3-methyl-5-phenylpentanol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980-04-05 to 1980-04-19

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was performed in compliance with GLP, and to a method similar to the standardised guideline OECD 402. Some deficiencies were present in the of the study, such as no methods to prevent the animals from ingesting the test material, a massive sensitivity difference between sexes and a lack of vehicle controls.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

(no prevention of the animals ingesting the test material)

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, colourless

Test animals

Species:

rat

Strain:

Sprague-Dawley

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 weight range of 180 to 280 grams
- Housing: Individually housed in wire cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 7 days

IN-LIFE DATES: From: 1980-04-05 To: 1980-04-19

Administration / exposure

Type of coverage:

open

Vehicle:

other: alcohol

Details on dermal exposure:

TEST SITE
- Area of exposure: The back, from the scapular region to the hips
- % coverage: Less than 30%
- Type of wrap if used: The site was left open to the air

REMOVAL OF TEST SUBSTANCE
- Washing: Any excess material was removed by wiping with a clean cloth
- Time after start of exposure: 24 hours post dosing.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL/100 g bw

Duration of exposure:

24 hours

Doses:

2000, 2500, 3100, 4000 and 5000 mg/kg bw

No. of animals per sex per dose:

8 males and 8 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality and pharmacotoxic signs at 1, 3, 5 and 24 hours following dosing and twice daily (once daily on weekends) for the remainder of the 14 day observation period. Surviving animals were weighed at the end of the observation period. All animals were weighed prior to dosing.
- Necropsy of survivors performed: All the animals underwent a gross necropsy at the end of the experiment. the animals were killed using ether inhalation.

Statistics:

Probit analysis was 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:

Two rats of either sex were used. Each animal received a single dose of the test article, and was observed for the next 72 hours to determine the mortality only. The doses administered were 2400 and 5000 mg/kg bw. No animals died during the 72 hour observation period following dosing at 2500 mg/kg bw. All four rats died within 24 hours after being dosed at 5000 mg/kg bw.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

3 100 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was low in the male groups with only one of eight rats dead at 3100 and 5000 mg/kg bw. The females exhibited lethality as follows: 1/8 at 2500 mg/kg bw; 4/8 at 3100 mg/kg bw; 5/8 at 4000 mg/kg bw and 8/8 at 5000 mg/kg bw.

Clinical signs:

other: Clinical signs were first noted at 2500 mg/kg bw in the female rats and 3100 mg/kg bw in the male rats. The signs were of lethargy, ataxia, tremors and soft faeces; one female died on Day 3. At higher doses, the clinical signs included ataxia, lethargy, h

Gross pathology:

At necropsy, none of the animals that survived to term had any specific signs indicative of systemic toxicity. The predominant signs in animals that died during the study were hematuria in females at 5000 mg/kg bw and a change to greater fluidity in the consistency of the intestinal contents.

