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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From May 22th to June 6th, 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
Source study has reliability 1. Details on the read across are available in section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Qualifier:
according to guideline
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan no. 8147, 2000
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Similar Substance 01
IUPAC Name:
Similar Substance 01
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Specie: Rattus norvegicus.
- Source: TECAM Animal Facility (S. Roque, SP).
- Age at study initiation: young adult rats 8 - 10 weeks old.
- Variation in weight: not greater than 20 % of the mean weight.
- Housing: 3 animals per cage.
- Diet: pelleted commercial diet (Biobase Biotec), ad libitum. Feed is analysed by testing laboratory periodically for microbiological contaminants
- Water: filtered water, ad libitum.
- Fasting period before study: animals were fasted approxirnately 14 hours prior to the test substance administration. Animals returned to ad Iibitum feeding apprornmately 3 hours after dosing.
- Acclimatization period: 5 days prior to dosing in a controlled room.
- Selection: animals exhibiting abnormal signs during the acclimatization period were not used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 23 °C
- Humidity: 62 %
- Photoperiod: 12 hours cycle dark/light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionized
Details on oral exposure:
Rationale for the selection of the starting dose: as test substance was suspected not to be toxic, 2000 mgkg bw was the selected dose for starting. The time interval between treatment groups was determined by the onset, duration and severity of toxic signs.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Two groups of 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: body weights were recorded shortly before administration, weekly thereafter and at the end of the study. Animals were observed individually after dosing during the first 24 hours with special attention given during the first 4 hours (day 1).
- Necropsy of survivors performed: at the end of 14 days, carbon dioxide was used for euthanasia of the animals. Gross pathology examination was performed for 100 % of the animals. Necropsy findings were registered for the intestinal tract (duodenum, jejunum, ileum, cecum) and the major organs such as liver, kidney, heart, spleen, Iymph nodes, respiratory tract (lungs, trachea, bronchi, diaphragm), thyroid, oesophgus, stomach, pancreas, muscles, bladder, uteus and gonads. After examination, animals were wrapped and disposed as a special residue of the Municipal Health Service.
- Other examinations performed: sign and symptoms were recorded at least once each workday for individual animals. A check for dead or moribund animals were made once at least once each workday and once on Saturdays, Sundays and on public holidays. Clinical observations included possible changes in skin and fur, eyes and mucous membranes, dyspnoea, changes in the behaviour, tremors, convulsions, salivation, diarrhea, prostration, coma and death.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed among the tested animals.
Clinical signs:
No treatment related signs were observed after a single administration.
Body weight:
Body weight changes were within the range of physiological variability.
Gross pathology:
No macroscopic changes were observed in any of the major organs of the examined animals.

Any other information on results incl. tables

Individual and group rnean body weight (bw) of animals treated at 2000 mg/kg bw of the test substance

Animals Bw (g)
Day 1 Day 7 Day 14 Bw changes
1 172.9 202.5 219.7 + 46.8
2 185.8 206.9 221.4 + 35.6
3 163.6 185.6 198.6. + 35.0
4 176.7 194.1 204.8 + 28.1
5 184.2 212.0 223.9 + 39.7
6 184.9 189.5 197.9 + 13.0
Mean 178.0 198.4 211.0 + 33.0

 

Individual clinical observation of animals treated at 2000 mg/kg bw of the test substance

Animals Days of observation
1 2 3 – 5 6 7 8 9 – 14
1 NA NA NA NA NA NA NA
2 NA NA NA NA NA NA NA
3 NA NA NA NA NA NA NA
4 NA NA NA NA NA NA NA
5 NA NA NA NA NA NA NA
6 NA NA NA NA NA NA NA

NA: no alterations

Individual necropsies of animals treated at 2000 mg/kg bw of the test substance

Macroscopic observations Females
1 2 3 4 5 6
Oesophagus NA NA NA NA NA NA
Trachea NA NA NA NA NA NA
Thyroid NA NA NA NA NA NA
Lungs NA NA NA NA NA NA
Bronchi NA NA NA NA NA NA
Heart NA NA NA NA NA NA
Diaphragm NA NA NA NA NA NA
Stomach NA NA NA NA NA NA
Intestine NA NA NA NA NA NA
Spleen NA NA NA NA NA NA
Pancreas NA NA NA NA NA NA
Liver NA NA NA NA NA NA
Lymph nodes NA NA NA NA NA NA
Muscles NA NA NA NA NA NA
Kidney NA NA NA NA NA NA
Bladder NA NA NA NA NA NA
Ovarium NA NA NA NA NA NA
Uterus NA NA NA NA NA NA

NA: no alterations

Applicant's summary and conclusion

Interpretation of results:
other: not classified, according to the CLP Regulation (EC 1272/2008)
Conclusions:
LD50 > 2000 mg/kg bw
Executive summary:

The study was carried out to assess acute toxicity following a single oral administration to rats of the test substance according to the OECD guideline 423. Wistar rats (Rattus norvegicus) were selected and maintained under controlled environmental conditions. Based on individual body weight, dosing of the test substance was calculated in mg/kg body weight (bw). Two groups of three female rats received 2000 mg/kg bw. Animals were observed for 14 days.

At the end of this period, no mortality or signs of evident toxicity were observed. Gross pathology examination was performed on all tested animals. No macroscopic alterations were observed in any of the major organs of the examined animals. Under the test conditions, the LD50 was found to be greater than 2000 mg/kg bw. Therefore, the test substance is not acutely toxic via the oral route.

Conclusion

LD50 > 2000 mg/kg bw

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