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Administrative data

Description of key information

- Acute oral toxicity: LD50 1000 - 2000 mg/kg (rat; 1988); LD50 2158 mg/kg bw (rat; Bomhard, 1997)
- Acute inhalation toxicity: inhalation hazard test, no mortality (rat; 1989); LC50 > 9.219 mg/L (rat; Bomhard, 1997)
- Acute dermal toxicity: no data; waiver due to corrosivity

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:
comparable to guideline study with acceptable restrictions
Remarks:
without GLP status
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. Thomae, Biberach/Germany
- Weight at study initiation: 181 g (mean weight males), 180 g (mean weight females)
- Fasting period before study: 16 hours before administration, except water
- Housing: groups of 5
- Diet: Kliba Labordiaet, 343; ad libitum
- Water: tap water; ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20, 10, 4.64 mg/ 100 mL
- Amount of vehicle (if gavage): 10 mL/kg
Doses:
464, 1000, 2000 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
- Frequency of observations: Recording of signs and symptoms several times on the day of administration, at least once each workday. Check for moribund and dead animals twice each workday and once on holidays.
- Frequency of weighing: at day 0, 7 and 13 of the study
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 000 - 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 4 male and 4 female animals of the 2000 mg/kg bw dose group died. Observed clinical signs were reversible within 14 days.
Mortality:
4 male and 4 female animals of the 2000 mg/kg bw dose group died during the first two days post treatment. No further mortality observed.
Clinical signs:
2000 mg/kg bw dose group:
Dyspnea, apathy, staggering, piloerection and poor general state was observed post treatment (4 hours) and up to 2 days after treatment in all animals. Twitching was observed 4 hours after treatment in the female animals. Afterwards, no clinical signs were observed.
No clinical signs were observed in the 464 and 1000 mg/kg bw dose groups.
Body weight:
Mean male body weights 7/13 days post treatment (2000, 1000, 464 mg/kg bw dose groups): 224, 245, 265 / 262, 280, 301 g
Mean female body weights 7/13 days post treatment (2000, 1000, 464 mg/kg bw dose groups): 203, 209, 234 / 213, 218, 249 g
Gross pathology:
Animals that died (male + female): General congestion.
Stomach: atonic; reddened mucosa; striking liquid contents.
Intestines: atonic; reddened mucosa; liquid contents, in most animal bloody.
No pathological findings noted in surviving animals.
Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
1 000 mg/kg bw
Quality of whole database:
Available data is reliable and sufficient for assessment.

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:
comparable to guideline study with acceptable restrictions
Remarks:
Inhalation hazard test; Annex of OECD 403 as adopted (1981)); 3 animals per sex, no definition of chamber volume, no data on body weight gain, no determination of test atmosphere concentration
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(IHT, adopted on 1981, 12th of may)
Deviations:
yes
Remarks:
(only 3 animals per sex were used, no definition of chamber volume, no data on body weight gain, no determination of test atmosphere concentration)
GLP compliance:
no
Test type:
other: IHT
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. Thomae, Biberach/Germany
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 279 g (mean male weight), 208 g (mean female weight)
- Housing: groups of 3 (singly during exposure)
- Diet (ad libitum in the period without exposure): KLIBA 24-343-4 rat/mouse laboratory diet
- Water (ad libitum in the period without exposure): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The product was introduced to a height of 5 cm into a glass bottle (generator) with a sintered glass disc (pore-size 90 - 150 µm, diameter 30 mm), and the weight was determined. The generator containing the product was placed in a waterbath maintained at 20°C by a thermostat, and a stream of 200 L/h compressed air was supplied to a downstream mixing chamber. The mixture of air and test substance generated in this way was passed through a glass distributor to 6 glass tubes in which 3 male and 3 female animals had been placed. The emerging mixtures of test substance and air were exhausted.
Suitable measures were applied to ensure that the air supply had the same temperature as in the laboratories, so that the temperature in the exposure apparatus was between 19 and 25°C. There were no deviations from these set conditions which might have adversely affected the results of the study.
After 30 minutes, the generator was replaced by a new one containing fresh test substance as described above. This generator was then used for the remainder of the test.

TEST ATMOSPHERE
The amount of test substance used was determined by reweighing the generators. The nominal concentration was calculated from the amount of test substance consumed and the air volume.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
7 h
Concentrations:
The mean nominal concentration of the test substance, calculated for a test lasting 7 h was 10.43 mg/L.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical examinations took place each work day. Lethality was checked each day.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
other: IHT
Effect level:
10.43 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
7 h
Remarks on result:
other: No animals died after exposure to the saturated vapour of the test substance at 20°C.
Mortality:
No animals died.
Clinical signs:
other: Immediately after exposure, accelarated respiration, reddish nasal/eye discharge, squatting posture, piloerection, urine-contaminated fur and high-stepping gait were observed in male and female animals. On the first day post exposure piloerection was obes
Body weight:
No data on body weight changes.
Gross pathology:
No pathologic findings were observed.
Other findings:
During the exposure, irritating effects to the eyes and the respiratory tract (accelerated/intermittent respiration, eyelid closure, wiping of snouts, salivation, nasal discharge, reddish nasal/eye discharge) were observed.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available data is reliable and sufficient for assessment. There is an IHT-test where male and female rats were exposed to a saturated 1-ethylpiperazine vapor-air mixture (nominal concentration: 10.43 mg/L) for 7 h. Additionally, literature data is available describing an acute inhalation test, conducted similar to OECD 403.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

