Calcium diethyl bis[[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate]

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study performed under quality controlled conditions. Meets generally accepted scientific standards, well documented and acceptable for assessment. No test substance purity available.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

no

Remarks:

but QAU statement available

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Calcium diethyl bis[[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate]

EC Number:

265-512-0

EC Name:

Calcium diethyl bis[[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate]

Cas Number:

65140-91-2

Molecular formula:

C17 H29 O4 P. 1/2Ca

IUPAC Name:

calcium diethyl bis[[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate]

Details on test material:

- Physical state: solid

Test animals

Species:

rat

Strain:

other: Tif:RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 216-265 g
- Housing: Rats, segregated by sex, were group-housed with 10 animals per cage in Macrolon Cages, Type 4 (Ehret, 783 Emmendingen/Germany).
- Diet: Rat chow (NAFAG, Gossau/SG, Switzerland), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55+/-10
- Photoperiod: 14 hrs dark / 10 hrs light

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: All exposures were conducted in a nose-only exposure system. For inhalation, the rats were placed in separate PVC-tubes positioned radially around the exposure chamber such that the snout and nostrils of the animals only were exposed to the aerosol. The chamber was maintained at a slightly negative pressure to prevent leakage of the test aerosol from the system.
- Exposure chamber volume: approximately 100 liter plexiglass exposure chamber
- System of generating particulates/aerosols: The aerosol was generated by introducing the solid test material with the aid of a Grafix Exaktomat Injector (Cerutti AG, Bern, Switzerland) into an air stream which was then discharged into the exposure chamber at a rate of 10 L/min. The control animals were exposed to filtered air under the same conditions as described above.
- Method of particle size determination: Particle size analysis was conducted twice during all exposures using a 4 stage Cascade Impactor (CF. Casella and Co., Ltd., Regent House, Britannia Walk, London) with Solectron Filters (Schleicher and Schuell AG, Feldbach, Switzerland) of 25 mm diameter and a pore size of 0.2 µm at an air flow rate of 17.5 L/min.
- Temperature, humidity, pressure in air chamber: Environmental conditions within the inhalation chamber were monitored at approximately the same intervals that chamber concentration was measured.
Temperature: 23.6+/-0.4 (control group); 23.4+/-0.3 (test group)
Relative humidity: 43+/-3 (control group); 47+/-2 (test group)
O2 content: 20.3+/-0.3 (control group); 20.4+/-0.5 (test group)

TEST ATMOSPHERE
- Brief description of analytical method used: The chamber concentration was determined 5 times (at approximately 1/2 hour and hourly thereafter) gravimetrically by sampling the test atmosphere through a Solectron filter of 50 mm diameter and a pore size of 0.2 µm chamber concentration for each exposure is presented as the mean + the standard deviation.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: Ca. 20%: >7 µm; ca. 40%: 3-7 µm; ca. 30%: 1-3 µm; ca. 10%: < 1 µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetrically

Duration of exposure:

4 h

Concentrations:

2350 mg/m3

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
Animals were observed during exposure at 1, 2 and 4 hours as well as at 2 hours post-exposure and daily for 14 days. Toxicological signs and mortality was recorded. Body weights were recorded immediately prior to exposure and at day 7 and 14. Gross pathologic evaluation was conducted at random on all animals dying within the 14 day observation period as well as the survivors killed at 14 days by asphyxiation with CO2. Particular attention was given to the respiratory tract.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC0

Effect level:

2 350 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality was observed.

Clinical signs:

other: After exposure to 2350 mg/m3 animals exhibited slight exophthalmus and curved body positions. Slight to moderate ruffled fur was also noted. All animals recovered within 6 days.

Body weight:

Overall body weights and weight gains were within normal limits when measured at day 7 and 14 of the observation period except the body weight gain for male rats for the interval from 1 to 7 days was reduced when compared to control rats (for details see table 1"Any other information on results").

Gross pathology:

Gross necropsies were performed on all animals at the end of the 14 day observation period. No gross pathological changes were noted in the control or in the test groups.

Any other information on results incl. tables

Table 1: Mean body weight of male and female rats at day 1, 7, and 14.

Mean body weight (g) ± sd	Control	2350 mg/m^3
Day 1 male	265±6	255±9
Day 1 female	216±6	220±7
Day 7 male	309±7	287±11
Day 7 female	229±8	233±10
Day 14 male	348±10	329±16
Day 14 female	244±13	246±14

Applicant's summary and conclusion

Conclusions:

The LC50 of a 4 hour aerosol exposure for rats of both sexes is greater than 2350 mg/cubic meter air, when evaluated for a 14 day post-treatment observation period.

Executive summary:

In an acute inhalation study performed similarly to the protocol outlined in OECD guideline 403, 10 male and 10 female rats were exposed to an atmosphere containing the test substance as aerosol. Exposure occurred in a nose-only exposure system for 4 hours and a concentration of 2350 mg/m³ followed by a 14-day observation period. The aerosol was generated by introducing the solid test material with the aid of a Grafix Exaktomat Injector into an air stream which was then discharged into the exposure chamber. The chamber concentration was determined gravimetrically 5 times (at approximately 1/2 hour and hourly thereafter). Particle size analysis was conducted twice during all exposures using a 4 stage Cascade Impactor. At least 83 % of the chamber airborne particles were smaller than 7 micrometers in diameter (Figure 2) for all exposures. In this experiment no mortality was observed. Test animals exhibited slight exophthalmus and curved body positions. Slight to moderate ruffled fur was also noted. All animals recovered within 6 days. Overall body weights and weight gains were within normal limits when measured at Day 7 and 14 of the observation period except the body weight gain for male rats for the interval from 1 to 7 days was reduced when compared to control rats. No gross pathological changes were noted in the control or in the groups. Based on the results of this study, The LC50 of a 4 hour aerosol exposure for rats of both sexes is greater than 2350 mg/cubic meter air.