Reaction products of fatty acids, tall oil and fatty acids, C18 unsaturated, trimers and fatty acids, C18 unsaturated, dimers with (9Z)-octadec-9-en-1-amine

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:

weight of evidence

Study period:

2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study, evaluated as reliable in the EU RAR report, but only secondary sources available

Data source

Reference

Reference Type:

review article or handbook

Title:

European Union Risk Assessment Report - Primary Alkyl Amines

Author:

Germany

Year:

2008

Bibliographic source:

Published Draft, page 172, Reproductive Screening Assay for Tallow Alkylamines

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

Reference substance name:

Amines, tallow alkyl

EC Number:

263-125-1

EC Name:

Amines, tallow alkyl

Details on test material:

- Name of test material (as cited in study report): Genamin TA 100
- Analytical purity: > 96%

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on exposure:

VEHICLE
- Justification for use and choice of vehicle (if other than water): sesame oil (solubility reasons)

ADMINISTRATION VOLUME: 10mL/kg b.w.

Details on mating procedure:

- M/F ratio per cage: 1:1
- Length of cohabitation: a maximum of 14 days

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

males: max. 28days (14 days prior to mating and until the end of the mating period)
females: 14 days prior to mating, through mating, gestation and 3 days of lactation.

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
12.5, 50, 150 mg/kg b.w.
Basis:
actual ingested

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes

Sperm parameters (parental animals):

PAS-hematoxylin staining of testes sections

Litter observations:

number and sex of pups
stillbirths
live births
postnatal mortality
presence of gross anomalies
weight gain (day 0, day 4)

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals on the day after the end of treatment
- Maternal animals: All surviving animals on day 4 of lactation with their pubs

GROSS NECROPSY: yes

HISTOPATHOLOGY / ORGAN WEIGHTS
The following tissues were prepared for microscopic examination and weighed, respectively:
- ovaries
- uteri (including horns, cervix, and vagina), only uteri of non pregnant females were stained for implantation sites
- testes (with special emphasis on stages of spermatogenesis and histopathology of interstitial cell structure)
- epididymides
- accessory sex organs
- all gross lesions

Postmortem examinations (offspring):

SACRIFICE
- The F1 offspring were sacrificed on day 4 of lactation and necropsied

GROSS NECROPSY: yes

Reproductive indices:

- Pregnancy index: the percent ratio of females with live births to the pregnant females.
- Pre-coital interval: calculated on the dams which proved pregnant and was expressed for each group as the mean time lapse (in days) between the beginning of the mating period and the ascertainment that copulation had occurred.
- Pregnancy period: the duration of pregnancy was determined for all those dams that reached term of pregnancy as being the time that elapsed between the day vaginal smear proved positive and the day of parturition.
- The post-implantation losses were calculated for each litter m the following manner: Post- implantation losses equals (No. implantations) negative (No. live pups) divided by (No. implantations) x 100

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
- 150 mg/kg: salivation, hunched posture, soft stools, piloerection; 6/10 male and 5/10 female animals died (5 males and 3 females during premating)
- 50 mg/kg: salivation; 1/10 male and 1/10 female animals died
- 12.5 mg/kg: no changes observed

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
- 150 mg/kg: body weight loss of about 22g (m) and 17g (f)
- 50mg/kg: reduced body weight gain during premating together with lower food consumption in both sexes

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
- mating and fertility indices, mean pre-coital time and parturition were unaffected up to 50 mg/kg/day (a slightly reduced fertility index at 50 mg/kg was not statistically significant and is within the normal variation for this rat strain. When looking at the percentages only, one also should keep in mind that 2 animals of this dose group died.)
- in the high dose group, only 3 out of the 7 mated females had positive vaginal smears, and only 1 female became pregnant, but didn't deliver. This finding is due to the excessive maternal toxicity of the test substance in this group.

ORGAN WEIGHTS (PARENTAL ANIMALS)
- lower absolute weight of epididymides and higher value of testis weight relative to body weight at 150 mg/kg/day, corresponding to decreased body weight in this group
- no differences in ovary weights among the experimental groups

HISTOPATHOLOGY (PARENTAL ANIMALS)
- histology of testes, epididymides and ovaries did not show any compound-related changes in all dose groups
- no changes in testicular staging performed in the PAS-hematoxylin stained sections of control and high dose groups

Effect levels (P0)

1

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: based on death and reduced body weight in mid dose animals

2

Dose descriptor:

NOAEL

Remarks:

fertility

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: mortality of more than 50% of parental animals was observed in the high dose

Results: F1 generation

Details on results (F1)

VIABILITY (OFFSPRING)
- no litters present at 150 mg/kg/day
- no effects on postnatal survival up to day 4 of lactation and no effects on sex ration at 50 mg/kg/day

CLINICAL SIGNS (OFFSPRING)
- no litters present at 150 mg/kg/day
- no significant effects up to 50 mg/kg/day

BODY WEIGHT (OFFSPRING)
- no litters present at 150 mg/kg/day
- slightly lower pup body weight seen in 50 mg/kg/day group
- no effects seen at 12.5 mg/kg/day

GROSS PATHOLOGY (OFFSPRING)
- no abnormalities observed in any pub either at birth or at autopsy on day 4 of lactation neither of the 50 or of the 12.5 mg/kg/day group

Effect levels (F1)

Dose descriptor:

NOAEL

Remarks:

developmental

Generation:

F1

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: slightly lower pub weight on day 4 only was considered secondary to maternal toxicity, especially since no effects were observed in two developmental toxicity studies in rats and rabbits.

Overall reproductive toxicity

Reproductive effects observed:

not specified