3-Methoxy-3-methylbutyl acetate

Endpoint summary

Description of key information

Oral LD50 in rats for both sexes combined = 4600 mg/kg.

Dermal LD50 in rats > 2000 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983-07-07 to 1983-07-27

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No GLP compliance claim, no International Test Guidelines quoted (but all parameters are closely comparable to a guideline method) and the purity of the test substance is not reported.

Qualifier:

no guideline followed

Principles of method if other than guideline:

A preliminary study was conducted using single oral doses of 1.0 and 5.0 g/kg in two male and two female rats at each dose level. The preliminary rats were observed for clinical signs and mortality over a period of five days.
On the basis of the results of the preliminary study, the main study was conducted at dose levels 0 (control), 1.6, 2.5, 4.0, and 5.0 g/kg bodyweight. Five rats of each sex were used at each dose level. Following a single oral dose, the rats were observed for clinical signs and mortality over a period of fourteen days. Bodyweights were recorded on days 1, 8, and 15. All surviving animals were sacrificed at day 15, and a macroscopic post mortem examination was conducted on all rats at death.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hacking and Churchill Limited, Huntingdon, Cambridgeshire, England
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 90 - 131 g
- Fasting period before study: Overnight
- Housing: Metal cages with wire mesh floors
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Minimun period of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25-29
- Mean Relative Humidity (%): 57
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Not applicable - test material was dosed as supplied.

MAXIMUM DOSE VOLUME APPLIED: 5.2 mL/Kg (specific gravity = 0.96 g/mL)

Doses:

0 (control=distilled water), 1.6, 2.5, 4.0, and 5.0 g/kg in main study
1.0 and 5.0 g/kg in preliminary study

No. of animals per sex per dose:

5/sex/group in the main study
2/sex/group in preliminary study

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days (5 days for preliminary study)
- Frequency of observations and weighing: observations were taken regularly on day 1, and at least twice daily on subsequent days. Bodyweights were recorded on days 1, 8, and 15, and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of:
Finney (1971) Probit Analysis (3rd Edition) Cambridge University Press.

Preliminary study:

The results of the preliminary study indicated that the acute median lethal oral dose (LD50) to rats of 3-methyl-3-methoxybutyl acetate was between 1.0 and 5.0 g/kg bodyweight.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 600 mg/kg bw

Based on:

test mat.

95% CL:

4 200 - 5 000

Sex:

male

Dose descriptor:

LD50

Effect level:

4 700 mg/kg bw

Based on:

test mat.

95% CL:

4 100 - 5 400

Sex:

female

Dose descriptor:

LD50

Effect level:

4 500 mg/kg bw

Based on:

test mat.

95% CL:

3 900 - 5 100

Mortality:

Mortailties occurred amongst rats treated at 4.0 and 5.0 g/kg bodyweight within 22 to 71 hours of dosing.
3 males and 3 females dosed at 5.0 g/kg were found dead at the first observation of day 2; a further male from this group was found dead at the first observation on day 3 and a further female at the second observation of day 3. One female rat dosed at 4.0 g/kg was found dead at the first observation of day 4.

Clinical signs:

Abnormal body carriage (hunched posture), lethargy, decreased respiratory rate, increased salivation and ataxia was observed amongst treated rats.
Ptosis was seen in all rats treated at 2.5 g/kg and above.
Comatose-like condition was seen amongst rats treated at 4.0 and 5.0 g/kg.
Increased lacrimation was seen in four rats at 4.0 g/kg.
Pilo-erection only was observed in control animals.

Body weight:

Poor weight gain was recorded in the occasional male rat at 2.5 g/kg and above and the occasional treated female rat on Day 8. Bodyweight gains were normal on Day 15.

Gross pathology:

Terminal autospy findings were normal.

Dose (g/kg)	Mortality ratio(No.ofdeaths)/(No.dosed)			Time of death after dosing
	Males	Females	Combined
1.0	0/2	0/2	0/4	-
5.0	2/2	2/2	4/4	<22

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal oral dose and their 95% confidence limits to rats of MMB-Ac were estimated to be:
Males and females combined: 4.6 (4.2 to 5.0) g/kg bodyweight
Males Only: 4.7 (4.1 to 5.4) g/kg bodyweight
Females Only: 4.5 (3.9 to 5.1) g/kg bodyweight

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

4 600 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992-07-02 to 1992-07-16

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Although a good quality report and conducted to GLP and documented test parameters are based on specific national guidelines, the purity of test substance is not reported and actual guidelines refs not quoted in test report.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

No official test guidelines were cited, although on review of the test report, the methodology used was broadly consistent with OECD test guideline 402.

GLP compliance:

yes

Remarks:

The test report includes a statement of GLP compliance signed by the Study Director, and a statement of Quality Assurance, however no certificate of GLP compliance issued by an independant body (such as an official GLP monitoring authority) was included.

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: males: 9-10 weeks; females: 11-12 weeks
- Weight at study initiation: males: 259-287 g; females:225-256 g
- Fasting period before study:
- Housing: housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays with maximum 5 animals per cages
- Diet: ad libitum
- Water: ad libitum)
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Mean Relative Humidity (%): 48
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- Area % - 10
- Type of wrap if used: gauze dressing (5x5 cm)

REMOVAL OF TEST SUBSTANCE
- Washing: skin was wiped with a water dampened tissue
- Time after start of exposure: 24 h

Duration of exposure:

24 hours

Doses:

2000 mg/kg

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: frequently on the day of dosing and once daily for 14 days following dosing; Animals were weighted immediatey prior to doing, 7 days after dosing and at sacrifice at the end of the 14 day observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: red nasal discharge 4 hours after dosing; low body weight gains for females

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortalities and no abnormal clinical signs were observed in any of the 5 males and 5 females dosed.

Mortality:

No moralities

Clinical signs:

Red nasal discharge 4 hours after dosing

Body weight:

Low body weight gains for females

Interpretation of results:

GHS criteria not met

Conclusions:

The Median Dermal Lethal Dose (LD50) of MMB-Ac in rats is greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute oral toxicity

An acute oral toxicity study was conducted in rats. No formal official test guideline was available at the time of the test, and no formal claim of GLP compliance was made, although the study report contained a quality assurance statement.

A preliminary test was conducted at dose levels 1000 and 5000 mg/kg; two animals per sex per dose level were administered a single oral dose, then observed for clinical signs for five days. On the basis of this preliminary study, dose levels for the main study were determined.

In the main study five rats per sex per dose level were administered a single oral dose by gavage. Dose levels in the main study were 0 (control level), 1600, 2500, 4000, and 5000 mg/kg bodyweight. Following test substance administration, the animals were observed for clinical signs and mortality for 14 days. Surviving animals were sacrificed on day 14 of the observation period and a macroscopic post mortem examination of each animal was conducted.

The acute median lethal oral dose and their 95% confidence limits to rats of the test substance were estimated to be:

Males and females combined: 4600 (4200 to 5000) mg/kg bodyweight..

Males Only: 4700 (4100 to 5400) mg/kg bodyweight.

Females Only: 4500 (3900 to 5100) mg/kg bodyweight.

Justification for classification or non-classification

The determined acute oral toxicity gave an LD50 value greater than 2000 mg/kg for both sexes. On this basis the test substance does not require classification as acutely toxic according to either the Dangerous Substances Directive (Directive 67/548/EEC) or the CLP Regulation (EC Regulation 1272/2008).