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Toxicological information

Acute Toxicity: oral

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
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:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
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)

Test animals

Species:
rat
Strain:
other: Crl : COBS CD (SD) BR
Sex:
male/female
Details on test animals 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.

Administration / exposure

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.

Results and discussion

Effect levelsopen allclose all
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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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