N,N,N-trimethylanilinium chloride

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data from secondary source

Data source

Reference

Reference Type:

secondary source

Title:

Robust Summaries & Test Plans for test material Joint Venture HPV Chemicals Challenge

Author:

Consumer Specialty Products Association (CSPA)

Year:

2011

Bibliographic source:

Robust Summaries & Test Plans for test material, Joint Venture HPV Chemicals Challenge 2011

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: U. S. EPA FIFRA 83-3

Principles of method if other than guideline:

Reproductive and developmental toxicity study oftest material was performed on Sprague Dawley rats.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides

EC Number:

270-325-2

EC Name:

Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides

Cas Number:

68424-85-1

Molecular formula:

Unspecified

IUPAC Name:

Alkyl dimethyl benzyl ammonium chloride

Details on test material:

- Name of test material (as cited in study report):Alkyl dimethyl benzyl ammonium chloride
- Molecular formula:unspecified
- Molecular weight :368.0448g/mol
- Substance type: Organic

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

No data available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

Details on exposure
PREPARATION OF DOSING SOLUTIONS: test material dissolved in Milli-Q water

DIET PREPARATION
- Rate of preparation of diet (frequency):No data available
- Mixing appropriate amounts with (Type of food)
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle:10, 30 and 100 mg/kg/day
- Amount of vehicle (if gavage): 5 ml/kg/day.

- Lot/batch no. (if required): No data available
- Purity: No data available

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

timed-pregnant female rats

Duration of treatment / exposure:

10 days (Days 6 through 15 of gestation)

Frequency of treatment:

Daily

Duration of test:

Day 21 of gestation

Doses / concentrations

Remarks:

0,10, 30 and 100 mg/kg/day

No. of animals per sex per dose:

Total:100
0 mg/kg/day:25 female
10 mg/kg/day:25 female
30 mg/kg/day:25 female
100mg/kg/day:25 female

Control animals:

yes

Details on study design:

- Dose selection rationale: A range-finding study was conducted to determine dose levels for the definitive developmental toxicity study. Five groups of five timedpregnant female rats each were dosed with test material at concentrations of 25, 50, 100, 200 or 400 mg/kg/day by oral gavage on gestation days (GD) 6 through 15.

Examinations

Maternal examinations:

Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: yes

DETAILED CLINICAL OBSERVATIONS: Yes

Time schedule: female rats were observed for mortality twice daily, clinical
signs of toxicity daily (twice daily during dosing)


BODY WEIGHT: Yes
Time schedule for examinations: maternal body weights and food consumption were
measured at varying intervals.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes Food consumption was determined weekly.

Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data available


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
Time schedule for examinations:

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other:

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: No data

Statistics:

Quantitative continuous variables were compared for the three treatment groups and the control group by use of Levene’s test for equality of variances, analysis of variance (ANOVA), and t-tests. Nonparametric data were evaluated using the Kruskal-Wallis test, followed by the Mann- Whitney U test when appropriate. Incidence data were compared using the Fisher’s Exact Test.

Indices:

No data available

Historical control data:

No data available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Treatment-related clinical signs included perioral wetness in 67% of dams in the 100 mg/kg group. Audible respiration during and subsequent to the treatment period also was observed in three dams in the 100 mg/kg group.
One dam in this group exhibited dehydration, unkempt appearance, loose feces, urine stains and perioral wetness. Audible respiration was observed in two dams in the 30 mg/kg group. One of these dams also exhibited urine stains, gasping, perinasal encrustation, loose feces and perioral wetness. No treatment-related clinical signs were observed in animals in the 10 mg/kg group during or subsequent to treatment.

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

There were no effects of treatment on gestational body weight and weight gain, corrected body weight.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Food consumption was reduced for days 6 - 9 of gestation in the 30 and 100 mg/kg groups.

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

There were no effects of treatment on gravid uterine weight.

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Maternal developmental toxicity

Number of abortions:

not specified

Pre- and post-implantation loss:

no effects observed

Total litter losses by resorption:

no effects observed

Early or late resorptions:

no effects observed

Dead fetuses:

not specified

Changes in pregnancy duration:

not specified

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed

Changes in number of pregnant:

no effects observed

Other effects:

not specified

Details on maternal toxic effects:

Pregnancy rate was equivalent among groups and ranged from 84 to 100%. Twenty-one to 25 live litters were available for evaluation from each group. There were no statistically significant differences between treated and control animals in gestational parameters
(including total number of implantations, number of viable and nonviable implants per litter).

