12-hydroxy-N-(2-hydroxyethyl)octadecan-1-amide

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data from Secodary source

Data source

Reference

Reference Type:

secondary source

Title:

Reproductive toxicity study of test material was performed on rats.

Author:

HSDB® - Hazardous Substances Data Bank

Year:

2018

Bibliographic source:

HSDB® - Hazardous Substances Data Bank

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Prenatal development toxicity study(OECD 414)

Principles of method if other than guideline:

Reproductive and developmental toxicity study of test material was performed on Sprague-Dawley CD rats.

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Test material

Test material information

Constituent 1

Reference substance name:

Amides, coco, N,N-bis(hydroxyethyl)

EC Number:

271-657-0

EC Name:

Amides, coco, N,N-bis(hydroxyethyl)

Cas Number:

68603-42-9

Molecular formula:

C13H13Cl8NO4

IUPAC Name:

Amides, coco, N,N-bis(hydroxyethyl)

Details on test material:

- Name of test material (IUPAC name): Amides, coco, N,N-bis(hydroxyethyl)
- Common name: Coconut diethanolamide
- Substance type: Organic

Specific details on test material used for the study:

No data available

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on species / strain selection:

No data available

Sex:

female

Details on test animals or test system and environmental conditions:

No data available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: arachis oil, DAB 9

Details on exposure:

Details on exposure
PREPARATION OF DOSING SOLUTIONS:
Test material dissolved in arachis oil, DAB 9
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): arachis oil, DAB 9
- Concentration in vehicle: 0, 100, 300 and 1000 mg/kg/day
- Amount of vehicle (if gavage): 5ml/kg

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

Details on mating procedure:

Females were mated at the supplier and received at the testing facility on day 0 of gestation.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

10 days ( Days 6 - 15 of gestation)

Frequency of treatment:

7 days/week

Details on study schedule:

No data available

Doses / concentrations

Remarks:

0, 100, 300 and 1000 mg/kg/day

No. of animals per sex per dose:

No data available

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

No data available

Examinations

Parental animals: Observations and examinations:

Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: yes
DETAILED CLINICAL OBSERVATIONS: Yes
Time schedule: Animals were observed at least twice daily for signs of reaction to treatment and/or symptoms of illness.
BODY WEIGHT: Yes
Time schedule for examinations: Body weights were recorded on day 0, 6, 16 and 20 of gestation.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes Food consumption was determined weekly.

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

Live fetuses were weighed individually including placenta and examined for external abnormalities

Postmortem examinations (parental animals):

Postmortem examinations (Parent Animal)
SACRIFICE : Females were sacrificed by on overdose of
ether on day 20 of gestation

GROSS NECROPSY: The uterus was weighed and the fetuses were removed by caesarean section. Corpora
lutea were counted and the number and distribution of intrauterine implantations were classified as live or dead fetuses, late intrauterine deaths (resorptions), or early intrauterine deaths (resorption sites). Intrauterine deaths were classified on the basis of the presence (late) or absence (early) of fetal or decidual tissue in addition to placental tissue.
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.:
macroscopic examination was performed

Postmortem examinations (offspring):

Postmortem examinations (offspring)
SACRIFICE
One half of the fetuses for each litter were fixed in Bouin’s solution to examine the viscera and brain by Wilson’s slicing technique. After examination these tissues were discarded. The remaining fetuses were processed (alizarin red staining), examined for skeletal abnormalities and retained.

Statistics:

If normal distribution, Dunnett-Test comparing treated groups to control. The Steel-Test was applied when the data could not be assumed to follow normal distribution. Fisher’s Exact Test for 2 x 2 tables was applied if the variables could be dichotomized without loss of information (Bonferroni-Holm-corrected).

