Benzenamine, N-phenyl-, styrenated

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-03-23 - 2016-04-06 (experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

OECD Guideline for the Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Issued by 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:

Benzenamine, N-phenyl-, styrenated

EC Number:

270-485-3

EC Name:

Benzenamine, N-phenyl-, styrenated

Cas Number:

68442-68-2

Molecular formula:

not applicable (UVCB substance)

IUPAC Name:

4-(1-phenylethyl)-N-[4-(1-phenylethyl)phenyl]aniline

Test material form:

liquid: viscous

Details on test material:

- Storage Conditions: 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: supplied by Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: At the start of the study the animals weighed at least 200 g, the weight variation did not exceed ±20% of the mean weight for each sex.
- Fasting period before study: no
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-Hour exposure period and in groups of five, by sex, for the remainder of the study. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK, ad libitum
- Water (e.g. ad libitum): mains tap water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: backs and flanks
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with cotton wool moistened with arachis oil BP to remove any residual test item
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg resp. 1.86 ml/kg
- Constant volume or concentration used: yes, only single dose

Duration of exposure:

24h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 / sex / dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored. Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes, this consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Remarks:

at 2000 mg/kg, there were no deaths.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

- Other observations: There were no signs of dermal irritation.

Applicant's summary and conclusion

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

The study was conducted under GLP according to OECD guideline 402 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies in documentation or any deviations. Hence, the results can be considered as reliable to assess the dermal toxicity of Benzenamine, N-phenyl-, styrenated. The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight, so, the substance does not need to be classified as acute toxic via the dermal route.

Executive summary:

The OECD 402 study was performed under GLP to assess the acute dermal toxicity of the test item in the Wistar strain rat.

A group of ten animals (five males and five females) was given a single, 24 hour and 40 minute, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. There were no signs of dermal irritation.

Body Weight. Animals showed expected gains in body weight except for three females which showed body weight loss during the first week with expected gain in body weight during the second week.

Necropsy. No abnormalities were noted at necropsy.

Conclusion: The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.