Any other information on results incl. tables

Table 1: Body weights and doses administered

MALES
2000 mg/kg bw	Animal No.	2705	2706	2707	2708	2709	2710	2711	2712	Mean
	Vol test material administered (mL)	1.1	1.1	1.3	1.2	1.1	1.1	1.1	1.1
	Pre-dose body weight (g)	225	222	262	236	218	215	220	218	227.0
	Terminal body weight (g)	314	309	349	316	316	330	344	303	322.6
	Gain/Loss (g)	+89	+87	+87	+80	+98	+115	+124	+85	+95.6
2500 mg/kg bw	Animal No.	2713	2714	2715	2716	2717	2718	2719	2720	Mean
	Vol test material administered (mL)	1.3	1.1	1.1	1.2	1.3	1.3	1.2	1.2
	Pre-dose body weight (g)	262	228	226	234	256	251	240	246	242.9
	Terminal body weight (g)	350	308	319	310	353	308	320	327	324.4
	Gain/Loss (g)	+88	+80	+93	+76	+97	+57	+80	+81	+81.5
3100 mg/kg bw	Animal No.	2721	2722	2724	2725	2726	2728	2729	2730	Mean
	Vol test material administered (mL)	1.3	1.3	1.2	1.2	1.2	1.3	1.3	1.2
	Pre-dose body weight (g)	253	258	238	241	246	258	250	239	247.9
	Terminal body weight (g)	330	306	D	324	306	355	360	338	331.3
	Gain/Loss (g)	+77	+48	-	+83	+60	+97	+110	+99	+82.0
4000 mg/kg bw	Animal No.	2679	2680	2681	2682	2683	2684	2685	2686	Mean
	Vol test material administered (mL)	1.1	1.1	1.2	1.1	1.2	1.1	1.2	1.3
	Pre-dose body weight (g)	215	216	244	227	232	212	230	252	228.5
	Terminal body weight (g)	301	306	312	290	319	291	293	317	303.6
	Gain/Loss (g)	+86	+90	+68	+63	+87	+79	+63	+65	+75.1
5000 mg/kg bw	Animal No.	2687	2688	2689	2690	2691	2692	2693	2694	Mean
	Vol test material administered (mL)	1.1	1.2	1.2	1.1	1.2	1.3	1.2	1.2
	Pre-dose body weight (g)	216	226	222	220	238	254	240	234	231.3
	Terminal body weight (g)	284	275	D	318	308	280	300	301	295.1
	Gain/Loss (g)	+68	+49	-	+98	+70	+26	+60	+67	+62.6
FEMALES
2000 mg/kg bw	Animal No.	2862	2863	2864	2865	2866	2867	2868	2869	Mean
	Vol test material administered (mL)	1.2	1.1	1.2	1.3	1.2	1.3	1.1	1.0
	Pre-dose body weight (g)	249	227	232	260	240	250	215	208	235.1
	Terminal body weight (g)	259	211	230	253	261	271	234	228	243.4
	Gain/Loss (g)	+10	-16	-2	-7	+21	+21	+19	+20	+8.3
2500 mg/kg bw	Animal No.	2870	2871	2872	2873	2874	2875	2876	2877	Mean
	Vol test material administered (mL)	1.1	1.2	1.3	1.2	1.0	1.2	1.1	1.2
	Pre-dose body weight (g)	224	238	250	247	200	239	223	230	231.4
	Terminal body weight (g)	247	242	D	282	212	246	226	239	242.0
	Gain/Loss (g)	+23	+4	-	+35	+12	+7	+3	+9	+13.3
3100 mg/kg bw	Animal No.	2878	2879	2880	2881	2882	2883	2884	2885	Mean
	Vol test material administered (mL)	1.1	1.0	1.1	1.2	1.3	1.1	1.1	1.1
	Pre-dose body weight (g)	223	204	226	238	254	226	225	220	227.0
	Terminal body weight (g)	D	D	D	261	263	D	239	222	246.3
	Gain/Loss (g)	-	-	-	+23	+9	-	+14	+2	+12.0
4000 mg/kg bw	Animal No.	2854	2855	2856	2857	2858	2859	2860	2861	Mean
	Vol test material administered (mL)	1.2	1.2	1.2	1.2	1.1	1.1	1.1	1.2
	Pre-dose body weight (g)	236	232	238	230	228	228	225	247	233.0
	Terminal body weight (g)	255	247	D	225	D	D	D	D	242.3
	Gain/Loss (g)	+19	+15	-	-5	-	-	-	-	+9.7
5000 mg/kg bw	Animal No.	2786	2787	2788	2789	2790	2791	2792	2793	Mean
	Vol test material administered (mL)	1.1	1.3	1.1	1.3	1.1	1.3	1.2	1.3
	Pre-dose body weight (g)	221	248	215	248	218	248	230	247	234.4
	Terminal body weight (g)	D	D	D	D	D	D	D	D	-
	Gain/Loss (g)	-	-	-	-	-	-	-	-	-

Table 2: Mortality

Dose (mg/kg bw)	Male	%	Female	%
2000	0/8	0	0/8	0
2500	0/8	0	1/8	12.5
3100	1/8	12.5	4/8	50.0
4000	0/8	0	5/8	62.5
5000	1/8	12.5	8/8	100.0

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the test, the dermal LD50 in albino (Sprague Dawley CD) rats was determined to be greater than 5000 mg/kg bw for males and equal to 3100 (2900 - 3320) mg/kg bw for females.

Executive summary:

Eighty male and female albino rats (8 males and 8 females per group) were dosed dermally with the test material at concentrations of 2000, 2500, 3100, 4000 and 5000 mg/kg bw prepared in alcohol. The test site was left uncovered, after 24 hours excess material was wiped off and the animals were observed for 14 days for mortality and signs of pharmacotoxicity. The acute dermal LD₅₀ was determined to be > 5000 mg/kg bw in males and 3100 (2900-3200 mg/kg bw) in females.