Reproductive indices:

No data available

Offspring viability indices:

No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Compound-related symptoms were observed in all treatment groups as salivation (severe in the 1000 mg/kg/day group) and propulsion of the head

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Description (incidence):

No deaths occurred in any dams in the control or treated groups.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Body weight, body weight gains and corrected body weight gains were comparable across all groups

Food consumption and compound intake (if feeding study):

not specified

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:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

Post-implantation loss and total embryonic deaths were statistically significantly increased in all treated groups compared to the control group. These findings were considered incidental because in each group there was one single female with a high incidence of embryonic deaths and the incidence of post weight loss was not dose dependent.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

gross pathology

reproductive performance

Remarks on result:

other: No effects on reproductive performance

Target system / organ toxicity (P0)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

There were no significant differences in the body weights of live fetuses (on a litter or individual basis) between the treated and control groups

Food consumption and compound intake (if feeding study):

not specified

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

Sexual maturation:

no effects observed

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not specified

Other effects:

no effects observed

Description (incidence and severity):

The sex ratio of the fetuses was not affected by the treatment with the test substance.

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not specified

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

viability

sexual maturation

mortality

body weight and weight gain

gross pathology

Remarks on result:

other: developmental toxic effects observed

Target system / organ toxicity (F1)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Overall reproductive toxicity

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

No Observed Adverse Effect Level (NOAEL) was considered to be 1000mg/kg bw for reproductive and embryo-foetal toxicity. When female Sprague Dawley rats were treated with test material orally.

Executive summary:

The reproductive and prenatal development toxicity study oftest materialwas performed on female SpragueDawley CD(SD)rats. The test materialdissolved in arachis oil, DAB 9were administered in dose concentration 0, 100, 300 and 1000 mg/kg/dayfrom day 6 through day 15 of gestation by oral gavage route.Dose volume was 5 ml/kg body weight, adjusted for body weighed on day 6 of gestation. Females were mated at the supplier and received at the testing facility on day 0 of gestation. Animals were observed at least twice daily for signs of reaction to treatment and/or symptoms of illness. Body weights were recorded on day 0, 6, 16 and 20 of gestation. Females were sacrificed by on overdose of ether on day 20 of gestation. The uterus was weighed and the fetuses were removed by caesarean section. Corpora lutea were counted and the number and distribution of intrauterine implantations were classified as live or dead foetuses. Live fetuses were weighed individually including placenta and examined for external abnormalities. One half of the fetuses for each litter were fixed in Bouin’s solution to examine the viscera and brain by Wilson’s slicing technique. After examination these tissues were discarded. The remaining fetuses were processed (alizarin red staining), examined for skeletal abnormalities and retained.

 

No deaths occurred in any dams in the control or treated groups. Compound-related symptoms were observed in all treatment groups as salivation (severe in the 1000 mg/kg/day group) and propulsion of the head. Body weight, body weight gains and corrected body weight gains were comparable across all groups. There were no significant macroscopic findings in any of the control or treated animals. Post-implantation loss and total embryonic deaths were statistically significantly increased in all treated groups compared to the control group. These findings were considered incidental because in each group there was one single female with a high incidence of embryonic deaths and the incidence of post weight loss was not dose dependent. The sex ratio of the fetuses was not affected by the treatment with the test substance. There were no significant differences in the body weights of live fetuses (on a litter or individual basis) between the treated and control groups. There were no external macroscopic findings noted in any fetus that were considered to be an effect of the treatment with the test article. Visceral examinations of the preserved fetuses did not reveal any treatment-related abnormalities. Statistically significant retardation in ossification was observed in the 300 and 1000 mg/kg/day groups compared to the controls. The incidence of two sternebrae unossified was significantly increased in the 300 and 1000 mg/kg/day groups compared to the control group. The incidence of incomplete ossification of the skull bones was also significantly increased in the 1000 mg/kg/day group compared to the control group but was essentially due to two dams, which had a total of 10 incomplete ossified skull bones of the 17 observed for this group. The skeletal retardation effects were considered to be incidental because the values were within the normal range of variation for this strain. Hence No Observed Adverse Effect Level (NOAEL) was considered to be 1000mg/kg bw for reproductive and embryo-foetal toxicity.When femaleSprague Dawley rats were treated withtest material orally.