4,4'-methylenebis[N-sec-butylaniline]

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 March 2018 - 23 April 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

2017

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-methylenebis[N-sec-butylaniline]

EC Number:

226-122-6

EC Name:

4,4'-methylenebis[N-sec-butylaniline]

Cas Number:

5285-60-9

Molecular formula:

C21H30N2

IUPAC Name:

4,4'-methylenebis[N-sec-butylaniline]

Test material form:

liquid

Details on test material:

Appearance: Slight yellow liquid
Storage conditions: At room temperature protected from light

Specific details on test material used for the study:

Adjustment was made for specific gravity of the test item.

Test animals

Species:

rat

Strain:

other: Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant:yes
- Age at study initiation: approx. 10 - 12 weeks old
- Weight at study initiation: Females: 191 - 226 g.
- Housing: During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm) containing sterilized sawdust as bedding material and paper as cage-enrichment. During the study the animals were individually housed in Makrolon cages (MIII type, height 18 cm.).
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

IN-LIFE DATES: From: 26 March 2018 To: 23 April 2018

Periodic analysis of the water was performed and feed was analyzed by the supplier for nutritional components and environmental contaminants.
It is considered that there were no known contaminants in the feed or water that would interfere with the objectives of the study.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): 43 - 51
- Air changes (per hr): >= 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 18 cm^2
- % coverage: approx. 10% of the total body surface
- Type of wrap if used: a surgical gauze patch (Surgy 1D), successively covered with Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages

REMOVAL OF TEST SUBSTANCE
- Washing: tap water
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

Main study: 2 females at 2000 mg/kg bodyweight
Range finding study: 1 female at 1000 mg/kg bodyweight and 1 female at 2000 mg/kg bodyweight

Control animals:

not required

Details on study design:

RANGEFINDING STUDY:
A range finding study was performed in order to select the dose causing no mortality or significant toxicity to be used in the main study. Initially, one animal was dosed at 1000 mg/kg bodyweight. A period of at least 48 hours was allowed between the dosing of each animal. Based on the results one additional animal was dosed at 2000 mg/kg.

MAIN STUDY:
- Duration of observation period following administration: 14 days
- Frequency of observations:
- Mortality: twice daily
- Clinical observations: at periodic intervals on the day of dosing and once daily thereafter.
- Body weights: on day 1 (pre-administration), day 8 and day 15.
- Irritation: The skin reactions were assessed approximately 24, 48 and 72 hours after the removal of the dressing and test item. Adjacent areas of untreated skin of each animal served as controls.
- Necropsy of survivors performed: yes

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.

Clinical signs:

other: No clinical signs were noted in any of the animals.

Gross pathology:

No abnormalities were seen at necropsy.

Other findings:

Irritation effects: General erythema of the right flank was noted for one animal on day 4.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of an acute dermal study, performed according to OECD guideline 402 and GLP principles, the dermal LD50 value of 4,4’-methylenebis-N-sec-butylaniline in Wistar rats was determined to exceed 2000 mg/kg bodyweight. As a consequence, 4,4’-methylenebis-N-sec-butylaniline is not classified according to CLP criteria.

Executive summary:

An acute dermal study was performed according to OECD guideline 402 and GLP principles. two female rats were exposed at test item concentration of 2000 mg/kg bodyweight and observed for 14 days. No mortality occurred. General erythema of the right flank was noted for one animal on day 4 only. No unexpected changes in body weight gain occurred, no clinical signs were observed and no abnormalities were seen at necropsy. These results demonstrate that the dermal LD50 value of 4,4’-methylenebis-N-sec-butylaniline in Wistar rats exceeds 2000 mg/kg body weight. As a consequence, 4,4’-methylenebis-N-sec-butylaniline is not classified according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).