1H-Imidazolium, 3-ethyl-1-methyl-, chloride (1:1)

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

A Comparison of the Effects of Prenatal Exposure of CD-1 Mice to Tree Imidazolium-Based Ionic Liquids

Author:

Bailey, Melissa M.; et. al.

Year:

2010

Bibliographic source:

Birth Defects Research (Part B), 89 (233-238)

Reference 2

Reference Type:

other: Poster Abstract

Title:

A comparison of the Effects of Prenatal Exposure of CD-1 Mice to Three Inidazolium-Based Ionic Liquids

Author:

Lovich, A.N.

Year:

2009

Bibliographic source:

Birth Defects Research, 85 (5), p. 431

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

1-Ethyl-3-methylimidazolium chloride (C2mim)Cl

IUPAC Name:

1-Ethyl-3-methylimidazolium chloride (C2mim)Cl

Details on test material:

- Name of test material (as cited in study report):1-ethyl-3-methylimidazolium chloride (C2mim)Cl
- Physical state: off-white crystalline solid

Test animals

Species:

mouse

Strain:

CD-1

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Lab. Internationa (Wilmington, MA)
- Use of restrainers for preventing ingestion (if dermal): yes/no
- Diet (e.g. ad libitum): ad libitum (Teklad LM-485 rodant diet (Harlan Teklad, Madison, WI))
- Water (e.g. ad libitum): ad libitum (tap water)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 40 - 60 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sterile water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Stock solutions were prepared by dissolving the inioc liquids in sterile water at final concentrations: 500.35 mg/ml

Details on mating procedure:

Mice bred naturally, two females with one male. Observaton of a copulation plug designated gestation day 0 (GD 0).

Duration of treatment / exposure:

from GD 6-GD 16

Frequency of treatment:

Once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
1000, 2000, 3000 mg/kg bw
Basis:

No. of animals per sex per dose:

25 female

Control animals:

yes, concurrent vehicle

Details on study design:

rangefinder: 4000 mg/kg day

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: on GD 0 and as well as prior to each dosing

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of implantations: Yes

Fetal examinations:

On GD 17 the mated females were authanized by CO", the uteri were exposud, and the numbers of resorptions and dead or live fetuses were recorded- Live fetuses were removed from the uterus, weighed individueally and examined for gross malfromations. All fetuese were subsequently examined for skeletal abnormalities.

Statistics:

The data from each study replicate were calculated independently, tested for homogenicity of variance by means of the Levene statistic, using SPSS, and then pooled and analyszed to give the results reported. All tabular data are presented as the mean +/- standard error (SEM). Data were analyzed by one-way analysis of variance (ANOVA) followed by a least significant difference (LSD) posthoc test determine specific significant differences P ≤ 0.05 or by Pearson Z2 test (P ≤ 0.05).

Historical control data:

Historicla control data from more than 180 litters/2300 fetuses contained 2 incidences of bent tail and 2 incidences of ablepharia, but in the current study there were no incidences of any of the other malformations observed in fetuses from IL treated dams.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS): Maternal weight was not significantly affected by exposure. There was an apparent treatment effect on maternal weight gain in the highes dose group; the differences from their respective control values were not statisically significant.

OTHER FINDINGS (PARENTAL ANIMALS): The percentage of animals dying or becoming moribund and necessitationg euthanization prior to the completion of dosing were significantly greater inthe 3000 mg/kg day treatment group as compared to the control and lower doses.

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The numbers of implantations and the percentages of resorbed or dead fetuses did not differ significantly among treatment groups.
There was no effect on fetal weight among the exposed fetuses. No gross malformations were observed in fetuses.
There was an increased litter incidence of supernumerary ribs, but not statisically significant. The stuy did not find significant differences in the number of implantations, vialble fetuses or resorbed/dead fetuses among the treatment groups. There were no morphological aberrations.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

> 3 000 mg/kg bw/day (nominal)

Basis for effect level:

other: embryotoxicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Maternal Weight Gain and litter Parameters of CD-1 Mice

	Treatment and dose (mg/kg/day)
	Vehicle control	[C2min]Cl (1000)	[C2min]Cl (1000)	[C2min]Cl (1000)
Maternal weight gain (g ± SEM)	12.46 ± 0.68	13.51 ± 0.80	13.72 ± 0.74	11.31 ± 0.90
Maternal morbility/Mortality (No./% affected dams)	0	0	0	8/33.3^a
Fetus/litters examined	243/20	192/17	206/17	72/6
Implantations (mean ± SEM)	12.30 ± 0.53	12.12/0.54	11.50 ± 0.68	12.33 ± 0.84
Resorbed or dead fetuses (No. ± SEM)	0.90 ± 0.64	0.47 ± 0.47	2.51 ± 1.22	2.67- 1.69
Litters with resorbed or dead fetuses (No./%)	2/10.0	1/5.9	4/22.2	2/33.3
Malformed fetuses (% ± SEM)^bc	0 ± 0.0	0 ± 0.0	0 ± 0.0	0 ± 0.0
Malformed fetuses (% affected litters)^b	0.0	0.0	0.0	0.0
Supernumerary Ribs (% ± SEM)	13.64 ± 3.47	15.41 ± 3.66	19.36 ± 5.82	23.00 ± 3.47
Rudimentary Ribs (% ± SEM)	11.12 ± 3.84	15.91 ± 3.42	10.43 ± 2.59	10.33 ± 2.72

^aSignificantly different from all other mean values (P≤0.01)

^bFetuses displaying any gross malformation

^cGrand mean of litter mean percentages.