Benzyltriphenylphosphonium chloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Dec 1987 to 29 January 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Principles of method if other than guideline:

- Principle of test: determine a 4-hrs inhalation Approximate Lethal Concentration (lowest concentration that caused the death of at least one rat).
- Short description of test conditions:
- Parameters analysed / observed:

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Benzyltriphenylphosphonium chloride

EC Number:

214-154-3

EC Name:

Benzyltriphenylphosphonium chloride

Cas Number:

1100-88-5

Molecular formula:

C25H22P.Cl

IUPAC Name:

benzyltriphenylphosphonium chloride

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl:CD BR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, NY
- Rationale for use of males: no data
- Age at study initiation: young adults, 8 weeks old
- Weight at study initiation: 230 - 297 g
- Fasting period before study: no
- Housing: animals were housed in pairs in 8"x14"x8" suspended stainless steel, wire-mesh cages
- Diet : ad libitum
- Water: ad libitum
- Acclimation period: one week prior testing
- Method of randomisation in assigning animals to test and control groups : not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): target: 23°C +/- 2°C
- Humidity (%): target: 50% +/- 10%
- Chamber oxygen concentration: 21%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hr light/12 hr dark

IN-LIFE DATES: From: 31-DEC-1987 To: 25-JAN-1988

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

ca. 2 - ca. 2.6 µm

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The test material was metered into a Model 00 Jet-0-Mizer with a K-TRON Model T-20 Twin screw Volumetric feeder.
- Exposure chamber volume: 38-L cylindrical glass exposure chamber
- Method of holding animals in test chamber: rats were restrained in perforated, stainless steel cylnders with conical nose pieces
- Source and rate of air (airflow): air stream of 56 L/min
- System of generating particulates: test material was suspended as supplied in a high-pressure air stream with an air-driven jet mill, and pulverized by impaction with other particles within the mill's reduction chamber. Airflow to the mill's primary grinding jets was restricted to minimize the amount of trituration. The particles exited the jet mill and entered the exposure chamber where they were dispersed with a baffle to promote uniform distribution within the chamber. Atmospheric concentrations were controlled by varying the test material feed rate into the jet mill.
- Method of particle size determination: particle size (MMAD and % < 10 μm) was determined using a Sierra Series 210 cascade impactor during each exposure.
Sampler.
- Treatment of exhaust air: high capacity fiberpac dust filter and MSA cartridge filter prior to discharge into a fume hood.
- Temperature in air chamber: 20-23°C
- Humidity in air chamber: 23-27%

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: gravimetric analysis every 30 min during each exposure. Known volumes of chamber atmospheres were drawn through preweighed Gelman glass fiber (Type A/E) filters. Filters were weighed on a Cahn Model 26 Automatic Electrobalance. The difference in the pre- and post-sampling filter weights were used to calculate the atmospheric concentration of test material.
- Time needed for equilibrium of exposure concentration before animal exposure : not specified.

VEHICLE : air

TEST ATMOSPHERE (see Table 1)
- Particle size distribution: 92 to 97% < 10 µm of aerodynamic diameter
- MMAD (Mass median aerodynamic diameter) : 2.0 to 2.6 µm

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Mean concentrations for each group: 71, 77, 120, 130, 190 mg/m3 (see details in Table 1)

No. of animals per sex per dose:

6 males/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: rats were weighed before exposure, and observed for clinical signs during exposure. Surviving animals were weighed and observed daily for 14 days following exposure.
- Necropsy of survivors performed: no
- Clinical signs including body weight : yes, daily during the 14-day post-exposure period

Statistics:

None

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LCLo

Remarks:

lowest test concentration causing death

Effect level:

ca. 130 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

>= 80 - <= 200 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There was no death at concentrations 71 to 120 mg/m3.
Mortality occurred at concentrations of 130 mg/m3 and above. (details in Table 2)

Clinical signs:

other: Details below (other information on results)

Remarks:

Clinical signs consistent with organophosphate intoxication.

Body weight:

Surviving animals from all groups showed slight to severe weight losses (up to 17% of initial body weight) within 24 hours of exposure. (Details not available)

Gross pathology:

Not performed.

Any other information on results incl. tables

Table 2: results

Mean concentration + SD (mg/m3)	Mortality (# dead / # exposed)	%	Time of death
71	0/6	0	-
77	0/6	0	-
120	0/6	0	-
130	2/6	33	1 rat died during exposure, 1 rat was found dead on day 7
190	6/6	100	5 rats died during exposure, 1 rat was found dead with 24 hours of exposure

Details on Clinical observations:

During the 4-hour exposure: Lethargy, spasms, gasping, clear or red nasal, ocular or oral discharges.  

At the end of exposure period: lethargy, wet perineum, diarrhea, clear nasal or ocular discharges. Surviving animals from groups treated at 130 or 190 mg/m3 also exhibited either lung noise, labored breathing or gasping.

Post-exposure period:

- In some of the surviving animals from groups treated with 77 or 130 mg/m3: lethargy, prostration, lung noise, labored breathing, gasping, red ocular and nasal discharges, urine-stained perineum, diarrhea, and brown-discolored fur.

- in 1 rat from the 120 mg/m3 group: lung noise.

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

Under the conditions of the study, a 4-hr inhalation exposure to BTPPC particles (average MMAD 2.0 to 2.6 µm) caused death at 130 mg/m3 and above. The clinical signs of toxicity were consistent with organophosphate intoxication. The LC50 could not be determined from this set of results but was considered to be between 80 and 200 mg/m3.

Executive summary:

BTPPC was assessed for acute inhalation toxicity in a standard assay. Groups of 6 male rats were exposed by inhalation (nose-only) to test atmospheres containing respirable concentrations of BTPPC particles (average MMAD 2.0 to 2.6 µm) between 71 and 190 mg/m3 for a single 4-hour exposure. Animals were observed for clinical signs and weighed daily for 14 days.

No death occurred at 71, 77 and 120 mg/m3. Two of six animals died at the concentration of 130 mg/m3, and all 6 animals died within 24 hours following exposure to the concentration of 190 mg/m3. Clinical signs included ocular, nasal and oral discharges, respiratory distress (lung noise, labored breathing or gasping), urination, diarrhea and lethargy, and weight loss.

Under the conditions of the study, the acute LC50 was estimated to be between 80 and 200 mg/m3, which triggers a classification as acute toxic category 2, H330 according to criteria of CLP Regulation 1272/2008.