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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 18 December 1996 to 21 July 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
the certificate of analysis is missing from the study report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
29 December 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Pyrrolidine, 1-[2-[2-nitro-4-(phenylmethoxy)phenyl]ethenyl]-
Cas Number:
99474-22-3
Molecular formula:
C19H20N2O3
IUPAC Name:
Pyrrolidine, 1-[2-[2-nitro-4-(phenylmethoxy)phenyl]ethenyl]-
Test material form:
other: solid granular powder
Details on test material:
- Other: beige brown-coloured granular powder
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD (SD)BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: animals bred Charles River and supplied by CRIFFA, S.A. (C/Paraires, 1-7, Nave 5, Centro Industrial Santiga, 08130-SANTA Perpetua de Mogoda, Barcelona, Spain)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 5 weeks
- Weight at study initiation: 104-116 g
- Fasting period before study: approximately 18 hours priors to treatment
- Housing: Animals were housed in Makrolon cages (55 x 32.7 x 19 cm) with sawdust bedding. Each cage contained up to 5 rats of the same sex. The sawdust bedding was replaced by a wire floor for the preadministration fasting period
- Diet: free access (except during the fasting period and the 3-4 hours following administration of the test substance) to a standard rat diet UAR A04C (Usine d'Alimentation Rationnelle, 91360-Villemoisson sur Orge, France, lot n° 60918). The diet was analyzed by the manufacturer to detect possible contaminants.
- Water: ad libitum in bottles. The water was supplied by "Compania de Aguas de Sabadell, S.A." and is periodically checked for the presence of possible contaminants.
- Acclimation period: at least seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23; occasionally reaching temperatures of 24 °C
- Humidity (%): 48-70; occasionally reaching levels of relative humidity of 71-74%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 (7:00 to 19:00)

IN-LIFE DATES: From: 08 January 1997 To: 29 January 1997

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: other: 0.2% sodium carboxymethyl cellulose and 10% Tween 80
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/ kg bw

ADMINISTRATION OF THE TEST SUBSTANCE: the quantity of test substance administred to each animal was determined based on its bodyweight at the moment of administration.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Following treatment, animals were monitored at intervals throughout the day. Then, at least 2 times a day for 14 days. All rats were weighted before administration, half-way through the observation period and before sacrifice.
- Observations: included but were not limited to, changes in skin or fur, eyes and mucous membranes, respiratory, circulatory, central nervous and autonomic nervous systems, somotomotor activity and behaviour.
- Sacrifice: by CO2 inhalation
- Necropsy of survivors performed: yes; included a revision of the intact animal and all its superficial tissues followed by an observation of the cranial, thoracic and abdominal cavities bot in situ and after evisceration.
Statistics:
Not applicable.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality, no clinical signs and no macroscopic findings
Mortality:
No mortality was observed among all the animals of the study.
Clinical signs:
No clinical signs were recorded during the study.
Body weight:
The evolution of the bodyweights was normal throughout the study.
At the start of the treatment, the rats weighted 104-116 g while at the end of the observation perdiod they weighted 176-270 g.
Gross pathology:
No macroscopic alterations were observed in any of the necropsies carried out.
Other findings:
None.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the oral LD50 of the test material is higher than 2000 mg/kg body weight without mortality, clinical signs or macroscopic findings. Thus, the test material is not classified as hazardous for acute oral toxicity according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.
Executive summary:

This GLP-compliant study was performed to assess the acute oral toxicity of the test material, according to OECD Guideline 401 (dated February 24th, 1987) and EU method B.1 of the E.E.C. directive n°92/69 (dated December 29th, 1992).

Material and methods

The test material -suspended in 0.2% sodium carboxymethyl cellulose and 10% Tween 80- was administered by gavage to a group of 10 Sprague Dawley rats (5 males and 5 females) at a single dose of 2000 mg/kg body weight. Animals were monitored at least 2 times a day for 14 days. All rats were weighted before administration, half-way through the observation period and before sacrifice. Necropsies were performed on all the animals.

Results

No mortalities or notable clinical signs were recorded during the study. The evolution of the bodyweights was normal throughout the study. The macroscopic examination of the animals at the end of the study did not reveal any treatment-related change.

Conclusion

Under the experimental conditions of this study, the oral LD50 of the test material is higher than 2000 mg/kg body weight without mortality, clinical signs or macroscopic findings. Thus, the test material is not classified as hazardous for acute oral toxicity according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.