Fatty acids, rape-oil, mixed esters with 1,4:3,6-dianhydro-d-glucitol, sorbitan and sorbitol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP-Guideline study tested with the source substance anhydro-D-glucitol trioleate (CAS No. 26266-58-0). 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

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Anhydro-D-glucitol trioleate

EC Number:

247-569-3

EC Name:

Anhydro-D-glucitol trioleate

Cas Number:

26266-58-0

Molecular formula:

C60H108O8

IUPAC Name:

1,4-anhydro-2,3,6-tri-O-oleoyl-L-iditol

Details on test material:

- Name of test material (as cited in study report): anhydro-D-glucitol trioleate
- Physical state: amber coloured liquid
- Analytical purity: no data
- Storage condition of test material: at room temperature in the dark
- Other: total ester content 86.8%

Test animals

Species:

rat

Strain:

other: RccHan:WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Oxon, UK
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 200 - 350 g
- Housing: groups of three by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes and provided with environmental enrichment items: wooden chew blocks and cardboard "fun tunnels"
- Diet (ad libitum): Harlan 2014C Rodent Diet
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- 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 chamber volume: cylindrical exposure chamber (30 m³)
- 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.
- Method of conditioning air: 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 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. The chamber flow rate was maintained at 60 L/min providing 120 air changes per hour.
- System of generating particulates/aerosols: The test item was aerosolised using a glass concentric jet nebuliser located at the top of the exposure chamber. The nebuliser was connected to a plastic syringe attached to an infusion pump, which provided a continuous supply of test item under pressure, and to a metered compressed air supply.
- 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.
- Temperature, humidity: 20°C, 72-76% (at least 19% oxygen)

TEST ATMOSPHERE
- Brief description of analytical method used: the test atmosphere was sampled at regular intervals 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 in the animals´ breathing zone. A known quantity of the exposure chamber atmosphere was drawn through the filter using a vaccum pump. After sampling, the filter was dried, under similar conditions as those previously described, and weighed again 24 h later. The difference in the pre and post sampling weights, divided by the volume of atmosphere sampled, was the chamber concentration in terms of non-volatile component.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: inhalable fraction (< 4 µm) of 73.8%
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.14 µm / 2.68 µm

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.27 ± 0.41 mg/L (analytical 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 hourly during exposure, immediately on removal from the restraining tubes at the end of the exposure, 1 h after termination of exposure and subsequently once daily for the remaining 14 days. Individual bodyweights 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

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.27 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Common abnormalities noted during the study included increased respiratory rate, hunched posture, piloerection, red/brown staining around the snout and wet fur. The animals recovered to appear normal from Days 3 to 5 post-exposure.

Body weight:

All animals exhibited bodyweight losses on the first day post-exposure. Reasonable bodyweight development was noted in all male animals during the recovery period. In contrast, one female animal exhibited a further bodyweight loss from Days 1 to 3 post-exposure, two females showed either a slight bodyweight loss or no bodyweight gain from Days 3 to 7 post-exposure. Reasonable bodyweight development was noted in all female animals during the final week of recovery (see Table 1).

Gross pathology:

Necropsy examination revealed no substance-related findings.

Any other information on results incl. tables

Table 1: Individual body weights

	Bodyweight (g) on Day:
Animal number and sex	-8	0	1	3	7	14
1 male	218	253	247	258	269	287
2 male	236	275	266	281	292	317
3 male	217	275	271	284	292	326
4 female	188	200	198	204	204	211
5 female	222	251	248	240	235	246
6 female	218	233	232	240	245	253

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

DSD: not classified
CLP: not classified