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Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether (= N 8424-2) obtained from a solvent-based manufacturing process is not isolated throughout the process. The solvent-free N 8424-2 is a solid which would significantly complicate the manufacturing process. Beyond that N 8424-2 is not marketed as such. At the end of the process a blend of 53 weight-% N 8424-2 and 47 weight-% of a corresponding PO adduct of the alkylene oxide reactive solvent are dissolved in Tris(chloroisopropyl) phosphate (TCPP) to facilitate handling of the substance by downstream users and to improve the flame-retardant action. 70% of the blend (N 8424-2 and corresponding PO adduct of the alkylene oxide reactive solvent) and 30% TCPP represent the commercial product for which a base set of toxicological information was already available. Further, analysis of the toxicity profile of the solvents in the commercial product demonstrates that the available studies with the commercial product, which contains 37% N 8424-2 (0.7 x 53%), is sufficient for an adequate hazard characterisation of N 8424-2.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Already existing data of good quality deriving from a test for skin sensitisation as described in EU B.6/OECD TG 406.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Porcellus Animal Breeding Ltd.
- Age at the time of receipt: 5 to 9 weeks
- Body weight at time of receipt:
- Housing: Initially in single sex groups of ten animals and after acclimatisation period they were re-allocated to cages accommodating two or three animals
- Acclimation period: two weeks

Route:
intradermal
Vehicle:
corn oil
Concentration / amount:
intradermal induction: 0.1% (m/v)
topical induction: undiluted
for first challenge: undiluted
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
intradermal induction: 0.1% (m/v)
topical induction: undiluted
for first challenge: undiluted
No. of animals per dose:
10/sex
Details on study design:
RANGE FINDING TESTS:
- for intradermal induction (% (m/v) in corn oil): concentrations of 0.05, 0.1, 0.5 and 1 % were tested
Response on day after administration:
grade 1 (0.05%, 2/2 males and 2/2 females)
grade 2 (0.1%, 1/2 males)
grade 1 (0.1%, 1/2 males, 2/2 females)
grade 2 (0.5%, 2/2 males and 2/2 females)
grade 2 (1 %, 2/2 males and 2/2 females)
- for topical induction (% (m/m) in vaseline): concentrations of 0, 10, 25, 50, 75 and 100 % were tested
Response on day after administration:
grade 0 (100, 75, 50, 25 and 10% each 2/2 males and 2/2 females)

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2; first induction intradermal, second induction topical 7 days later
- Exposure period: 48 h occusive in the topical induction
- Test groups: 10 animals
- Control group: 5 animals
- Concentrations: no data available for intradermal induction, 100 % for topical induction

B. CHALLENGE EXPOSURE
- No. of exposures: 1, first challenge topical
- Day(s) of challenge: first challenge started 3 weeks after intradermal induction
- Exposure period: 24 hours occlusive
- Concentrations: 100 %
- Evaluation (hr after challenge): 48 and 72 hours after start of challenge

Challenge controls:
yes: control group animals were treated in challenge experiments according to test group animals
Positive control substance(s):
not specified
Positive control results:
no data
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no data.
Reading:
1st reading
Hours after challenge:
48
Group:
other: test group (females)
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: test group (females). Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
72
Group:
other: test group (females)
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: other: test group (females). Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.
Reading:
1st reading
Hours after challenge:
48
Group:
other: test group (males)
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: test group (males). Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
72
Group:
other: test group: (males)
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: other: test group: (males). Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.
Conclusions:
not sensitising
Executive summary:

In the Guinea Pig Maximization Test (GPMT) on 15 female/male guinea pigs (10 for the test item group, 5 control animals) according to OECD TG 406 the test item was shown to exhibit no skin sensitization potential. 0.1% test item in corn oil and the undiluted test material was used for intradermal induction and topical induction/challenge. None of the 20 test animals showed any positive response either 24 or 48 hours after removal of the challenge patches.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether (= N 8424-2) obtained from a solvent-based manufacturing process is not isolated throughout the process. The solvent-free N 8424-2 is a solid which would significantly complicate the manufacturing process. Beyond that N 8424-2 is not marketed as such. At the end of the process a blend of 53 weight-% N 8424-2 and 47 weight-% of a corresponding PO adduct of the alkylene oxide reactive solvent are dissolved in Tris(chloroisopropyl) phosphate (TCPP) to facilitate handling of the substance by downstream users and to improve the flame-retardant action. 70% of the blend (N 8424-2 and corresponding PO adduct of the alkylene oxide reactive solvent) and 30% TCPP represent the commercial product for which a base set of toxicological information was already available. Further, analysis of the toxicity profile of the solvents in the commercial product demonstrates that the available studies with the commercial product, which contains 37% N 8424-2 (0.7 x 53%), is sufficient for an adequate hazard characterisation of N 8424-2.

As displayed in table 1 the comparison of the data available for the commerial product and for some constituents showed that the commercial product is suitable as surrogate for  2,2',6,6'-Tetrabromo-4,4'-iso-propylidene-diphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether (= N 8424-2).

Table 1 Base set of toxicological data with regard to the commercial product as surrogate for 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether (= N 8424-2)

Target Substance

Acute oral

[mg/kg]

Acute dermal

[mg/kg]

Local irritation

Skin sensitization

Ames-Test

 

 

 

 

 

 

Commercial Product

(mixture of A + B +C)

LD50: 1977

 

 

C & L: Cat 4

LD50: > 2000

 

 

C & L: no category

Skin: no irritation

Eye: slight irritation

 

C & L: no category

Negative

 

 

C & L: no category

Negative

A: a corresponding PO adduct of the alkylene oxide reactive solvent

LD50: > 2000

 

 

C & L: no category

LD50: > 2000

 

 

C & L: no category

Skin: no irritation

Eye: no irritation

 

C & L: no category

Negative

 

 

C & L: no category

Negative

B: Tris(chloroisopropyl) phosphate

500 > LD50< 2000

 

 

C & L: Cat 4

LD50: > 2000

 

 

C & L: no category

Skin: slight irritation

Eye: no irritation

 

C & L: no category

Negative

 

 

C & L: no category

Negative

C: 2,2',6,6'-Tetrabromo-

4,4'-iso-propylidene-diphenol, oligomeric reaction products with Propylene oxide and

n-butyl glycidyl ether (= N 8424-2)

No data

 

 

 

 

 

 

C & L: Cat 4

No data

 

 

 

 

 

 

C & L: no category

No data

 

 

 

 

 

 

C & L: no category

No data

 

 

 

 

 

 

C & L: no category

No data

 

 

 

 

No evidence for induction of point mutation in bacteria

In particular the comparison of the acute oral toxicity study with the results of the dose range finding study which was conducted before starting the subacute oral study proves that the toxicity of the commercial product well reflects the toxicity of N 8424 -2 (for details see IUCLID Chapter 7.2 Endpoint Summary "Acute Toxicity") because 2,2’,6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether (= N 8424-2) as constituent of the commercial product behaves like the dissolved parent compound.

In the Guinea Pig Maximization Test (GPMT) on 15 female/male guinea pigs (10 for the test item group, 5 control animals) according to OECD TG 406 the commercial product was shown to exhibit no skin sensitization potential. 0.1% test item in corn oil and the undiluted test material was used for intradermal induction and topical induction/challenge. None of the 20 test animals showed any positive response either 24 or 48 hours after removal of the challenge patches.


Justification for selection of skin sensitisation endpoint:
only one study available

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitisation

Based on the available study result (non-sensitizing) a classification according to EU-Directive 67/548/EEC, Annex VI and according to Regulation (EC) No 1272/2008, Annex I is not warranted.

Respiratory sensitisation:

no data available