Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
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.
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Commercial supplier (Froxfield Farms (U.K.) Ltd)
- Age at study initiation: 3 - 5 months
- Body weight at study initiation: between 3.0 anfd 4.0 kg
- sex: male/female
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral untreated skin area of test animals served as control
Amount / concentration applied:
Amount: 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
0.5, 24, 48, 72 hours  and 7 days after patch removed
Number of animals:
3 per sex
Details on study design:
TEST SITE
- Area of exposure: approx. 6 cm²
- Type of wrap if used: covered with gauze and held in place by a semi-occlusive elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: treated skin area carefully washed with water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal: 1-6
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal: 1-6
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Other effects:
No data available.
Conclusions:




Classification: not irritating
Executive summary:

In the 4 hour rabbit skin irritancy test according to OECD TG 404 the test material caused no dermal irritation reactions.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
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 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Commercial supplier (Froxfield Farms (U.K.) Ltd)
- Age at study initiation: 3 - 5 months
- Body weight at study initiation: between 3.0 anfd 4.0 kg
- sex: male/female
Vehicle:
unchanged (no vehicle)
Controls:
other: The other eye, which remained untreated, served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
The lids were gently held together for about one second in order to prevent loss of the test compound.
Observation period (in vivo):
1, 4, 24, 48, 72 hours and 7 days after instillation.
Number of animals or in vitro replicates:
3/sex
Irritation parameter:
cornea opacity score
Basis:
animal: 1-6
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal: 1-6
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
other: conjunctivae (redness)
Basis:
animal: 1-6
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: 1h and 4 h: score 1 and slight ocular discharge
Irritation parameter:
chemosis score
Basis:
animal: 1-6
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Executive summary:

In the rabbit eye irritancy test according to OECD TG 405 the test material caused in 6/6 animals minor conjunctival irritation reactions one hour and four hours after instillation but were reversible within 24 hours after treatment.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

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.

Skin irritation:

In the 4 hour rabbit skin irritancy test according to OECD TG 404 the test material caused no dermal irritation reactions.

Eye irritation:

In the rabbit eye irritancy test according to OECD TG 405 the test material caused in 6/6 animals minor conjunctival irritation reactions one hour and four hours after instillation but were reversible within 24 hours after treatment.

Respiratory Irritation:

No data available.


Justification for selection of skin irritation / corrosion endpoint:
only one study available

Justification for selection of eye irritation endpoint:
only one study available

Justification for classification or non-classification

Skin irritation:

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

Eye irritation:

Based on the available study result (slightly irritant) 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 Irritation:

No data available.