Reaction mass of Octadec-9-en-1-yl ammonium di-n-hexyl phosphorodithioate and Octadec-9-en-1-yl ammonium mono- and di-butylphosphate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 23 April 2002 and 19 June 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Octadec-9-en-1-yl ammonium mono and di-butylphosphate

Molecular formula:

C22H48NO4P - C26H56NO4P

IUPAC Name:

Octadec-9-en-1-yl ammonium mono and di-butylphosphate

Constituent 2

Reference substance name:

Octadec-9-en-1-yl ammonium di-n-hexyl phosphorodithioate

Molecular formula:

C30H64NO2PS2

IUPAC Name:

Octadec-9-en-1-yl ammonium di-n-hexyl phosphorodithioate

Test material form:

liquid: viscous

Details on test material:

Material is a yellow viscous liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Conditions
A controlled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21±3°C, a relative humidity of 30-70% and 12 hours artificial fluorescent light and 12 hours dark per day. Deviations from the maximum level for relative humidity (with a maximum of 20%) occurred which might have been caused by cleaning procedures in the room. Based on laboratory historical data these deviations were considered not to have affected the study integrity.

Accommodation
Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet
Standard laboratory rabbit diet (Teklad Global Rabbit Diet, code 2030, Harlan, Blackthorn, England) approx. 100 g. per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, hay (BMI, Helmond, the Netherlands) was provided twice a week.

Water
Free access to tap-water. Certificates of quarterly analysis were examined and retained in the NOTOX archives.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

Skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7, 14 and 21 days.

Number of animals:

3

Details on study design:

At the request of the sponsor, this skin irritation study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 12 days later, after considering the degree of skin irritation observed in the first animal.

Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters ( 1Ox15 cm2). Whenever considered necessary the treated skin areas were re-clipped at least 3 hours before the observations, to facilitate scoring.

A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.

Each animal was treated by dermal application of 0 .5 ml of the test substance. The test substance was applied to the skin of one flank, .using a metalline patch of 2 x 3 cm. The patch was mounted on Micropore tape·, which was wrapped around the abdomen and secured with Coban elastic bandage·.

Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using mineral oil (white spirit).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 249 Sentinel)

Time point:

other: mean of scores at 24, 48 & 72 hr

Score:

3.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

erythema score

Basis:

animal: 336

Time point:

other: mean of scores at 24, 48 & 72 hr

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

erythema score

Basis:

animal: 350

Time point:

other: mean of scotes at 24,48 & 72 hr

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

edema score

Basis:

animal: 249 Sentinel

Time point:

other: mean of cores at 24, 48 & 72 hrs

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 5

Irritation parameter:

edema score

Basis:

animal: 336

Time point:

other: 24 hours

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Scored after 24 hours only

Results 6

Irritation parameter:

edema score

Basis:

animal: 350

Time point:

other: 24 hours

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Scored after 24 hours only

Irritant / corrosive response data:

Four hours exposure to 0.5 ml of OLOA 289M resulted in severe erythema and severe! oedema in the treated skin-areas of the three rabbits. No scoring for oedema was possible among the animals between 48 hours and 7 days, due to fissuring of the skin. In all animals the erythema and oedema were also noted outside the application area.

(Superficial) grey- yellowish discolouration of the skin (sign of necrosis), reduced flexibility and fissuring of the skin was noted among the animals between 24 hours and 7 days after exposure. Scaliness and bald skin were noted in all animals after 14 days. No skin abnormalities were noted in the animals after 21 days.

Corrosion
There was no evidence of a corrosive effect on the skin.

Other effects:

Colouration
Yellow disclouration of the treated skin was observed 24 hours after exposure in one animal.

Toxicity I Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: EU