Reaction mass of diethyl adipate and diethyl glutarate and diethyl succinate

Endpoint summary

Description of key information

Acute oral study: LD50 (rat) > 2000 mg/kg

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:

From 27 June to 15 September 2017

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:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- batch No.of test material:CY71353002
- Expiration date of the lot/batch: 01 June 2019
- Purity test date: 01 June 2017
- Analytical purity: 98.2%
- Commercial name of the registered substnace: Innroad Protect


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Refrigerated (2-8 °C)
- Stability under test conditions: Not assessed
- Solubility and stability of the test substance in the solvent/vehicle: soluble PEG 400 (polyethylene glycol 400). Stability not assessed
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: Not assessed

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks old
- Weight at study initiation: 225 – 249 g
- Fasting period before study: The animals were fasted on the night before treatment.
- Housing: 3 animals / cage
- Diet (e.g. ad libitum): ssniff® SM R/M "Autoclavable complete diet for rats and mice ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 15-20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3 – 24.9 °C
- Humidity (%): 31 – 70 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: 27 June To: 12 July 2017

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400 (polyethylene glycol 400)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: one of the recommended vehicles in the OECD guideline
- Lot/batch no. (if required): BCBS1795V
- Purity: 100%

MAXIMUM DOSE VOLUME APPLIED: 10 mL

- Rationale for the selection of the starting dose:In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.

Doses:

2000 mg/kg bw/day

No. of animals per sex per dose:

6 animals
Initially, three female animals were treated with 2000 mg/kg bw of the test item. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required according to the test guideline.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: Macroscopic examination was performed on all animals.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed.

Clinical signs:

other: There were no systemic clinical signs noted in any animal throughout the study.

Gross pathology:

There was no evidence of macroscopic observations at necropsy at a dose level of 2000 mg/kg bw.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item Innroad Protect was found to be above 2000 mg/kg bw in female Crl:WI rats. In the absence of mortality and clinical signs, the registered substance Reaction mass of diethyl adipate and diethyl glutarate and diethyl succinate can be ranked as "Unclassified" for acute oral exposure according the GHS.

Executive summary:

The single-dose oral toxicity of Innroad Protect was assessed according to the acute toxic class method (OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.tris Test Guidelines) in Crl:WI rats.

Two groups of three female Crl:WI rats were treated with the test item at a dose level of 2000 mg/kg bw (Group 1 and Group 2). A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered formulated in PEG 400 at a concentration of 200 mg/mL at a dose volume of 10 mL/kg bw.

Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore, no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.tris Test Guidelines.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and 14 (before necropsy). All animals were subjected to a necropsy and a macroscopic examination.

RESULTS

Innroad Protect did not cause mortality at a dose level of 2000 mg/kg bw.

There were no systemic clinical signs noted in any animal throughout the study.

There were no treatment related body weight changes. Body weight gains of Innroad Protect treated animals during the study showed no indication of a test item related effect.

There was no evidence of macroscopic observations at necropsy at a dose level of 2000 mg/kg bw.

CONCLUSION

Under the conditions of this study, the acute oral LD50 value of the registered substance was found to be above 2000 mg/kg bw in female Crl:WI rats.

In the absence of mortality and clinical signs, Reaction of diethyl adipate and diethyl glutarate and diethyl succinate can be ranked as "Unclassified" for acute oral exposure according the GHS.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and OECD 423 compliant study

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

On study, of reliability 1 according to Klimisch cotation criteria, is available for the oral route (Weisz, 2017). Following oral gavage of 6 female rats at the dose of 2000 mg/kg bw, no death occured and no clinical signs were reported during the 2 -week observation period. The LD50 for oral route in rats was higher than 2000 mg/kg bw. No classification for acute oral toxicity is therefore warranted on the basis of this in vivo data.

Justification for classification or non-classification

Due to the absence of mortality following oral exposure of rats to limit test dose of 2000 mg/kg bw, no classification for acute toxicity is warranted according to the criteria of EU Regulation 1272/2008 (CLP).