Fatty acids, C14-18 and C16-18 unsatd., compds. with triethanolamine

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes

Test material

Test material information

1

Reference substance name:

Fatty acids, C14-18 and C16-18 unsatd., compds. with triethanolamine

EC Number:

268-369-2

EC Name:

Fatty acids, C14-18 and C16-18 unsatd., compds. with triethanolamine

Cas Number:

68082-25-7

Molecular formula:

Not applicable (UVCB substance)

IUPAC Name:

Fatty acids, C14-18 and C16-18 unsatd., compds. with triethanolamine

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on mating procedure:

Mating will be performed using a ratio of 1:1 (male to female) (if possible). The vaginal smear of the females will be checked every morning after the start of the mating period to confirm the mating. If the vaginal smear of a particular female is not found to be sperm-positive, the actual stage of the estrus cycle on that day will be documented. The day of the vaginal plug and/or sperm will be considered as day 0 of gestation.
The cages will be arranged in such a way that possible effects due to cage placement are minimised. In case of unsuccessful mating, re-mating of females with proven males of the same group can be considered.

Duration of treatment / exposure:

7 days per week for a maximum period of 63 days, i.e. during 14 days of pre-mating and maximum 14 days of mating in both males and females. Then in females, treatment will be done during the gestation period and up to post-natal day 12. Males will be dosed after the mating period until the minimum total dosing period of 28 days is completed.

Frequency of treatment:

7 days per week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

100 mg/kg bw/day (nominal)

Remarks:

LD

Doses / concentrations 2

Dose / conc.:

300 mg/kg bw/day (nominal)

Remarks:

MD

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Remarks:

HD

No. of animals per sex per dose:

Group 1 (C, control): 0 mg/kg bw/day. 10 males and 10 females.
Group 2 (LD, low dose): 100 mg/kg bw/day. 10 males and 10 females.
Group 3 (MD, medium dose): 300 mg/kg bw/day. 10 males and 10 females.
Group 4 (HD, high dose): 1000 mg/kg bw/day. 10 males and 10 females.

Control animals:

yes, concurrent no treatment

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, non-treatment-related

Description (incidence and severity):

In this study there were no clinical findings related to a systemic effect of the test item.
During the weekly detailed clinical observation, no significant changes or differences between the groups were found.
Female number 55 of the LD group was observed with the clinical findings of pale skin, hypothermia, half eyelid closure, moderate piloerection, and slow movements on post-natal day 0. However, these signs were not assumed to be test item-related but to be result of the abortion of pregnancy.
The finding of wound in two males of the HD group (male number 37: wound on snout, male number 40 wound on the head) were not considered to be test item-related.

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, non-treatment-related

Description (incidence):

One female of the LD group (No. 55) was euthanized on post-natal day 0 due to animal welfare reasons

Body weight and weight changes:

no effects observed

Description (incidence and severity):

The test item had no effect on body weight development in this study. Body weights of male and female animals were in the normal range of variation throughout the treatment period of this study

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

The test item had no effect on food consumption in this study. Mean daily food intake of male and female animals was in the normal range of variation throughout the treatment period of this study.

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Description (incidence and severity):

The test item had no toxicologically relevant effect on haematology and blood coagulation parameters analysed at the end of the treatment period of this study.
Besides, all haematological parameters were within the normal range of historical data variation. Differences between the animals are due to the natural occurring inter-individual variation and are not assumed to be biologic ally relevant.
Blood coagulation was not affected by the test item as the individual values were within the normal range of variation for this strain

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

The test item had no toxicologically relevant effect on parameters of clinical biochemistry analysed at the end of the treatment period of this study.
All parameters of clinical chemistry were within the normal range of variation for this strain and without biological relevance.

Urinalysis findings:

effects observed, non-treatment-related

Description (incidence and severity):

The test item had no significant or toxicologically relevant effect on urinary parameters analysed at the end of the treatment period of this study.
One female of the MD group (number 24) showed an elevated level of erythrocytes in the urine. This was considered to be blood contamination during urine sampling and not related to treatment with the test item.
Further, one male of the LD group (number 59) was observed with a high level of ketones and one male of the MD group (number 68) showed a high level of protein in the urine. Both findings were considered to be incidental and not to be test item-related.

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, non-treatment-related

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Effect levels (P0)

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects treatment-related observed

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity (P0)

Critical effects observed:

no

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:

not examined

Dermal irritation (if dermal study):

not examined

Mortality:

not examined

Body weight and weight changes:

not specified

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 specified

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

not examined

Effect levels (P1)

Remarks on result:

not measured/tested

Target system / organ toxicity (P1)

Critical effects observed:

no

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not examined

Mortality / viability:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not examined

Other effects:

not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not examined

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not examined

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects treatment-related observed

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity (F1)

Critical effects observed:

no

Results: F2 generation

General toxicity (F2)

Clinical signs:

not examined

Dermal irritation (if dermal study):

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

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

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Other effects:

not examined

Developmental neurotoxicity (F2)

Behaviour (functional findings):

not examined

Developmental immunotoxicity (F2)

Developmental immunotoxicity:

not examined

Effect levels (F2)

Remarks on result:

not measured/tested

Target system / organ toxicity (F2)

Critical effects observed:

no

Overall reproductive toxicity

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

No treatment related effects were observed up the maximum dose tested. NOAEL >= 1000 mg/kg bw/day