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Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
9 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Aug 07 -21, 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed according to OECD TG 403.
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Wölferstrasse 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: Males: 9 weeks, Females: 10 weeks
- Weight at study initiation: Males: 264.2 to 275.7 g, Females: 207.5 to 224.2 g
- Fasting period before study: no

- Housing: housed in groups of maximally 5 of the same sex in Makrolon® type-IV cages with wire mesh tops and standard softwood bedding ("Lignocel", Schil AG, 4132 Muttenz, Switzerland).

- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C,
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12 hours
Route of administration:
inhalation
Type of inhalation exposure:
nose only
Remarks:
Inhalation by nose-only, flow-past exposure
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus:
Inhalation exposure was performed using a system similar to that originally described by Sachsse
et al. (1973). The animals were confined separately in restraint tubes which were
positioned radially around the flow-past, nose-only exposure chamber as described by Cannon et
al. (1983). The design of this chamber is based upon the fluid dynamic modeling of the
test aerosol flow.

Refs:
K. Sachsse, 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, 15, 239-251, Zürich,
1973.

W.C. Cannon, 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, 923-928, 1983.


- Method of holding animals in test chamber: restraint tubes
- Rate of air: 1.0 L/min
- Method of conditioning air: rotating brush aerosol generator
- System of generating particulates/aerosols: micronising jet mill connected to a rotating brush aerosol generator
- Method of particle size determination: 7 stage cascade Mercer Impactor (Model 02-130, In-Tox. Products Inc., Albuquerque, New Mexico, USA)
- Temperature, humidity, pressure in air chamber: Vaisala HMI 32 recorded each 30 min

TEST ATMOSPHERE
- Brief description of analytical method used:
The concentration of the test item determined gravimetrically, the particle size distribution
determined gravimetrically, temperature, relative humidity and oxygen concentration were
measured on test atmosphere samples collected directly from the delivery tube at an empty port
of the exposure chamber, as specified below. The position at which these test atmosphere
samples were taken was considered to be representative for the breathing zone of the animals.
Airflow rates were determined for the recording of temperature, relative humidity and oxygen
concentration and during the collection of samples for the determination of test aerosol
concentration and particle size using a dry-test meter and a pressure gauge, calibrated with a
reference dry-test meter.

- Samples taken from breathing zone: no


TEST ATMOSPHERE (if not tabulated)

- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): median aerodynamic diameter of 2.44 μm with
geometric standard deviations of 2.18 and 2.20
Analytical verification of test atmosphere concentrations:
yes
Remarks:
dry-test meter and a pressure gauge,
Duration of exposure:
4 h
Concentrations:
5.1 mg/L
No. of animals per sex per dose:
5 (m) / 5 (f)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: days 1 (before exposure), 4, 8 and 15 (before necropsy).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights
Statistics:
no statistics (single dose)
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals survived the scheduled observation period.
Clinical signs:
other: No clinical signs were recorded during the exposure or the observation period.
Body weight:
From test day 1 to test day 4, marginal body weight loss was noted in two females. This was
considered to be related to stress caused by the restraint during exposure and not an effect of the
test item. From test day 4 onwards, all animals showed a normal body weight development.
There were no effects on body weight in the remaining animals.
Gross pathology:
There were no macroscopic findings.

Inhalative treatment of HanRcc:WIST(SPF) rats with the test material at a concentration of 5.1 mg/L for 4 hours was well tolerated and did not result in any signs of toxicity.

In conclusion, the LC50 of the test material obtained in this study was estimated to be greater than 5.1 mg/L air (gravimetrically determined mean aerosol concentration).

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, the LC50 of the test material obtained in this study was estimated to be greater than 5.1 mg/L air (gravimetrically determined mean aerosol concentration). Thus there is no need for classification for acute inhalative toxicity according to CLP-Regulation (EC) No 1272/2008.
Executive summary:

Study Design

A group of five male and five female albino rats [HanRcc:WIST(SPF)] was exposed by nose-only, flow-past inhalation to the test item at a gravimetrically determined mean concentration of 5.1 mg/L air (s.d. ± 0.0 mg/L air, n = 4). Two gravimetric measurements of particle size distribution during exposure produced a mass median aerodynamic diameter (MMAD) of 2.44 μm with geometric standard deviations of 2.18 and 2.20. All animals were observed for clinical signs and mortality during the inhalation exposure and the 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. On day 15, all animals were killed and necropsied.
The ranges of aerosol concentration, temperature, relative humidity, oxygen content and airflow measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item aerosol was considered to be appropriate for acute inhalation toxicity testing and respirable to rats.

Results

All animals survived the scheduled observation period.
No clinical signs were recorded during exposure or the observation period.
Transient effects on the body weight were noted in two females between test days 1 and 4 which were considered not to be test item related. From day 4 until the end of the observation period all animals showed a normal body weight gain.
No macroscopic findings were recorded.

Conclusion


In conclusion, the LC50 of the test material obtained in this study was estimated to be greater than 5.1 mg/L air (gravimetrically determined mean aerosol concentration).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 100 mg/m³
Quality of whole database:
A acute inhalation toxicity study (limit test) has been performed with Fluorphlogopite according to Guideline OECD 403 under GLP regulation.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of acute toxicity – oral endpoint
The results of an oral toxicity study with Fluorphlogopite in rats (LD50 > 9000 mg/kg) has been published in an review article (CIR, 2012, Final Report on the Safety Assessment of Synthetic Fluorphlogopite as used in Cosmetics).

Justification for selection of acute toxicity – dermal endpoint
No study is available for the acute dermal toxicity of Fluorphlogopite in rats. However, due to 1) the composition of Fluorphlogopite (magnesium, potassium, aluminum, fluoride and silicate), 2) the very low solubility in water, and 3) the assumed negligible bioavailability after dermal application, the performance of an acute dermal toxicity study in rats is considered not necessary.
In addition, the results of an dermal toxicity study with VEEGUM (magnesium aluminum silicate) in rabbits (LD50 > 3.5 g/kg) has been published in an review article (CIR, 2012, Final Report on the Safety Assessment of Synthetic Fluorphlogopite as used in Cosmetics). However, no details have been provided and the quality of the data cannot be evaluated.

Justification for classification or non-classification

Based on the available data, the substance is not classified.