Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
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 401 (Acute Oral 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:
8-9 weeks of age.
Housed in single sex groups of five rats to a cage with free access to drinking water and food throughout the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The rats were fasted vernight, weighed and given a single dose using a ball pointed cannula and syringe. Approx. three hours after dosing on Day 1 the animals were allowed food again ad libitum.
Doses:
females: 1020, 1430, 2000 and 2800 mg/kg bw single dose
males: 2000, 2800, 3920 and 5490 mg/kg bw single dose
No. of animals per sex per dose:
five
Control animals:
no
Details on study design:
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 7 and day 14 bw were recorded, and changes in bw calculated. The study was terminated on day 14. One animal was retained until day 28 to ascertain if it recovered completely from effects of treatment that persisted to day 14.
Statistics:
the 14 day LD50, 95% confidence interval and the dose-mortality slope were calculated using a method based on probit analysis.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
1 977 mg/kg bw
Based on:
test mat.
95% CL:
1 676 - 2 236
Remarks on result:
other: >= 1020 mg/kg bw 5/5 animals with toxic signs
Sex:
female
Dose descriptor:
LD50
Effect level:
732 mg/kg bw
Based on:
other: 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether
Sex:
male
Dose descriptor:
LD50
Effect level:
4 359 mg/kg bw
Based on:
test mat.
95% CL:
3 561 - 5 779
Remarks on result:
other: >= 2000 mg/kg bw 5/5 animals with toxic signs
Sex:
male
Dose descriptor:
LD50
Effect level:
1 613 mg/kg bw
Based on:
other: 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether
Mortality:
Mortalities occurred on days 2, 3 and in one case on day 7.
Clinical signs:
Lethargy, salivation, abasia/ataxia and hunched back were observed among rats at all dose-levels within three hours of dosing. Other common reactions were:
- diarrhoea among all rats from dose levels from day 2
- unkepmpt appearnce among rats from all dose-levels and first apparent at intervals from within 1.5 hours after dosing to day 2
- lachrymation among rats terated at 1430 mg/kg and above from within 6 hours of dosing
Cases of twitching. prostration, hypothermia, coma and cyanosis were almost exclusively limited to rats that succumbed to the test material.
The recovery of rats surviving treatment was advanced by day 4 and complete by day 12. Diarrhoea, hunched back and unkempt apperance persisted to day 8 and the unkempt appearance of one animal was unresolved until day 27.
Body weight:
All surviving rats had gained weight relative to their Day 1 bodyweights by the end of the observation period.
Gross pathology:
no data available

Any other information on results incl. tables

Table 1: Acute oral toxicity of FOX-O-POL VD 280 S

 Sex dose (mg/kg bw) Toxicological results  Onset and duration of signs  Onset of mortality
 male 2000 0 / 5/ 5  3h - 7d --- 
  2800 0 / 5 / 5 3h - 7d --- 
  3920 2 / 5 / 5 0.5h - 11d  1d-7d 
  5490 4/ 5 / 5  0.5h - 27d 2d-3d
 female 1020  0 / 5 / 5   1h - 4d --- 
  1430 0 / 5 / 5  0.5h - 12d  --- 
  2000 3 / 5 / 5 3h - 7d  3d 
  2800  5 / 5 / 5 3h - --- 2d - 3d 

Toxicological results:

number of dead animals / number of animals with signs after cessation of exposure / number of animals exposed

Table 2: Acute oral toxicity of 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether (= N 8424-2)calculated from the acute oral study of FOX-O-POL VD 280 S (commercial product)

 

Sex

 

Dose [mg/kg]

Toxicological result 

Onset and duration of diarrhea

 Onset of mortality

males

2031

4 / 2 / 5

2d – 9d

2d (2 males)

3d (2 males)

males

1450

2 / 3 / 5

2d – 9d

2d (1 male)

7d (1 male)

males

1036

0 / 5 / 5

2d – 4d

 

females

1036

5 / 0 / 5

 

2d (3 females)

3d (2 females)

 males

740

0 / 5 / 5

 2d – 4d

--- 

females

740

3 / 4 / 5

2d - 4d

---3d 

females

529

0 / 5 / 5

2d - 4d

--- 

females

377

0 / 1 / 5

2d - 3d

---

 

Toxicological results:

number of dead animals / number of animals with diarrhoe / number of animals exposed

 


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 approx. 732 mg/kg bw based on the the LD50 = 1977 mg/kg (female rat) of the commercial product which was determined according to OECD TG 401 (Gardner, 1989). Groups of five male and five female rats were dosed with the undiluted test material by gavage. Rats of all dose levels showed unkempt appearance first apparent at intervals from within 1.5 hours after dosing to day 2 and diarrhoe from day 2. From the mortality data the LD50 -values were calculated to be 4359 mg/kg (male) and 1977 mg/kg (female).