Tetrabutylphosphonium bromide

Endpoint summary

Description of key information

Reliable skin irritation study with Tetrabutylphosphonium bromide performed according to GLP principles, methods used equivalent to OECD guideline 404 (Klimisch 2).

Reliable eye irritation study with Tetrabutylphosphonium bromide according to GLP principles, methods used equivalent to OECD guideline 405, but with deviations.

Based on the results of these studies, the substance does not need to be classified for skin irritation/corrosion and needs to be classified as corrosive for eye irritation/corrosion.

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

Study period:

13 June 2006 - 03 July 2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study conducted according to GLP principles, methods used equivalent to OECD guideline 404.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

also application to abraded skin in the same rabbit (one animal died 4 hrs post-dose)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA, USA
- Age at study initiation: 3-4 months
- Weight at study initiation: 2.5-3.4 kg
- Housing: individually in suspended cages
- Diet: PMI Rabbit Chow, provided daily
- Water: ad libitum
- Acclimation period: at least 3 days

ENVIRONMENTAL CONDITIONS
- Experiments conducted in temperature-controlled animal room
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 13 June 2006 - 03 July 2006

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5g

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 (1 male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm * 2.5 cm
- Type of wrap if used: surgical gauze patches were secured with non-adhesive tape, the torso was wrapped with plastic fitted with a window to allow dermal observations during the 4 hour exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):no, test substance was removed by gentle wiping
- Time after start of exposure: 4 hours

SCORING SYSTEM: According to Draize, J.H., J. Pharm. Exp. Ther. 82: 377-390, 1944), additional signs were described.

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Erythema was absent to very slight at 3 minutes after dosing and very slight to well defined at 1 and 4 hours. Edema was absent at 3 minutes after dosing, absent to very slight at 1 hour after dosing and absent to well defined at 2 hours.
At 24 hours after the 4 hour exposure, erythema was very slight to well defined. At 48 hours, erythema was well-defined and by 72 hours erythema was very slight to well defined. Edema was absent to very slight at 24, 48 and 72 hours. By day 7, erythema was absent in one animal, but very slight in another. Edema was absent on day 7. By day 14, both erythema and edema were absent.

Other effects:

One female died during 4 hour exposure period.

The results of the abraded skin are as follows:

		Erythema	Eschar formation
24 hours	Mean of two animals	2	1
48 hours	Mean of two animals	2	0.5
72 hours	Mean of two animals	1.5	0.5

 

All skin effects were reversible within maximally 2 weeks.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

An in vivo skin irritancy study was conducted according to GLP principles and equivalent to OECD guidelines.Based on the outcome of this study, the test substance is not classified as corrosive or irritant to the skin.

Executive summary:

In an in vivo skin irritancy study, three rabbits were dosed with 0.5 g test substance to intact (right flank) and abraded skin (left flank). One female died within 4 hour expsoure period. Erythema was absent to very slight at 3 minutes after dosing and very slight to well defined at 1 and 4 hours. Edema was absent at 3 minutes after dosing, absent to very slight at 1 hour after dosing and absent to well defined at 2 hours. At 24 hours after the 4 hour exposure, erythema was very slight to well defined. At 48 hours, erythema was well-defined and by 72 hours erythema was very slight to well defined. Edema was absent to very slight at 24, 48 and 72 hours. By day 7, erythema was absent in one animal, but very slight in another. Edema was absent on day 7. By day 14, both erythema and edema were absent. One female died during 4 hour exposure period, however this does not influence the validity of the study as all effects in two remaining animals were reversible and scores were <2 in 2 animals. Based on the outcome of this study, it can be concluded that the test substance is not classified as corrosive or irritant to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 June 2006 - 03 July 2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study conducted according to GLP principles, methods used equivalent to OECD guideline 404, but with deviations (0.081mg instilled instead of 0.1mg). As this amount resulted in severe effects, the test is regarded to be sufficient to fill this endpoint.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Lower amount test substance instilled, instillation into both eyes (one washed, one unwashed)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA, USA
- Age at study initiation: 3-4 months
- Weight at study initiation: 3.4 kg
- Housing: individually in suspended cage
- Diet: PMI Rabbit Chow, provided daily
- Water: ad libitum
- Acclimation period: at least 3 days

