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Diss Factsheets

Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not specified
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:
The Effects of DHEA on Reproductive Toxicity in Rats
Author:
Lin J, He L, Lin S, Liu S
Year:
2006
Bibliographic source:
Carcinogenesis, Teratorgenesis & Mutagenesis 18(6) 479-481
Report date:
2006

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Prasterone
EC Number:
200-175-5
EC Name:
Prasterone
Cas Number:
53-43-0
Molecular formula:
C19H28O2
IUPAC Name:
(3S,8R,9S,10R,13S,14S)-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one
Test material form:
solid
Details on test material:
white solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female

Administration / exposure

Route of administration:
not specified
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
From day 7 to day 16 of pregnancy
Frequency of treatment:
continuous administration (no further specifications)
Details on study schedule:
Rats were given test item from day 7 to day 16 of pregnancy, and sacrificed on day 20 of pregnancy.
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Remarks:
Distilled water-negative control
Dose / conc.:
10.4 mg/kg bw/day
Dose / conc.:
20.8 mg/kg bw/day
Dose / conc.:
41.7 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Remarks:
Aspirin-positive control
No. of animals per sex per dose:
16 pregnant females per dose group
Control animals:
yes
Positive control:
Aspirin, 300 mg/kg

Examinations

Postmortem examinations (parental animals):
SACRIFICE
- Maternal animals: All surviving animals sacrified on day 20 of pregnancy

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not examined
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
20.8 and 41.7 mg/kg slowed down the weight increase of mother and fetuses and slowed sternum growth.
Food consumption and compound intake (if feeding study):
not specified
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:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
effects observed, treatment-related
Description (incidence and severity):
DHEA at 10.4 mg/kg caused miscarriages in pregnant rats.

Effect levels (P0)

Key result
Dose descriptor:
LOAEL
Effect level:
10.4 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reproductive performance

Target system / organ toxicity (P0)

Critical effects observed:
yes
Lowest effective dose / conc.:
10.4 mg/kg bw/day (nominal)
System:
female reproductive system
Treatment related:
yes
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: P1 (second parental generation)

Reproductive function / performance (P1)

Reproductive performance:
effects observed, treatment-related
Description (incidence and severity):
All three concentrations of DHEA decreased the number of living fetuses

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not examined
Mortality / viability:
mortality observed, treatment-related
Description (incidence and severity):
Miscarrriages increased at 10.4 mg/kg. All three concentrations of DHEA decreased the number of living fetuses.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
20.8 and 41.7 mg/kg slowed down the weight increase of mother and fetuses and slowed sternum growth.
Food consumption and compound intake (if feeding study):
not specified
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
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
effects observed, treatment-related
Description (incidence and severity):
At 41.7 mg/kg, visceral abnormality in fetuses increased.

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
LOAEL
Generation:
F1
Effect level:
10.4 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
viability
body weight and weight gain

Target system / organ toxicity (F1)

Critical effects observed:
yes
Lowest effective dose / conc.:
10.4 mg/kg bw/day (nominal)
System:
other: viability, body weight
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified

Results: F2 generation

General toxicity (F2)

Organ weight findings including organ / body weight ratios:
effects observed, treatment-related

Overall reproductive toxicity

Reproductive effects observed:
yes
Lowest effective dose / conc.:
10.4 mg/kg bw/day (nominal)
Treatment related:
yes
Relation to other toxic effects:
not specified
Dose response relationship:
yes
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
Maternal and fetal toxicity of DHEA is investigated. SD pregnant female rats were divided randomly into 5 gorups, 16 rats per group. The rats in the positive control group received aspirin 300 mg/kg and distilled water was given to rats as the negative control group. Three DHEA groups were treated with 10.4, 20.8 and 41.7 mg/kg. The rats were given DHEA from 7d to 16d pregnant continuously for 10 days, and were sacrificed on 20th day of pregnancy. Adverse effects on pregnant rats and fetuses were assessed. DHEA at 10.4 mg/kg caused miscarriages in pregnant rats. 20.8 and 41.8 mg/kg slowed down the weight increase of mothher and fetuses, and slowed sternum growth. At 41.7 mg/kg visceral abnormality in fetuses increased. All three concentrations of DHEA decreased the number of living fetuses. In conclusion, DHEA had adverse effects in both pregnant rats and fetuses.