water


Doses:
0.024-0.038 mL/kg corresponding to 24.1-39.0 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
Probit analysis
Sex:
female
Dose descriptor:
LD50
Effect level:
33.7 mg/kg bw
Based on:
test mat.
95% CL:
31.1 - 36.5
Sex:
male
Dose descriptor:
LD50
Effect level:
31.6 mg/kg bw
Based on:
test mat.
95% CL:
28.6 - 34.8
Sex:
male/female
Dose descriptor:
LD50
Effect level:
32.7 mg/kg bw
Based on:
test mat.
95% CL:
30.8 - 34.4
Mortality:
Mortality (if any) was observed within 30 min after administration
males: 24.5 mg/kg bw: 0/5
29.6 mg/kg bw: 1/5
35.7 mg/kg bw: 4/5
38.8 mg/kg bw: 5/5

females: 29.6 mg/kg bw: 0/5
32.6 mg/kg bw: 2/5
35.7 mg/kg bw: 3/5
38.8 mg/kg bw: 5/5
Clinical signs:
other: Clonic (and tonic) convulsions, tremor, decrease of  muscle tone, general loss of reflexes, dyspnea, redness of the skin in females. Symptoms appeared 2 min after administration and persisited in surviving animals 1 to 6 h.
Gross pathology:
Only red decoloration of mucosa of the gastrointestinal tracts observed in some animals. No other changes were found.
Interpretation of results:
Category 2 based on GHS criteria
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
31.6 mg/kg bw
Quality of whole database:
Klimisch 2

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study. The concentrations in the air are nominal concentrations and were not measured by a specific analysis. From the data given in the report the nominal concentrations cannot be calculated (data on flow rate, volume missing).
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, Fuellinsdorf/Switzerland
- Housing: except for exposure housing 5 per groups
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: one week prior to exposure


ENVIRONMENTAL CONDITIONS
according to guideline


Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Born & Co, Mechanische Werkstatt Moehlin/Switzerland
- Method of holding animals in test chamber: separate radial polyvinylchloride tubes
- Source and rate of air: no data, different air rates to get different concentrations
- Temperature in the air chamber: 20°C


TEST ATMOSPHERE
- Brief description of analytical method used: no specific analytical method, weighing of the glass bottle filled with test substance before starting the test and afterwards; from the weight difference and the known air volume the test article concentration [mg/L] was calculated
- Samples taken from breathing zone: no


Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
6.5 mg/L
7.8 mg/L
9.3 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observation hourly, after 24 h daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, necropsy
Statistics:
LOGIT estimation
Sex:
male/female
Dose descriptor:
LC50
Effect level:
7.9 mg/L air (nominal)
95% CL:
7.4 - 8.4
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
7.7 mg/L air (nominal)
95% CL:
6.7 - 8.5
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
8 mg/L air (nominal)
95% CL:
7.3 - 9.5
Exp. duration:
4 h
Mortality:
All deaths occured on the test day or killed in moribund state, respectively.
Clinical signs:
other: all dose groups: sedation, dyspnea, ruffled fur, rhinorrhea, ventral- and curved body position symptoms increased with increasing concentration
Body weight:
loss of body weight during observation period
Gross pathology:
lung: dark red discoloured and foam excretion, intestinal tract: meteorism
Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
7 700 mg/m³ air
Quality of whole database:
Klimisch 2

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1981
GLP compliance:
no
Test type:
standard acute method
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Savo, Ivanovas Kisslegg
- Fasting period before study: on test day
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: > 5 days


ENVIRONMENTAL CONDITIONS
according to guideline


Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
according to guideline

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.00681-0.0681 mL/kg (males), 0.0147-0.0681 mL/kg (females)
- Constant concentration used: yes



Duration of exposure:
24 h
Doses:
6.95-69.5 mg/kg bw (males)
15.0-69.5 mg/kg bw (females)
No. of animals per sex per dose:
2-3
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Probit Analysis
Sex:
male
Dose descriptor:
LD50
Effect level:
> 6.95 - < 15 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
32.2 mg/kg bw
Mortality:
Deaths occurred between 30 min and 2 h after application.
Clinical signs:
other: decrease of muscle tone, general loss of reflexes, streneous respiration, cyanosis, mydriasis. First symptoms 3-40 min post appl. persistant 2 to 3 h.
Gross pathology:
no substance related changes
Other findings:
formation of eschar at the exposed skin site; severe local reactions: nose bleedings, redness and crusts

The test substance was applied undiluted and caused severe local reactions (nose bleedings, redness and crusts) in addition to the systemic toxicity.

