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Description of key information

The LD50 value of the test item was determined to be higher than 2000 mg/kg after single oral administration in rats.

The test item can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats based on the results of the structural analogue substance.

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:
April 9, 1997 - May 26, 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Ferbuary 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Annex to Directive 92/69 EEC
Version / remarks:
Official Journal of the European Communities L383 A, Vol. 15, 29.Dezember 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Batch No.: E96017746
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 5 to 8 weeks
- Weight at study initiation: 156 - 193g
- Fasting period before study: 17 hours before until up to 4 hours after treatment
- Housing: separately in type III Makrolon cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21°C
- Humidity (%): 54-68%
- Photoperiod (hrs dark / hrs light): 12 hour light - 12 hour dark regime

IN-LIFE DATES: From: day 1 To: day 15
Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
Methocel K4M Premium solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 g/L
- Amount of vehicle (if gavage): 20 mL/kg
- Justification for choice of vehicle: well tolerated and established standard vehicle

Doses:
2000 mg/kg
No. of animals per sex per dose:
5 (m) / 5 (f)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: day 1, 2, 4, 6, 8, 11, 13 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
Standard statistical methods have been applied for data processing.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
All the rats survived the observation period.
Clinical signs:
No signs of intoxication occurred after treatment.
Body weight:
Body weight development of the treated rats was normal.
Gross pathology:
At necropsy two rats showed either focal or diffuse grey-red discoloration of the thymus. In all other rats no organ alterations were seen.

Study design

The test material was tested for acute toxicity in rats after single oral administration of 2000 mg/kg body weight. Directly before administration the test material was prepared with aqueous Methocel K4M Premium solution as the vehicle. The study was performed according to the OECD Guideline for Testing of Chemicals, No. 401.

Results

No signs of intoxication occurred after treatment.
Body weight development of the treated rats was normal.
All the rats survived the observation period.
At necropsy two rats showed either focal or diffuse grey-red discoloration of the thymus. In all other rats no organ alterations were seen.

Conclusion

For regulatory purposes, the median lethal dose (LD50), after an observation period of 15 days can be declared as > 2000 mg/kg.

Interpretation of results:
GHS criteria not met
Conclusions:
For regulatory purposes, the median lethal dose (LD50), after an observation period of 15 days can be declared as > 2000 mg/kg bw.
Executive summary:

This study was performed according to GLP and is fully compliant OECD TG 401. Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP and Guideline conform study

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Test systemSpecies: Rat, Wistar HsdCpb: WU, males (m) and females (f) Breeder: F. Winkelmann, 33178 Borchen Age: approx. 6 to 8 weeksIdentification and adaptationHealthy young animals were allocated to the study group at least 7 days before dosing to allow for acclimatization. The rats were identified by an ear tattoo.- Housing and dietThe rats were housed in an air-conditioned room. Lighting was controlled by a timer to provide a 12 hour light - 12 hour dark regime.The rats were kept separately in type III Makrolon cages with a shelter, placed on mobile racks. Conventional softwood granulate was used as the bedding. One day before treatment, and up to 24 hours after dosing, metal grids were placed above the softwood granulate. Temperature and humidity were measured using a thermohygrograph. The room temperature during the experimental period was 22 to 23 °C and the relative atmospheric humidity 46 to 72 %. Diet was withheld from 17 hours before until up to 4 hours after treatment. At all other times food and tap water from Makrolon drinking bottles were available to the rats ad libitum.The diet, Provimi Kliba 3433.0, had been checked, according to the specifications of the manufacturer by independent laboratories.Analysis included qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.The drinking water was periodically analyzed according to the German regulations for human drinking water.The softwood granulate was analytically checked by independent laboratories.
Type of coverage:
occlusive
Vehicle:
other: aqua pro injectione
Details on dermal exposure:
The backs and abdomens of the rats were shaved with an electric hair clipper not later than one hour before treatment.The test material was prepared, spread on the shaven skin in an area of 6 x 6 cm, and covered with a gauze patch. This was kept in place by a self-adhesive fabric (Fixomull® stretch, Beiersdorf). The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 (m) / 5 (f)
Control animals:
no
Details on study design:
- Observation for clinical symptoms: On the day of treatment the general condition and motility of the rats were slightly affected by the tape. It was difficult to distinguish between slight clinical findings and reactions due to fixation by the tape. The behavior and general condition of all rats were monitored for at least 6 hours after administration and then checked daily.

- Body weight: All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.

- Pathology: All rats were sacrificed at the end of the experimental part by C02-asphyxia. They were subjected to a gross pathological investigation.

- Statistics and evaluation: The body weight data were recorded with a PC-program. The body weight development of each rat and group was determined. The group mean value was calculated for each measurement and printed on tables.
Statistics:
The body weight development of each rat and group was determined. The group mean value was calculated for each measurement and printed on tables.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All rats survived the observation period. The lethal dose was regarded to be > 2000 mg/kg.
Clinical signs:
No signs of toxicity were detected in the 5 male and 5 female rats after dermal treatment with 2000 mg/kg bw.
Body weight:
The body weight development of the treated rats was inconspicuous.
Gross pathology:
At necropsy, no organ alterations were seen.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the result of this study, the test item can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats.
Executive summary:

Purpose

The purpose of this assay was to provide information on possible health hazards for the test material and serve as a rational basis for risk assessment to the potential of acute dermal toxicity of the test item in man.

Study design

The test material was tested for acute toxicity in 5 male and 5 female rats after dermal administration of 2000 mg/kg body weight. Directly before administration the test material was moistened with aqua pro injectione, spread on the shaven skin in an area of 6 x 6 cm, and covered with a gauze patch. This was kept in place by a self-adhesive fabric (Fixomull® stretch, Beiersdorf), The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully.

Results

No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg. There were no deaths during the course of the study. The body weight development was inconspicuous. The gross pathological examination revealed no organ alterations.

Conclusions

Based on the result of this study, the test item can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Justification for type of information:
For this endpoint information from a structural similar compound is available. This study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 402. See chapter 13 report for a more detailed justification.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
For this endpoint information from a structural similar compound is available. This study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 202. See chapter 13 report for a more detailed justification.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP and Guideline conform study

Additional information

Based on the available information, the acute toxicity of the substance is low for oral and dermal routes of administration. For acute inhalation no experimental data are available, however, these data are not required as no exposure via inhalation is assumed based on the PC profile of the substance. Therefore, all most likely main routes are covered by experimental data for acute toxicity. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

Justification for classification or non-classification

Based on the available data, the test substance is not considered to be classified for acute toxicity according to Regulation (EC) No 1272/2008.