The first study (1988, reliability score 2) investigated acute toxic effects of the test substance after single oral administration to Wistar rats, similarly as adviced in OECD guideline 401. The test substance was administered once orally via gavage to 5 male and 5 female animals suspended in water at doses of 464, 1000, 2000 mg/kg bw. Body weights were determined at day 0, 7 and 13 of the study. Recording of signs and symptoms was performed several times on the day of administration, at least once each workday. Check for moribund and dead animals was done twice each workday and once on holidays during the 14 days observation period. All animals were sacrificed and necropsied 14 days post administration. 4 male and 4 female animals of the 2000 mg/kg bw dose group died during the first two days post treatment - no further mortality observed. In the 2000 mg/kg bw dose group, dyspnea, apathy, staggering, piloerection and poor general state was observed post treatment (4 hours) and up to 2 days after treatment in all animals. Twitching was observed 4 hours after treatment in the female animals. Afterwards, no clinical signs were observed. No clinical signs were observed in the 464 and 1000 mg/kg bw dose groups. The animals gained body weight as excepted. At necropsy, general congestion, an atonic stomach with reddened mucosa and striking liquid contents and an atonic intestine with reddened mucosa and liquid contents was observed in animals that died. No pathological findings noted in surviving animals. Thus, under the test conditions chosen the LD50 for male and female rats after single oral treatment was between 1000 and 2000 mg/kg bw.

In a second acute oral toxicity study (Bomhard E. et al., 1997, reliability score 2) seven groups of 5 male and 5 female young adult Wistar rats each were dosed at 500, 1000, 2000, 2300, 2500, 2800 and 4000 mg/kg bw (the test substance was solved in water). The animals were observed for mortality, body weights, clinical signs and gross pathological changes through day 14. Corresponding mortality was 0, 0, 40, 50, 70, 100 and 100%, respectively. Clinical signs included poor general condition, sedation and nausea. Onset of symptoms was 30 min after administration. On day 3 all clinical signs disappeared. Deaths occurred from 3 to 24 h after administration. Necropsy of dead animals showed reddening of the lungs and of the gastric and intestinal mucosa. The stomach was filled with a dark-red fluid and was partly distended. No findings were observed at final necropsy except one female of the 2300 mg/kg bw group which showed a strongly stunted growth of the spleen. The calculated acute oral rat LD50 combined for male and female rats is 2158 mg/kg bw (95% confidence interval: 1947 - 2393 mg/kg bw).

 

Acute inhalation toxicity

In an inhalation hazard test (IHT, 1989, reliability score 2), 3 male and 3 female rats were exposed to a test atmosphere saturated with vapours of the test substance for 7 hours. The product was introduced to a height of 5 cm into a glass bottle (generator) with a sintered glass disk (pore-size 90 - 150 µm, diameter 30 mm), and the weight was determined. The generator containing the product was placed in a water bath maintained at 20°C by a thermostat, and a stream of 200 L/h compressed air was supplied to a downstream mixing chamber. The mixture of air and test substance generated in this way was passed through a glass distributor to 6 glass tubes in which the animals had been placed. The temperature in the exposure chamber was between 19 and 25°C. The concentration of the test atmosphere was stated to be 10.43 mg/L, an analytical verification was not performed. The calculated vapour saturation is 11.7 mg/L (vapour pressure: 2.48 hPa at 20°C). Comparing with the mean nominal concentration of 10.43 mg/L, incubation of animals with a saturated vapor-air-mixture can therefore be assumed. During the exposure, irritating effects to the eyes and the respiratory tract (accelerated/intermittent respiration, eyelid closure, wiping of snouts, salivation, nasal discharge, reddish nasal/eye discharge) were observed. The animals were then observed daily for 14 days for clinical signs and mortality. Immediately after exposure, accelerated respiration, reddish nasal/eye discharge, squatting posture, piloerection, urine-contaminated fur and high-stepping gait were observed in male and female animals. On the first day post exposure piloerection was observed in all animals and aggressiveness in all male animals. Weighing was performed only at the beginning of the study. No mortality resulted from the exposure to the test atmosphere.No abnormalities at necropsy were observed.

Additionally, acute inhalation toxicity was analyzed in a study performed equivalent to OECD Guideline 403 (Bomhard E. et al., 1997, reliability score 2). Four groups of 5 male and 5 female young adult Wistar rats were subjected to a single 4-hour head-nose exposure to analytical vapour concentrations of 0.448, 1.209, 3.889, and 9.219 mg/L air. Five animals were exposed to air and served as controls. The animals were observed for mortality, body weights, clinical signs and gross pathological changes through day 14. No mortality was observed. The animals of the 0.448, 1.209, and 3.889 mg/L groups showed red noses and serous nasal discharge after exposure. These findings disappeared on day 1. In addition bradypnoea was seen in the 3.889 and 9.219 mg/L group. Besides this, in the highest dose-group decreased motility, bloody and necrotic rhinarium as well as liver-like changes in the lungs at final necropsy were seen. All other animals showed no dose-related pathological signs or changes at final necropsy. The acute inhalation 4h-LC50 for male and female rats was > 9.219 mg/L.

 

Acute dermal toxicity

There is no data available concerning acute dermal toxicity. In accordance with column 2 of REACH Annex VIII, the study does not need to be conducted as the substance is classified for skin corrosivity.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for acute oral toxicity is warranted (Cat. 4), but not for inhalation and dermal toxicity.