3-methyl-5-phenylpentanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980-03-20 to 1980-04-05

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was performed in compliance with GLP to a standardised guideline with some limitations in the level of detail in the reporting of the materials and methods.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Remarks:

Federal Register, Volume 43, No. 247

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-5-phenylpentanol

EC Number:

259-461-3

EC Name:

3-methyl-5-phenylpentanol

Cas Number:

55066-48-3

Molecular formula:

C12H18O

IUPAC Name:

3-methyl-5-phenylpentan-1-ol

Test material form:

other: liquid (not specified)

Details on test material:

- Physical state: Liquid, clear

Test animals

Species:

rat

Strain:

other: TAcN(SD)fBR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: Within the range of 180-280 g
- Fasting period before study: Overnight
- Housing: Singly housed in wire cages
- Diet: Ad libitum
- Water : Ad libitum
- Acclimation period: 7 days

IN-LIFE DATES: 1980-03-20 to 1980-04-05

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: alcohol

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 0.5 mL/100 g bw

Doses:

Range Finding test: 1000 and 2500 mg/kg bw administered as 5 mL/kg
Main test: 1000, 1600, 2500, 3200 and 5000 mg/kg bw

No. of animals per sex per dose:

Range finding study: 2 groups of 2 male and 2 female rats
Main test: 5 groups of 8 males and 8 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days in total.
- Frequency of observations and weighing: Animals were observed for toxic signs at 1, 3, 5 and 24 hours post dosing and twice daily (once daily on weekends) for the fourteen day observation period. Surviving animals were weighed at the end of the observation period.
- Necropsy: Animals that died and all animals that survived through the observation period underwent a gross necropsy. Survivors were killed at the end of the study using ether inhalation.

Statistics:

Probit analysis was used to calculate the LD50, performed using the method of Litchfield JT Jr & Wilcoxon F (1949) A Simplified Method of Evaluating Dose-Effect Experiments; J. Pharm. Exp. Therap., 96:99-115.

Results and discussion

Preliminary study:

At 2500 mg/kg 1/2 male and 0/2 female animals died within the 72 hour observation period. All animals from the 1000 mg/kg group survived. Other dilutions at 10 mL/kg were used however this resulted the death of all the animals.

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

1 850 mg/kg bw

Based on:

test mat.

Remarks on result:

other: (1190-2870 mg/kg bw)

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: (1800-3500 mg/kg bw)

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: (1760-3010 mg/kg bw)

Mortality:

Most deaths ath the lower dose levels occurred more than 24 hours after dosing. At higher doses most deaths occurred during the first night after dosing.

Clinical signs:

other: At 1000 mg/kg bw lethargy, ataxia or adoption of the prone position were observed in 35 % of males and in all the females; the signs were observed in the first twenty four hours and survivors had recovered by 48 hours after having been dosed. Similar sign

Gross pathology:

There were no signs indicative of toxicity in any of the animals necropsied at term. In animals that died prior to scheduled termination, the only effects noted with yellow fluid (most likely test substance) in the stomach and reddish fluid in the intestines.

Any other information on results incl. tables

Table 1: Body weight and doses administered- males

MALES
1000 mg/kg bw	Animal No.	2176	2177	2178	2179	2180	2316	2314	2315	Mean
	Vol test mat. administered (mL)	1.00	1.00	1.00	0.98	0.96	1.00	1.10	1.10
	Pre-fast body weight (g)	235	232	233	218	250	228	255	257	238.5
	Dosing body weight (g)	207	207	207	195	192	203	223	225	207.4
	Terminal body weight (g)	298	303	280	278	250	321	324	329	297.9
	Gain/Loss (g)	+63	+71	+47	+60	0	+93	+69	+72	+59.4
1600 mg/kg bw	Animal No.	2181	2182	2183	2184	2185	2342	2343	2344	Mean
	Vol test mat. administered (mL)	1.00	0.91	1.00	1.10	0.97	1.10	1.20	1.10
	Pre-fast body weight (g)	238	203	227	249	209	241	268	251	235.8
	Dosing body weight (g)	209	181	201	220	193	215	235	220	209.3
	Terminal body weight (g)	284	275	281	292	D	295	D	D	285.4
	Gain/Loss (g)	+46	+72	+54	+43	-	+54	-	-	+53.8
2500 mg/kg bw	Animal No.	2186	2187	2188	2189	2190	2345	2346	2347	Mean
	Vol test mat. administered (mL)	1.10	1.20	1.20	1.10	1.00	1.10	1.00	1.20
	Pre-fast body weight (g)	248	263	252	247	227	253	231	270	248.8
	Dosing body weight (g)	222	232	234	228	202	217	200	236	221.4
	Terminal body weight (g)	298	D	307	325	D	324	D	333	317.4
	Gain/Loss (g)	+50	-	+45	+78	-	+29	-	+63	+53.0
3200 mg/kg bw	Animal No.	2191	2192	2193	2194	2195	2348	2349	2350	Mean
	Vol test mat. administered (mL)	1.10	1.00	1.10	1.20	1.10	1.00	1.10	1.20
	Pre-fast body weight (g)	243	253	241	268	238	240	248	264	249.4
	Dosing body weight (g)	215	209	214	249	218	209	212	232	219.8
	Terminal body weight (g)	D	D	D	D	D	D	D	D	-
	Gain/Loss (g)	-	-	-	-	-	-	-	-	-
5000 mg/kg bw	Animal No.	2196	2197	2198	2199	2200	2351	2352	2353	Mean
	Vol test mat. administered (mL)	1.20	1.10	1.20	1.10	1.10	1.10	1.10	1.00
	Pre-fast body weight (g)	255	243	249	237	236	258	233	238	243.6
	Dosing body weight (g)	230	217	229	208	212	224	202	204	215.8
	Terminal body weight (g)	298	D	D	D	D	D	D	D	-
	Gain/Loss (g)	+43	-	-	-	-	-	-	-	-

