Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: The potential of the test item to cause acute oral toxicity was determined in a study equivalent to OECD 401. The LD50 (males) was determined to be 2240 mg/kg bw, the LD50 of females was determined to be 1730 mg/kg bw. The mean LD50 rats was determined to be 1970 mg/kgbw. 
Acute dermal toxicity: The potential of the test item to cause acute dermal toxicity to rats was determined. No mortality was observed. The LD50 was determined to be >15000 mg/kg bw.

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:
other: Equivalent to guideline, no GLP study, probably technical pure quality was tested
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: BOR: WISW
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Firma Winkelmann, Versuchstierzucht, 4791 Borchen 1, Gartenstraße 300
- Weight at study initiation: 154-210 g (males), 145 -175 g (females)
- Fasting period before study: yes, 16 hours before test begin
- Housing: Makrolon cages III
- Diet: Ssniff, Versuchtstierdiäten GmbH, 4770 Soest/Westfalen
- Water: ad libitum, tap water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12 (Fluorescent lighting)

Route of administration:
oral: feed
Vehicle:
peanut oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 3.5 mL/kg

DOSAGE PREPARATION: in water bath and applicated by gavage

Doses:
1.5, 2.0, 2.5 and 3.5 mL/kg equivalent to 1500, 2000, 2500 and 3500 mg/kg bw. (Values based on calculation with density (appx. 1 g/cm^3))
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: after 20 min, 1 h, 3 h, 24 h, 48 h, 72 h, 7 and 14 days
- Weighing: Recorded immediately before treatment (day 0) and on day 14 of postadministration.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gross pathology
Statistics:
According to probit analysis, method of Finney.
Preliminary study:
2 rats were tested each in doses of 15, 10, 5, 2.5 and 1.0 mL/kg
Sex:
male
Dose descriptor:
LD50
Effect level:
2 240 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Values based on calculation with density (appx. 1 g/cm^3)
Sex:
female
Dose descriptor:
LD50
Effect level:
1 730 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Values based on calculation with density (appx. 1 g/cm^3)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 970 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Values based on calculation with density (appx. 1 g/cm^3)
Mortality:
Highest dose level: All animals died
2.5 mL/kg: 8 animals died
2.0 mL/kg: 6 animals died
1.5 mL/kg: 1 animal died
Clinical signs:
Reduced activity, partly total apathy, partly obvious abnormal body posture, obvious disturbance of coordination, redued reflex excitability, obvious piloerection and slight decreased body temperature were noted at this dose level and above.
Body weight:
Normal increase of body weight
Gross pathology:
Necropsy of deceased revealed slight hemorrhages of the gastrointestinal channel. Necropsy of survivors revealed no abnormalities.
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The potential of the test item to cause acute oral toxicity was determined in a study equivalent to OECD 401. The LD50 (males) was determined to be 2240 mg/kg bw, the LD50 of females was determined to be 1730 mg/kg bw. The mean LD50 rats was determined to be 1970 mg/kg bw.
Executive summary:

An acute toxicity study (equivalent to OECD guideline 401) was carried out to determine the acute oral toxicity potential of the test item. The study was conducted using albino Wistar rats weighing 154 – 210 g (males) and 145 – 175 g (females), which were acclimated for at least 7 days. Animals were group housed (5/cage) in macrolon type III cages. Fluorescent lighting, 12 hr light/12 hr dark was used in each animal room. Temperature was maintained at 21 °C and relative humidity at 45-55%. The toxicity of test compound was investigated in four groups of fasted male and female animals (5 animals/sex/dose group) at the following dose levels: 1.5, 2.0, 2.5, and 3.5 mL/kg body weight equivalent to 1500, 2000. 2500 and 3500 mg/kg bw. In each animal a number of clinical-toxicological signs were evaluated according to a modified Irwin Screening procedure. Any change from the normal condition was noted (increase or decrease) and the degree of severity of any clinical symptoms was assessed. The animals were examined at the following post-treatment intervals: 20 min, 1 h, 3 h, 24 h, 48 h, and 7 and 14 days. Body weights were recorded immediately before treatment (day 0) and on day 14 of postadministration. Animals were sacrificed after 14 days and gross pathological examinations were subsequently performed. If needed, the calculation of an oral LD50 was performed with the method of Finney.The following results were obtained:

A reduced activity, partly total apathy, partly obvious abnormal body posture, obvious disturbance of coordination, redued reflex excitability, obvious piloeretion and slight decreased body temperature were noted at this dose level and above. Necropsy of deceased revealed slight hemorrhages of the gastrointestinal channel. Necropsy of survivors revealed no abnormalities. Mortality was observed at 1500 mg/kg onwards.

The LD50 was determined to be 1970 mg/kg bw (male/females), 2240 mg/kg bw for males and 1730 mg/kg bw for females)

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 970 mg/kg bw
Quality of whole database:
No GLP and no guideline study, probably technical pure quality was tested

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

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
Study period:
1981-11-09 to 1981-11-30
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable and well documented publication, probably technical pure quality was tested
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: BOR: WISW
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Firma Winkelmann, Versuchstierzucht, 4791 Borchen 1, Gartenstraße 300
- Weight at study initiation: Males: 162-190 g, females: 155-170 g
- Housing: Macrolon cages Typ III with maximal 5 rats
- Diet: Ssniff, Versuchtstierdiäten GmbH 4770 Soest/Westfalen
- Water: ad libitum, in Macrolon drinkbottles, 300 mL, Firma Becker & Co., 4620 Castrop Rauxel, tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2 °C
- Humidity (%): 45-55 %
- Photoperiod: Room was artificially lit from 7 am to 7 pm

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 8 x 5 cm
- Type of wrap if used: gauze pads and several wrappings of plastic material

REMOVAL OF TEST SUBSTANCE
- Washing: After treatment the backs of all animals were secured with gauze pads and several wrappings of plastic material for 24 hours. Thereafter the patches were removed with wet disposable gauze
- Time after start of exposure: after 24 hours

TEST MATERIAL
- Amount(s) applied: 15 mL/kg
- Constant volume or concentration used: yes
Duration of exposure:
24 h
Doses:
15000 mg/kg bw (Value based on calculation with density (appx. 1 g/cm^3))
No. of animals per sex per dose:
5 males and 5 females
Two groups: The animals back of group I was abraded with a clean clipper blade so as to penetrate the horny layer of the epidermis, but without causing bleeding. The animals back of group II was left intact.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 2h, 4h, 24 h, 48 h, 72 h, 7 days, 14 days (clinical toxicological signs), 24 h, 3,7 and 14 days (skin alterations)
- Frequency of weighing: On day 0 and on day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
According to Draize et al.
Preliminary study:
To determine the toxicity of the test item the following doses were tested in 2 rats per dose: 15, 10, 5, 2.5 and 1 mL/kg
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 15 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Value based on calculation with density (appx. 1 g/cm^3)
Mortality:
No mortality occured
Clinical signs:
No abnormalities observed
Body weight:
No abnormalities were observed
Gross pathology:
No abnormalities observed
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The study was carried out to determine the acute dermal toxicity potential of the test item. No mortality occured. The LD50 was determined to be >15000 mg/kg bw.
Executive summary:

The study was carried out on male and female rats to determine the acute dermal toxicity and the skin irritation potential of the test item.The study was conducted with albino Wistar animals that were collectively housed up to a maximum of 5 animals per cage (Macrolon type III). The room was artificially lit from 7 AM to 7 PM. The temperature was 21 ° C and relative humidity was 45-55%. Animals weighed 162-190 g (males) and 155-170 g (females) at the initiation of the study. After an acclimatization time of 7 days the test was initiated. Evaluation of clinical-toxicological signs was done individually at 2, 4, 24, 48, 72 h and 7 and 14 days postadministration of test compound. Any skin alterations were recorded at 24 h, 3, 7 and 14 days after application of test compound per Draize. Body weights were recorded on Day 0 and on Day 14. Immediately after death, a complete necropsy was performed on all acute- and late mortalities as well as on animals surviving the 14-day observation period. Prior to treatment the back of each animal was clipped (8 x 5 cm) with a small animal clipper. The animals back of group I was abraded with a clean clipper blade so as to penetrate the horny layer of the epidermis, but without causing bleeding. The animals back of group II was left intact. After treatment the backs of all animals were secured with gauze pads and several wrappings of plastic material for 24 hours. Thereafter the patches were taken off and the substance was removed with wet disposable gauze. Test compound was applied as supplied. The sample of test compound was weighed per animal and then dosed once dermal onto the scarified and intact skin, respectively, and thereafter secured as described above. No mortality occurred. The LD50 was determined to be >15000 mg/kg bw. Also no skin irritating potential was determined. An erythema score of 0 was determined. Also the edema score was 0.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
15 000 mg/kg bw
Quality of whole database:
Acceptable and well documented publication, probably technical pure quality was tested

Additional information

Key

Acute oral toxicity

An acute toxicity study (equivalent to OECD guideline 401) was carried out to determine the acute oral toxicity potential of the test item. The toxicity of test compound was investigated in four groups of fasted male and female animals (5 animals/sex/dose group) at the following dose levels: 1.5, 2.0, 2.5, and 3.5 mL/kg body weight equivalent to 1500, 2000, 2500 and 3500 mg/kg bw. The following results were obtained: A reduced activity, partly total apathy, partly obvious abnormal body posture, obvious disturbance of coordination, redued reflex excitability, obvious piloeretion and slight decreased body temperature were noted at this dose level and above. Necropsy of deceased revealed slight hemorrhages of the gastrointestinal channel. Necropsy of survivors revealed no abnormalities. Mortality was observed at 1500 mg/kg onwards. The LD50 was determined to be 1970 mg/kg bw (male/females), 2240 mg/kg bw for males and 1730 mg/kg bw for females.

Supporting

An acute toxicity preliminary study was carried out to determine the dose levels for the main test. The study was conducted using 2 albino female Wistar rats for each dose level. The toxicity of test compound was investigated at the following dose levels: 1000, 2500, 5000, 10000, 15000 mg/kg bw. Mortality (all animals) was observed at 2500 mg/kg bw onwards. No LD50 was determined.

Conclusion: Both studies lay in the same range of acute oral toxicity effects testing the substance with rats in studies equivalent to OECD guideline 401. Mortality was observed at 1500 mg/kg bw onwards in the key study. This result is supported by the acute toxicity preliminary study revealing mortality effects from 2500 mg/kg bw onwards. The LD50 was determined to be 1970 mg/kg bw.

Acute dermal toxicity

The study was carried out on male and female rats to determine the acute dermal toxicity and the skin irritation potential of the test item. The study was conducted with albino Wistar animals. Evaluation of clinical-toxicological signs was done individually at 2, 4, 24, 48, 72 h and 7 and 14 days postadministration of test compound. Prior to treatment the back of each animal was clipped (8 x 5 cm) with a small animal clipper. No mortality occurred. The LD50 was determined to be >15000 mg/kg bw. Also no skin irritating potential was determined. An erythema score of 0 was determined. Also the edema score was 0.


Justification for selection of acute toxicity – oral endpoint
No GLP and no guideline study, probably technical pure quality was tested

Justification for selection of acute toxicity – dermal endpoint
Acceptable and well documented publication, probably technical pure quality was tested

Justification for classification or non-classification

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

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on the results of the acute oral toxicity the substance is considered to be classified as acute oral category 4., H302 under Regulation (EC) No 1272/2008.

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

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on the results of the acute dermal toxicity the substance is not considered to be classified for acute dermal toxicity under Regulation (EC) No 1272/2008.