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Description of key information

MMB has a low acute toxicity by oral and dermal routes. In rats, the LD50 value via the oral route is > 4000 mg/kg bw. In the acute dermal toxicity study with rabbits, the LD50 was > 2000 mg/kg bw. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-11-11 to 1989-01-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to
Guideline:
other: Annex V of the EEC Directive 79/831/EEc, Part B Methods for determination of toxicity. Method B1 Acute Oral Toxicity
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Species:
rat
Strain:
other: Crl:CD®(SD) BR VAF plus
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Portage, Michigan, USA
- Age at study initiation: Approximately four to six weeks of age
- Weight at study initiation: Weight range of 132 to 158 g prior to dosing (Day 1)
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 4 hours after dosing
- Housing: They were housed in groups of up to five rats the same sex in metal cages with wire mesh floors
- Diet (e.g. ad libitum): A standard laboratory rodent diet (Labsure LAD 1) were provided ad libitum
- Water (e.g. ad libitum): Domestic quality potable water were provided ad libitum
- Acclimation period: A minimum period of 14 days prior to the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean daily minimum and maximum temperatures of the animal room were 21°C and 22°C respectively
- Humidity (%): Mean daily relative humidity value was 53% R.H.
- Air changes (per hr): The rate of air exchange was maintained at approximately 15 air changes/hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a time switch to provide 12 hours artificial light in each 24-hour period

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Treatment procedure: The appropriate dose volume (volume not exceeding 5.39 ml/kg (specific gravity 0.927) in the main study) of the test substance was administered to each rat using a syringe and plastic catheter (8 choke)

Doses:
2.0, 3.2, 4.0, 5.0 g/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: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (day of dosing) (a period of six hours). On subsequent days the animals were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on week days or 11.30 hours on public holidays, including Saturday and Sunday. Clinical signs were recorded at each observation. The following were recorded: Approximate time of death of individual rats; The nature, severity, approximate time of onset and duration of each toxic sign; Individual bodyweights of rats on Day 1 (day of dosing), 8 and 15 and at death.
- Necropsy of survivors performed: yes
Statistics:
The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of: Finney (1971) Probit Analysis (3rd Editon) Cambridge University Press.
Seperate LD50 values for male and females were estimated by undertaking probit analysis on the mortality data by fitting two parallel lines on the data (males only and females only) unsing the techique described by Finney (1978, Statistically Method in Biological Assay, 3rd Edition, Charles Griffin, London).
A chi-squared test was carried out to check that the data did not certain any evidince for non-parallelism.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4.4 other: g/kg bw
95% CL:
>= 3.9 - <= 5.2
Sex:
male
Dose descriptor:
LD50
Effect level:
4.5 other: g/kg bw
95% CL:
>= 3.9 - <= 5.6
Sex:
female
Dose descriptor:
LD50
Effect level:
4.3 other: g/kg bw
95% CL:
>= 3.6 - <= 5.3
Mortality:
Deaths occurred amongst male and female rats dosed at 4.0 g/kg and above. Deaths occurred from within two hours of dosing until Day 3.
Clinical signs:
Pilo-erection was observed in all rats within 5 minutes of dosing and throughout the reminder of Day 1. This was accompanied by:
-Pilo-errection, lethargy and pallor of the extremities within 5 minutes of dosing in all rats,
-abnormal body carriage (hunched posture) and abnormal gait (waddling) within 5 minutes of dosing in all rats dosed at 2.0, 4.0 and 5.0 g/kg and females dosed at 3.2 g/kg, and at later intervals on Day 1 in male rats dosed at 3.2 g/kg,
-ataxia within 5 minutes of dosing in males dosed at 3.2 g/kg,
-decreased respiratory rate and ptosis within five minutes of dosing in rats dosed at 3.2 g/kg, and at later intervals on Day 1 in rats dosed at 4.0 and 5.0 g/kg.
-prostration in two males and two females dosed at 4.0 g/kg and in three males and one female dosed at 5.0 g/kg,
-pink extremities in three males and one female dosed at 5.0 g/kg.
Recovery, as judged by external appearance and behaviour, was completed by Day 2,3 or 4.
Body weight:
Slightly low bodyweight gains were recorded for one female dosed at 2.0 g/kg, one female dosed at 3.2 g/kg and one male and three females dosed at 4.0 g/kg on Day 8 of the study.
The majority of rats achieved anticipated bodyweight gains during the second week of the study

