2-Propenoic acid, (2,2-dimethyl-1,3-dioxolan-4-yl)methyl ester

Endpoint summary

Description of key information

LD50(oral, rat): >300 - 2000 mg/kg bw

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

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- Fasting period before study: feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum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

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 300 - < 2 000 mg/kg bw

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:

2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

2008

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline 12 Nousan No. 8147

Version / remarks:

2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: Manufacturer, Batch 0812-HS-0030
- Purity: 96.2%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: refrigerator

Species:

rat

Strain:

Wistar

Sex:

male/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: 9 weeks (males), 12 weeks (females)
- Weight at study initiation: 260g (males), 212g (females)
- Fasting period before study: no
- Housing: single
- Diet (e.g. ad libitum): ad lib.
- Water (e.g. ad libitum): ad lib.
- Acclimation period: 5 days

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

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 40cm² (at least 10% of body surface)
- fur clipped app. 24h before exposure

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.87 ml/kg b.w.

Duration of exposure:

24h

Doses:

2000mg/kg

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: shortly before application, weekly thereafter
- Necropsy of survivors performed: yes (gross-pathology
- Clinical signs: recorded several times on the day of exposure, daily thereafter
- Other examinations performed:
- scoring of skin findings: 30-60min after removal of the substance, several times thereafter
- mortality: at least once daily

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

none

Other findings:

local effects males:
In all male animals, well-defined erythema (grade 2) was noticed on study day 1 after application, but progressed to moderate to severe erythema (grade 3, from study day 2 until study day 3, 7 or 10. Thereafter, well-defined erythema (grade 2) was observed in one animal from study day 6 until study day 7, while very slight erythema (grade 1) was seen in all animals from study day 8 until study day 10 or from study day 13 until study 14.
Slight edema (grade 2) was seen in all male animals from study day 2 until study day 3, 7 or 10, which regressed in three animals to very slight edema (grade 1) from study day 6 or 8 until study day 10 after application. Incrustations were noticed in four out of five animals from study day 6 until study day 7 or 10. In addition, scaling was seen in four male animals from study day 8 until study day 10 or from study day 13 until study day 14. In one of these animals, erythema and edema beyond the application site were observed from study day 6 until study day 10 after application.

local effects females:
In all female animals, well-defined erythema (grade 2) was noticed from study day 1 until study day 3 and persisted in one of these animals until study day 10 after application, followed by very slight erythema (grade 1) in this female from day 13 until day 14. In the other four female animals, moderate to severe erythema (grade 3) was seen from study day 6 until study day 7 or 10 after application. Thereafter, well-defined erythema (grade 2) was observed from study day 8 until study day 10 in two of these animals, which decreased in one of these animals to very slight erythema from day 13 until day 14. In the other two animals well-defined erythema (grade 2) was observed from study day 13 until study 14. Slight edema (grade 2) was seen in all animals from study day 2 until study day 7 or 10, while in three of these animals very slight edema (grade 1) was observed from study day 8 until study day 10.
In addition, incrustations were noted from study day 2 until study day 14 in two female animals and from study day 6 until study day 7 in another animal. Scaling was noticed in three animals from study day 6 or 8 until study day 10 or 14.
Furthermore, erythema and edema beyond the application area were seen in one animal from study day 6 until study day 10 after application.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

In an acute oral toxicity study performed according to the Acute Toxic Class Method, doses of 2000 and 300 mg/kg bw of the test item Laromer IPGA (undiluted or preparations in corn oil) were administered by gavage to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 3 females, 300 mg/kg bw in 6 females). Clinical signs occurred within the first day after administration of 2000 mg/kg bw, mortality in two animals, one animal was sacrificed moribund, impaired general state in all animals, dyspnoea in all animals, gasping in one animal, piloerection in all animals, cowering position in all animals, abdominal position in one animal, reduced defecation in all animals, none defecation in one animal, poor general state in one animal, macroscopic pathological findings in the two animals that died and the single animal which was sacrificed moribund, 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 sacrificed animal). In the 300 mg/kg neither mortality nor clinical signs were observed, macroscopic pathological findings in the surviving animals that were sacrificed at the end of the study period, red discoloration of the small intestine and its contents in one animal of the second 300mg/kg bw test group. All animals gained weight in a normal range throughout the study period. 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.

 

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item IPGA to the clipped application site (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing during the 24-hour exposure period. The application area comprised at least 10% of the total body surface. The animals were observed for 14 days.
Neither mortality nor clinical signs were observed.
The following test item-related local effects were recorded during the course of the study, local skin effects occurred until the last day of observation at the latest:
- Very slight to moderate erythema (grade 1 to 3)
- Very slight to slight edema (grade 1 to 2)
- Incrustations
- Scaling
- Additionally, erythema and edema were noted beyond the application site.
All animals gained weight in a normal range throughout the study period.
No macroscopic pathologic abnormalities were noted in any animal examined at the end of the study (5 males and 5 females).
Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw

Justification for classification or non-classification

Based on the available studies data on acute toxicity properties the test item would have to be classified as harmful if swallowed, cat.4 (H302) to Regulation (EC) No 1272/2008 (CLP).