4H-Pyrazino[2,1-a]isoquinolin-4-one, 2-acetyl-1,2,3,6,7,11b-hexahydro-

Endpoint summary

Description of key information

According to the results of a Guinea Pig Maximisation Test in compliance with OECD TG 406 the test item is considered sensitising (reference 7.4.1 -1).

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

Study period:

2006-05-12 to 2006-06-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Based on the results of a pre-test, the test item was not sufficiently soluble in any of the vehicles applicable for an LLNA study. Therefore, an LLNA study was technically not feasible and a GPMT was conudcted instead. Furthermore, the in vivo assay OECD 406 was performed before the OECD 429 assay was mandatory.

Species:

guinea pig

Strain:

other: HsdPoc:DH

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6 weeks
- Weight at study initiation: 318 g (range from 304 to 335 g)
- Housing: in type (3M15 (EBECO) Makrolon cages with a shelter and placed on mobile racks
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 22°C
- Humidity: 50 to 62%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

Route:

intradermal

Vehicle:

other: Sodium chloride solution (isotonic)

Concentration / amount:

10 g/L

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

other: Sodium chloride solution (isotonic)

Concentration / amount:

100 g/L

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: Sodium chloride solution (isotonic)

Concentration / amount:

50 g/L

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Pre Test Group: 5 females
Control Group: 5 females
Test Group: 10 females

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2x inductions
- Exposure period: induction by intradermal injection on day 1; induction by topical application on day 8 with an exposure for 48 hours
- Test groups: 1
- Control group: 1
- Site: cranial, medial, caudal
- Frequency of applications: 2 x induction
- Concentrations: 10 g/L intradermal; 100 g/L epidermal


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 22
- Exposure period: 24 hours occlusive
- Test groups: 1
- Control group: 1
- Site: cranial, medial, caudal
- Concentrations: 50 g/L epidermal
- Evaluation (hr after challenge): 48 and 72 hours

Positive control substance(s):

yes

Remarks:

a-Hexylcinnamaldehyde (periodically tested)

Positive control results:

The sensitivity of the test system was checked and confirmed periodically.

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50 g/L

No. with + reactions:

5

Total no. in group:

10

Key result

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

50 g/L

No. with + reactions:

7

Total no. in group:

10

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0 g/L

No. with + reactions:

0

Total no. in group:

5

Key result

Reading:

2nd reading

Hours after challenge:

72

Group:

negative control

Dose level:

0 g/L

No. with + reactions:

0

Total no. in group:

5

Group:

positive control

Remarks on result:

not measured/tested

Table 1 (vehicle), indcution with sodium chloride solution

Animal No.	Vehicle (caudal)		Test material (cranial)
	48 hours*	72 hours*	48 hours*	72 hour*
86	0	0	0	0
87	0	0	0	0
88	0	0	0	0
89	0	0	0	0
90	0	0	0	0

*time after the start of the challenge

Table 2 (test material), induction with test item

Animal No.	Vehicle (caudal)		Test material (cranial)
	48 hours*	72 hours*	48 hours*	72 hours*
91	0	0	1	2 s
92	0	0	1	1 s
93	0	0	0	2
94	0	0	1	1
95	0	0	0	2
96	0	0	0	0
97	0	0	0	0
98	0	0	1	3 s
99	0	0	0	0
100	0	0	1	1

*time after the start og the challenge

Rating scheme according to Magnusson & Kligman.

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Under the conditions of the maximization test, the test material exhibits a skin-sensitization potential.

Executive summary:

The purpose of this GPMT assay conducted according to OECD TG 406 was to identify the contact allergenic potential of the test item. This study should provide a rational basis for risk assessment to the sensitising potential of the test item in man. The test item was evaluated for skin sensitizing properties in the guinea pig maximization test according to MAGNUSSON and KLIGMAN (1969). 5 Female guinea pigs in the negative control group (group 1) treated with the vehicle (sodium chloride solution) and 10 females in the test material group (group 2) were investigated. The induction included intradermal injection of test material preparation in sodium chloride solution (10 g/L with and without Freund's complete adjuvant) on experimental day 1, and topical application for 48 hours of test material preparation in sodium chloride solution (100 g/L) on experimental day 8. Challenge by topical application for 24 hours of the test material preparation in sodium chloride solution (50 g/L) was performed two weeks after topical induction and readings taken at 48 hours and 72 hours after start of treatment.

Challenge with 50 g/L test material revealed 7 of 10 animals (70 %) as positive responders. Under the conditions of the maximization test, the test material exhibits a skin-sensitization potential.  

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

GPMT

The purpose of this GPMT assay conducted according to OECD TG 406 was to identify the contact allergenic potential of the test item. This study should provide a rational basis for risk assessment to the sensitising potential of the test item in man. The test item was evaluated for skin sensitizing properties in the guinea pig maximization test according to MAGNUSSON and KLIGMAN (1969). 5 Female guinea pigs in the negative control group (group 1) treated with the vehicle (sodium chloride solution) and 10 females in the test material group (group 2) were investigated. The induction included intradermal injection of test material preparation in sodium chloride solution (10 g/L with and without Freund's complete adjuvant) on experimental day 1, and topical application for 48 hours of test material preparation in sodium chloride solution (100 g/L) on experimental day 8. Challenge by topical application for 24 hours of the test material preparation in sodium chloride solution (50 g/L) was performed two weeks after topical induction and readings taken at 48 hours and 72 hours after start of treatment. Challenge with 50 g/L test material revealed 7 of 10 animals (70 %) as positive responders. Under the conditions of the maximization test, the test material exhibits a skin-sensitization potential.  

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin sensitisation, the test item is classified and labelled as skin sensitiser Cat. 1 (H317: " May cause an allergic skin reaction") according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) 2019/521.