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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 January - 18 February 2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This summary is based on an unaudited draft report. The summary and reliability will be updated once the final report is available, however it is expected to be reliability 1 as it is a Guideline study performed under GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Sugar Factory Lime (Dry)
- Analytical purity: 100 % (UVCB)
- Composition of test material, percentage of components: 2.14 % water
- Lot/batch No.: SFL-OC-2013-D1
- Expiration date of the lot/batch: 31 December 2013
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature in the dark
- Other:The test material was dried to remove water (approx 30%w/w) prior to testing, as initial trials showed that it was not possible to produce an aerosol with the susbtance as manufactured. In order to facilitate aerosolisation and reduce particle size, the test item was ground using a Retsch Planetary Ball Mill (Retsch (UK) Ltd, Leeds, UK) prior to use. The absorption of the test item was not determined.

Test animals

Species:
rat
Strain:
Wistar
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
- Fasting period before study:
- Housing: Housed in groups of up to three by sex. Solid floor polypropylene cages/stainless steel lids/softwood flakes/ wooden chew blocks and cardboard 'fun tunnels' for enrichment.
- Diet: ad libitum except during exposure period
- Water: ad libitum except during exposure period. Harlan 2014C Rodent Diet, Harlan Laboratories UK Ltd, Oxon, UK
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 25
- Humidity (%): 30 – 70
- Air changes (per hr): >= 15
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: To: 29/01/13-18/02/13

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany)
- Exposure chamber volume: 30 L approximately
- Method of holding animals in test chamber: Tapered polycarbonate retraining tube
- Source and rate of air: Compressed air from an oil free compressor/ 60 L/min
- Method of conditioning air: Passed through a water trap and respiratory quality filters before it was introduced to the SAG 410.
- System of generating particulates/aerosols: The test item concentration within the chamber was controlled by adjusting the test item feed rate from the SAG 410.
- Method of particle size determination: The particle size of the generated atmosphere inside the exposure chamber was determined three times during the exposure period using a Marple Personal Cascade Impactor (Westech IS Ltd, Beds., UK). This device consisted of six impactor stages (7.8, 5.8, 3.6, 1.4, 0.74 and 0.34 µm cut points) with stainless steel collection substrates and a back up glass fiber filter, housed in an aluminum sampler. The sampler was temporarily sealed in a sampling port in the animals’ breathing zone and a suitable, known volume of exposure chamber air was drawn through it using a vacuum pump. The collection substrates and backup filter were weighed before and after sampling and the weight of test item, collected at each stage, calculated by difference. The mean amount for each stage was used to determine the cumulative amount below each cut-off point size. In this way, the proportion (%) of aerosol less than 7.8, 5.8, 3.6, 1.4, 0.74 and 0.34 µm was calculated. The resulting values were converted to probits and plotted against Log10 cut-point size. From this plot, the Mass Median Aerodynamic Diameter (MMAD) was determined (as the 50% point) and the geometric standard deviation was calculated. In addition the proportion (%) of aerosol less than 4 µm (considered to be the inhalable fraction) was determined.
- 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:

TEST ATMOSPHERE
- Brief description of analytical method used: The actual chamber concentration was measured at regular intervals during the exposure period. The gravimetric method used glass fiber filters placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals’ breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump.
Each filter was weighed before and after sampling in order to calculate the weight of collected test item. The difference in the two weights, divided by the volume of atmosphere sampled, gave the actual chamber concentration. The nominal chamber concentration was calculated by dividing the mass of test item used by the total volume of air passed through the chamber. The nominal concentration was 219% of the actual mean achieved atmosphere concentration and shows that keeping the aerosol airborne was relatively straightforward. See Table 1

- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- See Tables 2, 3 & 4

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Based on data from read-across substance (calcium carbonate)
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.09 mg/L
No. of animals per sex per dose:
3 male/ 3 female
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 up to fourteen days. Any evidence of overt toxicity was recorded at each observation. Individual body weights were recorded on arrival, prior to treatment on the day of exposure and on Days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight. All animals were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.09 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
There were no deaths during the study
Clinical signs:
other: Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection and wet fur. Occasional instances of red/brown staining around the snout were also noted. Animals recovered to appear normal from Days 7 to 9
Body weight:
All animals exhibited body weight losses or showed no bodyweight gain on the first day post-exposure. Reasonable body weight gains were noted for all male animals during the remainder of the recovery period. In contrast, all female animals exhibited bodyweight losses from Days 1 to 3, two of these animals also showed no bodyweight gain from Days 3 to 7. Reasonable bodyweight gains were noted in all females during the final week of recovery.
Gross pathology:
No macroscopic abnormalities were detected amongst animals at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

No deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 5.09 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of Sugar Factory Lime (Dry), in the RccHanTM: WIST strain rat, was greater than 5.09 mg/L