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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (no analytical purity reported)
Justification for type of information:
refer to analogue justification provided in IUCLID section 13

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted in 1996
no analytical purity reported
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Reference substance name:
Fatty acids, C5-9, tetraesters with pentaerythritol
EC Number:
EC Name:
Fatty acids, C5-9, tetraesters with pentaerythritol
Cas Number:

Test animals

other: Sprague-Dawley CD®
Details on test animals or test system and environmental conditions:
- Source: Charles River Laboratories, Klingston, NY, USA
- Age at study initiation: approximately 9 weeks (control group); approximately 10 weeks (test group)
- Weight at study initiation: 332 g (control group, males only); 358 g (test group, male) and 247 (test group, female)
- Fasting: feed was not provided during the exposure
- Housing: animals were group-housed in suspended, stainless steel, wire mesh cages during the acclimation period and individually-housed during all other non-exposure period.
- Diet: certified Rodent Diet, # 5002 meal, ad libitum
- Water: ad libitum
- Acclimation period: The control group animals were acclimated for 12 days. The test group animals were acclimated for 19 days.

- Temperature (°C): 20 - 23
- Humidity (%): 18 - 30
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Details on inhalation exposure:
- Exposure apparatus: cast aluminium and alloy exposure chamber with polycarbonate nose-only tubes housed within 10 m³ Harford glass and stainless steel exposure chamber.
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: animals were placed in polycarbonate tubes attached to the chambers.
- Source and rate of air: 20 L/min
- System of generating particulates/aerosols: Approximately 110 mL of test material were placed into a nebulizer. House-supply air was delivered from a regulator and backpressure gauge, via ¼” tubing, to a plastic Y tube which split the airflow into the generation and dilution systems. The generation air (7.0 Lpm) was directed, via ¼” tubing, through a flowmeter regulated by a metering valve, and a backpressure gauge, to the nebulizer. The test material-laden airstream was directed through a flowmeter regulated by a metering valve, into the dilution port at the top of the nose-only exposure chamber.
- Method of particle size determination: In the control group the particle size distribution measurements were performed each hour of exposure for the chamber and room air using a TSI Aerodynamic Particle Sizer. The samples were drawn for 20 seconds at a rate of 5.0 Lpm. The mass median aerodynamic diameter, geometric standard deviation and in the test group samples for particle size distribution assessment were drawn each hour of exposure using a cascade impactor. The samples were drawn for one minute at a flowrate of 1.00 Lpm. The mass median aerodynamic diameter, geometric standard deviation and percent of particles ≤1.0, ≤4.0 and ≤10 microns were calculated based on the amount of material collected on the seven impactor stages and a final filter stage using a graphical analysis of an assumed lognormal distribution.
- Temperature, humidity, pressure in air chamber: 21°C (average), 23% (average)

- Brief description of analytical method used: Sample concentration (mg/L) was determined gravimetrically on a total formulation basis. A drop of the test material was placed on a weighed filter, weighed immediately and again after drying overnight. This was done in triplicate. The resultant data were used to determine the fraction of solids in the test material. During the exposure, the filter was weighed before and immediately after sampling (wet weight). The exposure concentration (mg/L) was calculated on both a “wet” and “dry” basis by dividing the appropriate net weight (mg) by the volume of air sampled (liters). For the test group, only exposure levels were calculated on a formulation by dividing the exposure concentration on a “dry” basis (mg/L) by the fraction of solids.
- Samples taken from breathing zone: yes

- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.18/2.03
Analytical verification of test atmosphere concentrations:
Duration of exposure:
4 h
5.50 mg/L (analytical concentration)
6.6 mg/L (nominal concentration)
No. of animals per sex per dose:
10 (air control)
10 (males, test group)
5 (females, test group)
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days (5 males were sacrificed on Day 3)
- Frequency of observations and weighing: on day 1 all animals were observed individually immediately prior to the exposures, as a group at approximately 15 minute intervals during the first hour of each exposure, and hourly for the reminder exposure periods. All surviving animals were observed individually upon removal from the chambers (30 min after each exposure termination) and every hour for two hours post-exposure. Detailed physical observations (general condition, skin and fur, eyes, nose, oral cavity, abdomen and external genitalia as well as evaluations of respiration and palpation for tissue masses) were recorded at each interval. From day 2 to 15 detailed observations were recorded once daily. Individual body weights were recorded on day 1 (just prior to exposure), on Day 3 (just before sacrifice). Animal sacrificed on Day 15 were weighed on day 8 and 15 (just prior sacrifice)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology, gross pathology.

Results and discussion

Effect levels
Dose descriptor:
Effect level:
5.5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
No mortality occurred during the study period.

Clinical signs:
other: Test group: nasal discharge was noted as only sign of toxicity. Wet fur was noted as well but was considered an artefact of the nose-only exposure regimen. A few incidences of chromodacryorrhea were also noted to a comparable degree to the Group II animal
Body weight:
The test group females lost weight during the first week after the test material exposure, but gained weight during the second week after exposure. In all other animals no effect on body weight was noted.
Gross pathology:
Necropsy examination revealed no substance-related findings.

Other findings:
- Histopathology: There were no test material related microscopic findings. At the end of each of the post-exposure observation periods, incidental findings occurred with comparable incidence and severity in rats from the control and test groups or they occurred sporadically. The have been seen of this strain and age used in similar studies conducted in the study facility.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
CLP: not classified