ENVIRONMENTAL CONDITIONS
- Experiments conducted in temperature-controlled animal room
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 13 June 2006 - 03 July 2006

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.081mg

Duration of treatment / exposure:

Single instillation

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance was instilled in both eyes, one eye remained unwashed, one eye was flushed by lukewarm water for one minute.
- Time after start of exposure: 20 to 30 seconds

SCORING SYSTEM: Following numerical Draize technique (Draize, J.H. et al., J. Pharm. Exp. Ther. 82: 377-390, 1944), additional signs were described.

TOOL USED TO ASSESS SCORE: Mini-Maglite flashlight

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritant / corrosive response data:

Corneal opacity, iritis and conjunctival irritation persisted until termination of the experiment (day 7). Pannus was noted on day 7. Discharge was noted at every observation time point.

Other effects:

Vocalization was noted post-dose.

In the washed eye, corneal opacity and iritis were noted that had cleared on day 7. Conjunctival irritation was still noticeable at day 7. Animal exhibited lethargy, prostration and laboured breathing at time of ocular dosing and instances of lethargy and few faeces post-dosing.

Interpretation of results:

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

Conclusions:

An eye irritation study was performed by instillation of 0.081mg tetrabutylphosphonium bromide in each eye of a rabbit. One eye remained unwahsed, one eye was flushed with lukewarm water. This resulted in severe effects during 7 days, after which the animal was sacrificed. Based on these results, the test substance is classified corrosive to the eye (cat. 1).

Executive summary:

An eye irritation study was performed by instillation of 0.081mg tetrabutylphosphonium bromide in each eye of a rabbit. The test was done following GLP principles. One eye remained unwashed, one eye was flushed with lukewarm water. This resulted in severe irreversible effects during 7 days in the unwashed eye, after which the animal was sacrificed. Based on these results, the test substance is classified corrosive to the eye (cat. 1).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

In a reliable in vivo skin irritancy study (Klimisch 2), three rabbits were dosed with 0.5 g test substance to intact (right flank) and abraded skin (left flank). One female died within 4 hour exposure period. Erythema was absent to very slight at 3 minutes after dosing and very slight to well defined at 1 and 4 hours. Edema was absent at 3 minutes after dosing, absent to very slight at 1 hour after dosing and absent to well defined at 2 hours. At 24 hours after the 4 hour exposure, erythema was very slight to well defined. At 48 hours, erythema was well-defined and by 72 hours erythema was very slight to well defined. Edema was absent to very slight at 24, 48 and 72 hours. By day 7, erythema was absent in one animal, but very slight in another. Edema was absent on day 7. By day 14, both erythema and edema were absent. One female died during 4 hour exposure period, however this does not influence the validity of the study as all effects in two remaining animals were reversible and scores were <2 in 2 animals. Based on the outcome of this study, it can be concluded that the test substance is not classified as corrosive or irritant to the skin.

 

Eye irritation/corrosion:

A reliable eye irritation study (Klimisch 2) was performed by instillation of 0.081 mg tetrabutylphosphonium bromide in each eye of a rabbit. The test was done following GLP principles. One eye remained unwashed, one eye was flushed with lukewarm water. This resulted in severe irreversible effects during 7 days in the unwashed eye, after which the animal was sacrificed. Based on these results, the test substance is classified corrosive to the eye (cat. 1).

Justification for classification or non-classification

According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments), Tetrabutylphosphonium Bromide; CYPHOS® 442 Phosphonium Salt should be classified as: irreversible effects to the eye (Category 1).

According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), Tetrabutylphosphonium Bromide; CYPHOS® 442 Phosphonium Salt should be classified as Category 1 and should be labeled as H318: Causes serious eye damage.