 

Table 2: Body weight and doses administered- females

FEMALES
1000 mg/kg bw	Animal No.	2376	2377	2378	2379	2380	2506	2507	2508	Mean
	Vol test mat. administered (mL)	0.98	1.00	0.93	1.00	0.99	1.00	0.99	0.93
	Pre-fast body weight (g)	220	233	206	225	212	228	221	206	218.9
	Dosing body weight (g)	195	206	185	205	197	203	198	185	196.8
	Terminal body weight (g)	D	281	235	D	D	237	266	D	254.8
	Gain/Loss (g)	-	+48	+29	-	-	+9	+45	-	+32.8
1600 mg/kg bw	Animal No.	2381	2382	2383	2384	2385	2533	2534	2535	Mean
	Vol test mat. administered (mL)	0.92	0.94	1.00	0.95	0.95	0.92	0.92	1.00
	Pre-fast body weight (g)	203	200	225	201	209	208	204	227	209.6
	Dosing body weight (g)	184	188	208	189	189	183	183	207	191.4
	Terminal body weight (g)	230	233	253	D	238	D	222	259	239.2
	Gain/Loss (g)	+27	+33	+28	-	+27	-	+18	+32	+27.5
2500 mg/kg bw	Animal No.	2386	2387	2388	2389	2390	2536	2537	2538	Mean
	Vol test mat. administered (mL)	0.99	0.96	0.98	0.93	0.93	0.96	0.94	0.97
	Pre-fast body weight (g)	221	210	218	209	202	217	207	213	212.1
	Dosing body weight (g)	197	191	196	186	186	191	188	193	191.0
	Terminal body weight (g)	238	D	232	D	235	D	D	D	235.0
	Gain/Loss (g)	+17	-	+14	-	+33	-	-	-	+21.3
3200 mg/kg bw	Animal No.	2391	2392	2393	2394	2395	2539	2540	2541	Mean
	Vol test mat. administered (mL)	0.99	0.98	1.00	0.97	0.96	1.00	1.00	0.99
	Pre-fast body weight (g)	216	217	221	208	212	223	233	224	219.3
	Dosing body weight (g)	198	196	202	193	191	200	208	198	198.3
	Terminal body weight (g)	D	D	D	D	D	D	D	D	-
	Gain/Loss (g)	-	-	-	-	-	-	-	-	-
5000 mg/kg bw	Animal No.	2396	2397	2398	2399	2400	2542	2543	2544	Mean
	Vol test mat. administered (mL)	0.96	0.93	1.00	1.00	1.00	0.92	0.99	1.00
	Pre-fast body weight (g)	201	195	217	216	214	204	216	217	210.0
	Dosing body weight (g)	184	178	194	193	196	184	197	199	190.6
	Terminal body weight (g)	D	D	D	D	D	D	D	D	-
	Gain/Loss (g)	-	-	-	-	-	-	-	-	-

 

Table 3: Summary of mortality by sex, day and dose level

Dose (mg/kg bw)	Sex	Day															Total/sex	Total
		0	1	2	3	4	5	6	7	8	9	10	11	12	13	14
1000	Male (8)	No mortality															0	4/16
	Female (8)	0	1	3	No further mortality												4
1600	Male (8)	0	0	3	No further mortality												3	5/16
	Female (8)	1	0	0	0	1	No further mortality										2
2500	Male (8)	0	2	1	No further mortality												3	8/16
	Female (8)	0	2	3	No further mortality												5
3200	Male (8)	0	7	0	0	1	No Survivors										8	16/16
	Female (8)	1	3	3	1	No Survivors											8
5000	Male (8)	0	3	4	No further mortality												7	15/16
	Female (8)	0	5	3	No Survivors												8

 

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal doses (LD50) for test substance were 2500 mg/kg bw (1800-3500 mg/kg bw) in males and 1850 mg/kg bw (1190-2870 mg/kg bw) in females and 2300 mg/kg bw (1760-3010 mg/kg bw) combined.

Executive summary:

The acute oral toxicity of the test substance was investigated in male and female albino rats in a GLP study conducted to OECD guideline 401. Rats were doses via gastric intubation at doses of 1000, 1600, 2500, 3200 and 5000 mg/kg bw prepared as 0.5 mL/100 g bw in alcohol. The animals were observed for 14 days for mortality and any pharmacotoxic signs. The acute oral median lethal doses (LD₅₀) was determined to be 2500 mg/kg bw (1800-3500 mg/kg bw) in males and 1850 mg/kg bw (1190-2870 mg/kg bw) in females and 2300 mg/kg bw (1760-3010 mg/kg bw) combined.