3-(2,2-dimethyl-3-hydroxypropyl)toluene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985-05-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", by the Staff of the Division of Pharmacology, FDA.

Version / remarks:

1959

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(2,2-dimethyl-3-hydroxypropyl)toluene

EC Number:

403-140-4

EC Name:

3-(2,2-dimethyl-3-hydroxypropyl)toluene

Cas Number:

103694-68-4

Molecular formula:

C12H18O

IUPAC Name:

2,2-dimethyl-3-(3-methylphenyl)propan-1-ol

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: not specified
- Weight at study initiation: 200-210 in average
- Fasting period before study: not specified
- Housing: single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 2 °C
- Humidity: 50 - 60 %
- Air changes: not specified
- Photoperiod: 12 / 12 hrs dark / hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Tylose (CMC) + Tween 20

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 or 30 %
- Amount of vehicle: 1 to 1.7 mL/100 g bw, respectively

MAXIMUM DOSE VOLUME APPLIED: 1.7 mL / 100 g bw

Doses:

2; 3; 4; 5 mL/kg bw

recalculated with the relative density of 0.97 this corresponds to

1.94; 2.91; 3.76; 4.84 g/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: before administration and at day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: Slope of the mortality curve: 1.24

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 3 460 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 14-d LD50

Mortality:

Mortality / treated animals

Males
2 mL/kg bw (1940 mg/kg bw): 0/5
3 mL/kg bw (2910 mg/kg bw): 1/5
4 mL/kg bw (3760 mg/kg bw): 1/5
5 mL/kg bw (4840 mg/kg bw): 5/5

Females
2 mL/kg bw (1940 mg/kg bw): 0/5
3 mL/kg bw (2910 mg/kg bw): 0/5
4 mL/kg bw (3760 mg/kg bw): 3/5
5 mL/kg bw (4840 mg/kg bw): 5/5

Clinical signs:

other: In all dose groups the preparation caused apathy, sedation, tremor, incoordination, abdominal ache symptoms, bloody nose-secretion and readiness for reflexing. The above mentioned symptoms continued up to 4 days or caused mortalities. Animals of the hi

Gross pathology:

Animals who died within 24 hours did not show any remarkable symptoms. The late mortalities of group III showed hyperaemia of the digestive tract. The same findings were observed in the surviving animals after 14 days in dosage group III.

Any other information on results incl. tables

Table 1 Mortalities for both sexes, aggregated

Dose Group	Dose level	24 h	7 days	14 days
I	2 mL/kg bw (1940 mg/kg bw)	0/10	0/10	0/10
II	3 mL/kg bw (2910 mg/kg bw)	0/10	1/10	1/10
III	4 mL/kg bw (3760 mg/kg bw)	1/10	4/10	4/10
IV	5 mL/kg bw (4840 mg/kg bw)	10/10	10/10	10/10

 

 

 

 

Table 2 Mean body weights males (g)

Dose Group	Dose level	Day 1	Day 14
I	2 mL/kg bw (1940 mg/kg bw)	205.2 ± 2.68	259.6 ± 6.88
II	3 mL/kg bw (2910 mg/kg bw)	204.8 ± 2.77	255.8 ± 5.38
III	4 mL/kg bw (3760 mg/kg bw)	205.2 ± 2.95	248.5 ± 5.74
IV	5 mL/kg bw (4840 mg/kg bw)	204.4 ± 2.70	-

 

Table 2 Mean body weight females (g)

Dose Group	Dose level	Day 1	Day 14
I	2 mL/kg bw (1940 mg/kg bw)	205.0 ± 2.35	220.2 ± 4.97
II	3 mL/kg bw (2910 mg/kg bw)	204.2 ± 2.39	217.6 ± 5.41
III	4 mL/kg bw (3760 mg/kg bw)	205.4 ± 2.19	216.0 ± 4.00
IV	5 mL/kg bw (4840 mg/kg bw)	204.0 ± 1.87	-

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on this acute oral toxicity study in the rat the LD50 was determined to be > 2000 mg/kg bw.

Executive summary:

The test item was assessed for its acute oral toxicity in the rat at dose levels of 2, 3, 4, and 5 mL/kg bw, respectively, as a dilution in Tylose (CMC) and Tween20. The LD50 after 24 h was determined to be 4.25 mL/kg bw. The 14 -days LD50 was 3.57 mL/kg bw. Clinical signs of toxicity were observed and included apathy, sedation, tremor, incoordination, abdominal ache symptoms, bloody nose-secretion and readiness for reflexing. Mortalities occurred within 24 h in the highest dose group. Later mortalities were observed in dose group II and III. Body weight development was decreased in a dose-related manner. Pathological examination revealed hyperaemia of the digestive tract.