Registration Dossier

Administrative data

Description of key information

oral: A study according to OECD TG 423 was performed to determine the acute toxicity of the test item after oral administration to rats. The LD50 for males and females, after an observation period of 15 days, is expected to be between 200 - 2000 mg/kg bw (reference 7.2.1 -1).

dermal

Acute Toxicity Estimate (ATE): 1.100,1 mg/kg bw. The substance in corrosive to skin (please refer to section 7.3.1).

inhalative

Acute Toxicity Estimate (ATE): 1,6 mg/L (dust/mist). Symptoms: mucosal irritations, cough, shortness of breath, damage of respiratory tract

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:
May 26, 2000 - September 28, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
March 22, 1996
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
September 30, 1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: HsdCpb: WU
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen
- Age at study initiation: about 6 to 8 weeks
- Weight at study initiation: 172 (range from 159 to 181) g
- Fasting period before study: Diet was withheld from about 17 hours before dosing up to 4 hours after treatment.
- Housing: separately in Makrolon cages type HI with a shelter
- Diet: ad libitum, LONG LIFE for mice and rats 9439, Eberle Nafag)
- Water: ad libitum, tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 28
- Humidity (%): 50 to 66
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
other: Methocef K4M Premium solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1.25, 10, 100 g/L

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

Doses:
25, 200, 2000 mg/kg bw
No. of animals per sex per dose:
3 (see table1)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The behavior and general condition of all rats were monitored for at least 6 hours after the administration and then checked daily. All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 200 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals of the highest dose died within a few minutes after administration.
Clinical signs:
Signs of toxicity were seen from 1 to 15 minutes up to day 3 after administration.
2000 mg/kg bw (f): lateral position, motor excitation, and dyspnea.
200 mg/kg bw (m + f): abdominal and dorsal position, lococmotor disturbance, and dyspnea.
25 mg/kg bw(m): locomotor disturbance was the only symptom.
Body weight:
Body weight development of the surviving rats was inconspicuous.
Gross pathology:
At pathology all rats which died showed mild local changes in the gastro intestinal tract. All rats which were sacrificed at the end of the study showed no macroscopic abnormalities.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
According to the results of this study the LD50 value is expected between 200 - 2000 mg/kg bw.
Executive summary:

A study according OECD TG 423 (Acute Class Method) was performed to determine the acute oral toxicity of the test item. The test material was administered by oral gavage using doses of 25, 200, and 2000 mg/kg body weight. Directly before the administration the test material was prepared with aqueous Methocel® K4M Premium solution as vehicle.

Signs of toxicity were seen from 1 to 15 minutes up to day 3 after administration. In females of the 2000 mg/kg be dose group lateral position, motor excitation, and dyspnea was reported.

In all animals of the 200 mg/kg bw dose group abdominal and dorsal position, locomotor disturbance, and dyspnea was detected. In the 25 mg/kg bw dose group males showed locomotor disturbance.

All animals of the highest dose died within a few minutes after administration. Body weight development of the surviving rats was inconspicuous.

At pathology all rats which died showed mild local changes in the gastro intestinal tract. All rats which were sacrificed at the end of the study showed no macroscopic abnormalities.

According to the results of this study the LD50 value is expected between 200 - 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Quality of whole database:
OECD TG 423

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

oral

A study according OECD TG 423 (Acute Class Method) was performed to determine the acute oral toxicity of the test item. The test material was administered by oral gavage using doses of 25, 200, and 2000 mg/kg body weight. Directly before the administration the test material was prepared with aqueous Methocel® K4M Premium solution as vehicle.

Signs of toxicity were seen from 1 to 15 minutes up to day 3 after administration. In females of the 2000 mg/kg be dose group lateral position, motor excitation, and dyspnea was reported.

In all animals of the 200 mg/kg bw dose group abdominal and dorsal position, locomotor disturbance, and dyspnea was detected. In the 25 mg/kg bw dose group males showed locomotor disturbance.

All animals of the highest dose died within a few minutes after administration. Body weight development of the surviving rats was inconspicuous.

At pathology all rats which died showed mild local changes in the gastro intestinal tract. All rats which were sacrificed at the end of the study showed no macroscopic abnormalities.

According to the results of this study the LD50 value is expected to be between 200 - 2000 mg/kg bw (reference 7.2.1 -1).

Supporting data

Based on acute oral toxicity data, the LD50 of the substance was determined to be 200 mg/kg bw > LD5 < 2000 mg/kg bw/d (reference 7.2.1 -1). Data of a 28- day repeated dose oral toxicity study in rats (reference. 5.7.1 -1) revealed a NOAEL of 450 mg/kg bw/d, i. e. no mortalities occured at this dose level. Taken together, the LD50 of the test item is concluded to be 450 mg/kg bw < LD50 < 2000 mg/kg bw/d.

dermal

The substance in corrosive to skin (please refer to section 7.3.1). The Acute Toxicity Estimate (ATE) is 1.100,1 mg/kg bw.

inhalative

The Acute Toxicity Estimate (ATE) is 1,6 mg/L (dust/mist). Possible symptoms are mucosal irritation, cough, shortness of breath and damage of respiratory tract.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data for acute oral toxicity are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on acute oral toxicity data, the LD50 of the substance was determined to be 200 mg/kg bw > LD5 < 2000 mg/kg bw/d. Data of a repeated dose oral toxicity study (Ref. 7.5.1 -1) in rats revealed a NOAEL of 450 mg/kg bw/d. Based on this, oral LD50 was concluded to be greater than 450 mg/kg bw. In conclusion, the LD50 of the test item is 450 mg/kg bw < LD50 < 2000 mg/kg bw/d. Therefore, the test item is considered to be classified for acute oral toxicity Cat 4 (H302) under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.

The substance is corrosive to eyes and skin. In the acute oral toxicity study systemic effects including mortality have been reported. In a worst case approach systemic effects are also predicted for the acute dermal and the acute inhalative route of exposure. Based on this, the substance is considered to be classified for acute dermal (H312) and acute inhalative (H332) toxicity Cat 4 under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521. This procedure for classification and labelling of the substance for acute toxicity has already been agreed with the German Competent Authority (BAuA) as part of the new substance notification under Chemicals Act of the Federal Republic of Germany (ChemG) and according to Directive 67/548 EEC.