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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:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The present study is similar to the inhalation hazard test described in the Annex of OECD Guideline 403 of 1981. However, the test substance used is a non-sublimating powder, whereas the Annex of OECD 403 is foreseen for volatile liquids or sublimable solids. In the present study, documentation is restricted mainly in that the particle size of the generated test atmosphere (a dust aerosol) was not measured. In addition, the test atmosphere concentration is only presented as a nominal concentration usually being a considerable overestimate of the concentration to which the animals were exposed. The study was not conducted according to GLP.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976
Reference Type:
publication
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: Annex of OECD 403 (of 1981): Inhalation hazard test
Deviations:
yes
Remarks:
1) The test substance used is a non-sublimating powder, whereas the Annex of OECD 403 is foreseen for volatile test material. 2) Determination of the test concentration is restricted to nominal concentration. 3) The chamber volume is not clearly defined.
GLP compliance:
no
Test type:
other: Inhalation hazard test similar to the annex of OECD 403 of 1981, but using a non-volatile powder for test atmosphere generation.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): THEIC
- Physical state: solid
- Analytical purity: ca. 99%

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeder (not specified)
- Mean weight at study initiation (treatment day): males 212 g, females 187 g, mean males and females at study initiation: 199 g

ENVIRONMENTAL CONDITIONS
not reported

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Rats were exposed for 8 h, to a dust enriched atmosphere.

Dust was generated by bubbling dry air at a rate of 200 L/h through a fritted glass followed by a layer of test substance of 5 cm height inside a glass cylinder of approximately 50 mL volume. The study was conducted at room temperature. Dust formation, very marked in degree, was observed.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
9.33 mg/L air (mean of two trials). Each trial comprised 3 male and 3 female rats
No. of animals per sex per dose:
Treated animals: 6.
Air control animals: 3.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Weighing was done on the day of treatment (Day 1) and 7 days afterwards (Day 8).
Observation was presumably several times on the day of exposure and daily therafter with the exception of weekends and holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Not applicable, because no mortality and only one dose group.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
other: IHT (inhalation hazard test)
Effect level:
9.33 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
other: No mortality. Contrary to the claims of the cited OECD SIDS the nominal test atmosphere concentration documented in the raw data is only 9.33 mg/L air (mean of two replicate trials).
Mortality:
0/12 animals died
Clinical signs:
Nothing abnormal found.
Body weight:
Body weight gain was normal during the observation period:
- mean weight on the exposure day (Day 1): 212 g for males; 187 g for females; 199 g overall mean weight for both sexes on this day.
- mean weight at study termination (Day 8): 249 g for males; 198 g for females; 223 g overall mean weight for both sexes on this day.
Gross pathology:
Nothing abnormal found.
Other findings:
Strong dust formation in the inhalation chamber is circumstantial evidence for some exposure of the animals to the test substance. However, the degree of inhalability of the generated aerosol cannot be assessed, because the particle size distribution of the generated aerosol was not determined.

Applicant's summary and conclusion

Conclusions:
There were no deaths and no indication of any adverse effects induced by 8 hours of whole body exposure to a nominal mean aerosol concentration of 9.33 mg/L air in rats. Strong dust formation in the inhalation chamber is circumstantial evidence for some exposure of the animals to the test substance. However, the degree of inhalability of the generated aerosol cannot be assessed, because the particle size distribution of the generated aerosol was not determined. In addition, the test atmosphere concentration was only determined as a nominal concentration usually being a considerable overestimate of the concentration to which the animals were exposed.