Glycerol, propoxylated, esters with acrylic acid, reaction products with diethylamine

Endpoint summary

Description of key information

The acute toxicity potential of Glycerol, propoxylated, esters with acrylic acid, reaction products with diethylamine was evaluated in an oral acute test performed on rat. No mortality was observed in this study, the LD50 is also considered to be higher than 2000 mg/kg/d.

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:

06 January 2015 - 25 February 2015

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

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 219 g (range: 199 g to 242 g)
- Fasting period before study: yes, during the night before treatment
- Housing: the animals were housed in threes, from the same group, in polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

IN-LIFE DATES: 27 January 2015 to 25 February 2015.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Justification for choice of vehicle: the vehicle used in this study was selected from the results of solubility assays performed by the CiToxLAB France Pharmacy.
The solubility assay first started at the concentration of 200 mg/mL, and the first choice vehicle was drinking water treated by reverse osmosis and then 0.5% methylcellulose aqueous solution.
As unsatisfactory solubility of the test item was obtained in these vehicles (i.e. heterogeneous emulsion at the concentration of 200 mg/mL was obtained), corn oil was used. A visually homogenous solution was obtained at the concentration of 200 mg/mL in corn oil.
- Maximum dose-volume applied: 10 mL/kg

DOSAGE PREPARATION:
The test item was administered as a solution in the vehicle. The test item was mixed with the required quantity of vehicle.
Dose formulations preparations were prepared by the CiToxLAB France Pharmacy extemporaneously on the day of each administration.
The dose formulations were stored at room temperature and delivered to the study room in glass flasks.

CLASS METHOD:
- Rationale for the selection of the starting dose: the starting dose-level was selected in agreement with the Sponsor. Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data were taken into account by the Sponsor, the starting dose-level was 300 mg/kg for ethical reasons.

Doses:

300 and 2000 mg/kg.

No. of animals per sex per dose:

3 females per treatment step.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Statistics:

no

Sex:

female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

At 300 mg/kg, no clinical signs were observed in any animals.
At 2000 mg/kg, piloerection was noted in all animals within 4 hours after treatment. This was associated with hunched posture and half-closed eyes, in 3/6 females, dyspnea in 2/6 females and/or hypoactivity in 1/6 females. These clinical signs were no longer observed from Day 2.

Body weight:

When compared to CiToxLAB France historical control data, minimal differences were noted in the mean body weight gain in some animals at 300 and 2000 mg/kg between Days 1 and 8. As they were not associated to adverse effects, and had no impact on the final body weight, these differences were considered not to be toxicologically relevant.
The body weight of animals was unaffected by the test item treatment.

Gross pathology:

The mandibular lymph nodes were enlarged in 3/3 animals from group 2 treated at 2000 mg/kg.
As this observation may be occasionally seen in rats, was confined to the mandibular lymph nodes only without involvement of the other lymph nodes and in the absence of similar changes in group 3 animals treated at the same dose-level, any relationship to the test item was considered to be unlikely.

Other findings:

no

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of the test item was higher than 2000 mg/kg in rats.

Executive summary:

The objective of this study was to evaluate the potential acute toxicity of the test item following a single oral administration (gavage) to rats.

This study was conducted in compliance with OECD Guideline No. 423 and the principles of Good Laboratory Practices.

Methods

The test item was administered once by oral route (gavage) to three groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test item was prepared in corn oil.

Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data were taken into account by the Sponsor, the starting dose-level was 300 mg/kg for ethical reasons. After the first assay, the next higher dose-level of 2000 mg/kg was tested. Then, as no toxicity was observed at this higher dose-level, the results were confirmed in other females.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on Day 1 and then on Days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination.Macroscopic lesions were preserved in buffered formalin then destroyed at the finalization of the study report as no microscopic examination was performed.

 

Results

No unscheduled deaths occurred during the study and no clinical signs were observed in animals given 300 mg/kg.

At 2000 mg/kg, piloerection was noted in all animals within 4 hours after treatment along with hunched posture, half-closed eyes, dyspnea, and/or hypoactivity were observed in a few females. These clinical signs were no longer observed from Day 2.

Body weight was unaffected by the test item treatment, when compared to historical control data.

At the end of the observation period, no test item-related macroscopic changes were observed at necropsy.

Conclusion

Under the experimental conditions of this study, the oral LD50 of the test item was higher than 2000 mg/kg in rats.

Therefore, the test item should not be classifiedfor the acute toxicityby oral route according to the criteria of CLP Regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The study is considered to be reliable with a klimish score of 1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity study (Leclere 2015)

The objective of this study was to evaluate the potential acute toxicity of the test item following a single oral administration (gavage) to rats.

This study was conducted in compliance with OECD Guideline No. 423 and the principles of Good Laboratory Practices.

The test item prepared in corn oil was administered once by gavage to three groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg.

No unscheduled deaths occurred during the study and no clinical signs were observed in animals given 300 mg/kg (3 females).

At 2000 mg/kg (6 females), piloerection was noted in all animals within 4 hours after treatment along with hunched posture, half-closed eyes, dyspnea, and/or hypoactivity were observed in a few females. These clinical signs were no longer observed from Day 2. Body weight was unaffected by the test item treatment, when compared to historical control data. At the end of the observation period, no test item-related macroscopic changes were observed at necropsy.

Under the experimental conditions of this study, the oral LD50 of the test item was higher than 2000 mg/kg in rats.

Justification for classification or non-classification

According to the available data, Glycerol, propoxylated, esters with acrylic acid, reaction products with diethylamine should not be classified for acute toxicity. No classification is justified because no mortality was observed in the acute oral toxicity on rats.

No dermal acute study was available, but no dermal toxicity is expected for the following reasons: no oral toxicity was observed in the acute study, and the acrylate compounds are known to be not harmful or toxic after oral or dermal single exposure.

No inhalation acute study was available, but inhalation exposure is not expected due to the low vapour pressure of Glycerol, propoxylated, esters with acrylic acid, reaction products with diethylamine.