Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From January 19, 2006 to February 21, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD Guideline 423 and EU method B.1 tris, with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Erythromycin A-9 Oxime (E) Hydrochloride.
- Physical state: white powder.
- Lot/batch No.: B5310059
- Storage condition of test material: at ambient temperature, in the dark.
- Other:
pH: 6.16 (1% solution in deionised water, w/v, determined with a pH-Meter WTW pH340)

Test animals

Species:
rat
Strain:
other: Crl: CD(SD)IGS BR.
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-94633 Sulzfeld.
- Age at study initiation: approximately 8 weeks at the time of administration.
- Weight at study initiation:
Animal No. 41: 182 g
Animal No. 42: 184 g
Animal No. 43: 186 g
Animal No. 44: 192 g
Animal No. 45. 178 g
Animal No. 46: 193 g
Animal No. 51: 184 g
Animal No. 52: 194 g
Animal No. 53: 187 g
Animal No. 54: 182 g
Animal No. 55: 198 g
Animal No. 56: 190 g

- Housing: Single caging in Makrolon cages type III (39 cm x 23 cm x 18 cm). Wire mesh lids. Sanitation of cages once a week.
- Diet (e.g. ad libitum): Altromin 1324 forte (Producer: Altromin GmbH, D-32791 Lage) gamma irradiated with 25 kGy 60Co, ad libitum.
- Water (e.g. ad libitum): Tap water, offered in Makrolon bottles with stainless steel canules, ad libitum.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 22 ºC (continous control and recording)
- Humidity (%): Average of 48.0 % (continous control and recording)
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.
- Air change: 12 per hour

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: deionised water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: a homogeneus suspension could be prepared with deionised water and water shall be used preferably, according to the guidelines.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: as no prior information on the test substance was available, a starting dose of 300 mg/kg bw was chosen. The further proceeding was in accordance with the guideline/directive.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
300 mg/kg bw: two goups of 3 animals each; 2000 mg/kg bw: two groups of 3 animals each.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
Body weights: before administration, 7 and 14 days after administration.
Clinical observations: at least one a day (Observations: 0 - 0.5, 0.5 - 1, 1 - 2, 2 - 4 and 4 - 6 hours after administration of the test substance (p.a.) and then at least once a day for a total of 2 weeks; observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions)
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived until the scheduled termination of the study.
Clinical signs:
Only the high dosed animals were affected; the findings, with an earliest onset 1 h after administration and lasting untill 6 h p.a. were: signs of reduced well-being, this term encompasses uspecific alterations like sedation, apathy, piloerection, hunched posture or closed eyes, in single or multiple occurence.
Body weight:
All animals gained weight in both weeks.
Other findings:
- Other observations:
Necropsy findings: all animals were normal at necropsy 14 days p.a.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No severe toxic effects of the test substance were noted by signs in life and post mortem at dose of 2000 mg test substance/kg bw (LD50 > 2000 mg/kg bw). No mortality occurred.
Executive summary:

Assessment of acute oral toxicity of the test substance was determined according to the OECD 423 Guideline and B.1 EU Method (Acute Toxic Class Method), with CLP. The test substance was administered once orally via gavage as a suspension in deionised water to female Crl:CD(SD)IGS BR rats. The dosing was performed sequentially to groups of 3 animals per step using a starting dose of 300 mg/kg bw and 2000 mg/kg bw as the second dose. The oral LD50 value of the test substance in rats was established to exceed 2000 mg/kg body weight.