Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, acetates

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study predated formal guideline requirements and GLP but performed according to existing scientific standards. Reliabilty check by Expert Panel (American Chemistry Council Fatty Nitrogen Derivatives) passed.

Data source

Reference

Title:

Unnamed

Year:

1975

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

modifications in exposure period

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, dimethylditallow alkyl, chlorides

EC Number:

272-207-6

EC Name:

Quaternary ammonium compounds, dimethylditallow alkyl, chlorides

Cas Number:

68783-78-8

IUPAC Name:

68783-78-8

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

other: oral gavage; oral diet

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

days 6 - 13 or 6 - 18 of gestation

Frequency of treatment:

daily

Duration of test:

days 0 - 21 of gestation

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Remarks:

oral gavage

Doses / concentrations 2

Dose / conc.:

500 mg/kg bw/day (actual dose received)

Remarks:

oral gavage

Doses / concentrations 3

Dose / conc.:

508 mg/kg bw/day (actual dose received)

Remarks:

0.65% active in diet; oral diet

No. of animals per sex per dose:

25 rats per group (10 animals sacrified after 13 days, 15 animals after 21 days of gestation)

Control animals:

yes, concurrent vehicle

yes, plain diet

Details on study design:

Two concurrent control groups: One receiving the gavage vehicle isopropanol, one receiving control feed only

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Remarks:

via gavage

Effect level:

> 500 mg/kg bw/day (nominal)

Basis for effect level:

other: highest dose tested

2

Dose descriptor:

NOAEL

Remarks:

via diet

Remarks on result:

not determinable

Remarks:

slight effects on body weight gain

Maternal abnormalities

Abnormalities:

no effects observed

Results (fetuses)

Effect levels (fetuses)

1

Dose descriptor:

NOAEL

Remarks:

via gavage

Effect level:

> 500 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: highest dose tested

2

Dose descriptor:

NOAEL

Remarks:

via diet

Effect level:

> 508 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: highest dose tested

Fetal abnormalities

Abnormalities:

no effects observed

Overall developmental toxicity

Developmental effects observed:

no

Applicant's summary and conclusion

Conclusions:

Based on the results from this study ditallowdimethylammonium chloride is not considered to be a developmental toxicant.

Executive summary:

Ditallowdimethylammonium chlorid (DTDMAC)was investigated for developmental toxicity in the rat. 25 female rats per group were administered the test substance either by oral gavage at dose levels of 100 and 500 mg active ingredient per kg body weight per day (vehicle was 15% isopropanol) or in the diet at a dose level of 0.65% active ingredient beginning on day 6 of gestation. Two control groups were run concurrently. One received the gavage vehicle and the other received control feed only.

Ten rats per group were sacrificed after the day 13 treatment and 15 rats per group were treated through day 18 and sacrificed on day 21 of gestation. Body weights were taken on days 0, 6, 9, 12, 15, 18 and 21 of gestation. Food consumption was evaluated for days 12 and 18 of gestation. Clinical observations were made daily for signs of pharmacologic or toxicologic effect and mortality. Gross necropsies were conducted on all surviving rats, moribund rats and rats that died spontaneously. At necropsy, for rats sacrificed on day 13 of gestation, the uterus (number and location for each horn of resoptions, embryos and implantation sites) and ovaries (number of corpora lutea of pregnancy per ovary) were observed. At necropsy for rats sacrificed on day 21 of gestation, the uterus (number and location for each horn of live fetuses, dead fetuses, early and late resorptions and impantation sites) and ovaries ( number of corpora lutea of pregnancy per ovary) were observed. The necropsy for all maternal rats also included observations for obvious abnormalities and the following tissues were examined: heart, lung, stomach, liver, pancreas, spleen, mesenteric lymph nodes, jejunum, kidney, adrenal, bladder and ovary.

With regard to maternal data, no adverse effects attributable to DTDMAC administration were noted in comparison of pregnancy and mortality rates. Depressed body weight gains during gestation were noted in the group that received the test substance in the diet together with less food consumption values compared to the group that received control feed. Early deliveries and abortions, necropsy findings, and reproduction data were considered not to be affected by treatment with the test substance. An increase in resorptions was observed for the 100 mg/kg/day gavage group compared to the isopropanol control group (7.1% vs 2.1%). This difference was not considered a treatment-related effect due to the lack of dose response and a low value for the control group compared to historical data from the laboratory.

With regard to fetal data, no differences considered to be related to the adminsitration of ditallowdimethylammonium chloride were noted in fetal size and sex, variations in degree of ossification or malformations.

Based on the results of this study, the NOAEL for maternal toxicity was considered to be greater 500 mg/kg body weight per day by gavage. No NOAEL for maternal toxicity was established for dietary treatment because of the slight effects on body weight gain. With regard to developmental toxicity the NOAEL was established to be greater 500 mg/kg body weight per day by gavage and greater 508 mg/kg body weight per day via the diet.