2,2-dimethyl-3-phenylpropanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Equivalent to guideline, no GLP study, probably technical pure quality was tested

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2-dimethyl-3-phenylpropanol

EC Number:

236-400-9

EC Name:

2,2-dimethyl-3-phenylpropanol

Cas Number:

13351-61-6

Molecular formula:

C11H16O

IUPAC Name:

2,2-dimethyl-3-phenylpropan-1-ol

Test animals

Species:

rat

Strain:

other: BOR: WISW

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Firma Winkelmann, Versuchstierzucht, 4791 Borchen 1, Gartenstraße 300
- Weight at study initiation: 154-210 g (males), 145 -175 g (females)
- Fasting period before study: yes, 16 hours before test begin
- Housing: Makrolon cages III
- Diet: Ssniff, Versuchtstierdiäten GmbH, 4770 Soest/Westfalen
- Water: ad libitum, tap water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12 (Fluorescent lighting)

Administration / exposure

Route of administration:

oral: feed

Vehicle:

peanut oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 3.5 mL/kg

DOSAGE PREPARATION: in water bath and applicated by gavage

Doses:

1.5, 2.0, 2.5 and 3.5 mL/kg equivalent to 1500, 2000, 2500 and 3500 mg/kg bw. (Values based on calculation with density (appx. 1 g/cm^3))

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: after 20 min, 1 h, 3 h, 24 h, 48 h, 72 h, 7 and 14 days
- Weighing: Recorded immediately before treatment (day 0) and on day 14 of postadministration.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gross pathology

Statistics:

According to probit analysis, method of Finney.

Results and discussion

Preliminary study:

2 rats were tested each in doses of 15, 10, 5, 2.5 and 1.0 mL/kg

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

2 240 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Values based on calculation with density (appx. 1 g/cm^3)

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 730 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Values based on calculation with density (appx. 1 g/cm^3)

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 970 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Values based on calculation with density (appx. 1 g/cm^3)

Mortality:

Highest dose level: All animals died
2.5 mL/kg: 8 animals died
2.0 mL/kg: 6 animals died
1.5 mL/kg: 1 animal died

Clinical signs:

other: Reduced activity, partly total apathy, partly obvious abnormal body posture, obvious disturbance of coordination, redued reflex excitability, obvious piloerection and slight decreased body temperature were noted at this dose level and above.

Gross pathology:

Necropsy of deceased revealed slight hemorrhages of the gastrointestinal channel. Necropsy of survivors revealed no abnormalities.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The potential of the test item to cause acute oral toxicity was determined in a study equivalent to OECD 401. The LD50 (males) was determined to be 2240 mg/kg bw, the LD50 of females was determined to be 1730 mg/kg bw. The mean LD50 rats was determined to be 1970 mg/kg bw.

Executive summary:

An acute toxicity study (equivalent to OECD guideline 401) was carried out to determine the acute oral toxicity potential of the test item. The study was conducted using albino Wistar rats weighing 154 – 210 g (males) and 145 – 175 g (females), which were acclimated for at least 7 days. Animals were group housed (5/cage) in macrolon type III cages. Fluorescent lighting, 12 hr light/12 hr dark was used in each animal room. Temperature was maintained at 21 °C and relative humidity at 45-55%. The toxicity of test compound was investigated in four groups of fasted male and female animals (5 animals/sex/dose group) at the following dose levels: 1.5, 2.0, 2.5, and 3.5 mL/kg body weight equivalent to 1500, 2000. 2500 and 3500 mg/kg bw. In each animal a number of clinical-toxicological signs were evaluated according to a modified Irwin Screening procedure. Any change from the normal condition was noted (increase or decrease) and the degree of severity of any clinical symptoms was assessed. The animals were examined at the following post-treatment intervals: 20 min, 1 h, 3 h, 24 h, 48 h, and 7 and 14 days. Body weights were recorded immediately before treatment (day 0) and on day 14 of postadministration. Animals were sacrificed after 14 days and gross pathological examinations were subsequently performed. If needed, the calculation of an oral LD50 was performed with the method of Finney.The following results were obtained:

A reduced activity, partly total apathy, partly obvious abnormal body posture, obvious disturbance of coordination, redued reflex excitability, obvious piloeretion and slight decreased body temperature were noted at this dose level and above. Necropsy of deceased revealed slight hemorrhages of the gastrointestinal channel. Necropsy of survivors revealed no abnormalities. Mortality was observed at 1500 mg/kg onwards.

The LD50 was determined to be 1970 mg/kg bw (male/females), 2240 mg/kg bw for males and 1730 mg/kg bw for females)