Phosphorus(1+), dichloro[(P,P-dichlorophosphinimyl-.kappa.N)phosphorimidic trichloridato](phosphorimidic trichloridato-.kappa.N)-, (T-4)-, hexachlorophosphate(1-) (1:1)

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP with exceptions: 1. Analyses to determine the uniformity, concentration, or stability of the test or control mixtures were not performed by the Testing Facility* 2. The stability of the test or control material under the test conditions was not determined by the Testing Facility.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Bertil Magnusson, M.D., and Albert M. Kligman, M.D., Ph.D. in "The Identification of Contact Allergens by Animal Assay: The Guinea Pig Maximization Test", Journal of Investigative Dermatology, Vol. 52, pp 268-276 and in Allersic Contact Dermatitis in the

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

419-940-1

EC Name:

-

Cas Number:

21246-63-9

Molecular formula:

Hill formula: Cl16 N3 P5 CAS formula: Cl10 N3 P4. Cl6 P

IUPAC Name:

decachlorotetraphosphaza-1,3,5-trien-7-ium; bis(hexachloro-λ⁵-phosphanuide); octachlorotriphosphaza-1,3-dien-5-ium

Details on test material:

Test Material: Dow Corning' 3-0224
(also known as 3-0224 SPARC Catalyst)
Lot/Batch No.: WH116001
Description: Dark green liquid with pungent odor
Date of Receipt: 28 January 1998
Expiration Date: 30 November 1998
Received from: Dow Corning Corporation
Midland, Michigan
Storage: Room temperature
Sampling: An archival sample of approximately
10 grams is stored in the Archives of
the Testing Facility.

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Study design: in vivo (non-LLNA)

Induction

Concentration / amount:

Concentration of test material and vehicle used at induction:
a) 1% Dow Corning (R) 3-0224 in 50% FCA/40% mineral oil/10%

absolute ethanol (intradermal)

b) 50% Dow Corning (R) 3-0224 in 10% absolute ethanol/40%
mineral oil (topical)

Concentration of test material and vehicle used for each challenge:
a) 1% Dow Corning (R) 3-0224 in 0.2% absolute ethanol/99.8%

mineral oil

b) 10% Dow Corning (R) 3-0224 in 2% absolute ethanol/88%
mineral oil

Challenge

Concentration / amount:

Concentration of test material and vehicle used at induction:
a) 1% Dow Corning (R) 3-0224 in 50% FCA/40% mineral oil/10%

absolute ethanol (intradermal)

b) 50% Dow Corning (R) 3-0224 in 10% absolute ethanol/40%
mineral oil (topical)

Concentration of test material and vehicle used for each challenge:
a) 1% Dow Corning (R) 3-0224 in 0.2% absolute ethanol/99.8%

mineral oil

b) 10% Dow Corning (R) 3-0224 in 2% absolute ethanol/88%
mineral oil

No. of animals per dose:

Number of animals in test group: 20
Number of animals in negative control group: 10

Study design: in vivo (LLNA)

Concentration:

Intradermal Induction: 1% Dow Corning(R) 3-0224 in 50% oil/10% absolute ethanol
1% Dow Corning(R) 3-0224/10% absolute ethanol/89% mineral oil
Topical Induction: 50% Dow Corning(R) 3-0224/10% absolute ethanol/40% mineral oil
Challenge: 10% Dow Corning(R) 3-0224/2% absolute ethanol/88% mineral oil
1% Dow Corning(R) 3-0224/0.2% absolute ethanol/98.8% mineral oil
-

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1 %

No. with + reactions:

18

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1 %. No with. + reactions: 18.0. Total no. in groups: 20.0.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10 %

No. with + reactions:

20

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10 %. No with. + reactions: 20.0. Total no. in groups: 20.0.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Maximum concentration not causing irritating effects in preliminary test: 1 %

Evidence of sensitisation of each challenge concentration:
For 1% Dow Corning (R) 3-0224 the Incidence Index of
Sensitisation at challenge was 90% (18 ut of 20 test
animals), the dermal score was 2, 24 and 48 hours after
challenge. For 10% Dow Corning (R) 3-0224 the Incidence
Index at challenge is 100% (all the 20 test animals), the
dermal score was 2.9 and 2.6 at 24 and 48 hours.

