Reaction mass of 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene] and 1,3-dibromo-2-(2,3-dibromo-2-methylpropoxy)-5-{2-[3,5-dibromo-4-(2,3,3-tribromo-2-methylpropoxy)phenyl]propan-2-yl}benzene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 Dec 2009 - 09 Feb 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

adopted Oct 2008

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom, UK

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene]

EC Number:

306-832-3

EC Name:

1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene]

Cas Number:

97416-84-7

Molecular formula:

C23H24Br8O2

IUPAC Name:

1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene]

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

other: Wistar (HsdRccHan:WIST)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Bicester, UK
- Age at study initiation: 8 - 12 weeks old
- Weight at study initiation: 156 - 205 g
- Fasting period before study: overnight until 3 - 4 hours after dosing
- Housing: animals were individually housed in suspended solid-floor polypropylene cages furnished with woodflakes and with enviromental enrichment items
- Diet: 2014 Teklad Global Rodent diet (Harlan Teklad, Bicester, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 17.5, 55 and 200 mg/mL
- Justification for choice of vehicle: arachis oil BP was used as the test substance did not dissolve in water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): the test material was formulated within 2 hours of administration. No analysis was conducted to determine the homogeneity, concentration or stability of the formulation.

Doses:

175, 550 and 2000 mg/kg bw

No. of animals per sex per dose:

5 females per dose group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for mortality and clinical signs 0.5, 1, 2 and 4 hours after dosing, and thereafter once daily for the rest of the observation period; the body weight was recorded on Day 0 (prior to dosing), 7 and 14
- Necropsy of survivors performed: yes
-Other: No information was available regarding the toxicity of the test substance. Therefore, the default values for LD50 and sigma were entered into AOT425 Statistical Program. The program gave a recommended dose progression of 2000, 550, 175, 55, 17.5, 5.5 and 1.75 mg/kg bw. The first animal was dosed with 175 mg/kg bw, the second with 550 mg/kg bw and animal 3 - 5 were dosed with 2000 mg/kg bw. The animals were treated sequentially, with at least 48 hours between each one to confirm the outcome of the previously dosed animal.

Statistics:

The mortality data was used by the statistical program to calculate an oral LD50 (the maximum likelihood method).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Hunched posture was observed from 2 hours after dosing on the day of dosing only in 2/3 rats administered 2000 mg/kg bw. No other clinical signs were observed during the 14-day observation period.

Gross pathology:

Necropsy did not reveal substance-related findings.

Any other information on results incl. tables

Table 1. Mortality and clinical signs

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Females
175	0/0/1	---	---	0
550	0/0/1	--	--	0
2000	0/2/3	2 h – Day 1	--	0
LD50 = 2000 mg/kg bw

* first number = number of dead animals

 second number = number of animals with clinical signs

 third number = number of animals used

 

Applicant's summary and conclusion

Interpretation of results:

other: not classified