Fatty acids, C18-(unsaturated) dimers and their monoesters and diesters with 2-ethylhexanol

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

Type of information:

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

Adequacy of study:

key study

Study period:

2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Robust summary of study published in official document submitted to US EPA. There the study was classified as Klimisch 1a. The study was GLP compliant and performed according to OECD guideline 421. As the robust study summary is taken from a secondary source the reliability was downgraded.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Details on test material:

fatty acids, C18-unsaturated dimers

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Four groups of 10 male and 10 female Sprague-Dawley rats

Administration / exposure

Route of administration:

oral: feed

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

Males were treated for at least 4 weeks overall, starting from 2 weeks prior to mating until termination; females were treated for 2 weeks prior to mating, then through mating until termination after Day 4 of lactation.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
200 ppm
Basis:

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2,000 ppm (appr. 180 mg/kg/day)
Basis:

Doses / concentrations 3

Remarks:

Doses / Concentrations:
20,000 ppm (appr. 1,858 mg/kg/day)
Basis:

No. of animals per sex per dose:

10

Control animals:

yes

Examinations

Parental animals: Observations and examinations:

The animals were monitored for clinical signs, body weight, food consumption, mating and litter performance.
All animals were submitted for necropsy, which included weighing male reproductive organs. Histopathology was conducted on the epididymides and testes of all control and high dose males and on the ovaries of all control and high dose females.

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

Paternal toxicity was exhibited at 20000 ppm as a slight decrease in weight gain and an increase in piloerection. There were no obvious maternal effects at this level. There were no obvious parental effects at 200 or 2,000 ppm, nor were there any effects of treatment on the reproductive parameters at any dose level applied. The testes and epididymides weights were essentially similar in all groups.
The mean number of implants per pregnancy was higher in all the treated groups compared to controls. However, historical data shows that the findings in the treated groups were within background ranges for animals of this age and strain. Rather, it was considered most likely that the control value was at the lower end of the background range. There were no obvious effects of treatment on litter size, litter survival, or pup weights at any dose level and no abnormalities noted among pups.

Effect levels (P0)

1

Dose descriptor:

NOEL

Effect level:

180 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: slight decrease in weight gain and an increase in piloerection

2

Dose descriptor:

NOEL

Effect level:

1 858 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: reproductive parameters

Results: F1 generation

Effect levels (F1)

Remarks on result:

not measured/tested

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study, the parental No Observed Effect Level (NOEL) of fatty acid, C18-unsaturated dimers in rats was considered to be 2,000 ppm (approximately 180 mg/kg/day) and for reproductive parameters the NOEL was considered to be 20,000 ppm (approximately 1,858 mg/kg/day).