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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:
1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to OECD 403.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method

Test material

Constituent 1
Reference substance name:
veratrylcyanid, krist. SF
IUPAC Name:
veratrylcyanid, krist. SF
Details on test material:
- Name of test substance: Veratrylcyanid, krist . SF
- Batch No.: 23539
- Purity: 98 .5%
- Date of manufacture: May 1989
- Physical state/appearance: solid ( powder) light yellowish to light brownish
- Storage conditions: was stored at room temperature protected from air and excluded from light
- Stability: Stability was ensured for 12 months
- Homogeneity: was guaranteed by high purity .

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Strain: SPF Wistar/Chbb:THOM; breeding facility: O. K . Thomae GmbH, 0-7950 Biberach, FRG.
Mean body weight at the beginning of the study: male animals 300 ± 9.3 g, female animals 202 ± 9.5 g.
Age at the beginning of the study: approx. 8-9 weeks
The animals were identified by color marking on the tail.
The animals were offered KLIBA rat/mouse laboratory diet 24-343-4 10 mm pellets, Klingentalmühle AG, CH-4303 Kaiseraugst, Switzerland, and drinking water ad libitum during the post-exposure observation period.
The animals were kept in fully air-conditioned rooms in which a temperature in the range 20-24°C and relative humidity in the range 30-70 % were regulated by means of a central air-conditioning system.
They were housed in groups of five in cages type D III of Becker, without bedding, with a light/dark rhythm of 12 hours.
Deviations from these specifications that might have had any adverse effect on the results of the study did not occur.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Exposure system
Head-nose inhalation system INA 20 (glass-steel construction, BASF Aktiengesellschaft, volume V >= 55 L): the animals were restrained in tubes and their snouts projected into the inhalation chamber.

Generation of the inhalation atmosphere
A dust aerosol was generated by means of a dosing-wheel dust generator (Gericke/BASF). The test substance was mixed with 1 wt% of Aerosil E 200 in order to achieve a more uniform dust concentration in air. The concentration was adjusted by varying the rotation of the metering disc.

Exposure
The following air flows (supply air) were set: compressed air, 1500 L/h.
The exposure system was placed in an air-conditioned laboratory. Temperatures in the exposure system were 19 - 25°C . Deviations from this specification which would have had any adverse effect on the results of the study did not occur. By means of an exhaust air system the pressure ratios in the inhalation system were adjusted in such a way that the amount of exhaust air was about 10% lower (excess pressure). This ensured that the mixture of test substance and air was not diluted with laboratory air in the breathing zones of the animals. The inhalation atmosphere was offered to the animals for inhalation for 4 hours .
Analytical verification of test atmosphere concentrations:
yes
Remarks:
For information on analytical measurements refere to "attached background material" below.
Duration of exposure:
4 h
Concentrations:
1.93 and 5.5 mg/L
No. of animals per sex per dose:
5
Control animals:
no

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.5 mg/L air
Exp. duration:
4 h
Remarks on result:
other: dust aerosol
Mortality:
No mortality observed.
Clinical signs:
other: During exposure: - 1.93 and 5.5 mg/L dose groups: irregular respiration, accelerated respiration, eyelid closure, attempts to escape. After exposure: irregular respiration, nose with reddish smear and crust (blood test positive), fur discoloured with tes
Body weight:
Mean body weights [g] in males of the 1.93 mg/L dose level before inhalation/after 7 days/after 14 days: 301/325/350
Mean body weights [g] in females of the 1.93 mg/L dose level before inhalation/after 7 days/after 14 days: 205/225/239
Mean body weights [g] in males of the 5.5 mg/L dose level before inhalation/after 7 days/after 14 days: 300/324/351
Mean body weights [g] in females of the 1.93 mg/L dose level before inhalation/after 7 days/after 14 days: 200/213/225

Any other information on results incl. tables

Two groups of 5 male and 5 female Wistar rats were exposed to a dust aerosol of
 the test substance at concentrations of 1.93 and 5.5 mg/l. The animals were 
exposed for 4 hours using a head-nose inhalation system and were then observed 
for 14 days.

A particle size analysis was conducted to determine the mass median aerodynamic diameter (MMAD) with its geometrical standard deviation (GSD) and the respirable dust fraction that might reach the alveolar region.

test concentration 1.93 mg/l 5.5 mg/l
----------------------------------------------
MMAD 50% 3.2 µm 1.4 µm
GSD 3.8 3.8
respirable fraction 81% 95%

No deaths occurred. During the observation period, irregular/accelerated respiration, eyelid closure and attempts to escape were observed in both dose groups. During the observation period, accelerated respiration, reddish smear and crusts at the nose (blood test positive at the high dose level but not at the low dose level), fur discolored with the test substance and staggering unsteady gait was observed in both test groups. The clinical signs had disappeared by day 2 post-exposure in the low dose group and by day 3 post- exposure in the high dose group. Body weight gain was not affected in the low dose animals and slightly retarded in high dose animals during the second week of the observation period. Post-mortem examination of the animals revealed no pathological findings.

Applicant's summary and conclusion

Conclusions:
Based on the results of this study, the test substance veratrylcyanid, krist. SF does not need to be classified according to Regulation (EC)No. 1272/2008 and Directive 67/548/EEC.