Santicizer 2148

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-07-08 to 1999-11-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Scientifically valid and well documented guinea pig maximization test. The testing using the guinea pig maximisation test protocol was completed on 17 November 1999. The LLNA 429 was not formally adopted by the OECD until 22 July 2010.

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of dodecyldiphenyl phosphate and tetradecyldiphenyl phosphate

Molecular formula:

CH24H35O4P.C26H39O4P

IUPAC Name:

Reaction mass of dodecyldiphenyl phosphate and tetradecyldiphenyl phosphate

Test material form:

liquid

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

Young adult, Hartley-derived albino guinea pigs were received at SLI from Hilltop Lab Animals, Inc., Scottdale, Pennsylvania. Upon receipt, plastic ear tags displaying unique identification numbers were used to individually identify the animals. Cage cards displaying at least the study number, animal number and sex were affixed to each cage. The animals were housed individually in suspended stainless steel cages. All housing and care were based on the standards recommended by the Guide of the Care of Use of Laboratory Animals

The animal toom temperature and relative humidity ranges were 64-74°F and 54-89%, respective. Environmental control equipment was monitored and adjusted as necessary to minimise fluctuation in the animal room environment. Light timers were set to maintain a 12-hourlight/12-hour dark cycle and room ventilation was set to produce 10-15 air changes/hour. The room temperature and relative humidity were recorded a minimum of once daily.

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, semiocclusive

Vehicle:

propylene glycol

Concentration / amount:

5.0% / 0.1 ml

Day(s)/duration:

0

Adequacy of induction:

not specified

Induction 2

Route:

intradermal

Vehicle:

propylene glycol

Concentration / amount:

100% / 0.8 ml

Day(s)/duration:

6

Adequacy of induction:

not specified

Challenge

Challenge 1

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

propylene glycol

Concentration / amount:

0.1% / 0.3 ml

Day(s)/duration:

21

Adequacy of challenge:

not specified

Challenge 2

No.:

#2

Route:

epicutaneous, occlusive

Vehicle:

propylene glycol

Concentration / amount:

0.1% / 0.3 ml

Day(s)/duration:

29

Adequacy of challenge:

not specified

No. of animals per dose:

5 animals/sex/dose

Details on study design:

This study consisted of an intradermal range-finding group, two topical range-finding groups, a test group, a challenge control group and a rechallenge control group.

Challenge controls:

0.1% / 0.3 ml Santicizer 2148 on 25 mm Hilltop Chamber

Positive control substance(s):

no

Remarks:

Hexylcinnamaldehyde used as noncpncurrent positive control. Tested at the facility within 6 month of the test with Santicizer 2148

Results and discussion

Positive control results:

Hexylcinnamaldehyde was used as a nonconcurrent positive control and tested at the facility within 6 months of the Santicizer 2148 test. The positive control produced evidence of dermal sensitization (mean dermal score at 24 and 48 hours were 1.2 and 0.8, respectively for a 1% challenge vs. 0.2 and 0.1 for control; mean dermal scores at 24 and 48 hours were 0.7 and 0.6, respectively for 0.5% rechallenge vs. 0.0 and 0.0 for control.

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.8 mL (100% concentration)

Remarks on result:

other: Mean dermal score = 0.1

Results 2

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.8 mL (100% concentration)

Remarks on result:

other: Mean dermal score = 0.1

Results 3

Key result

Reading:

rechallenge

Hours after challenge:

24

Group:

negative control

Dose level:

0.8 mL (100% concentration)

Remarks on result:

other: Mean dermal score = 0.3

Results 4

Key result

Reading:

rechallenge

Hours after challenge:

48

Group:

negative control

Dose level:

0.8 mL (100% concentration)

Remarks on result:

other: Mean dermal score = 0.2

Results 5

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1%

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

score of 1 in erythema

Remarks on result:

no indication of skin sensitisation

Remarks:

score of 1 - slight, but confluent or moderate patchy erythema

Results 6

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1%

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

score of 0.5 in erythema

Remarks on result:

no indication of skin sensitisation

Remarks:

score of 0.5 - slight patchy erythema

Results 7

Key result

Reading:

rechallenge

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Results 8

Key result

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Results 9

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

1% challenge

Remarks on result:

other: Mean dermal score = 1.2

Results 10

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

Dose level:

1% challenge

Remarks on result:

other: Mean dermal score = 0.8

Results 11

Key result

Reading:

rechallenge

Hours after challenge:

24

Group:

positive control

Dose level:

0.5%

Remarks on result:

other: Mean dermal score = 0.7

Results 12

Key result

Reading:

rechallenge

Hours after challenge:

48

Group:

positive control

Dose level:

