Methyl 3,3-dimethylpent-4-enoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-02-10 to 1988-03-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to guidelines: OECD 401, EEC Directive 79/831/EEC Method B.1. Fully documented; no significant deviations observed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 3,3-dimethylpent-4-enoate

EC Number:

264-431-8

EC Name:

Methyl 3,3-dimethylpent-4-enoate

Cas Number:

63721-05-1

Molecular formula:

C8H14O2

IUPAC Name:

methyl 3,3-dimethylpent-4-enoate

Details on test material:

- Substance type: ester
- Physical state: colorless liquid
- Purity test date: not reported
- Expiration date of the lot/batch: not reported
- Stability under test conditions: not determined
- Storage condition of test material: at 4°C in the dark

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 92-150 g
- Fasting period before study: overnight
- Housing: in groups by sex and dose, in metal cages with wire mesh floors
- Diet: standard laboratory rodent diet, ad libitum
- Water: ad libitum
- Acclimation period: minimum 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22°C
- Humidity (%): 47%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From 1988-02-10 to 1988-03-09

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- none

MAXIMUM DOSE VOLUME APPLIED: 8.95 ml/kg body weight (bw)

DOSAGE
- Rationale for the selection of the starting dose: Preliminary study at 5000 mg/kg bw

Doses:

Preliminary study: 5000 mg/kg bw
Main study: 3200, 5000, and 8000 mg/kg

No. of animals per sex per dose:

Preliminary study: 2
Main study: 5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (preliminary study 5 days)
- Frequency of observations: frequently on day 1, twice daily thereafter
- Frequency of weighing: days 1, 8, 15, or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

None applied (maximum mortality 2/5)

Results and discussion

Preliminary study:

5000 mg/kg bw: 1/2 males died on day 2, no mortality in 2 females

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No confidence limits could be calculated, because the maximum mortalities were 1/5 in males and 2/5 in females

Mortality:

Main study:
Males: dose 5000 mg/kg bw: 1/5 on day 3 after treatment (morning)
Females: dose 8000 mg/kg bw: 2/5 on days 2 and 3 after treatment (both in the morning)
No furher mortalities

Clinical signs:

other: Pilo-erection and increased salivation in all rats at all doses, within five minutes of dosing, abnormal body carriage (hunched posture) and pallor of the extremities in all rats at 5000 and 8000 mg/kg, onset five minutes after treatment, abnormal gait (w

Gross pathology:

No findings at terminal autopsy.

Other findings:

None

Any other information on results incl. tables

Bodyweight Development: Main Study

Dose	Bodyweight		Males	[g]	Bodyweight		Females	[g]
mg/kg bw	Day 1	Day 8	Day 15	Death	Day 1	Day 8	Day 15	Death
3200	142	196	258		100	144	170
3200	144	207	261		128	168	203
3200	150	225	286		119	164	196
3200	92	142	190		110	163	197
3200	109	173	224		132	170	195
3200, Mean	127	189	244		118	162	192
5000	131	-	-	114	118	158	187
5000	130	199	265		113	148	173
5000	127	180	240		120	148	182
5000	128	192	254		110	140	160
5000	126	172	235		106	148	181
5000, Mean	128	186	249		113	148	177
8000	112	165	229		114	-	-	106
8000	130	189	248		115	150	177
8000	125	177	238		105	143	168
8000	109	169	228		116	154	184
8000	130	194	254		112	-	-	109
8000, Mean	121	179	239		112	149	176

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of the test substance was estimated to be greater than 5000 mg/kg bw to male and female rats. Confidence limits could not be calculated. The study report is relevant, adequate and reliable for risk assessment, classification and labeling.

Executive summary:

Based on a preliminary study with two rats of either sex receiving 5000 mg/kg body weight (bw), the acute oral toxicity of the liquid test material was assessed according to OECD 401 in groups of five male and five female rats, at doses of 3200, 5000, and 8000 mg/kg bw. The test substance was applied undiluted by oral gavage. Mortalities, signs of toxicity, and body weight development were recorded during 15 days; animals dying on test and survivors were examined by necropsy for macroscopic abnormalities.

Mortalities in all dose groups were less than 50% (1/5 or 2/5 animals), so that a statistical calculation of the LD50 (by interpolation) was not performed. The clinical symptoms observed were pilo-erection and increased salivation at all dose levels, hunched posture, pallor of the extremities, abnormal gait, lethargy, decreased respiratory rate, and ptosis at the higher two doses; the symptoms subsided within 4 - 5 days. Body weight gains were lowered during the first week, but reached normal values in the second. No macroscopic abnormalities were detected.

The author estimates an acute oral LD 50 of > 5000 mg/kg bw to male and female rats.