Triphenylphosphine

Endpoint summary

Description of key information

Skin irritation/corrosion: non-irritating, non-GLP, rabbit, 1971, K2
Eye irritation: WoE, non-irritating, non-GLP, rabbit, 1971, K2

Eye corrosion: WoE, non-corrosive, according to OECD TG 437, GLP-compliant, BCOP, 2022, K1

No data available for the respiratory system.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

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:

- detection of skin irritation according to BASF-internal standards
- Principle of test: The test substance was applied to the back (A) or ear skin (B) of rabbits. Signs of local irritation and intoxication were recorded 24 hours and 8 days after application.
A) Back skin: The test substance was administered as a 2.5 x 2.5 cm patch loaded with a 50% alcoholic suspension (quanitity not specified) to the shaved skin of 2 rabbits for defined time intervals of either 1 min, 5 min, 15 min or 20 h. After the short exposure times of 1 - 15 min the skin was washed, no washing was conducted after the 20 hour exposure.
B) Ear: Cotton-wool soaked with approx. 2 g of the 50% alcoholic suspension (equivalent to 1g test substance) were applied to the pinna and held in place gauze bandages for 20 h.

GLP compliance:

no

Specific details on test material used for the study:

- Purity: 99%.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: preparation of a 50% alcoholic suspension

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

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: purchased freely.
- Weight at study initiation: 3.1 kg.
- Diet: ad libitum.
- Water: ad libitum.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: alcoholic suspension

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not specified for apllication on back skin; 2g 50% alcoholic preparation on rabbit ear.

Duration of treatment / exposure:

A) Back skin: 1 min, 5 min, 15 min or 20 hours
B) Ear: 20 hours

Observation period:

8 days

Number of animals:

2

Details on study design:

A) Back Skin:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm.
- Type of wrap if used: patch loaded with the suspension.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin was washed with undiluted Lutrol and 50% Lutrol/Water solution.
- Time after start of exposure: Washing conducted after 1, 5, 15 min exposure but not after 20 h exposure.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): Text indicates readings 0, 1, 2, and 7 days after removal, however, results are given for 1 and 8 days.

SCORING SYSTEM:
- Method of calculation: grading system for reddening and edema (no effect, slight, marked).
---------------------------------------------------------
A) Ear:

TEST SITE
- Area of exposure: soaked Cotton-wool (no further details).
- Type of wrap if used: gauze bandages to hold cotton wool in place.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): Text indicates readings 0, 1, 2, and 7 days after removal, however, results are given for 1 and 8 days.

SCORING SYSTEM:
- Method of calculation: grading system for reddening and edema (no effect, slight, marked).

Irritation parameter:

erythema score

Remarks:

Back skin

Basis:

other: 1 of 2 animals

Time point:

24 h

Score:

2

Reversibility:

fully reversible within: 8 days

Remarks on result:

other:

Remarks:

slight reddening (R+)

Irritation parameter:

erythema score

Remarks:

Ear

Basis:

other: 1 of 2 animals

Time point:

24 h

Score:

2

Reversibility:

fully reversible within: 8 days

Remarks on result:

other:

Remarks:

slight reddening (R+)

Irritant / corrosive response data:

A) Back skin: After exposures of up to 15 min, no skin reactions were observed. 20-h exposure caused slight reddening at the application site in 1/2 animals 24 h after removal of the patch, which was fully reversible within 8 days.
B) Ear: 20-h exposure caused slight reddening at the application site in 1/2 animals 24 h after removal of the bandage, which was fully reversible within 8 days.

Other effects:

No systemic clinical effects were observed.

Table 1: Local irritation

Application site	Application time	Number and Sex  of animals	findings
			after 24 hours	after 8 days
Back Skin	1 min	1 female 1 male	- -	- -
	5 min	1 female 1 male	- -	- -
	15 min	1 female 1 male	- -	- -
	20 h	1 female 1 male	- R+	- -
Ear	20 h	1 female 1 male	- R+	- -

R+ = slight reddening

Interpretation of results:

GHS criteria not met

Conclusions:

A 20-hour application of an 50% alcoholic TS prepration induced a slight reddening of the back skin and ears of 1/2 rabbits, which was fully reversible within 8 days. Therefore, the TS is considered to be not irritating.

