(3-methacrylamidopropyl)trimethylammonium chloride

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1 June 2012 to 21 July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 422

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(3-methacrylamidopropyl)trimethylammonium chloride

EC Number:

257-182-1

EC Name:

(3-methacrylamidopropyl)trimethylammonium chloride

Cas Number:

51410-72-1

Molecular formula:

C10 H21 N2 O. Cl

IUPAC Name:

trimethyl-[3-(2-methylprop-2-enoylamino)propyl]azanium chloride

Test material form:

other: fluid liquid

Details on test material:

Identity : 3-Trimethylammonium propyl methacrylamide chloride (50% solution in water)
Alternative names : VISIOMER® MAPTAC; VISIOMER® MAPTAC 50% in water;
N-Trimethylammoniumpropylmethacrylamid-chlorid
CAS number : 51410-72-1
EINECS number : 257-182-1
Appearance at first use: Undefined clear free-flowing yellow liquid
Storage conditions : Room temperature, protected from light

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Italy S.p.A., Calco (Lecco), Italy

- Age at study initiation: (P) Males/females: approximately 8 - 9 wks
- Weight at study initiation: (P) Males: 196.5 - 204.7 g; Females: 166.1 - 189.3 g

- Fasting period before study:
- Housing: Pre mating period: no more than 5 per cage in clear polycarbonate cages measuring 59X39X20 cm with a stainless steel
mesh lid and floor (Techniplast - Gazzada S.a.r.l., Buguggiate, Varese). Each cage tray will hold absorbent material which will be
inspected daily and changed at least three times a week.
During mating period: 1 male to one female per cage in clear polycarbonate cages measuring 36X19X24 cm with a stainless steel
mesh lid and floor (Techniplast - Gazzada S.a.r.l., Buguggiate, Varese). Each cage tray will hold absorbent material which will be
inspected daily.
Pregnant females: will be transferred to individual cages after mating: solid bottomed, breeding cages (Techniplast - Gazzada S.a.r.l.,
Buguggiate, Varese), for the gestation period, birth and lactation.
Suitable nesting material will be provided and will be changed as necessary.
- Diet: ad libitum, commercially available laboratory rodent diet (4 RF 21, Mucedola S.r.l., Via G. Galilei, 4,
20019, Settimo Milanese (MI), Italy)
- Water: ad libitum, supplied via water bottles

- Acclimation period: aproximately 14 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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: The test item was administered orally by gavage and the formulations were prepared daily.

DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:

VEHICLE
- Justification for use and choice of vehicle (if other than water): solubility of test item
- Concentration in vehicle: 10, 35 and 100 mg/mL
- Amount of vehicle (if gavage): 5 mL/kg body weight
- Lot/batch no. (if required): ----
- Purity: ----

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Once during week 1 and week 6 of treatment, samples of prepared formulations were analysed for verification of concentration.

Details on mating procedure:

Mating was monogamous (one male to one female). A vaginal smear was taken from the
day after the start of pairing until positive identification of copulation (sperm identification,
vaginal plug in situ or copulation plugs found in the cage tray).
The female was paired with the same male until positive identification occurred.

Duration of treatment / exposure:

Males
Animals were dosed once a day, 7 days a week, for a minimum of 2 consecutive weeks prior
to pairing and thereafter through the day before necropsy.
Dose volumes were adjusted once per week for each animal according to the last recorded
body weight.

Females
Animals were dosed once a day, 7 days a week, for a minimum of 2 consecutive weeks prior
to pairing and thereafter during pairing, post coitum and post partum periods until Day 3
post partum or the day before sacrifice.
Dose volumes were adjusted once per week for each animal according to the last recorded
body weight. During the gestation period, dose volumes were calculated according to
individual body weight on Days 0, 7, 14 and 20 post coitum and on Day 1 post partum.
Thereafter individual dose volumes remained constant.

Doses / concentrations

Remarks:

Doses / Concentrations:
0 (Vehicle), 100, 300, and 1000 mg/kg/d
Basis:
nominal conc.

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

Dose levels had been selected in consultation with the Sponsor based on information from a previous non GLP Compliant study (RTC Study no.:
90940EXT).

Examinations

Maternal examinations:

yes

Ovaries and uterine content:

yes

Fetal examinations:

yes

Statistics:

Standard deviations were calculated as appropriate. For continuous variables the
significance of the differences amongst group means were assessed by Dunnett’s test or a
modified t test, depending on the homogeneity of data.
Statistical analysis of histopathological findings was carried out by means of the nonparametric
Kolmogorov-Smirnov test if n was more than 5.
The non-parametric Kruskal-Wallis analysis of variance was used for the other parameters.
Intergroup differences between the control and treated groups were assessed by the nonparametric
version of the Williams test. The criteria for statistical significance were p<0.05
and p<0.01.
The mean value, standard deviations and statistical analysis were calculated from actual
values in the computer without rounding off.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

3-Trimethylammonium propyl methacrylamide chloride (MAPTAC) did not show developmental toxicity via oral gavage to rats at doses as high as 1000 mg/kg bw/day in the decribed reproductive/developmental toxicity screening study according to OECD 422.

Executive summary:

3-Trimethylammonium propyl methacrylamide chloride (MAPTAC) did not show developmental toxicity via oral gavage to rats at doses as high as 1000 mg/kg bw/day in the decribed reproductive/developmental toxicity screening study according to OECD 422 (for more details please also see IUCLID chapter 7.5.1 and 7.8.1). There were no signs of neonatal toxicity or external malformations at doses of 1000 mg/kg bw/day.