Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19. Feb. 2003 - 17. Mar. 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification : Benzoic acid isononylester
Description : Colourless liquid
Batch number : 1276/00576
Date received : 06 January 2003
Storage conditions : Room temperature, in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Male and female Sprague-Dawley Crl:CD® (SD) lOS BR strain rats were supplied by Charles River (UK) Ltd, Margate, Kent. On receipt the animals were randomly allocated to cages. After an acclimatisation period of at least five days the animals were given a number unique within the study by ear punching and a number written on a colour coded cage card. At the start of the study the animals were approximately eight to twelve weeks old and within the weight range of 200g to 350g. The females were nulliparous and non-pregnant.
The animals were housed in groups of five by sex In solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes (Datesand Ltd., Cheshire, UK) and provided with environmental enrichment items: wooden chew blocks (B & K Universal Ltd, HuIl, UK) and cardboard "fun tunnels" (Datesand Ltd., Cheshire, UK). With the exception of the exposure period, free access to drinking water and food (EU Rodent Diet 5LF2, IPS Limited, Wellingbofough, Northants, UK) was allowed throughout the study. The diet, drinking water, bedding and chew blocks are routinely analysed and are considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
The environmental controls were set to achieve values of 21 ± 2°C and 55 ± 15% relative humidity. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled to give twelve hours continuous light and twelve ho urs darkness. The animals were retained in this accommodation at all times except during the exposure period.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Details on inhalation exposure:
The test material was aerosolised using a glass concentric jet nebuliser (Radleys, Saffron WaIden, Essex, UK) located at the top of the exposure chamber. The nebuliser was connected to a glass syringe attached to an infusion pump, which provided a continuous supply of test material under
pressure, and to a metered compressed air supply.
Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the nebuliser. The cylindrical exposure chamber had a volume of approximately 30 litres (dimensions: 28 cm diameter x 50 cm high). The concentration within the exposure chamber was controlled by adjusting the rate of the infusion pump. The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system. The chamber was maintained under negative pressure.
Homogeneity of the test atmosphere within the chamber was not specifically determined during this study. Chambers of the same design (ADG Developments Ltd, Hitchin, Herts, UK) have been fully validated and shown to produce evenly distributed atmospheres In the animals breathing zone with a wide variety of test materials. Prior to the start of the study, test material atmospheres were generated within the exposure chamber. During this characterisation period air flow settings and test material input rates were varied to achieve the required atmospheric concentrations.
Duration of exposure:
4 h
Concentrations:
nominal : 53.9 mg/L
mean measured : 5.22 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for clinical signs at hourly intervals during exposure, immediately on
removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for fourteen days. Any evidence of overt toxicity was rceorded at each observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.22 mg/L air
Exp. duration:
4 h
Mortality:
There were no death.
Clinical signs:
other: Signs of hunched posture, pilo-erection and red/brown staining around the eyes are commonly seen in animals for short periods on removal from the chamber following 4-hour inhalation studies. Wet fur is commonly recorded both during and for a short period
Body weight:
Normal bodyweight development was recorded during the study. One female showed reduced bodyweight gain during Week 1 but such variations are not uncommon in female rats of this strain or age and are not considered significant.
Gross pathology:
No abnormalities were detected at necropsy.

Applicant's summary and conclusion

Interpretation of results:
relatively harmless
Remarks:
Migrated information
Conclusions:
No deaths occurred in a group often rats exposed to a mean achieved atmosphere concentration of 5.22 mg/L. It was therefore considered that the acute inhalation median lethaI concentration (LC50) of Benzoic acid isononylester, in the Sprague-Dawley Crl:CD® (SD) IGS BR strain rat,
was greater than 5.22 mg/L.
Executive summary:

A study was performed to assess the acute inhalation toxicity of the test material according to OECD 403 "Acute Inhalation Toxicity" referenced as Method B2 in Commission Directive 92/69/EEC "Acute Toxieity - Inhalation" (which constitutes Annex V of Couneil Directive 67/548/EEC).

A group of ten Sprague-Dawley Crl:CD® (SD) IGS BR strain rats (five males and five females) was exposed to an aerosol atmosphere. The animals were exposed far four hours using a no se only exposure system, followed by a fourteen day observation period. No deaths occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 5.22 mg/L. It was therefore considered that the acute inhalation median lethal concentration (LC50) of Benzoic acid isononylester, in the Sprague-Dawley Crl:CD® (SD) IGS BR strain rat, was greater than 5.22 mg/L.