Registration Dossier

Administrative data

Description of key information

In both the acute toxicity: oral and the acute toxicity: dermal studies the LD50 was >2000 mg/kg bw. The inhalation toxicity study demonstrated that, under the test conditions and at the maximum achievable test concentrations, the substance vapours were not toxic.

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Test species/strain/quality: Rat/Wistar/Crl:WI (Han)
Reason for selection of the test species: Rats were selected since this rodent species is recommended in the respective test guidelines. Wistar rats were selected since there is extensive experience available in the laboratory with this strain of rats.
Age on day 0: Young adult animals (female animals approx. 10 weeks)
Sex: As suggested by the OECD guideline nulliparous and non-pregnant female animals were used for the test, because there is no indication that male animals are likely to be more sensitive to the acute effects of the test item.
Supplier: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfed, Germany.
Arrival in the testing facility: Acclimatization period of at least 5 days before the beginning of the experimental phase: during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.
Identification: Individual identification by cage cards and tail marking.
Body weight on day 0: Animals of comparable weight (+/- 20% of the mean weight)
Room temperature/relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 22°C ± 3°C for temperature and of 30-70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Route of administration: Single oral administration by gavage
Fasting period: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
Time of day of administration: In the morning
Observation period: 14 days
Doses:
2000 mg/kg/bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
By request of the sponsor a starting dose of 2000 mg/kg/bw was chosen in the first step with 3 female animals. Because no mortality occurred in the first step, 2000 mg/kg/bw were administered to another group of 3 females animals in the second step.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
No clinical signs were observed during clinical examination.
Body weight:
The mean body weight of the test groups increased throughout the study period within the normal range.
Gross pathology:
There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material was found to be > 2000 mg/kg bodyweight. The test substance is not classified as an acute oral toxin.
Executive summary:

The acute oral toxicity of the test substance to Wistar rats was determined in accordance with the OECD Guideline for Testing of Chemicals 423. The rats were exposed to a dose of 2000 mg/kg bw of the test substance via oral gavage route. The observation period was 14 days. The acute oral median lethal dose (LD50) of the test material was found to be > 2000 mg/kg bodyweight. The test substance is not classified as an acute oral toxin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Four studies were conducted to assess the acute oral toxicity of the substance. All studies were considered reliable as they were conducted on the registered substance, as defined in section 1.1.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study on read-across substance conducted using OECD Testing Guideline 403.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(Inhalation hazard test described in the Annex V; adopted 1981)
Deviations:
yes
Remarks:
observation period of 7 days
Principles of method if other than guideline:
Standardized test method (BASF-Test): The test was performed in principle as described in OECD test guideline 403. It demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of a test substance at 20°C. Young adult laboratory rats, 3 per sex, were exposed sequentially to the vapours generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 8 h. The exposure was subsequently repeated in the same manner. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was calculated as quotient of the amount of test substance weight loss during exposure, and the amount of air used during exposure. Group-wise documentation of clinical signs was performed over a 7 day study period. Body weight of groups was determined before the start of the study and at the end of the observation period.
GLP compliance:
no
Test type:
other: inhalation risk test
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

Rats were exposed for 8 h to a vapour saturated atmosphere. Vapour was generated by bubbling 200 l/h air through the liquid substance column (volume ca. 50 mL) of about 5 cm above a fritted glass disc in a glass cylinder. The air pressure was 754 mm Hg. Temperature in the exposure chamber was 20°C. Concentration was stated in the raw data to be 0.021 mg/L in the case of the 8 h exposure.

TEST ATMOSPHERE

Brief description of analytical method used: no analytics performed
Samples taken from breathing zone: no



Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
No verification of the concentration was performed. Nominal concentration: 0.021 mg/L
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
Duration of observation period following administration: 7 days
Frequency of observations and weighing: group wise documentation on working days
Necropsy of survivors performed: yes
Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
other: IHT
Effect level:
0.021 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
other: No mortality.
Mortality:
No mortality observed.
Clinical signs:
other:
Gross pathology:
No abnormality detected.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The IHT was given as 0.021 mg/L (air). No deaths or abnormalities were recorded. The substance vapours were not toxic at the maximum achievable test concentrations.
Executive summary:

