5-[(2-hydroxyethyl)amino]-o-cresol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 25 October 2007 to 04 December 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24th February 1987

Deviations:

yes

Remarks:

Relative humidity sometimes outside of the target ranges. This minor deviation was not considered to have compromised the validity or integrity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

31st July 1992

Deviations:

yes

Remarks:

Relative humidity sometimes outside of the target ranges. This minor deviation was not considered to have compromised the validity or integrity of the study.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5-[(2-hydroxyethyl)amino]-o-cresol

EC Number:

259-583-7

EC Name:

5-[(2-hydroxyethyl)amino]-o-cresol

Cas Number:

55302-96-0

Molecular formula:

C9H13NO2

IUPAC Name:

5-[(2-hydroxyethyl)amino]-2-methylphenol

Test material form:

solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Analytical purity: 99.8%
- Purity test date: 15 October 2007
- Lot/batch No.: 0135289
- Expiration date of the lot/batch: February 2008
- Description: very light beige to beige fine powder
- Trade name: IMEXINE OAG

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at +4°C, protected from light and from humidity and under inert gas.
- Stability under test conditions: Fresh test item dosage forms were prepared extemporaneously under inert atmosphere on the morning of the administration and were kept under inert gas. Test item dosage forms were used within 30 minutes after preparation.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Rj: SD (IOPS Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Weight at study initiation (mean ± standard deviation): 308 ± 9 g for the males and 208 ± 5 g for the females
- Fasting period before study:
- Housing: animals were housed in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals of the same sex during the acclimation period and one animal during the treatment period. Each cage contained autoclaved sawdust (SICSA, Alfortville, France). Sawdust was analyzed by the supplier for composition and contaminant levels.
- Diet: ad libitum to SsniffR/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany). Each batch of food is analyzed by the supplier for composition and contaminant levels (diet formula provided in the study report).
- Water: ad libitum to drinking water filtered by a FG Millipore membrane (0.22 micron). Bacteriological and chemical analyses of water are performed regularly by external laboratories, including the detection of possible contaminants (pesticides, heavy metals and nitrosamines).
No contaminants were known to have been present in the diet, drinking water or bedding material at levels which may be expected to have interfered with or prejudiced the outcome of the study.
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 30 to 70
- Air changes (per hr): 12 cycles of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment are verified and calibrated at regular intervals.

IN-LIFE DATES: From beginning of November 2007: To: 27 November 2007

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Remarks:

purified water was used to moisten the test item

Details on dermal exposure:

TEST SITE
- Preparation of the animals: On the day before treatment, the dorsal area of each animal was clipped (i.e. approximately 5 cm x 7 cm for males and 5 cm x 6 cm for females) using an electric clipper. Only animals with healthy intact skin were used for the study
- Area of exposure: 10% of the total body surface of the animals, calculated according to Meeh's formula (i.e. approximately 5 cm x 7 cm for the males and 5 cm x 6 cm for the females)
- % coverage: 10% of the total body surface of the animals
- Type of wrap if used: The test item and the gauze pad were held in contact with the skin for 24 hours by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage. This dressing prevented ingestion of the test item by the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): On removal of the dressing, any residual test item was removed using a dry cotton pad.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A single dose of 2000 mg/kg of the test item in its original form was placed on a hydrophilic gauze pad (pre-moistened with 2 mL of purified water) and then applied to an area of the skin representing approximately 10% of the total body surface of the animals. The dose applied to each animal was adjusted according to the body weight determined on the day of treatment.

Duration of exposure:

24h

Doses:

2000 mg/kg

No. of animals per sex per dose:

one group of 10 animals (5 males and 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test item (45 mn, 2h -4h), for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15. Type, time of onset and duration of clinical signs were recorded for each animal individually. From day 2, any local cutaneous reaction was recorded.
Animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15. The body weight gain of the treated animals was compared to that of testing laboratory control animals with a similar initial body weight.
- Sacrifice: On day 15, all animals were sacrificed by carbon dioxide asphyxiation.
- Necropsy of survivors performed: yes; macroscopic examination as soon as possible after death. Macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed. No organ samples were taken for preservation of tissues.

Statistics:

Not applicable.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality, no clinical signs and no macroscopic findings

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed during the study. An orange coloration of the skin was observed in all animals from day 2 until day 6 (1/5 males), day 10 (another male) or day 15 (3/5 males and 5/5 females). An erythema was noted in 2/10 animals on day 2;

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Other findings:

None.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the dermal LD50 of the test item is > 2000 mg/kg body weight without mortality, clinical signs or macroscopic findings. Thus, the test item is not classified as hazardous for acute dermal toxicity according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.

Executive summary:

This GLP-compliant study was performed to assess the acute dermal toxicity of 2-Methyl-5-hydroxyethylaminophenol, according to OECD 402 (dated 24th February 1987) and EC 92/69/EEC, B.3 (dated 31st July 1992) guidelines.

Material and methods

The test item was applied in its original form at the dose-level of 2000 mg/kg to the skin of one group of 10 Sprague-Dawley rats (5 males and 5 females). The test site was then covered by a semi-occlusive dressing for 24 hours.

The animals were observed for clinical signs, mortality and body weight gain for a period of 14 days following the single application of the test item. All animals were subjected to necropsy.

Results

No deaths and no clinical signs were observed during the study.

An orange coloration of the skin was observed in all animals from day 2 until day 6 (1/5 males), day 10 (another male) or day 15 (3/5 males and 5/5 females). An erythema was noted in 2/10 animals on day 2; it persisted in one of them until day 6. A dryness of the skin was noted in 1/10 animals from day 3 until day 6. Crusts were observed in 3/10 animals from day 7 until day 10 (2/3 animals) or day 15 (1/3 animals).

When compared to the testing laboratory historical control animals, a slightly lower body weight gain was noted in 1/5 males and 1/5 females between day 1 and day 8; it returned to normal thereafter. The body weight gain of the other animals was not affected by treatment with the test item.

No apparent abnormalities were observed at necropsy in any animal.

Conclusion

Under the experimental conditions of this study, the dermal LD50 of the test item is > 2000 mg/kg body weight without mortality, clinical signs or macroscopic findings. Thus, the test item is not classified as hazardous for acute dermal toxicity according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.