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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: oral

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 401 (Acute Oral 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:

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.

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.

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:

other: 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 do

Gross pathology:

no data available

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

 

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).

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 401 (Acute Oral 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:

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 levels

Effect levels 1

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

Effect levels 2

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

Effect levels 3

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

Effect levels 4

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:

other: 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 do

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 2the Test item was calculated to be approx. 1977 mg/kg bw based on the the LD50 in female rat 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).