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Toxicological information

Skin irritation / corrosion

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Administrative data

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.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrabutylphosphonium bromide
EC Number:
221-487-8
EC Name:
Tetrabutylphosphonium bromide
Cas Number:
3115-68-2
Molecular formula:
C16H36P.Br
IUPAC Name:
tetrabutylphosphonium bromide
Test material form:
other: waxy solid
Details on test material:
- Name of test material (as cited in study report): CYPHOS 442 (CT-851-06)
- Substance type: organic
- Physical state: White waxy solid (odorless)
- Storage condition of test material: Room temperature and humidity

Test animals

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

Test system

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.

Results and discussion

In vivo

Resultsopen allclose all
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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.

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