1,1'-(methylenedi-4,1-phenylene)bis(3-butylurea)

Endpoint summary

Description of key information

HAT ISO was assessed for skin sensitization in two studies. In the key study, a guinea pig maximization test EU Method B.6 (Skin Sensitisation), no sensitization by skin contact was revealed. The second study was also a guinea pig maximization test. However, the disregarded study was considered not valid (reliability grade 3), as the test material was contaminated with solvent residues.

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:

1996-12-09 to 1997-01-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

EC 92/69

Deviations:

no

Qualifier:

according 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:

The study was conducted in 1997. By this time the LLNA was not established yet.

Specific details on test material used for the study:

Analytical purity: treated as 100 % pure
Lot/batch No.: V96/16

Species:

guinea pig

Strain:

Himalayan

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland;
- Age at study initiation: approx. 6 weeks;
- Weight at study initiation: max. 500 g,
- Housing: groups of 5 in metal wire cages with wire-mesh floors;
- Diet: standard guinea pig diet ad libitum; Suppl.: Hope Farms, Woerden, The Netherlands;
- Water: tap-water, diluted with decalcified water, ad libitum;
- Acclimation period: at least 5 days;


ENVIRONMENTAL CONDITIONS
- Temperature: 21°C;
- Humidity: 50 % R.H.
- Air changes: approx. 15 air changes per hour;
- Photoperiod: 12 hours artificial fluorescent light/12 hours dark;

Route:

intradermal and epicutaneous

Vehicle:

CMC (carboxymethyl cellulose)

Concentration / amount:

Induction: 0.2 % test substance concentration

Route:

epicutaneous, occlusive

Vehicle:

CMC (carboxymethyl cellulose)

Concentration / amount:

Challenge: 50 % test substance concentration;

No. of animals per dose:

Experimental group: 10 females,
Control group: 5 females;

Details on study design:

Test substance concentrations (in 1 % aqueous carboxymethyl cellulose) selected for the main study were based on the results of a preliminary study. In the main study, ten experimental animals were intradermally injected with a 0.2 % concentration and epidermally exposed to a 50 % concentration. Five control animals were similarly treated, but with vehicle only. Approximately 24 hours before the epidermal induction exposure all animals were treated with 10 % SDS. Two weeks after the epidermal application all animals were challenged with a 50 % test substance concentration and the vehicle.

Positive control substance(s):

not specified

Positive control results:

None

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Key result

Group:

positive control

Remarks on result:

not measured/tested

Based on the results of a preliminary study, the test substance concentrations selected for the main study were a 0.2 % concentration for the intradermal induction and a 50 % concentration for the epidermal induction exposure.

Since no signs of irritation were observed at the concentrations selected for the epidermal induction, all animals were treated with 10 % SDS (Sodium Dodecyl Sulfate) approximately 24 hours before the epidermal induction. A 50 % test substance concentration was selected for the challenge phase.

Induction phase:

The skin effects caused by the intradermal injections and epidermal exposure during the induction phase are given in the table. The reactions noted in two experimental animals after the epidermal induction exposure were considered to be enhanced by the SDS treatment.

Induction

 

Animal Number	Intradermal Injection (DAY 3)			Epidermal Exposure (DAY 10) 50%#
	A	B	C
Control				Erythema	Oedema
72	E1	NA	E1	0	0
73	E1	NA	E1	0	0
74	E1	NA	E1	0	0
75	E1	NA	E1	0	0
76	E1	NA	E1	0	0
Experimental
77	E1	NA	E1	0	0
78	E1	NA	E1	0	0
79	E1	NA	E1	0	0
80	E2	NA	E2	0a	0
81	E1	NA	E1	0	0
82	E2	NA	E1	0a	0
83	N3	NA	E1	0	0
84	E1	NA	E1	0	0
85	E1	NA	E1	0	0
86	E1	NA	E1	0	0

 

A. 1 : 1 mixture of FCA and water for injection.

B. A 0..2% test substance concentration (Experimental); vehicle (Control).

C. 1 : 1 mixture of FCA and a 0.4% concentration (Experimental) or vehicle (Control).

#. Test Substance concentration.

a. Small scabs

 

Skin effects intradermal injections:

NA No abnormalities

E( . ) Erythema (grade)

N ( . ) Signs of necrosis (mm in diameter)

 

Challenge phase:

No skin reactions were evident after the challenge exposure in the experimental and control animals (see table).

Challenge

 

CHALLENGE
Animal No.	DAY 24		DAY 25		COMMENTS
	50%#	Vehicle	50%	Vehicle
Control
72	0	0	0	0	0
73	0	0	0	0	0
74	0	0	0	0	0
75	0	0	0	0	0
76	0	0	0	0	0
Experimental
77	0	0	0	0	not sensitised
78	0	0	0	0	not sensitised
79	0	0	0	0	not sensitised
80	0	0	0	0	not sensitised
81	0	0	0	0	not sensitised
82	0	0	0	0	not sensitised
83	0	0	0	0	not sensitised
84	0	0	0	0	not sensitised
85	0	0	0	0	not sensitised
86	0	0	0	0	not sensitised

 

# . Test substance concentration.

Interpretation of results:

GHS criteria not met

Conclusions:

HAT S2 was tested for skin sensitization properties in the albino guinea pig maximization test. No skin reactions were evident after the challenge exposure in the experimental and control animals. This result indicates a sensitisation rate of 0 %. No classification and labelling for skin sensitization is necessary according to Regulation 1272/2008/EC (CLP).

Executive summary:

HAT S2 was tested for skin sensitization properties in the albino guinea pig maximization test.

No skin reactions were evident after the challenge exposure in the experimental and control animals. No evidence was obtained that HAT S2 had caused skin hypersensitivity in the guinea pig, since no responses were observed in the experimental animals in the challenge phase. This result indicates a sensitisation rate of 0 %. Therefore, HAT S2 can be regarded as not sensitizing

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Key study:

HAT S2 was tested for skin sensitization properties in the guinea pig maximization test according to EU Method B.6. No skin reactions were evident after the challenge exposure in the experimental and control animals. No responses were observed in the experimental animals in the challenge phase, thus no evidence was obtained indicating HAT S2 to cause skin hypersensitivity in the guinea pig. This result indicated a sensitization rate of 0 %. Therefore, HAT S2 was regarded as not sensitizing.

Disregarded study:

Mastic base PATE HAT was tested for cutaneous delayed hypersensitivity in the albino Hartley guinea pig. This test was performed with a method equivalent or similar to EU-Method B.6. From the results obtained under the experimental conditions employed, the test article provoked a reaction of cutaneous sensitization in 63 % of the animals examined. Its sensitizing potential to the skin of the guinea-pig is moderate (grade III). Further investigation showed that the test sample was contaminated with solvent residues, which caused the sensitization reactions. Therefore, the results of this study were not used to derive the classification and labelling. For more details on classification and labelling see the INRS/BERPC Official Notice (2006) attached in section 13.

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 sensitisin properties, the test item does not require classification according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.