2-methyl-1-phenylpropan-2-ol

Endpoint summary

Description of key information

Acute oral toxicity: LD50 (male/female) = 1280 mg/kg bw with 95% confidence limits of 934 -1770 mg/kg bw (equivalent or similar to OECD 401)

Read-across to PEA (CAS No. 60 -12 -8) - Acute inhalation toxicity: LC50 (male/female) = > 4.63 mg/L (nominal concentration) (Equivalent or similar to OECD 403/GLP)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Fasting period before study: 18 hr prior to treatment
- Diet: Food was replaced in cages as soon as animals received their respective doses
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

No data

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

All animals were maintained under close observation for recording toxic signs and time of death. Such observation was continued until animals appeared normal and showed weight gain. The usual observation period was 2 weeks.

Statistics:

The LD50's, slope function, and their confidence limits were recorded. LD50'S were computed by the method of Litchfield & Wilcoxon.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 280 mg/kg bw

95% CL:

> 934 - < 1 770

Mortality:

Death within 1 hour to 3 days

Clinical signs:

other: Depression within 10 min, coma within 1 hour.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 for acute oral toxicity of Dimethyl benzyl carbinol in Osborne-Mendel rats is 1280mg/kg bw with 95% confidence limits of 934-1770 mg/kg bw.

Executive summary:

In an acute oral toxicity study (Jenner, 1964), Osborne Mendel rats (5/dose/sex) were given dimethyl benzyl carbinol and observed for 14 days.

Deaths occurred between 1 hr and 3 days. Depression was evident within 10 mins and coma within 1 hour.

The LD50 (male/female) is 1280 mg/kg bw with 95% confidence limits of 934 -1770 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Doses:

0.99, 1.48, 2.22, 3.33 and 5.00 g/kg

No. of animals per sex per dose:

10

Control animals:

no

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1.35 mg/kg bw

Based on:

test mat.

95% CL:

> 1.02 - < 1.68

Mortality:

see Distribution of Mortality.

Clinical signs:

other: 0.99 g/kg: none; 1.48, 2.22 g/kg: depression, negative righting reflex; 3.33 g/kg: depression, piloerection, negative righting reflex; 5.00 g/kg: death within 3 hours.

Distribution of Mortality

		Observation Day
Dose g/kg	Deaths/No. of animals	1	2	3	4	5	6	7	8	9	10	11	12	13	14
0.99	1/10	1	0	0	0	0	0	0	0	0	0	0	0	0	0
1.48	6/10	4	2	0	0	0	0	0	0	0	0	0	0	0	0
2.22	9/10	5	2	0	0	0	0	0	0	0	1	0	0	1	0
3.33	10/10	10	0	0	0	0	0	0	0	0	0	0	0	0	0
5.00	10/10	10	0	0	0	0	0	0	0	0	0	0	0	0	0

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 for acute oral toxicity of Dimethyl benzyl carbinol in rats is 1350mg/kg bw with 95% confidence limits of 1020-1680 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 280 mg/kg bw

Quality of whole database:

There are 2 studies available (equivalent or similar to OECD 401) and both have a Klimisch score of 2. The quallity of the database is medium.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please see the read-across justification.

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.63 mg/L air (nominal)

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.38 mg/L air (analytical)

Exp. duration:

4 h

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute inhalation study in Sprague-Dawley rats, the LC50 fro PEA was >4.63 mg/L (nominal concentration).

Executive summary:

In an acute inhalation toxicity study (5692-07/14), a group of young adult Sprague Dawley strain rats (5/sex) were exposed to a test atmosphere of PEA for 4 hours (whole body) at a target concentration of 4.63 mg/L. Animals were then observed for 14 days.

LC50 male/female = > 4.63 mg/L (nominal concentration)

The mean achieved concentration was 1.38 ±0.19 mg/L (MMAD: 1.08 µm; GSD: 0.05). There were no deaths and no clinical changes of possible toxicological importance. Although small body weight losses occurred on the days following exposure the losses were generally made good by day 7 of the study. Focal grey-green areas observed grossly on the lungs were characterized histologically by aggregates of mononuclear leucocytes mainly about blood vassels· and air passages and occasionally extending to alveolar walls., some interstitial fibrosis and infiltration by foamy macrophages. These lesions were considered to be spontaneous and caused as a result of mild infection with murine respiratory mycoplasmosis. Pulmonary edema and mild congestion revealed in 3 rats could be attributed to euthanasia.

