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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 28, 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
not applicable
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Test material form:
liquid: viscous
Remarks:
Clear water-white viscous liquid
Specific details on test material used for the study:
Test material: (Alkyl (C12-C18) dimethylethylbenzylammonium chloride as a.i.) in aqueous solution
Lot/Batch number: Notebook #1607-3684; Sample #676-09/L
Description: Clear water-white viscous liquid
Purity: 50% w/w a.i.
Stability: The a.i., ADEBAC, is hydrolytically and photolytically stable under the conditions of this study and its related quaternary ammonium compounds have been shown to be stable in aqueous, alcohol and alcohol/aqueous solutions for extended periods, e.g. at least five years under standard laboratory conditions.

Test animals

Species:
rat
Strain:
other: Female Wistar derived albino
Details on test animals or test system and environmental conditions:
-Individual mesh bottom cages in temperature controlled quarters
-Free access to food and fresh tap water

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Dose levels: 0, 5, 15 and 50 mg/kg bw/day (0, 2.5, 7.5 and 25 mg/kg bw/day a.i.)
Details on mating procedure:
Adult female rats were mated with young adult male and detection of the vaginal sperm plus was considered to occur on day 0 of gestation
Duration of treatment / exposure:
Days 6 - 15 of gestation
Frequency of treatment:
Once daily during exposure period
Duration of test:
Dams were scacrificed on day 20 of gestation
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Remarks:
Without test substance (Only vehicle - Water)
Dose / conc.:
5 mg/kg bw/day
Remarks:
2.5 mg/kg bw/day (a.i.)
Dose / conc.:
15 mg/kg bw/day
Remarks:
7.5 mg/kg bw/day (a.i.)
Dose / conc.:
50 mg/kg bw/day
Remarks:
25 mg/kg bw/day (a.i.)
No. of animals per sex per dose:
22-37/group female rats
Control animals:
yes
yes, concurrent no treatment

Examinations

Maternal examinations:
Clinical signs: Daily
Mortality: Daily
Bodyweight: Days 0, 6, 11, 15 and 20
Number of corpora lutea
Number of implantation and resorptions sites
Number of corpora lutea
Urogenital tract gross necropsy
Ovaries and uterine content:
Not examined
Fetal examinations:
Body weight
Gross necropsy
Skeletal examinations - Two thirds of the foetuses were used for this examination
Visceral examinations - One third of the foetuses were used for this examination
Statistics:
Confidence Belts for proportions with a confidence coefficient of 0.95 was used to compare the experimental and control groups. If the significance was not clearly definable, the probability of the occurrence was determined by the computation of exact probabilities.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not examined
Mortality:
mortality observed, treatment-related
Description (incidence):
3 dams died in the 50 mg/kg/day test group.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
There were no effects of treatment on gestational body weight.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined

Maternal developmental toxicity

Number of abortions:
not examined
Pre- and post-implantation loss:
not examined
Total litter losses by resorption:
not examined
Early or late resorptions:
not examined
Dead fetuses:
not examined
Changes in pregnancy duration:
not examined
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not examined
Changes in number of pregnant:
not examined
Other effects:
no effects observed
Description (incidence and severity):
Affects on gestation were not noted in any treatment group. Twelve females in the positive control group resorbed their uterine contents.

Effect levels (maternal animals)

Key result
Dose descriptor:
NOEL
Effect level:
ca. 15 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
mortality
Remarks on result:
other: i.e., equivalent to 7.5 mg a.i./kg bw/day

Maternal abnormalities

Key result
Abnormalities:
effects observed, treatment-related
Localisation:
other: General toxicity - Mortality
Description (incidence and severity):
3 dams in the 50 mg/kg bw/day test group died

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
No treatment-related effects were observed in all treated group. Decreased weights were observed in the positive control group.
Reduction in number of live offspring:
not examined
Changes in sex ratio:
not examined
Changes in litter size and weights:
not examined
Changes in postnatal survival:
not examined
External malformations:
not examined
Skeletal malformations:
no effects observed
Description (incidence and severity):
No treatment-related variations or malformations
Visceral malformations:
effects observed, non-treatment-related
Description (incidence and severity):
No treatment-related variations or malformations
Other effects:
no effects observed
Description (incidence and severity):
No malformations
Details on embryotoxic / teratogenic effects:
No developmental toxicity including teratogenicity was observed at any dosage employed, as compared to the negative control group.

Effect levels (fetuses)

Key result
Dose descriptor:
NOEL
Effect level:
> 50 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: No developmental toxicity, including teratogenicity was observed at any dosage employed.
Remarks on result:
other: NOEL 25 mg a.i./kg bw/day

Fetal abnormalities

Key result
Abnormalities:
no effects observed
Description (incidence and severity):
No developmental toxicity, including teratogenicity was observed at any dosage employed.

Overall developmental toxicity

Key result
Developmental effects observed:
no

Applicant's summary and conclusion

Conclusions:
Under study conditions, for test substance, the NOEL for maternal toxicity and developmental toxicity were determined to be 15 mg/kg bw/day (7.5 mg/kg bw/day a.i.) and >50 mg/kg bw/day (25 mg a.i./kg bw/day) respectively.
Executive summary:

A study was conducted to determine the developmental toxicity of test substance, C12-18 ADEBAC (active: 50%), according to a method equivalent or similar to OECD 414 guideline. 22-37 pregnant female Wistar rats/group were treated with test substance at concentrations of 0, 5, 15 and 50 mg/kg bw/day (0, 2.5, 7.5 and 25 mg a.i./kg bw/day) or aspirin (positive control) at 250 mg/kg bw/day. The dams were sacrificed at Day 20 and the foetuses were examined for visceral and skeletal variations and malformations. There were no treatment-related effects on the body weight or reproductive parameters. Increased mortality was observed at 50 mg/kg/day, however, this finding was not statistically significant. There were no treatment-related effects on foetal body weight or visceral/skeletal findings. In the positive control group, increased fetal resorption, decreased fetal weight and increase incidences of skeletal and soft tissue variations were observed. No developmental toxicity, including teratogenicity was observed at any dosage employed. Under study conditions, for test substance, the no observable effect level (NOEL) for maternal toxicity and developmental toxicity were determined to be 15 mg/kg bw/day (7.5 mg/kg bw/day a.i.) and >50 mg/kg bw/day (25 mg a.i./kg bw/day) respectively (Knickerbocker and Stevens, 1977).