Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-Pr) esters, zinc salts

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 Dec 1981 - 14 Jan 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study; restriction due to missing details in study report which did not affect ability to evaluate results

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

During preparation of the original submission, reporting of an existing guinea pig maximisation test was considered more appropriate than sacrifice of further vertebrate animals in the Local Lymph Node Assay.

Test material

Test material information

Constituent 1

Reference substance name:

Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-Pr) esters, zinc salts

EC Number:

272-723-1

EC Name:

Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-Pr) esters, zinc salts

Cas Number:

68909-93-3

Molecular formula:

Too complex

IUPAC Name:

Phosphorodithioic acid, mixed O,O-bis(2-ethylhexyl and iso-Pr) esters, zinc salts

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: no data.
- Age at study initiation: no data.
- Weight at study initiation: between 300 and 400 g.
- Housing: the animal were housed and maintained in compliance with the Animal Welfare Act 9 CFR part 3. Five guinea pigs per cage were housed in stainless steel with elevated wire mesh flooring.
- Diet (e.g. ad libitum): Charles River Guinea Pig Formula was provided ad libitum.
- Water (e.g. ad libitum): tap water was provided ad libitum.
- Acclimation period: no data.

ENVIRONMENTAL CONDITIONS
- Temperature: 70 ± 2 oF
- Humidity (%): 45 ± 5
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle.

IN-LIFE DATES: From: 28 December 1981 To: 14 January 1982

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

other: mineral oil

Concentration / amount:

5% w/v

Challenge

Route:

epicutaneous, occlusive

Vehicle:

other: mineral oil

Concentration / amount:

5% w/v

No. of animals per dose:

20 animals/dose

Details on study design:

RANGE FINDING TESTS: Unknown
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 1 week following injection and 2 days (48hrs) after dermal application
- Test groups: 1 group of 20 male animals.
- Control group: Not included.
- Site: skin over the shoulders.
- Frequency of applications: For induction stage: intradermal injections were made once at 3 pairs of sites simultaneously, 7 days later followed by dermal application of test material. Then the animals were allowed to rest for 2 weeks.
- Duration: total of 3 week time period.
- Concentrations: 5% w/v

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 21 h
- Test groups: 1 group of 20 male animals.
- Control group: Not included.
- Site: skin over the shoulders.
- Concentrations: 5% w/v
- Evaluation (hr after challenge): 24 hr and 48 hr

Challenge controls:

not included

Positive control substance(s):

not required

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5% w/v

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5% w/v

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

INDUCTION STAGE:

1.   An area of 4x6 cm was clipped free of hair with an electric clipper over the shoulders of

     the 20 guinea pigs.

2.   For induction, three pairs of intradermal injections were made simultaneously:

0.1 ml of Freunds complete adjuvant (50:50 dilution with distilled water)

0.1 ml of the test substance alone

0.1 ml of the test substance mixed with Freunds comple adjuvant (1:1)

3.   After 7 days, the test site area was re-clipped. A 2x4 cm filter paper was saturated with
  the experimental material and applied to the injection site area and occluded using an
  overlapping impermeable plastic adhesive tape. The dressing was kept in place for 48 h.

 

CHALLENGE STAGE:

1.      After 2 week rest period, a 3x3 cm area of the flank was shaved on the left side of the
guinea pig.

2.      A 2x2 cm filter paper was saturated with the experimental material and applied to the left side. The area was occluded using an overlapping impermeable plastic adhesive tape.

3.      The animal exposed to the test substance for 21 h, and 3 h later the skin sites were examined for elicited skin reactions.
Another 24 h later, the sites were re-examined. Scores was done on the basis of 0-3
(0: no reaction; 1: scattered mild redness; 2: moderate and diffuse redness; 3: intense redness and swelling)

. .

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

The test material does not appear to be a sensitizer in the albino guinea pig

Executive summary:

In a Magnusson-Kligman Guinea Pig maximization test, 20 Dunkin-Hartley strain albino Guinea Pigs were treated with 5% w/v test substance, scores of zero in all test animals were obtained at all time points examined. The test material does not appear to be a sensitizer in the albino guinea pig.