This acute inhalation toxicity test in rats is acceptable and satisfies the guideline requirement for an OECD 403 study.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 10th 1980 to 14th July 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source of test material: Research. Institute for Fragrance Materials, Englewood Cliffs, NJ.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories Ltd., Wilmington, Mass, USA.
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 175 to 225 g
- Fasting period before study:
- Housing: Housed individually in stainless steel, wire meshed-bottom cages
- Diet: Certified Purina Laboratory Rat Chow ad libitum
- Water: tap water ad libitum

ENVIRONMENTAL CONDITIONS (in inhalation chamber room)
- Temperature (°C): 22.3±0.29°C
- Humidity (%): 38.5±0.58%

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

1.08 µm

Geometric standard deviation (GSD):

0.05

Details on inhalation exposure:

Inhalation Exposure Equipment
A 27" cube (400 liter volume) stainless steel whole body exposure chamber was utilized. A complete group of rats (5 males and 5 females) was housed in the chamber during treatment in a stainless steel wire mesh compartmentalized cage with each compartment being 7" X 3" X 4". Temperature and relative humidity in the inhalation chamber were. monitored hourly by means of remote sensors (YSI model 705 Temperature Probe and 91HC Dew Point Hygrometer) located inside the chamber. Air flow rate through the chamber was set at 45 L/min and was measured in the exhaust line by means of an orifice plate and Magnehelic differential pressure gauge. ' This arrangement in turn had been calibrated against a conventional balltype flow meter. The negative pressure within the chamber with respect to the room atmosphere was set at less than 0. 5 inches of water. Decontamination of chamber air was accomplished by passing the air through ~ HEPA filter, an activated charcoal filter arid a liquid scrubber prior to eliminating it from the facility.

Generation of Test Atmospheres
An aerosol of the test article was generated using a Thermo Systems Inc. six jet atomizer. The atomizer was used at a pressure of 9 psig with two jets in operation.

Exposure Procedure
After loading into the chamber the test animals were exposed to an aerosol of the test article for a single period of four hours. Nominal chamber concentrations were calculated from the weight loss from the atomizer and total airflow through.the chamber during the exposure period.

Measurement of Chamber Concentration and Particle Size Distribution
Hourly air samples for measurement of chamber concentration were drawn from the chamber, at a rate of 5 L/min for two minutes, through a preweighed Gelman glass fibre filtet paper in a Gelman in-line filter holder. Chamber concentration was calculated from the increase in weight of the filter and volume of air sample. Hourly air samples from the inhalation chamber for particle size analysis were withdrawn and passed through a Casella Cascade Impactor. The distribution and size of particles which deposited on each of the four stages of the Impactor were determined by light microscopy. The method was originally described in Cascade Impactor Casella leaflet 3018/RT and was modified in this laboratory (see Bio Standard Operating Procedures No. I AC 01, 02 and 04) to include the following procedures:

1) Circular cover-slips upon which the aerosol had been impacted were mounted on a slide and examined microscopically.
2) A representative region of eaqh slide was selected for analysis.
3) An observing field of 0.47 mm X 0.47 mm (square grid) under 400 X magnification was superimposed on 'the region selected.
4) All particles falling within this grid were observed with a calibrated filar micrometer eyepiece and the numbers falling into various size ranges were recorded.
5) The numbers of particles in each size range were plotted against particle size on log probability graph paper. The line of best fit was drawn and the geometric mean particle size and its standard deviation calculated.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Nominal concentration of 4.63 mg/L
Measured chamber concentration of 1.38 mg/L ±0.19

No. of animals per sex per dose:

5 males
5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: All animals were observed closely during and immediately after exposure, and at least twice daily during the 14 day recovery period.
- Frequency of observations and weighing: Each animal was weighed on the_ day of exposure and on days 2, 3, 4, 7 and 14 of the study.
- Necropsy of survivors performed: Yes. All animals were killed 14 days. after exposure by intraperitoneal injection of Hoechst T-61 euthanasia solution and examined macroscopically. Liver and kidneys were preserved in 10% buffered formalin solution. Lungs were preserved by perfusion with the fixative. Bronchial lymph nodes were examined macroscopically but not retained·for histological assessment. All other macroscopically abnormal tissues were preserved.
- Histopathology: Samples of lung, liver, kidney and any macroscopic abnormality, from all animals were fixed in formalin for at least 48 hours, routinely processsed, embedded in paraffin wax stained with haematoxylin and eosin and examined microscopically.

Statistics:

Mean and standard deviatl6n will be determined for chamber temperature and humidity. In addition, animal. body weight will also be tabula.ted.
Clinical findings and gross and histopathological observations will be summarized in incidence tables.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.63 mg/L air (nominal)

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.38 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

There were no deaths.