0.5%

Remarks on result:

other: Mean dermal score = 0.6

Any other information on results incl. tables

Table 1: A dermal sensitisation study in guinea pigs – individual challenge data for test group

Animal no./sex	Dermal scores (0.1%)
	24hr	48hr
G1811/M	±	±
G1812/M	0	0
G1813/M	0	0
G1814/M	±	0
G1815/M	0	0
G1920/F	±	0
G1921/F	±	±
G1922/F	±	±
G1923/F	0	0
G1924/F	1	±
MEAN	0.4	0.2

± = 0.5

Score of 0.5 = slight patchy erythema

Score of 1 = slight, but confluent or moderate patchy erythema

Table 2. A dermal sensitisation study in guinea pigs – individual challenge data for control group

Animal No. / Sex	Dermal Scores (0.1%)
	24 hr	48 hr
G1816/M	0	0
G1817/M	0	0
G1818/M	0^IT	0
G1819/M	0^IT	0
G1821/M	0^IT	0
G1925/F	0^IT	0
G1926/F	±^IT	0
G1927/F	0^IT	±^IT
G1928/F	±^IT	±
G1929/F	0^IT	0
Mean	0.1	0.1

Note: For purpose of calculation ± = 0.5

IT: dermal irritation outside of test site

±: Erythema Grade ± slight patchy erythema

Table 3: A dermal sensitisation study in guinea pigs – individual rechallenge data for test group

Animal no./sex	Dermal scores (0.1%)
	24hr	48hr
G1811/M	±	0
G1812/M	±	±
G1813/M	0	0
G1814/M	±	±
G1815/M	±	0
G1920/F	0	0
G1921/F	±	0
G1922/F	±	0
G1923/F	0	0
G1924/F	±	0
MEAN	0.4	0.2

± = 0.5

Score of 0.5 = slight patchy erythema

Score of 1 = slight, but confluent or moderate patchy erythema

Table 4: A dermal sensitisation study in guinea pigs – individual rechallenge data for control group

Animal No. / Sex	Dermal Scores (0.1%)
	24 hr	48 hr
G1822/M	±	±
G1823/M	0^IT	0
G1824/M	0	0
G1825/M	±	0
G1826/M	0^IT	0
G1930/F	±	0
G1931/F	±^IT	±
G1932/F	0^IT	0^IT
G1933/F	0	0
G1934/F	0^IT	±
Mean	0.3	0.2

Note: For purpose of calculation ± = 0.5

IT: dermal irritation outside of test site

±: Erythema Grade ± slight patchy erythema

Applicant's summary and conclusion

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

One test animal at challenge (0.1%) had a score of 1 in erythema at the 24-hour scoring interval and a score of ± at the 48-hour scoring interval. At rechallenge (0.1%) the same animal had a score of ± at the 24 and 48 hour scoring intervals. Since none of the animals at test and rechallenge had an erythema score high than ±, Santicizer 2148 is not considered to be a contact sensitizer in guinea pigs. The results of the α-Hexylcinnamaldehyde historical control study demonstrated that a valid test was performed and indicated that the test design would detect potential contract sensitizer

Executive summary:

The dermal sensitisation potential of Santicizer 2148 was evaluated in Harley-derived albino guinea pigs. 5 male and 5 female guinea pigs received intradermal injections of 5.0% w/v Santicizier 2148 in propylene glycol along with injections of FCA and Santicizer 2148 in FCA. One week later, the test animals received a topical application of 100% Santicizer 2148. Challenge and rechallenge control animals received similar intradermal and topical treatments except propylene glycol was used in place of the test article/ following a two-week rest period, a challenge was performed whereby the 10 test and 10 challenge control guinea pigs were topically treated with 0.1% w/v Santicizer 2148 in propylene glycol. Challenge responses in the test animals were compared with those of the challenge control animals. Following an eight-day rest period, a rechallenge was performed whereby the 10 test animals and 10 previously untreated (naïve) rechallenge control guinea pigs were topically treated with 0.1% w/v Santicizer 2148 in propylene glycol. Rechallenge responses in the test animals were compared with those of the rechallenge control animals.

One test animal at challenge (0.1%) had a score of 1 in erythema at the 24-hour scoring interval and a score of ± at the 48-hour scoring interval. At rechallenge (0.1%) the same animal had a score of ± at the 24 and 48 hour scoring intervals. Since none of the animals at test and rechallenge had an erythema score high than ±, Santicizer 2148 is not considered to be a contact sensitizer in guinea pigs. The results of the α-Hexylcinnamaldehyde historical control study demonstrated that a valid test was performed and indicated that the test design would detect potential contract sensitizer.