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Description of key information

MPD has a low acute toxicity by the oral routes. In rats, LD50 value by oral route is 8000 mg/kg bw. Because of its very low vapour pressure, it can be conjectured that the test substance is unlikely to be toxic after acute inhalation (vapours). A well documented intraperitoneal study yielded a LD 50 value of 2100 mg/kg. Published results from a study with mice are available which indicate a LD50 value of 320 mg/kg when MPD is administered intravenously.

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:
1987-07-08 to 1987-09-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD standard and is well described, although not done under GLP
Qualifier:
according to guideline
Guideline:
other: Annex V of EEC Directive 79/831/EEC, Part B Method for determination of toxicity. Method B1 Acute Oral Toxicity
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Specific details on test material used for the study:
- Name of test material (as cited in study report): 3-Methyl-1,5 pentandiol
- Physical state: Colourless clear liquid
- Analytical purity: <99%
- Stability under test conditions: The stability and absorption of the test substance were not determined
- Storage condition of test material: 3-Methyl-1,5 pentandiol was received on 1 July 1987 and stored at ambient temperature
- Other: 3-Methyl-1,5 pentandiol was administered, as supplied by the Sponsor, at a volume not exceeding 10.29 ml/kg (S.G. 0.97)
Species:
rat
Strain:
other: Crl : COBS CD (SD) BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent, England.
- Age at study initiation: Approximately four to six weeks of age.
- Weight at study initiation: weight range of 90 to 149 g in the main study.
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
- Housing: The rats were allocated to cages within the treatment groups. They were housed in groups by 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): Ad libitum.
- Acclimation period: For a minimum period of 6 days prior to the start of the main study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The mean daily minimum and maximum temperatures of the animal room were 20°C and 23°C respectively.
- Humidity (%): The mean daily humidity value was 66%
- Air changes (per hr): Maintained at approximately 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hour period.

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The appropriate dose volume of the test substance was administered to each rat using a syringe and plastic catheter.
Doses:
5.0, 6.4, 8.0, 10.0 g/kg
5.14, 6.58, 8.23, 10.29 ml/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. 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 weekdays or 11.30 hours on Saturday and Sunday. Clinical signs were recorded at each observation. Individual bodyweights of rats on Days 1 (day of dosing), 8 and 15 and at death.
Necropsy of survivors performed: yes. Surviving animals on the main study were killed on Day 15 by cervical dislocation. All animals that died during the study and those killed on Day 15 were subjected to a macroscopic post mortem examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs when presented was recorded.

The animals on the preliminary study were observed for 5 days after dosing
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.
Separate LD50 values for males 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) using the technique described by Finney (1978, Statistical Method in Biological Assay, 3rd Edition, Charles Griffin, London). A chi-squared test was carried out to check that the data did not contain any evidence for non-parallelism.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
8 other: g/kg bw
95% CL:
7.1 - 9.5
Remarks on result:
other: High mortality affected females dosed at 8.0 g/kg and both males and females dosed at 10.0 g/kg. Slight renal pallor in four animals (8.0 g/kg), slight pallor of the liver in one female (5.0 g/kg). Bodyweight losses were recorded for all rats that died.
Sex:
male
Dose descriptor:
LD50
Effect level:
8.3 other: g/kg bw
95% CL:
6.9 - 10.5
Sex:
female
Dose descriptor:
LD50
Effect level:
7.8 other: g/kg bw
95% CL:
6.5 - 9.7
Mortality:
There were single deaths among female rats dosed at 5.0 g/kg and males treated at 6.4 and 8.0 g/kg. Higher mortality affected females dosed at 8.0 g/kg and both males and females given the test substance at 10.0 g/kg.
Clinical signs:
Signs of reaction to treatment observed in all rats within two hours of dosing were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate and pallor of the extremities. Other clinical signs apparent up to five hours after dosing were:
ptosis in all rats dosed at 5.0, 6.4 and 8.0 g/kg;
increased salivation in all rats treated at the highest dose level;
prostration among those dosed at 5.0, 8.0 and 10.0 g/kg.
Recovery of surviving rats, as judged by external appearance and behaviour, was advanced by Day 2 or Day 3 and complete by Day 4 or Day 5.
Body weight:
Low bodyweight gains were recorded on Day 8 for the majority of rats treated at 5.0 g/kg, for single male and female rats dosed at 6.4 g/kg and for the males surviving a dose level of 8.0 g/kg.
All rats, except for a single female (6.4 g/kg), achieved anticipated bodyweight gains during the second week of the study.
Bodyweight losses were recorded for all rats that died
Gross pathology:
Autopsy of rats that died revealed slight renal pallor in four animals (8.0 g/kg) and slight pallor of the liver in one female (5.0 g/kg). No other macroscopic abnormalities were found.
Terminal autopsy findings were normal

Preliminary study:

Results of the preliminary study indicated that the acute median lethal oral dose of 3-methyl-1,5 pentandiol was greater than 4.0 g/kg bodyweight.