Clinical signs:

other: There were no clinical changes of possible toxicological importance.

Body weight:

Although small body weight losses occurred on the days following exposure the losses were generally made good by day 7 of the study. Body weight gains during the second week of the observation period were considered to be satisfactory.

Gross pathology:

Focal grey-green areas observed grossly on the lungs were characterized histologically by aggregates of mononuclear leucocytes mainly about blood vassels· and air passages and occasionally extending to alveolar walls., some interstitial fibrosis and infiltration by foamy macrophages. These lesions were considered to be spontaneous and caused as a result of mild infection with murine respiratory mycoplasmosis. Pulmonary edema and mild congestion revealed in 3 rats could be attributed to euthanasia.

Other findings:

- Histopathology: There were no treatment related changes.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute inhalation study in Sprague-Dawley rats, the LC50 fro PEA was >4.63 mg/L (nominal concentration).

Executive summary:

In an acute inhalation toxicity study (5692-07/14), a group of young adult Sprague Dawley strain rats (5/sex) were exposed to a test atmosphere of PEA for 4 hours (whole body) at a target concentration of 4.63 mg/L. Animals were then observed for 14 days.

LC50 male/female = > 4.63 mg/L (nominal concentration)

The mean achieved concentration was 1.38 ±0.19 mg/L (MMAD: 1.08 µm; GSD: 0.05). There were no deaths and no clinical changes of possible toxicological importance. Although small body weight losses occurred on the days following exposure the losses were generally made good by day 7 of the study. Focal grey-green areas observed grossly on the lungs were characterized histologically by aggregates of mononuclear leucocytes mainly about blood vessels and air passages and occasionally extending to alveolar walls., some interstitial fibrosis and infiltration by foamy macrophages. These lesions were considered to be spontaneous and caused as a result of mild infection with murine respiratory mycoplasmosis. Pulmonary edema and mild congestion revealed in 3 rats could be attributed to euthanasia.

This acute inhalation toxicity test in rats is acceptable and satisfies the guideline requirement for an OECD 403 study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

4.63 mg/m³ air

Quality of whole database:

There is one acute inhalation toxcity study available (read-across to PEA, CAS No. 60-12-8). The quallity of the database is medium.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

There are two acute oral toxicity studies in rats available.

In the acute oral toxicity supporting study, (equivalent or similar to OECD 401; RIFM 1973), the LD50 for acute oral toxicity of dimethyl benzyl carbinol in rats is 1350mg/kg bw with 95% confidence limits of 1020-1680 mg/kg bw.

In the acute oral toxicity key study (equivalent or similar to OECD 401; Jenner, 1964), Osborne Mendel rats (5/dose/sex) were given dimethyl benzyl carbinol and observed for 14 days. Deaths occurred between 1 hr and 3 days. Depression was evident within 10 mins and coma within 1 hour. The LD50 (male/female) is 1280 mg/kg bw with 95% confidence limits of 934 -1770 mg/kg bw.

Acute inhalation toxicity

There is no acute inhalation toxicity study available for dimethyl benzyl carbinol. Read-across was performed to an acute inhalation toxicity study in rats from PEA (CAS No. 60 -12 -8).

In an acute inhalation toxicity study (equivalent or similar to OECD 403/GLP), a group of young adult Sprague Dawley strain rats (5/sex) were exposed to a test atmosphere of PEA for 4 hours (whole body) at a target concentration of 4.63 mg/L. Animals were then observed for 14 days. The mean achieved concentration was 1.38 ±0.19 mg/L (MMAD: 1.08 µm; GSD: 0.05). There were no deaths and no clinical changes of possible toxicological importance. Although small body weight losses occurred on the days following exposure the losses were generally made good by day 7 of the study. Focal grey-green areas observed grossly on the lungs were characterized histologically by aggregates of mononuclear leucocytes mainly about blood vessels and air passages and occasionally extending to alveolar walls., some interstitial fibrosis and infiltration by foamy macrophages. These lesions were considered to be spontaneous and caused as a result of mild infection with murine respiratory mycoplasmosis. Pulmonary edema and mild congestion revealed in 3 rats could be attributed to euthanasia. The LC50 (male/female) was > 4.63 mg/L (nominal concentration)

Justification for classification or non-classification

Based on the available information in the dossier, the substance DMBC (CAS No. 100-86-7) does need to be classified for acute toxicity for the oral route (Category 4) and does not need to be classified for acute toxicity or specific target organ toxicity - single exposure for the inhalation route, when the criteria outlined in Annex I of 1272/2008/EC are applied.