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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: Parent Screening Test
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)

Data source

Reference
Reference Type:
other: study report
Title:
Screening Information Data Set for Docosanoic acid
Author:
MHLW
Year:
1998
Bibliographic source:
Ministry of Health, Labour and Welfare (MHLW, former MHW), Japan (1998), Toxicity Testing Reports of Environmental Chemicals 6, 236-246.

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Docosanoic acid
- Substance type: Organic
- Physical state: Solid
- Analytical purity:85.9 %
- Impurities (identity and concentrations):(C14-C20) fatty acids (10.9 %) and C 24 fatty acid (2.3%)
- Storage condition of test material:Kept at room temperature until use

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: N/A
- Age at study initiation: 8 week old
- Weight at study initiation: 312.1-363.7 g for males, 205.3- 230.8 g for females.
- Fasting period before study: N/A
- Housing:N/A
- Diet (e.g. ad libitum):N/A
- Water (e.g. ad libitum):N/A
- Acclimation period:N/A

ENVIRONMENTAL CONDITIONS
- Temperature (°C):N/A
- Humidity (%):N/A
- Air changes (per hr):N/A
- Photoperiod (hrs dark / hrs light):N/A

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
corn oil
Details on exposure:
Males, 42 days; Females, from 14 days prior to mating to day 3 of lactation.
Premating exposure period: Male: 14 days, Female: 14 days

VEHICLE
- Justification for use and choice of vehicle (if other than water):corn oil
Details on mating procedure:
- M/F ratio per cage: 1/1
- Length of cohabitation: at the most 14days
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy : until proof of pregnancy (formation of vaginal closing or sperm detection in vagina)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
42 days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0(vehicle), 100, 300 or 1000 mg/kg/day.
Basis:

No. of animals per sex per dose:
0(Vehicle) : 13 male and 13 female
100 mg/kg/day : 13 male and 13 female
300 mg/kg/day :13 male and 13 female
1000 mg/kg/day :13 male and 13 female
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:Clinical signs were observed at least once a day.
Parent: Performed once a day

BODY WEIGHT: Yes
- Time schedule for examinations: once a week.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes,
Food consumption was measured nearly once a week except for mating period.

Estrous cyclicity (parental animals):
Estrous cycle length and pattern not performed.
Sperm parameters (parental animals):
Sperm examination were not performed.
Postmortem examinations (parental animals):
SACRIFICE
Males were killed on the day after the administration period. Females were sacrificed on the day 4 of lactation. Females with
no delivery were killed 4 days after the delivery expected date. Females with no copulation were sacrificed at the termination of mating period.

Parent: organ weight: heart, liver, kidneys, thymus, testes, epididymides.

Histopathological examinations: All animals in control and 1,000 mg/kg, and any organs which have histopathological changes at the higher doses: brain, heart, liver,spleen, thymus, kidney, adrenal, testis, epididymis, urinary bladder, ovary (only for females which were non pregnant or not
copulated).

Statistics:
Dunnett’s or Scheffe’s test for continuous data, Chi square test for copulated index and fertility index, and Mann-Whitney U test or Fisher’s test for histopathological examination data.
Reproductive indices:
No. of pairs with successful copulation, copulation index (No. of pairs with successful copulation/No. of pairs mated x 100),pairing days until copulation, frequency of vaginal estrus, No. of pregnant females, fertility index = (No. of pregnant animals/No. of pairs with successful copulation x 100), No. of corpora lutea, No. of implantation sites, implantation index (No. of implantation sites/No. of corpora lutea x 100), No. of living pregnant females, No. of pregnant females with parturition, gestation length, No. of pregnant females with live pups on day 0, gestation index (No. of females with live pups/No. of living pregnant females x 100), No. of pregnant females with live pups on day 4, delivery index (No. of pups born/No. of implantation sites x 100), No. of pups alive on day 0 of lactation, live birth index (No. of live pups on day 0/No. of pups born x 100), sex ratio (Total No. of male pups/Total No. of female pups), No. of pups alive on day 4 of lactation, viability index (No. of live pups on day 4/No. of live pups on day 0 x 100), body wt. of live pups (on day 0 and 4)

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No statistical significant difference from controls
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No statistical significant difference from controls
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
No statistically significant differences from controls in any organs.
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: estrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
Description (incidence and severity):
No statistical significant difference from controls

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No abnormalities were found in all reproductive parameters (fertility index, number of implantations and implantation index) in each dose group as well as no effects on mortality,body weight food consumption and organ weights.
Remarks on result:
other: not specified

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
No abnormalities were found in all pups examined in either the external observation at day 0 or the autopsy performed at day 4 after birth.
Histopathological findings:
no effects observed

Results: F2 generation

Effect levels (F2)

Remarks on result:
not measured/tested

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
No treatment related adverse effects were found in either dose group up to 1000 mg/kg. Thus, the NOAEL (No Observed adverse effect level) for maternal toxicity of docosanoic acid was considered to be 1000 mg/kg/day.
Executive summary:

The substance Docosanoic acid (CAS No : 112-85-6) was administered orally by gavage at three doses 100, 300 or 1000 mg/kg/day to groups of male/female Crj: CD(SD) rats. The compound showed no adverse effects on copulation or fertility. No changes related to the dosing of compound were observed in gestation length, gestation index, delivery and lactation.The compound did not demonstrate any adverse effects on the body weights, food consumption,mortality,organ weights or viability of pups.

Thus, the no observed adverse effect level (NOAEL) for maternal toxicity was considered to be 1000 mg/kg/day.