Time and number of deaths of rats dosed orally with 3 -methyl-1,5 pentandiol (main study)

Sex   Dose (g/kg)  Number of deaths in a group of 5 Day                               
                 1         2      3 to 15   
                    Hours after dosing               
       1/2  2  3  4  6  a  b
male  5.0   0                      
male   6.4                1      
 male  8.0                    
 male 10.0   5                    
 female 5.0   1                    
female   6.4  0                      
female   8.0  3                3      
 female  10.0  4                    

The hour/day indicated is the time that the animal was observed to die or found dead

a First observation

b Second observation

Conclusions:
LD50 = 8.0 g/kg for males and females combined

The acute median lethal oral doses (LD50) and their 95% confidence limits to rats of 3-methyl-1,5 pentandiol were estimated to be:
Males and females combined: 8.0 (7.1 to 9.5) g/kg bw
Males only: 8.3 (6.9 to 10.5) g/kg bw
Females only: 7.8 (6.5 to 9.7) g/kg bw
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
8 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (limited documentation, no analytical determination of test atmosphere)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted in 1981
Deviations:
yes
Remarks:
(limited documentation, no analytical determination of test atmosphere)
Principles of method if other than guideline:
Inhalation Hazard Test: Groups of 3 rats per sex are sequentially exposed to an atmosphere enriched with vapours of the volatile components of the test substance at 20 C° for 8 h.
GLP compliance:
no
Test type:
other: inhalation hazard test
Specific details on test material used for the study:
- Name of test substance (as cited in study report): 3-Methylpentanodiol-1,5
- Analytical purity: 99.5%
- Physical state: liquid
- Density: 0.973 g/mL
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: test group: 186 g; control group: 199 g
no additional details reported
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Rats were exposed sequentially to the vapours generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 8 h at 20 °C. The exposure was subsequently repeated in the same manner. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was claculated as quotient of the amount of test substance weight loss during exposure, and the amount of air used during exposure. Group-wise documentation of clinical signs was performed over a 8 day study period.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
0.07 mg/L (calculated as quotient of the amount of test substance weight loss and the amount of air used during the exposure)
No. of animals per sex per dose:
- Test group: 6
- Control group: 3
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of weighing: before exposure and at before sacrifice
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LC0
Effect level:
0.07 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
other: No mortality and no clinical signs were observed when test animals were exposed to a test atmosphere presumably saturated with vapours of test substance at 20 °C.
Mortality:
No mortality was observed during the study.
Clinical signs:
other:
Body weight:
Test groups:
- day 0: 199 g (males), 173 g (females)
- day 7: 232 g (males), 187 g (females)

Control group:
- day 0: 205 g (males), 193 g (females)
- day 7: 237 g (males), 213 g (females)
Gross pathology:
No abnormalities detected.
Conclusions:
No reliable conclusion can be made concerning classification for acute inhalative toxicity. However, because no mortality / clinical signs of toxicity was observed after 8 h exposure, and because of its very low vapour pressure, it can be conjectured that the test substance is unlikely to be toxic after acute inhalation (vapours).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
70 mg/m³
Quality of whole database:
reliable with restrictions

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity oral:

One key and one supporting study with MPD were carried out at doses which killed the rats. A third study supports the result, but did not test that high a dose level.

Acute toxicity dermal:

The acute toxicity study via the dermal route does not need to be conducted as reliable data via the oral and inhalation routes are available.

Acute toxicity inhalation:

In the acute inhalation toxicity study with rats and an estimated test concentration of 0.07 mg/l air (nominal), no mortality and no clinical signs were observed. The atmosphere was saturated with MPD vapour and had concentrations far below any expected toxic effects. From oral toxicity it is expected that vapour / aerosol concentrations above 10 g/m³ may be necessary to see an effect.

Acute toxicity intraperitoneal injection:

A well reported study with mice and intraperitoneal application of the substance resulted in a LD50 for male and female >2092 - <2500 mg/kg.

Published results from an intravenous application of the substance in mice indicates a LD 50 value of 320 g/kg.


Justification for selection of acute toxicity – oral endpoint
One key and one supporting study with MPD were carried out at doses (similar doses of 8 g/kg bw) which killed the rats. The more reliable study was chosen for this endpoint. The third study supports the result, but did not test that high a dose level.

Justification for selection of acute toxicity – inhalation endpoint
One reliable study (with acceptable restrictions) is available. In this test no mortality and no clinical signs were observed when test animals were exposed to a test atmosphere presumably saturated with vapours of test substance at 20 °C. It was a LC0 = 0.07 mg/L air (nominal) observed. The endpoint was not used for the safety assessment, see justification in section 5.2.3 of the CSR.

Justification for classification or non-classification

Based on the oral and inhalation values, classification for acute oral, dermal and inhalation 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.