The acute inhalation toxicity of the test substance to rats (strain not specified) was determined in accordance with the OECD Guideline for Testing of Chemicals 403. The rat was exposed to a whole body dose, nominally stated as 0.021 mg/L. The IHT was given as 0.021 mg/L (air). The animals were observed for 7 days. No deaths or abnormalities were recorded. The substance vapours were not toxic at the maximum achievable test concentrations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
N/A

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
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
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 species/strain/quality: Rat/Wistar/Crl:WI (Han) SPF
Reasons for selection: Rats were selected since this rodent species is recommended in the respective test guidelines. Wistar rats were selected since there is extensive experience available in the laboratory with this strain of rats.
Age on day 0: Young adult animals. (Male animals approx. 8 weeks, females approx. 12 weeks)
Sex: Males and females
Supplier: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
Arrival in the testing facility: Acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.
Identification: Individual identification by cage cards and tail marking.
Body weight on day 0: Animals of comparable weight.

Room temperature / relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 22°C ± 3°C for temperature and of 30 – 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.
Day/night rhythm: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of cage: Makrolon cage, type III
Number of animals per cage: Single housing
Feeding: VFR1(P); SDS Special Diets Services, 67122 Altrip, Germany
Drinking water: Tap water ad libitum

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The undiluted test item was applied to clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by a semi-occlusive dressing.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured.
Clinical signs:
No systemic clinical signs or local effects were observed during clinical examination.
Body weight:
The mean body weight of the male animals increased throughout the study period within the normal range. The mean body weights of the female animals stagnated during the first post-exposure observation week probably due to the bandage procedure, but increased during the second week within the normal range.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw. According to EU CLP classification guidelines the test substance is not classified as an acute dermal toxin.
Executive summary:

The acute dermal toxicity of the test substance to Wistar rats was determined in accordance with the OECD Guideline for Testing of Chemicals 402. In the acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item Pluriol BP 40E to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred during the study and no signs of systemic toxicity or skin effects were observed in the animal. The mean body weight of the male animals increased throughout the study period within the normal range, the mean body weights of the female animals stagnated during the first post- exposure observation week probably due to the bandage procedure, but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. The acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw. According to EU CLP classification guidelines the test substance is not classified as an acute dermal toxin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
N/A

Additional information

Two studies were conducted to assess the acute oral toxicity of the test material. These studies were considered reliable as they were conducted on the registered substance according to OECD Testing Guideline 401 and 423. Both studies gave an LD50 > 2000 mg/kg bw on, the key study was on BPA 1 -4.5EO and the supporting study was on BPA 2EO. The registered substance is not classified as an acute oral toxin based on the EU Classification, Labelling and Packaging (CLP) criteria.

The acute toxicity: inhalation was assessed on the registered substance according to OECD Testing Guideline 403. The IHT was given as 0.021 mg/L (air). The substance vapours were not considered toxic at the maximum achievable test concentrations.

The acute toxicity: dermal of the registered substance was assessed according to OECD Testing Guideline 402. The LD50 was > 2000 mg/kg bw on BPA 1 -4.5EO.

Based on the LD50 values obtained from these studies, the registered substance is not classified as acutely toxic via the oral, inhalation or dermal route based on the EU Classification, Labelling and Packaging (CLP) criteria.


Justification for selection of acute toxicity – oral endpoint
This study was selected as the key study as it was conducted on the registered substance according to OECD Testing Guideline 423. The LD50 was > 2000 mg/kg bw.

Justification for selection of acute toxicity – inhalation endpoint
The study is considered a weight-of-evidence study as the IHT test system used is not a valid test system for evaluating acute inhalation toxicity. The IHT demonstrates the toxicity of an atmosphere saturated with vapours of the volatile component of the test substance at 20°C. The test substance uses is not highly volatile and at the maximum achievable test concentrations the substance vapours were not found to be toxic (no deaths or abnormalities were recorded).

Justification for selection of acute toxicity – dermal endpoint
This study is considered reliable as it was conducted on the registered substance according to OECD Testing Guideline 402. The LD50 was > 2000 mg/kg bw.

Justification for classification or non-classification

In both the acute toxicity: oral and the acute toxicity: dermal the LD50 was > 2000 mg/kg bw.