Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Specific details on test material used for the study:
Identification: Frutonile
Description: Liquid
Batch Number: VE00002027 or 9000774502
Expiry Date: 19-Oct-2009
Storage conditions: At room temperature (range 20 +/- 5 °C, provided by Harlan Laboratories Ltd.), light protected.
Safety Precautions: Routine hygenic procedures (gloves, laboratory overall, goggles, fask mask). A full filtered, positive air-supplied respirator will be used during the inhalation process.

Test animals

Species:
rat
Strain:
Wistar
Remarks:
HanRcc: WIST(SPF)
Sex:
male/female
Details on test animals and environmental conditions:
Rationale: Recognised by international guidelines as a recommended rodent test system
Breeder: Harlan Laboratories Ltd.
Number of animals per group: 5 males and 5 females
Number of Groups: 1
Age at exposure: Males - 10 weeks, Females - 11 weeks
Body weight range at exposure: Males - 251.2 to 284.4 kg, Females - 217.0 to 223.2 kg (The weight variation did not exceed +/- 9% of the mean weight of the corresponding sex)
Identification: By unique cage numbers and individual unique tail numbers written with an inedlible felt-tip pen.
Acclimatization: Performed under Harlan Laboratories Study B68308 for eight dats under laboratory conditions, after clinical health examination. Only animals without any visible signed of illness were used for the study. A further observation of clinical signs was performed on the day of exposure, before exposure start.

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
Method: Inhalation by nose-only, flow-past exposure
Frequency of administration: single, 4-hour exposure period
Target aerosol concentration: slightly above 5 mg/L air
Rationale of aerosol concentration: The target concentration of 5 mg/L air (actual concentration of respirable substances) for 4 hours is the recommended concentration (OECD 403. 'Actue Inhalation Toxicity')
Duration of exposure:
4 h
Concentrations:
Target aerosol concentration: slightly above 5 mg/L air
No. of animals per sex per dose:
5 males and 5 females

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 5.3 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: gravimetrically determined mean aerosol concentration
Mortality:
All animals survived the scheduled observation period
Clinical signs:
other: Slight to moderate salivation was observed during the whole course of exposure in all animals. In addition tachypnea, slightly to moderately decreased activity and slightly to moderately ruffled fur was noted in all animals at the end of the exposure peri
Body weight:
From test day 1 to test day 4, marginal to slight body weight loss was noted in all males and 4 females. The remaining female showed reduced body weight gain from test day 1 to test day 8. Thereafter, normal bosy weight development was recorded in these animals.
Gross pathology:
No macroscopic findings

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Treatment of HanRcc: WIST(SPF) rats with Frutonile at a concentration of 5.3 mg/L for 4 hours resulted in no deaths.

Marginal body weight loss or stagnation of the body weight gain is not unusual in inhalation studies due to the restraining of the animals in the tubes during the nose-only exposure procedure. Nevertheless, the extent of the effects on the body weight on this study were considered to be mainly related to treatment with the test item although a contribution of restraining procedure is likely to have add the observed effect.

In conclusion, the LC50 of Frutonile obtained in this study was estimated to be greater than 5.3 mg/L air (gravimetrically determined mean aerosol concentration). There was no indication of relevant sex-related differences in toxicity of the test item.