Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
no pathology reported
GLP compliance:
not specified
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals 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 levelsopen allclose all
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:
No signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight over the study period.
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:

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.