1H-Isoindol-1-one, 2,3-dihydro-3,3-bis(4-hydroxyphenyl)-2-phenyl-

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD 406 (1992) and EPA OPPTS 870.2600 (2003);GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Remarks:

US EPA TSCA GLP (40 CFR, Part 792) and OECD GLP

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

Male and female Hartley guinea pigs were received from Elm Hill Breeding Labs, Inc., Chelmsford, MA. They weighed 363.5-440.2 g and were at least 21 days old. They were group-housed upon arrival in stainless steel suspended cages. The animals were acclimated for at least 5 days prior to dosing. Water and feed were provided ad libitum. The temperature and humidity were maintained at 68 +/- 5°F and 30-70%, respectively. Room lights were on a 12-hour light/dark cycle.

Route:

other: Intradermal and Topical

Vehicle:

cotton seed oil

Concentration / amount:

10% PPP-BP for intradermal induction
100% for topical induction and topical challenge

Route:

other: Topical

Vehicle:

cotton seed oil

Concentration / amount:

10% PPP-BP for intradermal induction
100% for topical induction and topical challenge

No. of animals per dose:

5 males/5 females Test group (10% PPP-BP intradermal; 100% PPP-BP topical)
2 males/3 females Negative control group
2 males/2 females for the preliminary irritation tests

Details on study design:

A preliminary intradermal irritancy test was conducted, in which PPP BP, at concentrations of 100, 50, 10 and 1% in CSO was injected intradermally (0.1 mL/site). It was determined that 10% PPP-BP in CSO caused well defined irritation without local toxicity while moderate to severe irritation was observed at the 50% concentration. In addition, a preliminary topical irritancy test was conducted and 100% PPP-BP was found to be non-irritating when applied topically. Therefore, PPP-BP at a concentration of 10% was chosen for the intradermal induction and a concentration of 100% was chosen as the topical induction and challenge doses.


The application sites were prepared by clipping the skin of the test site free of hair. On day 0 and day 7, an approximately 5 x7 cm area over the shoulder region was prepared. On day 21, an approximately 4 x 4 cm square of the flank was prepared.

On Day 0, for the intradermal induction, three pairs of intradermal injections were made so that on either side of the midline there were three injection sites. The dosing solution for each injection is listed below. Injection pairs 1 and 2 were given in close proximity to each other cranially and injection pair 3 was located more caudally. The injection sites were just within the boundaries of 2 x 4 cm.

Test Group
Injection Pair 1: 0.1 mL Freund’s Complete Adjuvant (FCA) 1:1 with CSO
Injection Pair 2: 0.1 mL PPP-BP at the selected concentration (10% formulation in CSO)
Injection Pair 3: 0.1 mL PPP-BP 1:1 with FCA

Negative Control Group
Injection Pair 1: 0.1 mL FCA 1:1 with CSO
Injection Pair 2: 0.1 mL CSO (undiluted)
Injection Pair 3: 0.1 mL 50% formulation of CSO 1:1 with FCA

The animals were not treated with sodium lauryl sulfate prior to the topical induction. On Day 7, for the topical induction, the experimental group was dosed with 100% PPP-BP. PPP-BP was placed on a 2 x 4 cm piece of filter paper in a thick even layer. The patch was placed on the dorsal surface of the animals, covered by an impermeable sheet, and secured with a non-adhesive bandage which was wound around the torso of the animal. The dressing was left in place for 48 hours. The negative control group was treated in a similar fashion with CSO.

On Day 21, for the topical challenge, pieces of filter paper measuring 2 x 2 cm were secured to the flanks for 24 hours, utilizing the same wrapping technique as previously described. For both the test and negative control groups, one patch was placed on the left side with PPP-BP at 100% and a second patch was placed on the right side with CSO.

Approximately 21 hours after patch removal, the flank skin was cleaned and clipped. Approximately 3 hours later, the first reading of the reactions was performed (Day 23) and the second reading was made on Day 24. For evaluation of skin reactions, the following four-point scale was used:

0 = No reactions
1 = Discrete or patchy erythema
2 = Moderate and confluent erythema
3 = Intense erythema and swelling

Challenge controls:

2 males/3 females Negative control group

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Vehicle (CSO)

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Vehicle (CSO). No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Vehicle (CSO)

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Vehicle (CSO). No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None.

All animals gained weight over the course of the study.  No systemic signs of toxicity were observed in any animal over the course of the study.  None of the test animals exhibited any signs of erythema at any of the observation points.  None of the negative control animals exhibited erythema at either the 24- or 48-hour observation periods following challenge application.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under the conditions of this study, PPP-BP elicited no reaction to the challenge in this skin sensitization study and was concluded to be a non-sensitiser.

Executive summary:

The study assessed the skin sensitisation potential of the test substance. Twenty female guinea-pigs were given test substance doses by intradermal injection and topical application of 10% PPP-BP intradermal; 100% PPP-BP topical in a cotton seed oil vehicle. PPP-BP at a concentration of 10% was chosen for the intradermal induction and a concentration of 100% was chosen as the topical induction and challenge doses following an initial intradermal irritancy test. Challenge sites were evaluated at 24, and 48 hours after removal against a negative control group. Daily observations were made for clinical signs of toxicity. Animals were weighed at the beginning and end of the observation period.

 

Reactions were scored on a scale from 0 to 5 for erythema, eschar formation and oedema formation. All test sites were scored 0 for both the test and control animals. The test substance did not produce evidence of delayed contact hypersensitivity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The study assessed the skin sensitisation potential of the test substance. Twenty female guinea-pigs were given test substance doses by intradermal injection and topical application of 10% PPP-BP intradermal; 100% PPP-BP topical in a cotton seed oil vehicle. Challenge sites were evaluated at 24, and 48 hours after removal against a negative control group. Reactions were scored on a scale from 0 to 5 for erythema, eschar formation and oedema formation. All test sites were scored 0 for both the test and control animals. The test substance did not produce evidence of delayed contact hypersensitivity.

Based on the available information, the test substance has no skin sensitisation potential.

Migrated from Short description of key information:
A skin sensitisation study (Magnusson & Kligman Maximisation Test) was performed (2004) in guinea pigs in accordance with OECD 406. The study was GLP compliant (OECD/EPA). The test substance did not elicit any signs of erythema or edema on challenge and was concluded to be a non-sensitiser.

Justification for selection of skin sensitisation endpoint:
GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The test substance does not meet classification criteria under EU Directive 67/548/EEC for skin sensitisation.

The test substance does not meet classification criteria under Regulation (EC) No 1272/2008 for skin sensitisation.