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Administrative data

Description of key information

Subchronic (90 d) oral study in rats (OECD 408); NOAEC in FOB: 300 mg/kg bw/d (RTC, 2007).

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Link to relevant study records
Reference
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:
guideline study
Remarks:
FOB segment in full oral guideline study
Guideline:
other: FOB in subchronic oral study
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
- Name of test material (as cited in study report): N-3-Dimethylaminopropyl methacrylamide
- Supplier: Evonik Röhm GmbH, D-64293 Darmstadt, Germany
- Substance type: organic
- Physical state at room temperature: liquid
- Stability under test conditions: Stability in water: > 160 hours in water; pure: stable for 3 month
- Storage condition of test material: +2-8 °C, light protected
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy S.r.l., San Pietro al Natisone (UD), Italy
- Age at study initiation: (P) Males/females: approximately 47-49 days old
- Weight at study acclimatisation: (P) 96 - 110 g (male and female), therefore slightly outside the range indicated in the study protocol
- Fasting period before study:
- Housing: No more than 5 per cage of one sex in clear polycarbonate cages measuring 59X38.5X20 cm with a stainless steel
mesh lid and floor (Code 1354 G, Techniplast - Gazzada S.a.r.l., Buguggiate, Varese). Each cage tray held absorbent material which was
inspected and changed at least 3 times a week.
- Diet: ad libitum, commercially available laboratory rodent diet (4 RF 21, Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI), Italy), except as indicated during week 13 of treatment, samples of blood were taken under conditions of food deprivation.
- Water: ad libitum, supplied via water bottles, except as indicated during week 13 of treatment, samples of blood were taken under conditions of
water deprivation.
- Acclimation period: 20 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±2 °C
- Humidity (%): 55 ±15 %
- Air changes (per hr): 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: The test item was dissolved in distilled water to give the required concentrations of 7.5, 15.0 and 30.0 mg/ml.

The test item was administered orally by gavage at a dose volume of 10 ml/kg body weight.
Control animals received the vehicle alone at the same dose volume.
The dose was administered to each animal on the basis of the most recently recorded body weight and the volume administered was recorded for
each animal.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Prior to commencement of treatment the proposed formulation procedure was checked by chemical analysis to confirm that the method was
acceptable. Stability over a 24 hour period at room temperature was assessed for content check prior to the start of treatment. Samples of the
formulations prepared at weeks 1 and 13 were analysed to check the concentration. Results of all the analyses were within the limits of acceptance
(95-105%).
Duration of treatment / exposure:
for a minimum of 13 consecutive weeks
All animals were dosed up until the day before necropsy.
Frequency of treatment:
daily, 7 days/week
Remarks:
Doses / Concentrations:
0 (vehicle alone), 75, 150 and 300 mg/kg/day
Basis:
nominal in water
No. of animals per sex per dose:
10/sex/dose
Control animals:
yes, concurrent vehicle
Details on study design:
Ten male and ten female Sprague Dawley rats per test group were whole body exposed to a vapor of the test substance on 6 hours per working day for 90 days (65 exposures). The target concentrations were 20, 40, 100 and 350 ppm (corresponding to 70, 141, 352 and 1232 mg/m3). A concurrent control group was exposed to conditioned air.
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.
Behaviour (functional findings):
no effects observed
Details on results:
Up to the highest dose tested (300 mg/kg bw/d) there were no effects in the functional observational battery and no effects on motor activity.
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw (total dose)
Sex:
male/female
Basis for effect level:
other: No neurotoxicity up to the highest investigated dose
Remarks on result:
other:

Up to the highest dose tested (300 mg/kg bw/d) there were no effects in the functional observational battery and no effects on motor activity.

Conclusions:
Up to the highest dose tested (300 mg/kg bw/d) there were no effects in the functional observational battery and no effects on motor activity.
Executive summary:

N-3-Dimethylaminopropylmethacrylamide was tested for subchronic oral toxicity. Up to the highest dose tested (300 mg/kg bw/d) there were no effects in the functional observational battery and no effects on motor activity.

(NOTE: Any of the data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the sense of a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities, who have paid the respective access fee for the intended purpose.)

Endpoint conclusion
Dose descriptor:
NOAEL
300 mg/kg bw/day

Effect on neurotoxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Effect on neurotoxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An FOB segment was performed during a subchronic (90 d) oral study in rats with DMAPMA. In the gavage study there was no indication of neurotoxicity up to the highest dose of 300 mg/kg bw/d (RTC, 2007).

Justification for classification or non-classification

In the absence of any specific neurotoxicity up to subchronic exposure, classification for neurotoxicity is not justified.