Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Study period:
October 29-November 13, 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Well documented and reported study, conducted according to internationally accepted technical guideline in recognized industrial research organization. A quality assurance inspection report with reference to GLP, but not a GLP compliance statement, was included in the study report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD of 1981
Deviations:
no
GLP compliance:
no
Remarks:
but Quality Assurance statement with reference to IKS GLP guidance document was included in the report
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): PBS 2354.0
- Expiration date of the lot/batch: December 1986
- Storage conditions: room temperature
Test Article Data Sheet of September 30, 1985, Pharma Toxicology, Basle

Test animals

Species:
rat
Strain:
other: Tif:RAIf(SPF)
Sex:
male/female
Details on test animals and environmental conditions:
- Initial Age: 36 -43 days
- Number and Sex: 5 males and 5 females
- Initial Weight Range: Minimum 116 g, maximum 147 g.
- Housing: Separate sexes were housed in Macrolon cages (type IV)
- Diet: Commercially available standard diet (NAFAG No. 890, batch 81/85, analysed by the
manufacturer, NAFAG, Gossau, Switzerland).
- Water (ad libitum): Tap water. (Periodically analysed)
- Acclimation period: At least 5 days.


ENVIRONMENTAL CONDITIONS

Air conditioned room:
- Temperature (°C): 22 ± 2°C
- Relative Humidity (%): 50 ± 10%
- Photoperiod: 14 hrs artificial light/day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% aqueous solution of Klucel HF 0.5%
Details on oral exposure:
Shortly before administration the test material was suspended in a 0.5% aqueous solution of Klucel HF 0.5% at a concentration of 25% test material in the vehicle. The animals were fasted overnight and weighed just prior to dosing. Between 08.00 and 11.00 a.m., each animal received a single oral dose by intubation (oral gavage).
Doses:
5000 (male/female) mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Symptoms and deaths were recorded daily for 14 consecutive days. At the end of the observation period, the animals were weighed and sacrificed (C02-gas evaporated from dry ice). Autopsies were performed on all animals.
Statistics:
Not applicable

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: No deaths
Mortality:
5000 mg/kg: 0/5 (m), 0/5 (f)


Clinical signs:
Reduced spontaneous activity, ataxia, muscular hypotonia, hyperreflexia, irregular respiration. Symptoms lasted more than 360 minutes.
After 24 hours no symptoms. Clinical signs noted were considered to represent a depression of the central nervous system associated with stimulation.
Body weight:
Body weight gain was not affected over the 14-day observation period.
Gross pathology:
Autopsies did not reveal any gross organ or tissue changes.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
In view of the oral LD50 value > 5000 mg/kg bodyweight attained in the present study, its outcome does not necessitate any labelling regarding acute oral toxicity according to EU regulations (DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008). In addition, relevant sex-related differences in toxicity of the test material after single oral administration were not evident.
Executive summary:

PBS 2354.0 was tested for its acute toxicity by oral (gavage) in the rat according to the respective OECD Technical Guideline of 1981.

 

Reliability grade 1 was assigned to the study. It was not conducted in compliance with GLP, but a Quality Assurance statement with reference to an IKS GLP guidance document* was included in the study report.

 

The study comprised 5 male and 5 female rats treated with a limit dose of 5000 mg/kg bodyweight.

 

There were no deaths and no adverse effects on bodyweight during the 14-day observation period. Clinical signs comprised reduced spontaneous activity, ataxia, muscular hypotonia, hyperreflexia and irregular respiration over more than 6 hours post dose. By 24 hours after dosing all animals were free from clinical signs. Autopsy did not reveal any gross organ changes. There was no indication of relevant sex-related differences in toxicity of the test material after single oral administration.

 

Consequently, the acute oral LD50 attained in the present study is higher than 5000 mg/kg bodyweight.

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*"Wegleitung der IKS betreffend gute Laboratoriumspraxis für nichtklinische Laborversuche,

Unterabschnitt B.4.a.v."