Interpretation of results:
Category 1 based on GHS criteria
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
15 mg/kg bw
Quality of whole database:
Klimisch 2

Additional information

Acute oral toxicity:

In a key study performed similar to OECD guideline 401 (non-compliant with GLP), the test item was administered to male and female rats (82-0008 -DKT). The test item was administered in tragacanth (0.5%) by gavage. The animals received doses of 24.1-39.0 mg/kg bw. Following administration, the animals were observed for a period of 14 days for clinical signs of toxicity and mortality. The were no information on body weight. At study termination, all decedent and surviving animals were subjected to gross necropsy.

Mortality was observed in males at > 29.6 mg/kg bw and in females at > 32.6 mg/kg bw; most deaths occurred within 30 minutes post-dosing. Clinical signs of toxicity were clonic (and tonic) convulsions, tremor, decrease of  muscle tone, general loss of reflexes, dyspnea, redness of the skin in females. Symptoms appeared 2 min after administration and persisited in surviving animals 1 to 6 h.

At the post mortem examination, only red decoloration of mucosa of the gastrointestinal tracts was observed in some animals. No other changes were found.

Under the conditions of the test, the acute oral LD50 value was 31.6 mg/kg bw in male and 33.7 mg/kg bw in female rats.

Acute inhalation toxicity:

In the key study conducted similar to OECD guideline 403 and (non-compliance with GLP), 5 male and 5 female Wistar rats were exposed for 4 h via nose-only inhalation (83-0012-DKT). The test item was administered as vapour at concentrations of 6.5 mg/L,

7.8 mg/L and 9.3 mg/L. The concentrations in the air were nominal concentrations and were not measured by a specific analysis. From the data given in the report the nominal concentrations cannot be calculated (data on flow rate, volume missing).

After exposure, the animals were observed for a period of 14 days. Clinical signs of toxicity and mortality were recorded after 24 h daily during the observation period. Body weights were recorded. At study termination all animals underwent gross pathology.

All deaths occured on the test day or killed in moribund state, respectively. In all dose groups sedation, dyspnea, ruffled fur, rhinorrhea, ventral- and curved body position symptoms increased with increasing concentration was observed. A loss of body weight during observation period. Macroscopic examination at scheduled necropsy showed dark red discoloured and foam excretion in the lung and meteorism in the intestinal tract.

Under the conditions of the test, the acute inhalation LC50value was >7.7 mg/L air for male and and 8 mg/L for female rats.

 

Acute dermal toxicity:

The acute dermal toxicity of ACA was investigated in two studies, of which one study was selected as key study.

The key study was performed similar to OECD guideline 402 (85 -0005 -DKT, non-GLP study). The test item was applied unchanged (no vehicle) to 2 -3 male/female rabbits for 24 h under occlusive conditions. Males were exposed to 6.95 -69.5 mg/kg bw and females were exposed to 15.0 -69.5 mg/kg bw.

During exposure and during the 14-days observation period thereafter, the animals were inspected for clinical signs and mortality. Body weights were not determined, and at study termination all surviving animals were examined for gross pathological abnormalities.

Deaths occurred between 30 min and 2 h after application. Clinical signs comprised decrease of muscle tone, general loss of reflexes, streneous respiration, cyanosis, mydriasis. First symptoms 3-40 min post appl. persistant 2 to 3 h. Other findings were formation of eschar at the exposed skin site and severe local reactions such as nose bleedings, redness and crusts. There were no substance related changes at gross pathology.

The acute dermal LD50value was >6.95 - <15 mg/kg bw in male rabbits and 32.2 mg/kg bw in female rabbits.

 

Within the other acute dermal toxicity study (83 -0011 -DKT) LD50 were 67.3 mg/kg bw in male rats and 70.4 mg/kg bw in female rats.

Justification for classification or non-classification

The available data on acute oral toxicity meet the criteria for classification as Acute Oral 2 (H300) according to Regulation (EC) No. 1272/2008 (CLP) and according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations.

The available data on acute inhalation toxicity with the vapour meet the criteria for classification as Acute Inhal 3 (H331) according to Regulation (EC) No. 1272/2008 (CLP) and according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations.

The available data on acute dermal toxicity meet the criteria for classification as Acute Dermal 1 (H310) according to Regulation (EC) No. 1272/2008 (CLP) and according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations.