Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
25 Jun - 26 Jul 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Heptanoic acid diester of neopentylglycol
- Physical state: clear colourless liquid
- Analytical purity: > 99%
- Purity test date: 2011-10-10
- Lot/batch No.: 595859
- Expiration date of the lot/batch: 2013-10-08
- Storage condition of test material: at room temperature, in the dark

Test animals

Species:
rat
Strain:
other: RccHanTM:WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200-350 g
- Housing: animals were housed in groups of up to 3/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 and cardboard “fun tunnels” (Datesand Ltd, Cheshire, UK)).
- Diet: Harlan 2014C Rodent Diet (Harlan Laboratories UK Ltd, Oxon, UK), ad libitum (with the exception of the exposure period)
- Water: mains drinking water, ad libitum (with the exception of the exposure period)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical exposure chamber (ADG Developments Ltd, Hitchin, UK)
- Exposure chamber volume: 30 L
- Method of holding animals in test chamber: each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring. Prior to the day of exposure, each rat was acclimatised for approx. 2 h to the tapered polycarbonate restraining tube.
- Source and rate of air: filtered air supplied from an oil-free compressor at 60 L/min
- System of generating particulates/aerosols: glass concentric jet nebuliser (Radleys, Saffron Walden, UK)
- Method of particle size determination: Marple Personal Cascade Impactor (Westech, IS Ltd, Beds., UK), consisting of 6 impactor stages (7.8, 5.8, 3.6, 1.4, 0.74 and 0.34 µm) with stainless steel collection substrates and a back-up glass filter, housed in an aluminium sampler
- Treatment of exhaust air: the extract from the exposure chamber passed through a ‘scrubber’ trap and was connected with a high efficiency filter to a metered exhaust system.
- Temperature, humidity, pressure in air chamber: 19-20 °C, 71-72%, negative

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric filter analysis was used to determine the actual concentration of the aerosol. The test atmosphere was sampled at regular intervals (approx. every 10-15 min) during the exposure period. A weighed glass fibre filter was placed in a filter holder and temporarily sealed in a vacant port of the exposure chamber. A known quantity of the exposure chamber concentration was drawn through the filter using a vacuum pump. After sampling, the filter was dried in a desiccator under reduced pressure at 19-21 °C for ca. 24 h and weight thereafter.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see Table 1 and 2 under "Any other information on materials and methods incl. tables"
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.42 µm/2.56 µm

CLASS METHOD
- Rationale for the selection of the starting concentration: a target concentration of 5 mg/L was chosen based on a preliminary sighting study in two rats treated with a mean achieved test atmosphere concentration of 2.14 mg/mL. In this experiment, no significant effects were observed in the animals after an exposure period of 4 h.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
4 h
Concentrations:
5.22 mg/L (mean achieved concentration)
13.5 mg/L (nominal concentration)
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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 over 14 days. Individual body weights were recorded on arrival, prior to treatment and on Days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes, full external and internal observation. Detailed macroscopic examination of the respiratory tract was performed to determine signs of irritancy or local toxicity.
- Other examinations performed: clinical signs, body weight
Statistics:
Mean values and standard deviations of the mean achieved atmosphere concentrations were determined.

Results and discussion

Preliminary study:
In a preliminary sighting study, 2 rats treated with a mean achieved test atmosphere concentration of 2.14 mg/mL (target: 2 mg/mL) showed no significant effects after an exposure period of 4 h. Clinical signs during exposure included wet fur and an increased respiratory rate. In addition, hunched posture and pilo-erection were observed directly after exposure and 1 h thereafter. The increase in respiratory rate was still present until Day 3 post-exposure. One day later, all animals were free of any clinical symptoms. No macroscopic findings were observed at necropsy. Thus, a starting concentration of 5 mg/mL was chosen for the main experiment.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.22 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: Signs of hunched posture and pilo-erection were seen in test animals for a short period after removal from the exposure chamber. Wet fur was recorded during the exposure period and for a short time period thereafter which were considered to be associated
Body weight:
All animals showed the expected body weight gain during the study, except for one female which did not gain weight during the 14-day observation period. In addition, one male exhibited a slight loss in body weight on the first day of exposure.
Gross pathology:
At necropsy, no macroscopic abnormalities were observed in the treated animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified