Triphenylphosphine

Endpoint summary

Description of key information

Based on key study results, the oral LD50 of the test material in rats is 700 mg/kg bw (BASF SE, 1952), the inhalation LC50 (4 hours) in rats is 12.5 mg/L (Waritz, 1975) and the dermal LD50 in rabbits is >4000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - September 1951

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Screening test; discrepancy between documented test parameters and standard methods, but scientifically acceptable.

Qualifier:

no guideline followed

Principles of method if other than guideline:

BASF-internal standard method, conducted before OECD 423 was in place
- Principle of test: The acute oral toxicity to rats was evaluated by a single administration of 10% oily suspension, equivalent to doses of 250, 500, 1000 and 2000 mg/kg test material. Afterwards, the animals were observed 8 days for mortality and syptoms of acute intoxication. Dead animals, time to death and symptoms of acute intoxication were recorded. The mean lethal dose was determined.

GLP compliance:

no

Limit test:

no

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a suspended solid: 10 %

FORM AS APPLIED IN THE TEST (if different from that of starting material): oily suspension

Species:

rat

Strain:

other: albino

Sex:

not specified

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10%

Doses:

250, 500, 1000, 2000 mg/kg bw

No. of animals per sex per dose:

- sex unspecified, 5-10 animals per dose group
- 250 mg/kg: 5 animals
- 500 mg/kg: 10 animals
- 1000 mg/kg: 10 animals
- 2000 mg/kg: 5 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 8 days
- Frequency of observations: daily

Sex:

not specified

Dose descriptor:

LD50

Effect level:

700 mg/kg bw

Remarks on result:

other: 1/10 dead at 500 mg/kg; 10/10 dead at 1000 mg/kg

Mortality:

No mortality at 250 mg/kg bw, but 1/10 at 500 mg/kg and 100% at doses > 1000 mg/kg. Death occured within 1 - 4 days after application.

Clinical signs:

other: Animals that died showed apathy, impaired balance and inappetence. No clinical findings in all surviving animals.

Table 1: Mortality

Dose [mg/kg]	Number of animals	Dead animals	Time to death [days]
2000	5	5/5	2-3
1000	10	10/10	1-4
500	10	1/10	2
250	10	0/5	-

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 = 700 mg/kg

Executive summary:

The acute oral toxicity to rats was evaluated according to a BASF-internal standard method. Therefore, a single administration of 10% oily suspension, equivalent to doses of 250, 500, 1000 and 2000 mg/kg test material was undertaken. Afterwards, the animals were observed 8 days for mortality and poisoning syptoms. No mortality at 250 mg/kg bw, but 1/10 at 500 mg/kg and 100% at doses > 1000 mg/kg. Death occurred within 1 - 4 days after exposure. Animals that died showed apathy, impaired balance and inappetence. Surviving animals showed no clinical findings. The mean lethal dose was determined to be 700 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

700 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: acceptable test method without detailed documentation; reliable experimental data

Principles of method if other than guideline:

- Principle of test: 6 male rats were whole body exposed to an aerosol of the test substance for 4 hours. Therefore, the test stubstance was molten to liquify, nebulized under a stream of dry nitrogen and diluted with 20 % oxygen. The animals were observed 7 days for mortality and syptoms of acute intoxication. Animals were examiened for gross pathological and histopathological changes.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

other: Chr-CD (Charles River-CD)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charales River.
- Age at study initiation: adult.
- Weight at study initiation: 250-275 grams.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: nitrogen stream diluted with 20 % oxygen

Remark on MMAD/GSD:

particel size distribution not specified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: boroilicate glass bell jars.
- Exposure chamber volume: 18 liter.
- System of generating particulates/aerosols: The test substance was nmelted in a glass flask and the molten material maintained at 90-115°C under dry, prepurified nitrogen . It was nebulized with a stainless steel nebulizer. Immediately prior
to entering the exposure chamber, the nitrogen-diluted stream of each material under study was again diluted with cylinder oxygen to an oxygen content of 20% (v/v) .

TEST ATMOSPHERE
- Brief description of analytical method used: Atmospheric samples were collected in an evacuated gas-sampling bulb of known volume. The sample was quantitatively transferred from the bulb with absolute alcohol and the washings diluted to a known volume. To calculate test substance concentrations, the O.D. of this solution was determined at 260 nm. The lower limit of quantitative detection by this method was 1.9 moles (500 ug) of test substance. The standard curve was linear for the ranges of concentrations used. Chamber atmospheres were analyzed at least hourly.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

not specified

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: not specified
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology, histopathology

Sex:

male

Dose descriptor:

LC50

Effect level:

12.5 mg/L air

95% CL:

>= 8.6 - <= 18.2

Exp. duration:

4 h

Remarks on result:

other: 32.6 - 69.6 μmol/l

Mortality:

No individual data on mortality available.

Clinical signs:

other: Clinical signs were typical of respiratory irritation: red ears, salivation, lacrimation, facepawing and dyspnea.

Gross pathology:

No macroscopic or histopathological findings.

Interpretation of results:

GHS criteria not met

Conclusions:

LC50 = 12.5 mg/L

Executive summary:

Six male rats were whole body exposed to an aerosol of the test substance for 4 hours. Therefore, the test stubstance was molten to liquify, nebulized under a stream of dry nitrogen and diluted with 20 % oxygen prior to entering the exposure chamber. The animals were observed 7 days for mortality and syptoms of acute intoxication. Animals were examiened for gross pathological and histopathological changes. The animals showed clinical signs typical of respiratory irritation: red ears, salivation, lacrimation, facepawing and dyspnea. No macroscopic or histopathological effects were observed. No individual data on mortality were reported, however, a LC50 of 12.5 mg/L was stated.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

12 500 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: test procedure in accordance with generally accepted standard methods

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: The acute dermal toxicity to rabbits was evaluated according to a BASF-internal standard method by a single application of an 50% alcoholic suspension to the shaven dorsal skin of 3 male and 3 female animals, equivalent to a dose of 4000 mg/kg test material. During 24 hour exposure period, the exposed skin area of 355 cm2 was covered with parchment paper and overlying bandages and the animals were restrained. After application, the animals were observed for 14 days for mortality and syptoms of acute intoxication or local irritation. Animals were evaluated for gross pathological changes. The mean lethal dose was determined

GLP compliance:

no

Limit test:

yes

Specific details on test material used for the study:

- Purity: 99%

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid, stock liquid or gel: 50% alcoholic suspension

FORM AS APPLIED IN THE TEST (if different from that of starting material): suspension

Species:

rabbit

Strain:

Vienna White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: 2/6 bred by the medical-biological research laboratory of BASF, 4/6 purchased.
- Weight at study initiation: average 3,24 kg.
- Diet (e.g. ad libitum): yes.
- Water (e.g. ad libitum): yes.

IN-LIFE DATES: From: 14.10.1971 To: 28.10.1971.

Type of coverage:

occlusive

Vehicle:

ethanol

Details on dermal exposure:

TEST SITE
- Area of exposure: 355 cm2.
- Type of wrap if used: the application area was covered with parchment paper and overlying bandages.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approx. 10 mL.
- Concentration (if solution): 50 %.

Duration of exposure:

24 hours

Doses:

4000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations: at least after 1h, 24h, 48h, 7d and 14d.
- Necropsy of survivors performed: yes.
- Other examinations performed: clinical signs, signs of local irritation.

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

> 4 000 mg/kg bw

Remarks on result:

other: no mortalities

Mortality:

No mortalities occured.

Clinical signs:

other: No signs of acute intoxication and local irritation were observed.

Gross pathology:

Necropsy revealed no macroscopic and/or organ pathological findings related to TS exposure.

Table 1: Mortality

Dose [mg/kg]	Concentration in alcohol [%]	Number of animals	Dead animals within
			1 hour	24 hours	48 hours	7 days	14 days
4000	50	3 male 3 female	0 / 3 0 / 3	0 / 3 0 / 3	0 / 3 0 / 3	0 / 3 0 / 3	0 / 3 0 / 3

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 > 4000 mg/kg

Executive summary:

The acute dermal toxicity of the test substance to rabbits was assessed according to a BASF-internal standard method. Therefore, the test substance was applied as an 50% alcoholic suspension to the shaven backs of 6 rabbits for 24 hours, equivalent to a dose of 4000 mg/kg test substance . During a 14-day observation period, mortality, signs of acute intoxication or local irritation were recorded. Pathological changes were evaluated in all animals. No mortalities occured. No signs of acute intoxication and local irritation were observed. Necropsy revealed no macroscopic and/or organ pathological findings related to test substance exposure. Therefore the dermal LD50 was determined to be > 4000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 000 mg/kg bw

Additional information

Acute oral toxicity:

The LD50 of the test substance in rats was > 6400 mg/kg bw, when administered as aqueous suspension in tragacanth (BASF, 1970) and 700 mg/kg bw, when administered in olive oil (BASF, 1952). Animals that died showed apathy, impaired balance and inappetence. Surviving animals showed no clinical symptoms.

In line with the results in rats, a clear vehicle dependence was observed in studies with rabbits (BASF, 1972), too. Mortality occured at lower concentrations of the oily preparation (2000 mg/kg, olive oil) compared to the aqueous suspension (4000 mg/kg, carboxymethylcellulose) and clinical signs were more pronounced when given in olive oil. Clinical effects included ataxia, ventral/lateral positioning, inappetence and weight loss.

In a study on mice (BASF, 1952) a variable death pattern was observed with 0/5 deaths at 125 mg/kg, 4/5 at 250 mg/kg, 2/5 at 500 mg/kg, 5/5 at 1000 mg/kg, 3/5 at 2000 mg/kg and 5/5 at 4000 mg/kg test substance suspended in olive oil. Animals that died showed accelerated respiration, tonic-clonic seizures and jumping seizures approximately 30 minutes after application. No clinical findings in all surviving animals.

Two Beagle dogs survived a single dose of 1200 mg/kg bw (administered in aqueous traganth) with transient diarrhea as the main clinical sign. None of four animals died after a dose of 1200 mg/kg bw, administered as 40% suspension in olive oil, while one of two dogs died after a dose of 600 mg/kg bw in olive oil. The surviving animal suffered from ataxia and impaired balance two days after the administration (BASF, 1972).

Acute inhalation toxicity:

The 4-hr LC50 of the test substance in rats was determined to be 12500 mg/m3 (whole-body exposure) (Waritz, 1975). No individual data on mortalities were given in this publication. Clinical signs during exposure were typical of respiratory irritation and included salivation, lacrymation, dyspnea, and red ears. No effects were reported at macroscopic examination including organ weights.

BASF (1971) reported an inhalation hazard test. Rats were exposed for up to 8 hours to air streams loaded with the volantiles arising from tempering the test substance either to 20°C or 200°C. Concentrations were not measured but estimated to be 20 mg/m3 (20°C) and 35000 - 90000 mg/m3 (200°C) based on the substance loss and air flow rate. (Avoidance reaction, severe irritation of mucous membranes and trembling were reported for animals treated with aerosols generated at 200°C. All animals survived a single exposure for 8 hours when the test substance was tempered to 20°C, whereas 1/6 and 1/12 animals died after 3 and 8 hours exposures when the test substance was heated up to 200°C. Deceased animals showed cardiac dilatation, hyperemic congestion in lung and liver, lung emphysema and hyperemia (8- and 3 -hour exposure). The exposure concentrations were estimated to be

Acute dermal toxicity:

In rabbits, the LD50 of the test substance administered as a 50% alcoholic solution under occlusive conditions was > 4000 mg/kg bw (BASF, 1971). No mortality, systemic toxicity or local irritation was noted, no pathological changes were found at necropsy.

In rats, the LD50 of test substance (administered as a 50% alcoholic solution) was > 2500 mg/kg bw (BASF, 1971). The type of coverage (occlusion) was not specified in this study. No systemic toxicity or local irritation was noted. 1/20 (female) died within 24 hours after administration without any obvious clinical symptoms. At necropsy, this animal showed liver congestion, and bloody, gel-like contents of the intestine. No signs of acute intoxication, local irritation or pathological changes were found in the surviving animals.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered to be classified for acute oral toxicity Cat. 4 under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776. The substance is not considered to be classified for acute dermal or inhalative toxicity.