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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:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Read-across to tetradonium bromide from data on dodecyltrimethylammonium chloride (with data reliability value of 2). R

Data source

Reference
Reference Type:
other: Assessment report for American Chemistry Council, Fatty Nitrogen Derivatives Panel, Cationics Task Group
Title:
Unnamed
Year:
2001

Materials and methods

Principles of method if other than guideline:
No guideline stated.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid - liquid: aqueous solution
Details on test material:
Purity = 35% in Dobanol 45E7
Mixture of C12-C14 isomers.
Study consider CAS RN 112-00-5 as appropriate for the chemical

Test animals

Species:
rabbit
Strain:
New Zealand White

Administration / exposure

Route of administration:
oral: gavage
Details on exposure:
Definitive study: Thirteen or 14 mated female rabbits per group were exposed to the test substance orally at doses of 0, 2, 8 and 24 mg/kg/day for days 6 through 18 of gestation. The control group was treated with deionized water only.
Range-Finding Study: Three mated female rabbits per group were exposed to the test substance orally at doses of 0, 25, 50, 100, 200 or 400 mg/kg/day for days 6 through 18 of pregnancy.
Duration of treatment / exposure:
Days 6 - 18 of gestation
Frequency of treatment:
Daily
Duration of test:
Days 6 - 18 of gestation
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2, 8, 24 mg/kg/day - definitive study
Basis:

Remarks:
Doses / Concentrations:
25, 50, 100, 200, 400 mg/kg/day – range-finding study
Basis:

No. of animals per sex per dose:
13 or 14
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
Definitive study: Animals were observed daily for signs of toxicity. Body weights were taken every three days during pregnancy. Food consumption was measured daily. All surviving dams were sacrificed at study termination on gestation day 29 using sodium pentobarbital.
Range-finding study: Body weights were determined on days 0, 6, 11, 17 and 29. Food consumption was measured daily. Animals found dead were necropsied.
Ovaries and uterine content:
Definitive study: An examination of the uterus, including the number corpora lutea, implantations, and resorptions was conducted. Uteri from females that appeared non-gravid were placed in 10% ammonium sulfide solution for confirmation of pregnancy.
Range-finding study: Uterine disposition of young was recorded, and corpora lutea and resorptions sites were counted
Fetal examinations:
Definitive study: At sacrifice fetuses were weighed, and examined externally for defects. Sex determination also was conducted on each fetus. Two thirds of the fetuses were examined for skeletal and 1/3 were examined for visceral abnormalities.
Range-finding study: Survivors were sacrificed on day 29 of gestation and fetuses were weighed and examined microscopically.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
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
Gross pathological findings:
no effects observed
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects. Remark: Definitive study

Details on maternal toxic effects:
Range finding study:
Morality occurred in the dams as follows: 1/3, 1/3, 2/3, 3/3, and 3/3 for the 25, 50, 100, 200, and 400 mg/kg/day groups, respectively. A decrease in body weight was observed at 50 and 100 mg/kg/day. Apparent resorptions occurred in the two surviving females at 50 mg/kg/day but the intercurrent mortality was considered to prohibit definitive judgment on a direct effect of the test substance on maintenance of pregnancy

Effect levels (maternal animals)

open allclose all
Key result
Dose descriptor:
NOEL
Effect level:
ca. 24 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
35% iin Dobanol 45E7
Basis for effect level:
other: maternal toxicity
Key result
Dose descriptor:
NOEL
Effect level:
ca. 24 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
35% in Dobanol 45E7
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
no effects observed
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
no effects observed
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
no effects observed
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects. Remark: Definitive study

Details on embryotoxic / teratogenic effects:
Range-finding study:
An indirect embryotoxic effect based on fetal body weight was considered to have been exhibited at 50 mg/kg/day.

Effect levels (fetuses)

Key result
Dose descriptor:
NOEL
Effect level:
ca. 24 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reduction in number of live offspring
changes in sex ratio
fetal/pup body weight changes
changes in litter size and weights
changes in postnatal survival
external malformations
skeletal malformations
visceral malformations

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Key result
Developmental effects observed:
no
Lowest effective dose / conc.:
24 mg/kg bw/day
Treatment related:
no

Applicant's summary and conclusion

Conclusions:
Within the limitations of the experimental conditions used, C12-14 trimethylammonium chloride was not directly fetotoxic or teratogenic. The NOEL for maternal systemic toxicity and developmental toxicity appeared to be 24 mg/kg bw/day. An indirect embryotoxic effect based on fetal body weight was considered to have been exhibited at 50 mg/kg/day in the range finding test.
Executive summary:

13 -14 mated female New Zealand white rabbits per group were exposed daily for days 6 to 18 of gestation to C12 -14 trimethylammonium chloride orally (gavage) at dosage levels of 0, 2, 8 and 24 mg/kg bw/day.

Animals were observed daily for signs of toxicity. An examination of the uterus, including the number corpora lutea, implantations, and resorptions was conducted. At sacrifice fetuses were weighed, and examined externally for defects. Sex determination also was conducted on each fetus. Two thirds of the fetuses were examined for skeletal and 1/3 were examined for visceral abnormalities.

No effects related to treatment were observed at the doses used in this study. Within the limitations of the experimental conditions used,

C12 -14 trimethylammonium chloride was not directly fetotoxic or teratogenic. The NOEL for maternal systemic toxicity and developmental toxicity appeared to be 24 mg/kg bw/day.

An indirect embryotoxic effect based on fetal body weight was considered to have been exhibited at 50 mg/kg/day in the range finding test.