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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)

Data source

Reference
Reference Type:
other: study report
Title:
Toxicity Testing Reports of Environmental Chemicals
Author:
MHLW
Year:
1998
Bibliographic source:
OECD SIDS ; 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:
other: 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
Test material form:
solid: crystalline
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)
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
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- M/F ratio per cage: 1/1
- Length of cohabitation: at the most 14days
- Further matings after two unsuccessful attempts: [no / yes (explain)] : no
- Verification of same strain and source of both sexes: [yes / no (explain)] : no
- 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)

Duration of treatment / exposure:
Males: 43 days; Females: from 14 days prior to mating to day 4 of lactation.
Frequency of treatment:
Daily
Duration of test:
43 days
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

Maternal examinations:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:Clinical signs were observed at least once a day.
Parent: Performed once a day
Foetus: Performed once a day after birth


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.

POST-MORTEM EXAMINATIONS: Yes
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.
- Organs examined:
Parent: organ weight: heart, liver, kidneys, thymus, testes,epididymides.

Histopathological examinations: Foetal: full macroscopic examinations on all of pups
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes

Fetal examinations:
Full macroscopic examinations on all of pups were done
- External examinations: Yes
- Sex ratio : Yes
- No. of pups born : Yes
- No. of pups alive : Yes
- Pups weight : Yes
- Viability : Yes
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.
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: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects. Remark: No abnormalities were found.

Details on maternal toxic effects:
No abnormalities were found in all reproductive parameters (fertility index, number of Implantations and implantation index) in each dose group.No statistically significant difference from controls in the case of body weight,food consumption and Reproductive responses.

Effect levels (maternal animals)

Dose descriptor:
other: not specified
Based on:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified
Description (incidence and severity):
not specified

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects. Remark: No abnormalities were found in all pups.

Details on embryotoxic / teratogenic effects:
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.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: fetotoxicity
Remarks on result:
other: not specified

Fetal abnormalities

Abnormalities:
not specified
Localisation:
other: not specified
Description (incidence and severity):
not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
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. There were no dose related abnormalities were observed .Thus, NOAEL (No Observed adverse effect level) for fetotoxicity study 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. No abnormalities were found in all indexes (No. of pups born, No. of pups alive, pups weight, sex ratio,viability etc.).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.

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