2-Butenedioic acid, 2-methyl-, 1,4-bis(2-ethylhexyl) ester, (2Z)-

Endpoint summary

Description of key information

An oral limit test in rats (OECD 423, non-GLP, Klimisch 2).

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:

2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP screening test

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

method based on 423 but only 2 animals were used

Principles of method if other than guideline:

Two female rats were treated with with bis-(2-ethylhexyl)-citraconate at 2000 mg/kg bw by oral gavage as a screening acute oral toxicity limit test. Adminstration of the single dose were folled by a 14 day observation period and gross necropsy. Two rats are considered to be the lowest number that can be used to make a realistic estimate for a limit screen, in line with animal welfare needs.

GLP compliance:

no

Remarks:

This Limit Test was conducted as a screening tests for the PPORD and intermediate registration purposes only. Even if it was not conducted under GLP, the laboratory had a valid GLP certificate.

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Source: RccHan: (WIST) rats, source Harlan Laboratories, R.r.l., S. Petro al Natisone (UD), Zona Industriale Azzida, 57, 33040 Italy.
Young, healthy, adult, 8 - 12 week old females, nulliparous, non pregnant animals, 150 - 300 g.
Acclimatisation period at least 5 days.
Group caging (2/cage), type II/polypropylene/polycarbonate, certified laboratory wood bedding.
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 +- 3oC, rH 30 - 70 %, 15 - 20 air exchanges/hour, recorded twice daily.
Food ssniff(R) SM R/M Autoclavable complete diet for rats and mice ad libitum, tap water from municipal supply 500 mL bottle ad libitum.

Route of administration:

oral: gavage

Vehicle:

other: sunflower oil

Details on oral exposure:

Freshly prepared test item at was administered as a single oral dose. The formulation was stirred with a magnetic stirrer up to finishing the treatment.

Doses:

Freshly prepared test item at concentration 200 mg/mL was administered as a single oral dose at a dosing volume 10 mL/kg bW.

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

Clinical observatios 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. 7 and 14 just before necropsy. Both animals were subjected to a necropsy and a macroscopic examination.

Statistics:

Two test animals, 20 clinical observations per animal, mean body weight and body weight gains were reported and standard deviations calculated.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality at a dose level of 2000 mg/kg bw (appendix 1).

Clinical signs:

other: There were no clinical signs during the 14 days observation period after treatment at 2000 mg/kg bw (Appendix 2).

Gross pathology:

There was no evidence of macroscopic effects at necropsy at a dose level of 2000 mg/kg bw (appendix 4).

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance was not toxic in an acute oral limit test in rats (LD50 was > 2000 mg/kg bw).

Executive summary:

The test substance was not toxic in an acute oral limit test in rats (LD50 was > 2000 mg/kg bw; non-GLP OECD 423 screening test). The non-GLP test is rated as reliable with restrictions (Klimisch 2).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 2

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

The test substance was not toxic in an acute oral limit test in rats (LD50 was > 2000 mg/kg bw; non-GLP OECD 423 screening test). The non-GLP test is rated as reliable with restrictions (Klimisch 2).

Justification for selection of acute toxicity – oral endpoint
The classification criterion is not met.

Justification for selection of acute toxicity – inhalation endpoint
In accordance with REACH Article 18, the study is not required.

Justification for selection of acute toxicity – dermal endpoint
In accordance with REACH Article 18, the study is not required.

Justification for classification or non-classification

The substance does not meet the classification criteria for acute oral toxicity.