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

body weight and weight gain

changes in number of pregnant

clinical signs

early or late resorptions

food consumption and compound intake

maternal abnormalities

number of abortions

pre and post implantation loss

total litter losses by resorption

Remarks on result:

other: No effects observed

Maternal abnormalities

Abnormalities:

not specified

Localisation:

not specified

Results (fetuses)

Fetal body weight changes:

no effects observed

Description (incidence and severity):

There were no statistically significant differences between treated and control fetal body weights per litter
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified

Reduction in number of live offspring:

not specified

Changes in sex ratio:

not specified

Changes in litter size and weights:

not specified

Changes in postnatal survival:

not specified

External malformations:

no effects observed

Skeletal malformations:

no effects observed

Visceral malformations:

no effects observed

Other effects:

not specified

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

fetal/pup body weight changes

external malformations

skeletal malformations

visceral malformations

Remarks on result:

other: No developmental toxic effects were observed

Fetal abnormalities

Abnormalities:

not specified

Localisation:

other: not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Treatment related:

not specified

Relation to maternal toxicity:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

No Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 100mg/kg bw/day. When female SpragueDawley rats were treated with test material orally.

Executive summary:

The reproductive and developmental toxicity of test material was performed ontimed-pregnant female Sprague-Dawley rats. The test material was dissolved in Milli-Q water in dose concentration 10, 30 and 100 mg/kg/day and adminstered in dose volume 5 ml/kg orally by gavage from Days 6 through 15 of gestation. The dose concentration selected on the bases of dose range finding atconcentrations of 25, 50, 100, 200 or 400 mg/kg/day by oral gavage on gestation days (GD) 6 through 15.study.In main study,three groups of 25 timed-pregnant female rats each were dosed group while a control group of 25 timed-pregnant rats received water. Administered dose volumes of water or aqueous solutions of test material were based on the individual dam’s body weight on GD 6 and a constant volume of 5 ml/kg/day. Concentrations were adjusted for percentactive ingredient. Throughout the study, (GD 0 - 21), female rats were observed for mortality twice daily, clinical signs of toxicity daily (twice daily during dosing) and maternal body weights and food consumption were measured at varying intervals. At scheduled sacrifice on GD 21, a gross necropsy was performed on all dams. In addition, the dams were evaluated for body weight, liver and gravid uterine weight, number of corpora lutea, and number and status of implantation sites. All live fetuseswere dissected from the uterus weighed and examined for external malformation and variations and gender determinations. Approximately one-half of the live fetuses in each litter were examined for thoracic and abdominal visceral abnormalities. These fetuses were decapitated and their heads were fixed in Bouin’s solution for examination of craniofacial structures by serial sectioning. Intactfetuses (approximately one-half) were processed for skeletal staining with alizarin red S and examined for skeletal malformations and variations.

Treatment-related clinical signs included perioral wetness in 67% of dams in the 100 mg/kg group. Audible respiration during and subsequent to the treatment period also was observed in three dams in the 100 mg/kg group. One dam in this group exhibited dehydration, unkempt appearance, loose feces, urine stains and perioral wetness. Audible respiration was observed in two dams in the 30 mg/kg group. One of these dams also exhibited urine stains, gasping, perinasal encrustation, loose feces and perioral wetness. No treatment-related clinical signs were observed in animals in the 10 mg/kg group during or subsequent to treatment. Food consumption was reduced for days 6 - 9 of gestation in the 30 and 100 mg/kg groups. There were no effects of treatment on gestational bodyweight and weight gain, corrected body weight or gravid uterine weight. Pregnancy rate was equivalent among groups and ranged from 84 to 100%. Twenty-one to 25 live litters were available for evaluation from each group. There were no statistically significant differences between treated and control animals in gestational parameters (including total number of implantations, number of viable and nonviable implants per litter). There were no statistically significant differences betweentreated and control fetal body weights per litter or in the incidences of external, visceral or skeletal malformations or variations.HenceNo Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 100mg/kg bw/day. When female Sprague Dawley rats were treated with test material orally.