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Description of key information

Oral (OECD 401), rat: LD50 = 5.24 mL/kg bw (corresponding to 4716 mg/kg bw based on a density of 0.9 mg/cm³)

Oral (OECD 401), rat: LD50 > 20 mL/kg bw (corresponding to > 18000 mg/kg bw based on a density of 0.9 mg/cm³)

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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
No information on purity was given.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
yes
Remarks:
no data on purity of test substance; body weight was not determined weekly.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation:
- Weight at study initiation: 155 - 175 g (males), 140 - 155 g (females)
- Fasting period before study: approximately 16 h prior to dosing
- Housing: in macrolon plastic cages (42 x 26 x 14 cm) on wood chips
- Diet: Ssniff Standard (Intermast, Soest, Germany)
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 22
- Humidity (%): 45 - 55
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw
Doses:
20 mL/kg bw (corresponding to 18000 mg/kg bw based on density of 0.9 g/cm³)
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for gross signs of systemic toxicity and mortality 20 min, 1 and 3 h after dosing and at least once daily thereafter. Animals were weighed prior to dosing and on Day 14.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 mL/kg bw
Based on:
test mat.
Remarks on result:
other: corresponding to 18000 mg/kg bw based on density of 0.9 g/cm³
Mortality:
One male and three females died 48 h after dosing. Two females died within 3 days and two males within 4 days after administration. One female died 7 days after administration.
Clinical signs:
Clinical signs such as lightly decreased activity, light reduced pain reaction, disturbances of coordination, diarrhoe and piloerection were observed 20 min after dosing. The signs were partly persistent for 24 hours. Afterwards animals appeared to be normal.
Body weight:
At the end of the observation period all surviving animals showed body weight gain.
Gross pathology:
Gross pathological examination of dead animals revealed irritation (reddening) of the mucous membrane of the digestive canal. No gross pathological findings were observed in rats sacrificed at study termination.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study a LD50 value > 20 mL/kg bw (corresponding to 18000 mg/kg bw based on density of 0.9 g/cm³) was derived in male and female rats.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 - 30 Jun 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
No information on purity was given.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
yes
Remarks:
no data on purity of test substance; body weight was not determined weekly.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: BOR: WISW
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 156.9 - 210.0 g (males), 140.0 - 178.0 g (females)
- Fasting period before study: 16 h prior to and approx. 4 h after dosing
- Housing: in groups of maximum 5 animals in Macrolon cages (Typ III) on sawdust
- Diet: Ssniff-R Alleindiät für Ratten (Ssniff Versuchstierdiäten GmbH, Soest, Germany), ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 45 - 55
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 7.5 mL/kg bw
Doses:
Range-finding study: 2.5, 5.0 and 7.5 mL/kg bw
Main study: 2.5, 3.75, 5.0 and 7.5 mL/kg bw (corresponding to 2250, 3375, 4500 and 6750 mg/kg bw based on density of 0.9 g/cm³)
No. of animals per sex per dose:
Range-finding study: 2 females
Main study: 5 males and 5 females
Control animals:
no
Details on study design:
Range-finding study:
- Duration of observation period following administration: 14 days

Main study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were recorded 15 and 45 min and 1.5, 3, 6, 24 and 48 h after administration and on Days 4 and 14. Individual body weights were determined on Days 0 and 14.
- Necropsy of survivors performed: yes
Statistics:
Probit Analysis according to Finney was used to calculate the oral LD50 values.
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
calculated using Probit Analysis acc. to Finney
Effect level:
5.24 mL/kg bw
Based on:
test mat.
Remarks on result:
other: (corresponding to 4716 mg/kg bw based on density of 0.9 g/cm³)
Mortality:
Range-finding study: All animals died at 5.0 and 7.5 mL/kg bw within 48 h after administration. No mortality occurred at 2.5 mL/kg bw.

Main study: At 2.5 mL/kg bw no mortality occurred during the study period. At 3.75 mL/kg bw one male and one female died within 24 and 48 h, respectively, after administration. At 5.0 mL/kg bw two males and one female died within 24 h and two females died within 48 h after administration. At 7.5 mL/kg bw four males and one female died within 24 h and 3 females died within 48 h after administration.
Clinical signs:
Disturbed awareness with apathy, abnormal body posture, disturbance of coordination, reduced reflex excitability, cyanosis, piloerection and reduced respiration rate were observed. The symptoms were observed 15 min after administration and lasted in surviving animals in increased or decreased intensity, respectively, partly up to 3 days. Afterwards and during the entire observation period the animals appeared to be normal.
Body weight:
At the end of the observation period all surviving animals showed expected body weight gain.
Gross pathology:
Gross pathological examination of dead animals revealed redness and partly liquid accumulation in the entire digestive system. No gross pathological findings were observed in rats sacrificed at study termination.

Table 1. Mortality.

Dose

(mL/kg bw)

Males

Females

2.5

0/5

0/5

3.75

1/5

1/5

5.0

2/5

3/5

7.5

4/5

4/5

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study a LD50 value of 5.24 mL/kg bw (corresponding to 4716 mg/kg bw based on density of 0.9 g/cm³) was derived in male and female rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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

Two acute oral toxicity studies similar to OECD Guideline 401 are available with the test substance.

In the first study (1983), groups of 5 male and 5 female rats were given a single dose of 2.5, 3.75, 5.0 and 7.5 mL/kg bw. A LD50 of 5.24 mL/kg bw (corresponding to 4716 mg/kg bw based on a density of 0.9 g/cm³) was calculated by the method of Finney (1971) in male and female rats.

In a second study (1978), 10 male and female rats were administered a single dose of 20 mL/kg bw via gavage. 9/20 animals died within 14 days. Thus, a LD50 > 20 mL/kg bw (corresponding to 18000 mg/kg bw based on density of 0.9 mg/cm³) was derived in male and female rats.

Justification for classification or non-classification

The available data on acute oral toxicity do not meet the criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.