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Description of key information

In an acute oral toxicity study in rats according to OECD Guideline 401 (BASF SE, 1989), a discriminating dose of > 5000 mg/kg bw was determined.

In a pre-GLP oral toxicity study in rats comparable to OECD Guideline 401 (BASF SE, 1977), a LD50 of 4722 mg/kg bw was determined.

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:
1989-04-01 to 1989-06
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987-02-24
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
1984-09
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No. of test material: 216096.89

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At 20 °C in the dark
- Stability of the test substance in the vehicle: At least 48 hours in carboxymethylcellulose

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The formulations were prepared immediately prior to dosing. The test article was weighed into a glass flask on an analytical balance and the vehicle (w/w) was added. Homogeneity of the test article in vehicle was obtained by a homogeniser, Concentration of test article in vehicle was varied to allow constant dosage volume in terms of ml/kg body weight.

OTHER SPECIFICS: Orange, solid
Species:
rat
Strain:
Wistar
Remarks:
outbred, SPF-Quality
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: ~ 8 weeks
- Weight at study initiation: ♂: 267 - 305 g; ♀: 177 - 200 g
- Fasting period before study: Food was withheld overnight prior to dosing until ~ 3 - 4 hours after administration of the test article.
- Housing: Housed in groups of five per sex in polycarbonate cages.
- Diet: standard pelleted laboratory animal diet (RMH-B from Hope Farms, Woerden, The Netherlands), ad libitum
- Water. tap-water, ad libitum
- Acclimation period: Five days under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 7.5 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
VEHICLE
- Amount of vehicle: 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test article was weighed into a glass flask on an analytical balance and the vehicle (w/w) was added.
Doses:
5000 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 and weighing: Clinical observation at periodic intervals on the day of dosing (day 1) and twice daily thereafter for at least 14 days. Body weights at test days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes, all animals were necropsied and descriptions of all macroscopic abnormalities were recorded. All animals surviving to the end of the observation period were sacrificed by carbon dioxide asphyxiation and subjected to necropsy.
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
Diarrhoea was noted in all animals on the day of treatment during the final observation (4.15 hours after dosing). No other clinical signs of toxicity or behavioural changes were seen over the 15 day observation period.
Body weight:
All animals showed normal body weight gain during the study period.
Gross pathology:
Macroscopic examination of all animals at termination did not reveal any abnormalities.
Interpretation of results:
GHS criteria not met
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987-02-24
GLP compliance:
not specified
Remarks:
pre-GLP study
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No. of test material: ENR 41
Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 160 - 180 g
- Fasting period before study: overnight before administration
- Housing: in groups of 5 in Macrolon cages (type 3).
- Diet: ad libitum, rat food - NAFAG, Gossau SG, Switzerland
- Water: ad libitum (not specified)
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
Route of administration:
oral: unspecified
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10, 20, or 30 %
Doses:
1000, 2150, 3590, 4640, and 6000 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: several times within the first hours after administration, thereafter at least once a day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
LD 50 including 95 % confidence limits were calculated by the probit analysis method (Goulden A., Methods of Statistical Analysis, John Wiley and Sons, 1960, 3rd printing, pages 404 - 408).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 722 mg/kg bw
Based on:
test mat.
95% CL:
> 3 770 - < 5 916
Mortality:
see Table 1
Clinical signs:
Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position, diarrhoea and ruffled fur. The surviving animals recovered within 12 to 14 days.
Gross pathology:
No substance related gross organ changes were seen.

Table 1: Rates of death

Dose mg/kg bw

Conc. % of Formulation

No of animals

Died within

1 h

24 h

48 h

7 d

14 d

 

 

1000

10

5

5

0

0

0

0

0

0

0

0

0

0

2150

20

5

5

0

0

0

0

0

0

0

0

0

1

3590

30

5

5

0

0

0

0

0

0

1

1

1

1

4640

30

5

5

0

0

0

0

0

1

0

2

0

4

6000

30

5

5

0

0

1

0

1

0

4

2

5

3

 

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
Klimisch code 2

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

In an acute oral toxicity study according to OECD Guideline 401 (BASF SE, 1989), the test substance was administered to wistar rats of both sexes (5 each) by oral gavage at a limit dose of 5000 mg/kg body weight, followed by a 15 day observation period. No mortality occurred during the study period. Diarrhoea was noted in all animals on the day of treatment during the final observation. All animals showed body weight gain during the study period. Macroscopic examination of all animals at termination did not reveal any abnormalities. The oral discriminating dose of the test substance in rats of both sexes, was estimated to be > 5000 mg/kg body weight.

This finding is supported by a pre-GLP acute oral toxicity study comparable to OECD Guideline 401 in Tif: RAIf (SPF) rats (BASF SE, 1977). In this study, a LD50 of 4722 mg/kg bw was determined.

It is noteworthy that the percentage shares of components in the composition of the test substance changed between the two studies. However, these changes did not lead to substantial changes in the acute toxic potential of the test substance.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008.

A discriminating dose for acute oral (> 5000 mg/kg bw) toxicity was determined. As a result the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.