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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:
16 January 2007 to 16 March 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD Guideline 403, EU Method B.2, GLP and other guidelines (see below)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF Test data for Registration of Agricultural Chemicals, Test Guidelines, Acute Inhalation Toxicity, 12 NohSan No. 8147, November 2000
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Study in compliance with Swiss Ordinance relating to GLP, which is based on OECD Principles of GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain specifics: HanBrl:WIST(SPF)
- Source: RCC Ltd, Laboratory Animal Services, Füllinsdorf, Switzerland
- Age at study initiation: males: 9 weeks, females: 10 weeks
- Weight at study initiation: males: 232.1-261.6 g, females: 210.0-221.9 g
- Housing: Animals of the same sex were housed in groups of five in Makrolon type IV cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): standard rat maintenance diet, ad libitum, except during the treatment period
- Water (e.g. ad libitum): community tap water ad libitum, except during the treatment period
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-20 °C
- Humidity (%): 30-72%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Remarks:
flow-past exposure
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Similar to the system originally described by Sachsee et al. (1973, 1976) and Cannon et al. (1983)
- Method of holding animals in test chamber: restraint tubes
- Source and rate of air: total airflow: 34 l/min, airflow of the aerosol arriving at the animal ports: 1 l/min per animal port
- System of generating particulates/aerosols: dust aerosol generated from the test item using a rotating brush aerosol generator connected to a micronising jet mill. The aerosol generated was then discharged into the exposure chamber through a 63Ni charge neutraliser.
- Method of particle size determination: gravimetrically (see below)
- Temperature, humidity, oxygen concentration in air chamber: measured on test atmosphere samples collected from the feed tubes in the breathing zone of the animals

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrically (weighing the generator cylinder containing the test item before and after the exposure to determine the quantity of test item used. The total weight used during the exposure was then divided by the total airflow volume to give the nominal concentration.
- Samples taken from breathing zone: yes (gravimetrically using Millipore filters)

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: measured gravimetrically twice during each exposure using a 7 stage cascade a Mercer Impactor
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): calculated on the basis of the results with the Mercer Impactor
For results, see below

References:
Sachsse, K., L. Ullmann, G. Voss and R. Hess: Measurements of Inhalation Toxicity of Aerosols in Small Laboratory Animals. In: Proceedings of the Europ. Soc. for the Study of Drug Toxicity, Vol. XV, pp. 239-251, Zürich, June 1973.
Sachsse, K., L. Ullmann, K. Zbinden: Toxikologische Prüfungen von Aerosolen im Tierexperiment, "Chemische Rundschau" 29 (1976), No. 38, p. 1.
Cannon, W.C., E.F. Blanton and K.E. McDonald: The Flow-Past Chamber: An Improved Nose-Only Exposure System for Rodents, Am. Ind. Hyg. Assoc. J., 44 (12): 923-928, 1983
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see above
Duration of exposure:
4 h
Remarks on duration:
Approx. 2 h after the start, exposure was interrupted for 3 min (cleaning the exposure system and changing the piston cylinder). Nevertheless, animals were exposed for a total of 4 hours.
Concentrations:
Nominal concentration: 4.419 mg/l
Actual concentration: 3.055 mg/l (± 0.068 mg/l, n = 5), MMAD (two measurements): 2.83 µm (GSD 4.04) and 2.64 µm (GSD 3.93)
Rationale: A target concentration of 3 mg/l air (actual concentration of test item in air) corresponds to the maximum technically feasible aerosol concentration as determined in technical trials.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days beginning on the day of exposure
- Frequency of observations and weighing: daily for mortality and clinical signs, weiging on days 1 (before exposure), 4, 8 and 15 (day of necropsy)
- Necropsy of survivors performed: yes (all animals)
- Other examinations performed:
clinical signs included, but were not limited to: changes in behaviour, somatomotor activity, body position, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, e.g. tremors or convulsions, reactivity to handling or sensory stimuli, altered strength, alteration of the skin, fur, nose, eyes and mucous membranes
Statistics:
The LOGIT model was not used as only one group was exposed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC0
Effect level:
3.055 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: mean analytical concentration of five measurements, see above for standard deviation
Mortality:
No mortality, all animals were sacrificed as scheduled on test day 15.
Clinical signs:
All animals showed rales, decreased spontaneous activity, hunched posture, tachypnea and ruffled fur on the day of exposure and the two following days in individually variable extent. These signs were not noted from day 4 onwards.
Body weight:
Four females showed a slight transient body weight loss between Day 1 and Day 4. All other animals gained body weight as expected.
Gross pathology:
There were no macroscopic pathology findings in any of the animals. No macroscopically visible coloration of the lungs by Hostaperm Rosa E was detected.
Other findings:
Temperature, relative humidity and oxygen concentration during exposure were considered to be satisfactory for this type of study.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
Conclusions:
No mortality was observed after nose-only inhalation exposure to the test item (Pigment Red 122) of male and female rats at the highest technically achievable aerosol concentration of 3.055 mg/L for 4 hours. Based on the lack of lethal effects, severe clinical symptoms indicating a life-threatening or moribund state, and gross morphological abnormalities, it may be reasonably assumed that the LC50 for the test item is greater than 5 mg/l air and that the test item has not to be classified as acutely toxic by the inhalation route according to Regulation (EC) No 1272/2008.
Executive summary:

The purpose of this study was to assess the acute inhalation toxicity of the test item when administered to rats for a single 4-hour period.

One group of five male and five female albino rats [HanBrl:WIST(SPF)], were exposed by noseonly, flow-past inhalation to the test item at mean aerosol concentrations of 3.055 ± 0.068 (n=5) mg/L air (gravimetrically determined). Two gravimetric measurements of particle size distribution during the exposure produced mass median aerodynamic diameters and geometric standard deviations (GSD) of 2.83 µm (GSD 4.04) and 2.64 µm (GSD 3.93), respectively.

All animals were observed for clinical signs and mortality during and following the inhalation exposure, i.e. over a 15-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 4, 8 and 15. All animals were sacrificed and necropsied on day 15.

The ranges of temperature, relative humidity, oxygen content and particle size measured during the exposure were satisfactory for a study of this type.

There were no spontaneous deaths.

All animals showed rales, decreased spontaneous activity, hunched posture, tachypnea and ruffled fur on the day of exposure and the two following days in individually variable extent.

Four females showed a slight transient body weight loss between Day 1 and Day 4. All other animals gained body weight as expected.

There were no macroscopic pathology findings in any of the animals.

In conclusion, at the highest technically achievable aerosol concentration of the test item of 3.055 mg/L air, none of the ten exposure animals died (LC0 = 3.055 mg/L). Based on the lack of lethal effects or severe clinical symptoms indicating a life-threatening or moribund state, it may be reasonably assumed that the LC50 for the test item is likely to be greater than 5 mg/L air.

Therefore, the test item has not to be classified as acutely toxic by the inhalation route according to Regulation (EC) No 1272/2008.