Executive summary:

The irritation/corrosion potential of the test substance was tested according to BASF-internal standards.

A 50% alcoholic preparation of the test substance was applied occluded to the back (1 min, 5 min, 15 min and 20 hours) and ear skin (20 hours) of two rabbits. Signs of local irritation and intoxication were recorded 24 hours and 8 days after application.

A exposure of rabbit back skin for up to 15 min produced no evidence of skin irritation. A 20-hour application induced a slight reddening of the back and ear skin of 1/2 rabbits (male), which was fully reversible within 8 days.

Therefore, the test substance is considered to be not irritating.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

18 Oct 2021 - 05 Nov 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

weight of evidence justification:
The results of the current study alone is not suitable to draw a final assessment. Therefore, results from another study would be needed. Please also refer to RSS of study BASF XXI/183.

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Version / remarks:

26th June 2020

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

Version / remarks:

Official Journal of the European Union, L 324, 9.12.2010

Qualifier:

according to guideline

Guideline:

other: Bovine Corneal Opacity and Permeability (BCOP) Assay, SOP of Microbiological Associates Ltd., UK, Procedure Details

Version / remarks:

April 1997

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch number of test material: 17266856P0
- Purity: 99.68238 area% (non-GLP GC-analysis)
- Appearance: white, solid

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability of the test material in the solvent: not indicated by the Sponsor
- Homogeneity: given
- Expiry date: 01 April 2022

Species:

other: Fresh bovine corneas

Strain:

not specified

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: AB Schlachthof GmbH & Co. KG, 63739 Aschaffenburg, Germany
- Number of animals: 3 corneas per dose group
- Characteristics of donor animals (e.g. age, sex, weight): 12-24 months old donor cattle
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): isolated eyes were stored in HBSS containing 1% (v/v) penicillin/streptomycin (100 units/mL penicillin and 100 μg/mL streptomycin) in the cooled slaughterhouse and during transportation on the same morning to the laboratory using a Styrofoam box
- Time interval prior to initiating testing: the corneas were isolated on the same day after delivery of the eyes
- Indication of any existing defects or lesions in ocular tissue samples: eyes presenting defects such as vascularization, pigmentation, opacity and scratches were discarded
- Indication of any antibiotics used: HBSS medium containing 1% (v/v) penicillin/streptomycin (100 units/mL penicillin and 100 μg/mL streptomycin)
- Selection and preparation of corneas: the cornea was carefully removed from the eye using scalpel and rounded scissors., a rim of about 2 mm of tissue (sclera) was left for stability and handling of the isolated cornea, corneas were mounted in cornea holders consisting of 2 chambers (anterior/posterior), equilibration with incubation medium (cMEM) at about 32°C for at least 1 h
- Incubation medium: MEM, supplemented with 1.1 g sodium bicarbonate, 5 mL L-glutamine, 5 mL penicillin/streptomycin per 500 mL medium (final concentration of 100 units penicillin per mL medium, and 100 μg streptomycin per mL medium), immediately before starting the test, MEM was supplemented with 1% fetal calf serum (FCS). MEM containing all supplements is called cMEM.
- Quality check of the isolated corneas: only corneas with a value of the basal opacity < 7 were used

Vehicle:

physiological saline

Remarks:

test item was tested as 20% suspension (w/v) in saline

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.75 ml of a 20% suspension (w/v)

VEHICLE
- Concentration (if solution): 0.9% NaCl in deionised water

Duration of treatment / exposure:

240 minutes

Number of animals or in vitro replicates:

3 corneas per group

Details on study design:

NUMBER OF REPLICATES: 3 per dose group

NEGATIVE CONTROL USED: Negative Control 1: Saline (0.9% NaCl in deionised water); Negative Control 2: deionised water

POSITIVE CONTROL USED: Positive Control 1: 10% (w/v) Benzalkonium chloride in 0.9% (w/v) NaCl (saline); Positive Control 2: 20% (w/v) Imidazole in saline

APPLICATION DOSE AND EXPOSURE TIME: 0.75 ml of a 20% suspension (w/v), 240 minutes

