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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:
2 to 16 April 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The test is non GLP and no test material analysis is present (including assessment of aerosol characteristics), therefore it cannot be Klimisch 1. However, concentration was checked and pathological examination was conducted. Moreover, guidelines are similar to the subsequent OECD 403, therefore a Klimisch 2 reliability score can be assigned.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
no data on acclimation period, on oxygen concentration, assessment of aerosol characteristics
Principles of method if other than guideline:
standard method in general compliance with the procedures subsequently incorporated into OECD TG 403
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories Ltd.; Wilmington Mass.
- Age at study initiation: 8 weeks old
- Weight at study initiation: 175-225 g
- Fasting period before study: no fasting period
- Housing: individually housed in stainless steel, wire meshed-bottom cages
- Diet (e.g. ad libitum): certified laboratory rat diet ad libitum except during the four hours of inhalation exposure
- Water (e.g. ad libitum): tap water ad libitum except during the four hours of inhalation exposure
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.5 ºC
- Humidity (%): 47.5%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel whole body exposure chamber
- Exposure chamber volume: 400 L chamber compartmentalised with each compartment being 7''x3''x4''
- Method of holding animals in test chamber: no data
- Source and rate of air: airflow rate through the chamber was set at 45 L/min
- Method of conditioning air: no data
- System of generating particulates/aerosols:aerosol was generated using a Thermo Systems Inc. six jet atomizer. The atomizer was used at a pressure of 13 psig with two jets in operation.
- Method of particle size determination: hourly air samples from the inhalation chamber were passed through a Casella Cascade Impactor. The distribution and size of particles which deposited on each of the 4 stages of the impactor were determined by light microscopy.
- Treatment of exhaust air: decontamination of chamber air was done by passing the air through a HEPA filter, an activated charcoal filter and a liquid scrubber.
- Temperature, humidity, pressure in air chamber: 23.5 ºC; 47.5% RH; the negative pressure within the chamber with respect to the room atmosphere was set at less than 0.5 inches of water

VEHICLE
- Composition of vehicle (if applicable): Not Applicable
- Concentration of test material in vehicle (if applicable): Not Applicable
- Justification of choice of vehicle: Not Applicable
- Lot/batch no. (if required): Not Applicable
- Purity: Not Applicable


Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
ca. 4 h
Concentrations:
The animals were exposed only to one concentration. They were exposed to a nominal concentration of hexyl cinnamic aldehyde (HCA) of 5.00 mg/L resulting in a measured chamber concentration of 2.12 mg/L
No. of animals per sex per dose:
A total of 10 animals were exposed, 5 male and 5 female
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed on the day of exposure and on days 2, 3, 4, 7 and 14 after the day of the exposure
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathology, clinical signs, body weight, histopathology
Statistics:
No information

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.12 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air (nominal)
Exp. duration:
4 h
Mortality:
There were no mortalities
Clinical signs:
other: There were no clinical changes of possible toxicological importance
Body weight:
Body weight losses occurred on the days following exposure; the losses were generally made good by day 7 of the study. Body weight gains during the second week of the observation period were considered to be satisfactory
Gross pathology:
The only changes considered to be of possible toxicological importance were enlarged bronchial lymph nodes sometimes accompanied by pulmonary congestion, or multiple grey-green pinpoint foci in the lungs
Other findings:
- Histopathology:

MALES:
animal 1. Chronic respiratory disease, mild
animal 2. Degeneration, tubular, diffuse, unilateral in left testis and pulmonary congestion and edema, diffuse, severe
animal 3. Chronic respiratory desease, severe
animal 4. Chronic respiratory disease, mild
animal 5. Chronic respiratory desease, severe


FEMALES:
animal 1. Chronic respiratory disease, mild
animal 2. No pathological alteration in kidneys and Chronic respiratory disease, severe with one section showing pulmonary congestion and edema
animal 3. Chronic respiratory disease, moderate
animal 4. Hydrometra in uterus and Chronic respiratory disease
animal 5. Dermatitis, ulcerative chronic focal in cervical region and chronic respiratory disease.

Any other information on results incl. tables

Administration of hexyl cinnamic aldehyde (HCA) by the inhalation route did not produce any systemic toxicity in the albino rat.

Focal greyish-green areas observed grossly on lungs were characterised histologically by aggregates of mononuclear leucocytes mainly about blood vessels and air passages and occasionally extending to alveolar walls, some interstitial fibrosis and infiltration by foamy macrophages. These lessions were considered to be spontaneous and caused as a result of a mild infection with murine respiratory mycoplasmosis. Pulmonary oedema and mild congestion revealed in some rats could be attributed to euthanasia. Testicular tubular degeneration and hydrometra in some rats were also considered incidental.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal concentration LC50 for rats following inhalation of 2-benzylidene octanal, (HCA), for combined sexes data was greater than 2.12 mg/L (analytical concentration) or 5.00 mg/L (nominal concentration).
Executive summary:

In a limit acute inhalation toxicity study performed similarly to the OECD test guideline No. 403, groups of young adult Sprague-Dawley rats (5/sex) were exposed by inhalation route to liquid aerosols of hexyl cinnamic aldehyde (HCA) for 4 hours to whole body at concentration of  5.00 mg/L (nominal, corresponding to 2.12 mg/L analytical). Animals then were observed for14days.

 

LC50 Combined > 2.12 mg/L (analytical concentration) / 5.00 mg/L (nominal concentration)

 

There were no mortalities under the test conditions. The only changes that were considered possibly to be attributable to treatment were a minimal loss of body weight on the days immediately following treatment and enlarged bronchial lymph nodes at the terminal kill, multiple grey-green foci on the lungs and occasional pulmonary congestion. As the actual concentration reached was only 2.12 mg/L, it is difficult to conclude on the classification of HCA. However it is mentioned in the OECD Guideline No. 403 (2009) that "when testing aerosol the primary goal should to be achieve a respirable particle size and this is possible with most test article at a concentration of 2.00 mg/L". Moreover, there was no mortality and observed lessions were considered by the study authors to be spontaneous and caused as a result of a mild infection with murine respiratory mycoplasmosis. Pulmonary edema and mild congestion revealed in some rats could be attributed to euthanasia. Testicular tubular degeneration and hydrometra in some rats were also considered incidental by the study authors.

Based on the above discussion, under the test conditions, HCA is not classified according to the Directive 67/548/EEC and the Regulation (EC) No. 1272/2008. This study is considered as acceptable and satisfies the guideline requirement for an acute inhalation toxicity study.