2-ethylhexyl methacrylate

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: sub-chronic oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: FOB segment in full guideline subchronic oral study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Guideline:

other: FOB in subchronic oral study

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl methacrylate

EC Number:

211-708-6

EC Name:

2-ethylhexyl methacrylate

Cas Number:

688-84-6

Molecular formula:

C12H22O2

IUPAC Name:

2-ethylhexyl methacrylate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Sulzfeld Germany
- Age at study initiation: male: 35-37 days; female: 33-35 days
- Housing: 5 animals per cage
- Diet (e.g. ad libitum): ad libitum (ground Kliba maintenance diet mouse/rat "GLP" meal)
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30-70
- Air changes (per hr): 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
The test substance was administered as an emulsion. The appropriate amount of test substance was weighed out depending on the desired concentration. Thereafter, the vehicle (drinking water containing 1% carboxymethyl cellulose) was filled up to the desired volume + Cremophor EL + one drop Hydrochloric Acid (1mol/L) and subsequently mixed using a magnetic stirrer. The test-substance preparations were produced daily.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Concentration control analyses of the test-substance preparations in samples of all concentrations were performed at the start of the administration period and thereafter weekly.

Duration of treatment / exposure:

about three months

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
60, 120 and 360 mg/kg/day
Basis:
nominal conc.
in vehicle

No. of animals per sex per dose:

Control and high dose groups: 15 animals per sex per group (thereof 5 animals per sex per group for 28-day recovery)
Low and mid dose groups: 10 animals per sex per group.

Control animals:

yes, concurrent vehicle

Details on study design:

- Post-exposure recovery period in satellite groups: 28 days (5 rats/sex of control and high dose groups only)

Examinations

Observations and clinical examinations performed and frequency:

Functional observation battery (FOB) was carried out on the assigned animals once before the exposure period and once against the end of the exposure period. Motor activity was measured on the same day and with the same animals as FOB was performed.

Neurobehavioural examinations performed and frequency:

rearing, grip strength forelimbs, grip strength hindlimbs, foot-splay test, and motor activity.

Sacrifice and (histo)pathology:

NECROPSY
All animals were sacrificed by decapitation under Isoflurane anesthesia. The exsanguinated animals were necropsied and assessed by gross pathology.

WEIGHT PARAMETERS
The following weight determinations were carried out on all animals: anesthetized animals, liver, kidneys, adrenal glands, testes, epididymides, ovaries, uterus, spleen, brain, heart, thymus, thyroid glands.

HISTOPATHOLOGY
After the organs were fixed, processing, examination by light microscopy and evaluation of findings in the following tissues of all control and high-dose animals of the main groups were performed: salivary glands (mandibular and sublingual glands), esophagus, stomach (forestomach and glandular stomach), duodenum, ileum, jejunum (with Peyer’s plaques), cecum, colon and rectum, liver, pancreas, brain, pituitary gland, sciatic nerve, spinal cord (cervical, thoracic and lumbar cords), eyes, adrenal glands, thyroid glands, parathyroid glands, trachea, lungs, nose (nasal cavity/level III), aorta, heart, bone marrow (femur), lymph nodes (mesenteric and axillary lymph nodes), spleen, thymus, kidneys, urinary bladder, testes, ovaries, oviducts, uterus and vagina, prostate, seminal vesicle and epididymides, female mammary gland, skin.
Additionally, nose tissue (nasal cavity/level III) was examined in all low- and mid-dose animals of the main groups and in all control and high-dose animals of the recovery groups. Furthermore, all gross lesions were examined in all affected animals of all groups.

Other examinations:

standard 90 d guideline examinations

Statistics:

KRUSKAL-WALLIS test (two-sided)/Wilcoxon-test (two-sided)

Results and discussion

Results of examinations

Behaviour (functional findings):

no effects observed

Details on results:

Up to the highest dose tested (360 mg/kg/day) there were no effects in the functional observational battery and no effects on motor activity.

Effect levels

Dose descriptor:

NOAEL

Effect level:

360 mg/kg bw (total dose)

Sex:

male/female

Remarks on result:

other:

Any other information on results incl. tables

Up to the highest dose tested (360 mg/kg/day) there were no effects in the functional observational battery and no effects on motor activity.

Applicant's summary and conclusion

Conclusions:

Up to the highest dose tested (360 mg/kg/day) there were no effects in the functional observational battery and no effects on motor activity.

Executive summary:

2 -EHMA was tested for subchronic oral toxicity. Up to the highest dose tested (360 mg/kg/day) there were no effects in the functional observational battery and no effects on motor activity.