Phenol, reaction products with 1-halo-4-phenoxybenzene and 1,1’–oxybis[4-halobenzene], halogenated

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20th April 2011 to 4th May 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: A GLP compliant study performed in line with appropriate guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Physical state: off-white solid
- Storage condition of test material: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd, Oxon., UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 221-258 g (female); 208-218 g (male)
- Housing: suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent Diet ad libitum
- Water (e.g. ad libitum): mains water ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25ºC
- Humidity (%): 30-70%
- Air changes (per hr): at least fifteen per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Remarks:

(the test material was moistened with arachis oil BP for application)

Details on dermal exposure:

TEST SITE
- % coverage: approximately 10% of total body surface area
- Type of wrap if used: self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- After the 24 hour contact period, the bandage was removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil to remove and residual test substance.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for death or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: test sites were examined once daily for signs of primary irritation and scored according to the following Draize scale:

Erythema and Eschar formation
No erythema 0
Very slight erythema 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema and slight eschar formation 4

Oedema formation
No oedema 0
Very slight oedema 1
Slight oedema 2
Moderate oedema 3
Severe oedema 4

Bodyweights were recorded on days 0, 7 and 14.

Statistics:

Data evaluations included consideration of incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects. Mortality data was used to determine an estimated acute dermal lethal dose (LD50).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived to the termination of the study.

Clinical signs:

Transient red/brown staining around the snout was noted in three males during the day of dosing.

Very slight erythema and haemorrhage of dermal capillaries was noted at the test sites of one male and one female the day after dosing. No other signs of dermal irritation were noted.

Body weight:

Animals showed expected gains in bodyweight over the study period except for one female which showed no gain in bodyweight during the first week but met expected bodyweight gain during the second week.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual bodyweights and weekly bodyweight changes

Dose level (mg/kg bw)	Animal number and sex	Bodyweight (g) at day			Bodyweight change (g) during week
		0	7	14	1	2
2000	1-0 male	239	250	296	11	46
2000	1-1 male	258	287	308	29	21
2000	1-2 male	221	246	273	25	27
2000	1-3 male	225	245	272	20	27
2000	1-4 male	243	269	293	26	24
2000	2-0 female	214	218	222	4	4
2000	2-1 female	213	215	227	2	12
2000	2-2 female	218	221	231	3	10
2000	2-3 female	210	218	239	8	18
2000	2-4 female	208	208	222	0	14

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the acute dermal toxicity of the test substance gave an LD50 value of >2000 mg/kg bw.

Executive summary:

In a GLP compliant acute dermal toxicity study conducted in line with OECD Guideline 402 and EU Method B.3, the acute dermal toxicity of the test substance was investigated. The LD₅₀of the substance was determined to be >2000 mg/kg bw.