No change in bodyweight or bodyweight losses were recorded for rats that died.
Gross pathology:
Terminal autopsy findings were normal.
Slightly pale cortex (kidney) was observed post-mortem in three males and three females (5.0 g/kg) and one female (4.0 g/kg) that died. Autopsy of rats that died revealed no other macroscopic abnormalities.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The acute LD50 of the substance determined in this study is 4.4 g/kg bw for males and females combined
Executive summary:

The acute oral toxicity of Solfit was evaluated in this single-dose study in rats. The appropriate dose volume of the test substance was administered to each rat by oral gavage. The study was conducted according to an appropriate national standard method and in compliance with GLP. Mortality, clinical observations, body weight and necropsy findings were evaluated. Deaths occurred amongst male and female rats dosed at 4.0 g/kg and above. Deaths occurred from within two hours of dosing until Day 3. No change in bodyweight or bodyweight losses were recorded for rats that died. Slightly pale cortex (kidney) was observed post-mortem in three males and three females (5.0 g/kg) and one female (4.0 g/kg) that died. Autopsy of rats that died revealed no other macroscopic abnormalities. The acute median lethal oral doses (LD50) and their 95% confidence limits to rats of Solfit were estimated to be:

Males and females combined: 4.4 (3.9 to 5.2) g/kg bw

Males only:                              4.5 (3.9 to 5.6) g/kg bw

Females only:                           4.3 (3.6 to 5.3) g/kg bw

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Principles of method if other than guideline:
oral acute test with 10 animals, original Japanese protocol available
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
ICR
Sex:
male
Details on test animals and environmental conditions:
10 male mice were doesed with each of the 10 concentrations
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Remarks:
T52-003:Non
Details on oral exposure:
no data
Doses:
2520, 3010, 3620, 4340, 5220, 6260, 7510, 9020, 10820, 12980 mg/kg
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
Observatin period: 7 days after administration
Sex:
male
Dose descriptor:
LD50
Effect level:
5 830 mg/kg bw
Remarks on result:
other: (5280 - 6420) mg/kg bw
Mortality:
no data
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 = 5830 (5280 - 6420) mg/kg bw
Executive summary:

In an acute oral toxicity study the LD50 for MMB was 5830 (5280 - 6420) mg/kg bw in mice for males.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Crj:CD(SD)IGS
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 114 (107 ~ 119)g male and 96 (90 ~ 103)g female
- Housing: 260W x 380D x 180H mm)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 55±10%
Vehicle:
water
Doses:
control, 1000 and 2000 mg/kg bw for both sexes
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: 1h, 3h and 6h followed daily until necropsy; body weight: day 1, 4, 8 and day of necropsy
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no
Clinical signs:
yes, slight reversible decreased locomotor activity in male (no. 012) after ~ 1 hrs, female (no. 513) after ~ 1 hrs and female (no. 511) after 3 hrs
Body weight:
no findings
Gross pathology:
no findings
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
LD50 > 2000 mg/kg bw for both sexes
Executive summary:

In an acute oral toxicity study the LD50 for MMB was > 2000 mg/kg bw in rats for both sexes

Doses were 0, 1000 and 2000mg/kgbw for both sexes. Result : There were no mortalities during the study. As a clinical sign, decreased locomotor activity was observed in 2000 mg/kgbw females. No abnormalities were detected in body weight gain and necropsy findings. The LD50 value was estimated to be more than 2000 mg/kgbw for both sexes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
4 300 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:
1991-05-07 to 1991-05-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Guideline:
other: Meeting Japanese MAFF (Ministry of Agriculture, Forestry and Fisheries) Testing Guidelines for Toxicity Studies (28 Januar 1985, 59 NohSan No. 4200) - Acute Dermal Toxicity Study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Manston Road, Margate, Kent
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: 204 - 324 g
- Housing: Housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays with a maximum of 5 animals per cage
- Diet (e.g. ad libitum): Rat and Mouse No. 1 Maintenance Diet, available ad libitum
- Water (e.g. ad libitum): Tap water, available ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21°C
- Humidity (%): 51%
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle (light hours 0700 - 1900 h)
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Approximately 23 cm^2
- Type of wrap if used: The test material was applied evenly onto a gauze dressing which was applied to the shaved back. The trunk of the rat was then encircled with a strip of non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin was wiped with a water dampened tissue
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500, 1000, 1500 and 2000 mg/kg for the range finding study; 2000 mg/kg for the main test

