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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
From 10 January to 06 February 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Detailed study report comparable to OECD guideline study but not performed according to GLP. The supporting substance is considered adequate for read-across purpose as data relates to a mixture of cis- and trans-isomers whereas the registered substance is the pure cis-isomer (see Iuclid section 13 for additional justification).
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Methyl 3-oxo-2-pentylcyclopentaneacetate
EC Number:
246-495-9
EC Name:
Methyl 3-oxo-2-pentylcyclopentaneacetate
Cas Number:
24851-98-7
IUPAC Name:
methyl (3-oxo-2-pentylcyclopentyl)acetate
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Methyl dihydrojasmonate
- Substance type: pure active substance

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (U.K.) Limited
- Age at study initiation: about 5 weeks old
- Weight at study initiation: 56 - 94 g
- Fasting period before study: From 17h00 the day before the study (overnight fasting)
- Housing: polypropylene cages measuring 56 x 38 x 18 cm, with stainless steel grid floors and tops (North Kent Plastics Limited). The grid floor ensured rapid removal of waste material to undertrays which were cleaned as necessary. A minimum floor area of 250 cm2 per rat was provided by grouping no more than six animals of the same sex in each cage.
- Diet (e.g. ad libitum): ad libitum excepted overnight fasting before dosing (quality certified and checked)
- Water (e.g. ad libitum): ad libitum (quality checked)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 50 ± 10 %
- Air changes (per hr): 17 complete air changes per hour without recirculation
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): constant volume dosage of 20 ml/kg (freshly prepared)
- Justification for choice of vehicle: solvent commonly used for hydrophobic substances
Doses:
Preliminary study: 1, 7.5 and 10.0 mL/kg bw (male + female) (eq. to 1, 7.5 and 10000 mg/kg bw)
Main study: 10.0 mL/kg bw (male + female) (eq. to 10 mg/kg bw)
No. of animals per sex per dose:
Preliminary study: 2 males + 2 females
Main study: 10 males + 10 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: daily (three times per day excepted the week-end: two times). Bodyweight: At day 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not applicable/Not relevant

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 95% CL: NA in this case
Mortality:
males: 3/10 ( two males were found dead during the first overnight period and a further male was found dead on Day 4).
females: 0/10
Total males + females: 3/20
Clinical signs:
other: The initial signs of reaction to treatment consisted of a decrease in motor activity, piloerection, diarrhoea and muzzle staining, which developed between 0.5 to 4.5 hours after dosing, and were absent by Day 3. Signs of delayed toxicity, consisting of ab
Gross pathology:
Necropsy of early decedents revealed, externally, staining of muzzle and urinogenital region, dorsal hair loss with occasional encrustations, autolytic changes and cannibalisation. Internal change, consisting of fluid and mucoid gastro-intestinal tract contents, was attributed to irritation. Findings at necropsy of surviving animals were confined to the presence of occasional petechiae on all lobes of the lungs of a single male, but this observation was not considered treatment-related.
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Oral combined LD50 > 10000 mg/kg bw
Executive summary:

Introduction.The acute oral toxicity of Methyl dihydrojasmonate was investigated in a group of ten fasted male and ten female rats of the Charles River CD strain at the maximum practicable dosage of 10 ml/kg using a test guideline equivalent to OECD TG 401 “AcuteOral Toxicity”. The test material was prepared as a solution in maize oil and administered at a constant volume-dosage of 20 ml/kg. Mortality and signs of reaction to treatment were recorded over a 14 -day period of observation. Decedents and animals killed on Day 15 were subjected to necropsy.

 

Results and discussion. Two ma1es died on the morning of Day 2 and a third was found dead on Day 4. None of the tested females died.

Initial signs of reaction to treatment consisted of reduced motor activity, piloerection, diarrhoea and muzzle staining. Signs of delayed toxicity became evident as abdominal bloat and dorsal hair loss in three animals on Day 4. In addition, the females of one cage were unkempt between Days 2 and 7. Excepting one case where hair loss continued until termination, all the observed effects were totally reversible after Day 7.

 

Necropsy of decedents revealed, externally, muzzle and urinogenital staining, dorsal hair loss with occasional encrustations,autolytic changes and cannibalisation. Internal changes consisted of fluid and mucoid.gastro-intestina1 tract contents which were attributed to irritation.

There were no treatment-related lesions in animals examined at necropsy on Day 15.

Survivors made normal bodyweight progress over the two-week assessment period, with the exception of a single female that showed reduced weight gain between Days 1 and 8.

 

Conclusions. From the observed mortality data the acute oral median lethal dosage (LD50) of Methyl dihydrojasmonate was found to lie in excess of the maximum practicable dosage of 10000 mg/kg bw (LD50 > 10000 mg/kg bw).

The supporting substance is considered adequate for read-across purpose as data relates to a mixture of cis- and trans-isomers whereas the registered substance is the pure cis-isomer (see Iuclid section 13 for additional justification).

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