Benzenamine, 3,3'-[[1,1'-biphenyl]-4,4'-diylbis(oxy)]bis-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was designed to meet the requirements of OECD Guideline for Testing of Chemicals No. 402 "Acute Dermal Toxicity", Adopeted: 24 February 1987, and EU Methods for the determination of toxicity, Annex to Directive 92/69/EEC, Part B, Method B.3 Acute toxicity (dermal) and was performed without any deviation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-{[4'-(3-aminophenoxy)-[1,1'-biphenyl]-4-yl]oxy}aniline

EC Number:

700-102-1

Cas Number:

105112-76-3

Molecular formula:

C24H20N2O2

IUPAC Name:

3-{[4'-(3-aminophenoxy)-[1,1'-biphenyl]-4-yl]oxy}aniline

Details on test material:

- Name of test material (as cited in study report): 3,3-(4,4-biphenylenedioxy)dianiline
- Substance type: Raw material for polymer
- Physical state: Off white powder
- Analytical purity: >99 %
- Lot/batch No.: 20070501
- Expiration date of the lot/batch: 30 April 2008
- Storage condition of test material: Room temperature
- Other: date of receipt 28 August 2007, supplied by Mitsui Chemicals Inc.

Test animals

Species:

rat

Strain:

other: Crl:CD 'SD'

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, England
- Age at study initiation:
- Weight at study initiation: 246 to 381 g
- Fasting period before study:
- Housing: Animals were housed individually from Day 1 until Day 7 when they were returned to cages with five rats of the same sex. Cages were solid bottomed polycarbonate cages with stainless steel mesh lids. Each cage contained a quantity of autoclaved wood flake bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals.
- Diet (e.g. ad libitum): free access to a standard rodend diet (Rat and Mouse No. 1 Maintenance Diet)
- Water (e.g. ad libitum): free access to potable water from the public supply via polycarbonate bottles fitted with sipper tubes
- Acclimation period: 9 days prior to the begin of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23
- Humidity (%): 40 to 70
- Air changes (per hr): not available
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: 1 % w/v methylcellulose

Details on dermal exposure:

TEST SITE
- Area of exposure: 50 mm x 50 mm
- % coverage: 100
- Type of wrap if used:


REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water (30-40 °C)
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.99 mL/kg bodyweight
- Concentration (if solution): 666.7 mg/mL



VEHICLE
- Concentration (if solution): 1 % w/v aqueous methylcellulose

Duration of exposure:

24 hours

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

Five males and five females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsquent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only).
- Necropsy of survivors performed: yes. All animals were subjected to a macroscopic examination which consisted of opening the cranial, thoraic and abdominal cavities.
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths and no systemic response to treatment in any animal.

Clinical signs:

other: Very slight to well defined erythema was seen in three males and one female with very slight oedema observed in one male. These reactions had resolved by Day 5. In addition, scabbing confined to a small area of the dose site was noted for one male and one

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Any other information on results incl. tables

Table 1: Dermal reactions

Dose (mg/kg)	Sex	Animal no.	E=Erythema O=Oedema	Day
				2	3	4	5-6	7-15
2000	Male	B1	E	2	0	0	0	0
2000	Male		O	1	0	0	0	0
2000	Male	B2	E	0	0	0	0	0
2000	Male		O	0	0	0	0	0
2000	Male	B3	E	2	1	0	0	0
2000	Male		O	0	0	0e	0e	0
2000	Male	B4	E	2	1	0	0	0
2000	Male		O	0	0	0	0	0
2000	Male	B5	E	0	0	0	0	0
2000	Male		O	0	0	0	0	0
2000	Female	B6	E	0	0	0	0	0
2000	Female		O	0	0	0	0	0
2000	Female	B7	E	0	0	0	0	0
2000	Female		O	0	0	0	0	0
2000	Female	B8	E	0	0	0	0	0
2000	Female		O	0	0	0	0	0
2000	Female	B9	E	0	0	0	0	0
2000	Female		O	0	0	0	0	0
2000	Female	B10	E	1	1	1	0	0
2000	Female		O	0	0	0e	0e	0

e: Eschar/Scabbing (several small scabs on dose site)

Table 2: Individual bodyweights (g)

Dose (mg/kg)	Sex	Animal Number	Bodyweight (g) at Day
			1*	8	15
2000	Male	B1	381	408	463
2000	Male	B2	348	382	422
2000	Male	B3	364	383	443
2000	Male	B4	362	389	436
2000	Male	B5	374	410	454
2000	Female	B6	273	279	308
2000	Female	B7	254	254	272
2000	Female	B8	259	259	282
2000	Female	B9	246	254	281
2000	Female	B10	253	272	302

* prior to dosing

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information

Conclusions:

The acute median lethal dermal dose (LD50) to rats was demonstrated to be greater than 2000 mg/kg bodyweight.

Executive summary:

The acute dermal toxicity of 3,3-(4,4-biphenylenedioxy)dianiline (a raw material for polymer), to the rat, was studied according to OECD Guideline for Testing of Chemicals No. 402 "Acute Dermal Toxicity".

A group of ten Crl:CD rats (five males and five females) received a single topical application of the test substance, formulated at a maximum practical concentration in 1% w/v aqueous methylcellulose, at a dosage of 2000 mg/kg body weight, for 24 hours. All animals were killed as scheduled and examined macroscopically on Day 15, the end of the observation period. There were no deaths and no systemic response to treatment in any animal. Very slight to well defined erythema was seen in three males and one female with very slight oedema observed in one male. These reactions had resolved by Day 5. In addition, scabbing confined to a small area of the dose site was noted for one male and one female from Day 4 resolving completely by Day 7. One female made no body weight gain and three further females all made low bodyweight gains on Day 8, but all these bodyweight changes had recovered by Day15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were noted in any animal at the macroscopic examination at the study termination on Day 15. The acute median lethal dermal dose (LD50) to rats of 3,3'-[biphenyl-4,4'-diylbis(oxy)]dianiline was demonstrated to be greater than 2000 mg/kg body weight