Duration of exposure:
24 hours
Doses:
500, 1000, 1500 and 2000 mg/kg for the range finding study; 2000 mg/kg for the main test
No. of animals per sex per dose:
2 in the range finding test
5 in the main test
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: They were weighed immediately prior to dosing, 7 days after dosing (main study only) and at sacrifice at the end of the 14 day observation period
- Necropsy of survivors performed: yes (sacrifice by carbon dioxide asphyxiation)
- Other examinations performed: clinical signs, body weight
Preliminary study:
In the dose ranging study there were no deaths and no abnormalities were noted at necropsy. Clinical signs, noted 2-4 h after dosing, were limited to reduced activity.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no Mortality
Clinical signs:
no clinical signs
Body weight:
Body weight gains were acceptable in males, but were slightly lower than in females.
Gross pathology:
No abnormalities were detected at necropsy.

Solfit: Acute Dermal Toxicity (LD50) Test in Rats; Test Results 2000 mg/kg

 Animal/Sex  Mortality  Clinical Signs  Necropsy Findings
 17¿  0  NAD  NAD
 18  0  NAD  NAD
 19  0  NAD  NAD
 20  0  NAD  NAD
21   0  NAD  NAD
 22¿  0  NAD  NAD
 23  0  NAD  NAD
 24  0  NAD  NAD
 25  0  NAD  NAD
 26  0  NAD  NAD

NAD = No abnormalities detected

Solfit: Acute Dermal Toxicity (LD50) Test in Rats; Body Weight 2000 mg/kg

 Animal/Sex

 Body Weight (g)         

   At Dosing  After 7 days  After 14 days  Gain (Loss)
 17¿  287  332  370  83
 18  281  318  340  59
 19  297  330  360  63
 20  324  369  404  80
 21  284  326  355  71
 Mean  295  335  365  71
 ± S.D.  18  20  24  10
22¿  204  232  227  23
 23  227  237  234  7
 24  227  244  241  14
 25  220  241  226  6
 26  231  249  240  9
 Mean  222  241  234  12
 ± S.D.  11  7  7  7
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The Median Dermal Lethal Dose (LD50) of Solfit in rats is greater than 2000 mg/kg
Executive summary:

The acute dermal toxicity potential of Solfit was investigated in rats. A dose ranging study in pairs of rats indicated that the LD50 value by dermal route is greater than 2000 mg.kg^-1. A main study dose level of 2000 mg. kg^-1 was selected accordingly. No further testing at other dose levels was necessary. In the main study, no deaths occurred and no clinical signs were noted after a 24 h dermal administration, under occlusion, of Solfit at a dose level of 2000 mg.kg^-1. The median Dermal Lethal dose (LD50) of Solfit in rats is greater than 2000 mg.kg^-1.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

In an acute dermal toxicity study with 3-methoxy-3-methyl-1-butanol (MMB) at 2000 mg/kg bw, there were no deaths, clinical signs or abnormalities at necropsy in SD rats. The acute dermal LD50 was considered to be more than 2000 mg/kg bw. In an acute oral toxicity study [OECD TG 401], Crj:rats (5 animals/sex/dose) were given MMB by gavage at 0, 2000, 3200, 4000 or 5000 mg/kg bw for males and females. Deaths occurred in males and females at 4000 mg/kg and higher. No changes in body weight were recorded for rats that died. The LD50 values were estimated to be 4500 and 4300 mg/kg bw in males and females, respectively. There is no available information on acute inhalation toxicity.


Justification for selection of acute toxicity – oral endpoint
Study was extended to high doses until effects were noted

Justification for classification or non-classification

Based on the oral and dermal LD50 values of > 2000 mg/kg bw, classification for acute oral and dermal toxicity is not warranted in accordance to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.