Octanoic acid, compound with dicyclohexylamine (1:1)

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dicyclohexylamine

EC Number:

202-980-7

EC Name:

Dicyclohexylamine

Cas Number:

101-83-7

Molecular formula:

C12H23N

Test material form:

not specified

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Males: 49 days
Females: from 14 days before mating to day 3 of lactation

Frequency of treatment:

once daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

20 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

40 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

80 mg/kg bw/day (nominal)

No. of animals per sex per dose:

12

Control animals:

yes

Examinations

Parental animals: Observations and examinations:

clinical signs of toxicity, body weight, mortality, pathology of male organs, number of pairs mated, number of pairs copulated, number of pregnant females, days until copulation, copulation index (no. of pairs with successful copulation / no. of pairs mated) X 100 fertility index (no. of pregnant rats / no. of pairs with successful copulation) X 100duration of gestation, ---gestation index(no. of females with live pups / no. of pregnant females) X 100, ---implantation index (no. of implantations / no. of corpora lutea) X 100

Oestrous cyclicity (parental animals):

estrus cycle length

Sperm parameters (parental animals):

not specified

Litter observations:

live birth index (no. of live pups on day 0 / no. of pups born) X 100, ---delivery index (no of pups born / no. of implantations) X 100, ---sex ratio (no of males /no of females), ---viability index (no of live pups on day 4 / no. of live pups on day 0) X 100, body weight of pups on day 0 and day 4

Postmortem examinations (parental animals):

ORGANS EXAMINED AT NECROPSY (reported organs): --Organ weight (absolute and relative): - male, right and left testes, right and left epididymides

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

unspecific signs of intoxication

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, treatment-related

Description (incidence):

In the 80 mg/kg bw/day-group, 1 dam died on day 21 and another dam on day 22 of gestation.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Suppression of body weight gain in both sexes (male: treated rat versus control: 507 g versus 543 g) and low food consumption were observed.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

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:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

not specified

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

80 mg/kg:
Number of stillborn pups was significantly increased (55 versus 11 in controls) and the number of live born pups significantly decreased (72 versus 169 in controls) as well as live born index (58 % versus 94 % in controls), viability index reduced in pups (20.8 % versus 99 % in controls), pup weights on day 0 significantly (m/f: 6.1 g/5.5 g versus 7.3 g/7.0 g) and on day 4 slightly but not statistically significantly reduced (m/f: 9.0 g/8.6 g versus 11.8 g/11.1 g), poor maternal behavior and nursing observed in 7 dams.

Effect levels (P0)

1

Key result

Dose descriptor:

NOAEL

Effect level:

40 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

mortality

body weight and weight gain

food consumption and compound intake

2

Key result

Dose descriptor:

NOAEL

Effect level:

80 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: no effects

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

mortality observed, treatment-related

Description (incidence and severity):

Offsprings of the 80 mg/kg bw/day-dosed animals:number of stillborn pups significantly increased (55 versus 11 in controls),number of live born pups significantly decreased (72 versus 169 in controls) as well as live born index (58 % versus 94 % in controls), viability index reduced in pups of the 80 mg/kg bw/day group (20.8 % versus 99 % in controls) and pup weights on day 0 significantly (m/f: 6.1 g/5.5 g versus 7.3 g/7.0 g) and on day 4 slightly but not statistically

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Pup weights on day 0 significantly (m/f: 6.1 g/5.5 g versus 7.3 g/7.0 g) and on day 4 slightly but not statistically
significantly reduced (m/f: 9.0 g/8.6 g versus 11.8 g/11.1 g)

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 specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not examined

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not examined

Effect levels (F1)

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

40 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

Target system / organ toxicity (F1)

Key result

Critical effects observed:

not specified

Overall reproductive toxicity

Key result

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

In an OECD reproduction/developmental toxicity screening test (OECD TG 421) in rats dicyclohexylamine revealed effects on reproduction only in females at the highest oral dose tested (80 mg/kg bw/day) including slightly reduced gestation index, increase in stillborn pups and decrease in live born pups. The NOAEL (reproductive toxicity) is 80 mg/kg bw/day for males and 40 mg/kg bw/day for females. The NOAEL (offspring) is 40 mg/kg bw/day based on significant reduction in pup weights on day 0 and slight reduction in pup weights on day 4 in offspring of the parents dosed with 80 mg/kg bw/day. These adverse effects on the development of the F1-generation occur only in the presence of severe maternal toxicity.

Executive summary:

In an OECD reproduction/developmental toxicity screening test (OECD TG 421) in rats dicyclohexylamine revealed effects on reproduction only in females at the highest oral dose tested (80 mg/kg bw/day) including slightly reduced gestation index, increase in stillborn pups and decrease in live born pups. The NOAEL (reproductive toxicity) is 80 mg/kg bw/day for males and 40 mg/kg bw/day for females. The NOAEL (offspring) is 40 mg/kg bw/day based on significant reduction in pup weights on day 0 and slight reduction in pup weights on day 4 in offspring of the parents dosed with 80 mg/kg bw/day. These adverse effects on the development of the F1-generation occur only in the presence of severe maternal toxicity.