Other observations:
Positive control substance : HCA (Hexylcinnamic aldehyde).

FCA : Freund's Complete Adjuvant

Applicant's summary and conclusion

Interpretation of results:

other: irritant

Executive summary:

This study was conducted for Dow Corning Corporation in order to evaluate the allergic contact sensitization potential of Dow Corning(R) 3-0224 in guinea pigs. Data from this study may serve as a basis for classification and labelling of the test material. This study was performed at Huntingdon Life Sciences, P.O. Box 2360, Mettlers Road, East Millstone, New Jersey 08875-2360. Dosing for the range-finding studies was initiated on 29 January 1998 and observations were completed on 20 February 1998. Dosing for the sensitization study was initiated on 09 February 1998 and observations were completed on 05 March 1998. The procedures used are based on the method described by Bertil Magnusson, M.D., and Albert M. Kligman, M.D., Ph.D. in "The Identification of Contact Allergens by Animal Assay: The Guinea Pig Maximization Test", Journal of Investigative Dermatology, Vol. 52, pp 268-276 and in Allersic Contact Dermatitis in the Guinea Pie: Identification of Contact Allersens, Thomas, Springfield, IL, 1970. The test material was administered at a 1% concentration for the intradermal induction, and at a 50% concentration for the topical induction, to 20 male Dunkin Hartley guinea pigs. Fourteen days after the last induction exposure, the challenge treatment was administered topically at 10% and 1% concentrations. To demonstrate the susceptibility of this shipment of animals to sensitization, a positive control group of ten male animals was treated with hexylcinnamic aldehyde (HCA). In addition, to demonstrate that the vehicle was not a sensitizer, a control group of ten male animals was treated with absolute ethanol/mineral oil. In order to differentiate dermal reactions produced by irritation from those produced by sensitization, 30 male animals were treated concurrently during induction with only vehicle and FCA; groups of 10 of these animals for the test material and each control material were then subjected to the same challenge procedures as the animals which received test, or control materials during the induction exposures. Observations for mortality were made twice daily. Body weights were measured pretest and two days after challenge. Animals were also observed prior to treatment and weekly during the study for general health. Dermal evaluations were made approximately 24 hours after the induction injections and after removal of induction patches and 24 and 48 hours after the removal of challenge patches. There were no test material-related deaths, and all survivors gained weight during the study and were free of clinical signs. During the induction phase, as is typically seen with this study design, all animals, in all groups, had severe dermal lesions at the intradermal injection sites. These lesions were still evident after the topical induction phase. These responses are primarily due to the FCA

which is injected at most of the sites during the initial induction in order to enhance responsiveness to sensitizers.

At challenge, all twenty test animals had clear dermal responses, at the sites treated with 10% Dow Corning(R) 3-0224, and eighteen of the twenty test animals had clear dermal responses at the sites treated with 1% Dow Corning" 3-0224. The fact that these responses were due to sensitization and not irritation was confirmed by a lack of clear dermal response in the

irritation control animals at the sites treated at the same concentrations. For 10% Dow Corning(R) 3-0224 the Incidence Index of

Sensitization at challenge was 100% and the Severity Indices for the test material animals at 24 and 48 hours were 2.9 and 2.6, respectively, compared to indices of 0.3 and 0.2, respectively, in the irritation control animals. For 1% Dow Corning(R) 3-0224 the Incidence Index of Sensitization at challenge was 90% and the Severity Indices for the test material animals at both 24 and 48 hours were 2.0 compared to indices of 0 in the irritation control animals. There was a positive response to the known sensitizer HCA,

demonstrating the susceptibility of this shipment of animals to sensitization in the guinea pig maximization test.

There was a negative response to the vehicle used for the test material demonstrating that any responses seen in the test group were due to the test material, and not the vehicle. Under conditions of this study, Dow Corning(R) 3-0224 exhibited a potential to produce dermal sensitization in guinea pigs and has an allergenicity rating of "Extreme", Kligman rating.based on the modified Magnusson and

For the purpose of European Union (EU) Classification and Labeling, Dow Corning(R) 3 -0224 "may cause sensitization by skin contact".