TREATMENT METHOD: open chamber

POST-INCUBATION PERIOD: no

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: at least 3 times with EMEM containing phenol red; since the test item proved difficult to remove by the rinsing method, the front cover of the holder was opened, and the cornea was carefully washed using a gentle stream of incubation medium, once the medium is free of test item the corneas are given a final rinse with cMEM without phenol red

- POST-EXPOSURE INCUBATION: not applicable

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: conducted with a opacitometer
- Corneal permeability: passage of 0.5% (w/v) sodium fluorescein dye in HBSS measured with the aid of microtiter plate reader (OD490)

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA: depending on the score obtained, the test item is classified into the category according to OECD guideline 437

Irritation parameter:

cornea opacity score

Run / experiment:

Mean of 1 run with 3 replicates

Value:

1.34

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

other: Permeability score

Run / experiment:

Mean of 1 run with 3 replicates

Value:

0.035

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

Mean of 1 run with 3 replicates

Value:

1.85

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: responses result in opacity and permeability values that are less than the established upper limits for background opacity and permeability values for bovine corneas treated with the respective negative control
- Acceptance criteria met for positive control: gives an IVIS that falls within two standard deviations of the current historical mean (updated every three months)
- Range of historical values if different from the ones specified in the test guideline: (1) Range of IVIS: 10 % Benzalkoniumchlorid: 87.39–146.55, saline: 0.77–2.85; (2) Range of Opacity (130 min): 10 % Benzalkoniumchlorid: 54.00–159.67, saline: 0.00–1.33; (3) Range of Permeability: 10 % Benzalkoniumchlorid: 0.00–1.96, saline: 0.05-0.10; historic period: Jan 2018 - Oct 2021 (no. of studies performed: 43)

Tab. 2: Opacity score, permeability score and in vitro irritancy score (IVIS) of the test substance, the negative controls and the positive controls

Test Group	Opacity value = Difference (t240-t0) of Opacity		Permeability at 490 nm (OD490)		IVIS	Mean IVIS	Standard Deviation IVIS
		Mean		Mean
Negative Control (Saline)	1	0.33	0.065	0.061	1.98	1.25	0.63
	0		0.065		0.98
	0		0.054		0.81
Negative Control (deionised water)	0		0.059		0.89	1.30	0.56
	1		0.063		1.95
	0		0.072		1.08
Positive Control 10% (w/v) Benzalkonium chloride in saline	85.67*		0.648*		95.38	90.61	5.82
	75.67*		0.564*		84.12
	82.67*		0.645*		92.34
Positive Control 20 % Imidazole in saline	104.67*		1.204*		122.72	111.08	10.09
	88.67*		1.076*		104.80
	86.67*		1.271*		105.73
Triphenyl phosphine	1.67*		0.027*		2.07	1.85	0.27
	0.67*		0.059*		1.55
	1.67*		0.019*		1.95

*Correction was performed with the values of the Negative Control Saline.

Interpretation of results:

GHS criteria not met

Remarks:

The result does not exclude an irritation potential of the test item. For final assignment of a risk phrase at present, results from another study would be needed.

Conclusions:

According to the BCOP test, the test substance has a mean IVIS of 1.85 and is identified as not corrosive or severe irritant.

Executive summary:

The in vitro BCOP test was performed according to the OECG guideline 437 (adapted 26th June 2020) and in compliance with GLP. The potential of the test substance to cause occular corrosion to the eyes was assessed by single application of 0.75 mL diluted substance (as a 20% suspension (w/v) in physiological saline) to the epithelial surface of isolated bovine corneas. In addition, two negative controls ((1) saline (0.9% NaCl in deionised water) and (2) deionized water) and two positive controls ((1) 10% (w/v) benzalkonium chloride in 0.9% (w/v) NaCl (saline) and (2) 20% (w/v) imidazole in saline) were applied. For each group, 3 corneas were treated for 240 min. Afterwards, the tissues were rinsed and corneal opacity was measured with an opacitometer and permeability was quantified at OD490. Both measurements were used to calculate an in vitro irritancy score (IVIS). Relative to the negative controls, the test substance caused an increase of the corneal opacity and permeability and the calculated IVIS was 1.85. These values do not indicate a corrosive or severe eye irritation potential of the test substance. The test method according to the regulatory accepted protocol at the time of reporting does not allow for the evaluation of eye irritation. The result does not exclude an irritation potential of the test item. For final assignment of a risk phrase at present, results from another study would be needed.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with generally accepted standard methods, but limited number of readings (not after 48, 72 h), 50 mg were applied (100 mg accordiin OECD TG 405) and the observation period was only 8 days (21 days in OECD TG 405).

Justification for type of information:

weight of evidence justification:
The results of the current study alone is not suitable to draw a final assessment. Therefore, results from another study would be needed. Please also refer to RSS of study 63V0358/13X539.

Principles of method if other than guideline:

- Principle of test: BASF-internal standard method. Approximately 50 mg of the solid test substance was inserted into the conjunctival sac and evenly distributed on the eye surface. Readings after 1 h, 24 h and 8 days. The test substance was not rinsed.

GLP compliance:

no

Specific details on test material used for the study:

- Purity: 99%.

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: purchased freely.
- Weight at study initiation: average 3.1 kg.
- Diet: ad libitum.
- Water: ad libitum.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

Amount / concentration applied:

50 mg

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

2

Details on study design:

SCORING SYSTEM: according to BASF scheme. Turbidity Grade 1-4. Erythema Grade 1-3. Edema Grade 1-3.

Irritation parameter:

other: erythema of the conjunctivae

Basis:

mean

Remarks:

animal 1-2

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritant / corrosive response data:

Solid test substance caused slight to significant erythema of the conjunctivae after 1 and 24 h in both animals, which was associated with slight edema after 24 hin one animal. Slight corneal opacity was seen in one animal after 8 days, whereas the effects were fully reversible after 8 days in the other animal.
The responses observed with the test substance corresponded to those seen with talcum which has been concurrently examined as a control compound.

Table 1: Findings

Application site	Compound	Number and Sex  of animals	findings
			after 1 hour	after 24 hours	after 8 days
Eye	50 mg test substance	1 female 1 female	R+ R++	R+ R++/Ö+	Tr+ -
	Talcum (control)	1 female 1 female	R+ R++/Ö+	R+/Ö+ R++/Ö++/Tr++	- Tr+

R: erythema; Ö: edema; Tr: Opacity

- : non irritant; +: slight; ++: significant

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Executive summary:

Approximately 50 mg of the solid test substance was inserted into the conjunctival sac and evenly distributed on the eye surface of 2 rabbits. Readings after 1 h, 24 h and 8 days. The test substance was not rinsed. The test substance caused slight to significant erythema of the conjunctivae after 1 and 24 h in both animals, which was associated with slight edema after 24 h in one animal. Slight corneal opacity was seen in one animal after 8 days, whereas the effects were fully reversible after 8 days in the other animal.

The responses observed with the test substance corresponded to those seen with talcum which has been concurrently examined as a control compound.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Occlusive exposure of two rabbits for up to 15 minutes to a 50% suspension of triphenylphosphine in ethanol resulted in no discernible skin effects. Skin was washed after removal of the test substance and readings were performed at day 0, 1, 2, and 7. After 20 hours of exposure, mild erythema was seen in one of the two animals after 24 hours and was reversible within 7 days (BASF, 1971).

 

Eye irritation:

In an eye irritation study performed on two rabbits 50 mg solid triphenylphosphine caused slight to marked redness of the conjunctivae 1 and 24 hours after instillation. Slight edema was seen in one animal after 24 hours, slight corneal opacity was present in one animal at day 8 (BASF, 1971). Mechanical effects might be causal and the observation period might have been to short to fully evaluate reversibility but that the test substance induced severe eye damaging effects cannot be conclusively excluded. 

Therefore, an in vitro study was conducted to clarify the corrosive effects of the substance (BASF, 2022). In a BCOP assay, no corrosivity or severe eye irritating potency of the test substance was found. This test method alone does not allow for the evaluation of eye irritation. Therefore, the results from the former mentioned in vivo study were taken into account for further evaluation.

Based on the observed effects a classification for eye irritation is not necessary.  

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. An in vivo study is available for skin irritation. A GLP-compliant OECD 437 study (BCOP) and an in vivo study are available for eye corrosion/irritation. In all studies, the scores for the test item treated tissues were below the thresholds for classification as irritating or corrosive. As a result, the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.