2-[tert-butyl(phenylmethyl)amino]-1-[4-hydroxy-3-(hydroxymethyl)phenyl] hydrochloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 January 2015 - 19 February 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: done under GLP and OECD method

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

440/208

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adapted 24 February 1987

GLP compliance:

yes

Remarks:

OECD Principles on Good Laboratory Practice (revised 1997, ENV/MC/CHEM(98)17); and are in accordance with, and implement, the requirements of Directives 2004/9/EC and 2004/10/EC.

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-[tert-butyl(phenylmethyl)amino]-1-[4-hydroxy-3-(hydroxymethyl)phenyl] hydrochloride

EC Number:

246-014-2

EC Name:

2-[tert-butyl(phenylmethyl)amino]-1-[4-hydroxy-3-(hydroxymethyl)phenyl] hydrochloride

Cas Number:

24085-08-3

Molecular formula:

C20H25NO3.HCl

IUPAC Name:

2-[tert-butyl(phenylmethyl)amino]-1-[4-hydroxy-3-(hydroxymethyl)phenyl] hydrochloride

Test material form:

other: Solid

Details on test material:

Off white

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK.
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: at least 200 g
- Fasting period before study: none
- Housing: suspended solid floor polypropylene cages furnished with woodflakes
- Diet: (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 10% of the total body surface area

REMOVAL OF TEST SUBSTANCE
- Washing: treated skin and surrounding hair wiped with cotton wool moistened with a suitable solvent to remove any residual test item
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg bw moistened with arachis oil (BP).

Duration of exposure:

24 hours

Doses:

2,000mg/kg bw

No. of animals per sex per dose:

5 males and 5 females at one dose level of 2,000mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 0.5hr, 1hr, 2hr, 4hr after dosing and subsequently once daily for 14 days.
- Frequency of weighing: Days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: erythema, edema and other.

Initially, two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of
2000 mg/kg body weight. Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Zero mortality

Mortality:

Male: 2,000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2,000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

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

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Body Weights:

DoseLevelmg/kg	AnimalNumberand Sex	Body Weight(g) at Day			Body Weight Change(g)During Week
		0	7	14	1	2
2000	1-0 Male	239	256	270	17	14
	3-0 Male	274	281	335	7	54
	3-1 Male	248	260	285	12	25
	3-2 Male	260	271	280	11	9
	3-3 Male	250	259	282	9	23
	2-0 Female	212	217	222	5	5
	4-1 Female	228	229	232	1	3
	4-2 Female	218	220	217	2	−3
	4-3 Female	200	203	211	3	8
	4-4 Female	212	212	222	0	10

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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.

Executive summary:

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

The test item does not meet the criteria for classification according to EU Labelling Regulations Commission Directive 2001/59/EC for Classification and Labelling of Dangerous Substances, Regulation (EC)No1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures or the Globally Harmonized System of Classification and Labelling of Chemicals.