2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

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.

Justification for type of 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.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: dermal

Type of 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.

Justification for type of 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.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

no pathology reported

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS:
- Source: charles River U.K. Ltd.
- Age: 8 to 9 weeks
- Weight at study initiation: > 200 g (male); > 130 g (female)
- Group size: individually housed druring exposure;for the post exposure period the animals returned to group housing

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

ADMINISTRATION:
- Area covered: approx. 6 x 8 cm
- Occlusion: lint dressing covered with waterproof adhesive tape
- Total volume applied: not specified
- Removal of test substance: the dressings were removed, the skin washed with warm dilute detergent solution, dried, and the animals returned to group housing.

Duration of exposure:

24 hours

Doses:

single dose: 2000 mg/kg b.w.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

EXAMINATIONS:
A careful clinical examination was made three times daily for the first three days and once daily thereafter for the remainder of the 14 day observation period. The initial (day 1), day 7 and day 14 bodyweights were recorded, and changes in bodyweight calculated. The study was terminated on day 14.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: without any effect

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 740 mg/kg bw

Based on:

other: approx. 37% 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether

Mortality:

There were no deaths during the study.

Clinical signs:

other: No signs of systemic toxicity.

Gross pathology:

No data available

Other findings:

Sites of application showed no dermal changes or other irritation reaction.

As displayed in table 1 the comparison of the toxicilogical 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

Executive summary:

The LD50 for 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether was thus calculated to be > 740 mg/kg bw based on the the LD50 > 2000 mg/kg of the commercial product which was determined according to OECD TG 402 (Gardner, 1989). 2000 mg/kg of the commercial product was applied occlusive on 5 male and 5 female rats for 24 hours. No mortalities, no clinical signs, no effects on weight development and local irritaion were observed during the 14 -days observation period.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

no pathology reported

GLP compliance:

not specified

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether

EC Number:

926-564-6

Cas Number:

1179964-22-7

Molecular formula:

not applicable

IUPAC Name:

2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS:
- Source: charles River U.K. Ltd.
- Age: 8 to 9 weeks
- Weight at study initiation: > 200 g (male); > 130 g (female)
- Group size: individually housed druring exposure;for the post exposure period the animals returned to group housing

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

ADMINISTRATION:
- Area covered: approx. 6 x 8 cm
- Occlusion: lint dressing covered with waterproof adhesive tape
- Total volume applied: not specified
- Removal of test substance: the dressings were removed, the skin washed with warm dilute detergent solution, dried, and the animals returned to group housing.

Duration of exposure:

24 hours

Doses:

single dose: 2000 mg/kg b.w.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

EXAMINATIONS:
A careful clinical examination was made three times daily for the first three days and once daily thereafter for the remainder of the 14 day observation period. The initial (day 1), day 7 and day 14 bodyweights were recorded, and changes in bodyweight calculated. The study was terminated on day 14.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: without any effect

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 740 mg/kg bw

Based on:

other: approx. 37% 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether

Mortality:

There were no deaths during the study.

Clinical signs:

other: No signs of systemic toxicity.

Gross pathology:

No data available

Other findings:

Sites of application showed no dermal changes or other irritation reaction.

Any other information on results incl. tables

As displayed in table 1 the comparison of the toxicilogical 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

Applicant's summary and conclusion

Executive summary:

2000 mg/kg of the Test Item was applied occlusive on 5 male and 5 female rats for 24 hours. No mortalities, no clinical signs, no effects on weight development and local irritaion were observed during the 14 -days observation period. The LD50 was determined to be > 2000 mg/kg bw.