Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(2,2-dimethyl-1,3-dioxolan-4-yl)methyl prop-2-enoate
Cas Number:
13188-82-4
Molecular formula:
C9H14O4
IUPAC Name:
(2,2-dimethyl-1,3-dioxolan-4-yl)methyl prop-2-enoate
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (female animals approx. 10 weeks)
- Weight at study initiation: animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum
- Housing: single housing (Makrolon cage, type I)
- Diet (e.g. ad libitum): R/M maintenance, low phytoestrogen; Ssniff, Spezialdiäten GmbH (Soest, Germany), ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C *+/- 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: Solution in corn oil Ph.Eur
Doses:
2000 and 300 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter, on the last day of observation and on the day of death or sacrifice moribund starting with study day 1. Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, pathology: yes

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg bw: two animals were found dead and one animal was sacrificed in a moribund state on study day 1.
300 mg/kg bw: No mortality occurred.
Clinical signs:
other: 2000 mg/kg bw: in all animals impaired general state, cowering position, piloerection and dyspnea from hour 3 until hour 5 after administration. In one animal, piloerection persisted until study day 1 after administration, additional findings at this read
Gross pathology:
The following macroscopic pathologic findings were observed in the animals that died or in the single animal which was sacrificed in a moribund state (2000 mg/kg bw test group, 3 females): Red to dark brown discoloration of the small intestine and its contents in two animals; Dark spotted discoloration of the liver in two animals; Enlarged, dark red spotted stomach in all animals (haemorrhages in the single, moribund sacrificed animal).
The following macroscopic pathologic findings were noted in the animals examined on the last day of observation (second 300 mg/kg bw test group, 1 female): Red discoloration of the small intestine and its contents. There were no macroscopic pathological findings in five animals of both 300 mg/kg bw test groups sacrificed at the end of the observation period.

Any other information on results incl. tables

Mortality

Mortality

Dose (mg/kg bw):

2000

Sex:

female

Administration:

1

No. of animals:

3

Mortality (animals):

3

Mortality

Dose (mg/kg bw):

300

300

Sex:

female

female

Administration:

1

2

No. of animals:

3

3

Mortality (animals):

No mortality

No mortality

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of this study the median lethal dose of Laromer IPGA after oral administration was found to be > 300 mg/kg bw - 2000 mg/kg bw in rats.