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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

No reliable, key reproductive toxicity study is available for T008506. Therefore, reliable data from the supporting substance DHEA is used to cover this endpoint. Published data from experimental studies with DHEA are considered. Neonatal treatment of male and female rats with DHEA has adverse effects on the growth and weight of sex organs of both sexes, as well as negatively impacting sexual behaviours (Gotz et al., 1983). It is assumed that the LOAEL is 1mg/day of 4mg/kg/day in rat after subcutaneous administration. The substance is classified as reproductive toxicant cat 1B.

Link to relevant study records

Referenceopen allclose all

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Justification of the read-across approach is included in section 13.
Reason / purpose for cross-reference:
read-across source
Conclusions:
No reliable reproductive toxicity data with the test substance is available. Data from the supporting substance DHEA is used to cover this endpoint. 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.
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Justification for type of information:
justification of the read-across approach is included in section 13.
Reason / purpose for cross-reference:
read-across source
Remarks on result:
not measured/tested
Critical effects observed:
not specified
Dose descriptor:
LOAEL
Generation:
F1
Effect level:
4 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: inhibition of growth of testes, seminal vesicles, adrenal glands and pituitary; diminished copulatory activity in males; dose-dependent impairment of cyclicity in females (accompanied by sub- or infertility)
Critical effects observed:
yes
Lowest effective dose / conc.:
4 mg/kg bw/day (nominal)
System:
male reproductive system
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified
Reproductive effects observed:
yes
Lowest effective dose / conc.:
4 mg/kg bw/day
Treatment related:
yes
Relation to other toxic effects:
not specified
Dose response relationship:
yes
Relevant for humans:
not specified
Conclusions:
No reliable, key reproductive toxicity study with T008506 is available. Data from the supporting substance DHEA is used to cover this endpoint.
Neonatal treatment of male and female rats with DHEA has adverse effects on the growth and weight of sex organs in both sexes, as well as negatively impacting sexual behaviours. It is assumed that the LOAEL is 1mg/day or 4 mg/kg/day after subcutaneous administration in rat.
Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
4 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
It is assumed that oral administration has equal bioavailaibility as subcutaneous administration.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

No reliable, key reproductive toxicity study with T008506 is available. Data from the supporting substance DHEA is used to cover this endpoint. Two publications were considered in this assessment of effects on fertility:

Lin et al. 2006 (supporting, K2)

Maternal and fetal toxicity of DHEA is investigated. SD pregnant female rats were divided randomly into 5 groups, 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 mother 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.

Gotz et al., 1983 (K2, key study)

No reliable, key reproductive toxicity study is available for T008506. Therefore, reliable data from the supporting substance DHEA is used to cover this endpoint. Published data from experimental studies with DHEA are considered. Neonatal treatment of male and female rats with DHEA has adverse effects on the growth and weight of sex organs of both sexes, as well as negatively impacting sexual behaviours. It is assumed that the LOAEL is 1mg/day or 4mg/kg/day in rat after subcutaneous administration.

Effects on developmental toxicity

Description of key information

No reliable developmental toxicity study with T008506 is available. Data from the supporting substance DHEA is used to cover this endpoint.

No effects on embryonic or fetal development were observed in New Zealand White rabbits , dosed orally during GD7-20 with DHEA at dose levels of 0, 20, 50 or 125 mg/kg/day (Kirchner et al., 1998, K2, supporting). In the same study, CD rats were dosed orally with DHEA during GD6-17 at dose levels 0, 5, 15 or 50 mg/kg/day. Embryolethality and increased early resorptions occurred at all dose levels in rats, including complete litter loss. Skeletal malformations were also observed. DHEA may interfere with the energy requirements of the developing embryo or perturb the hormonal balance necessary to maintain implantation. It can be assumed that the LOAEL is 5 mg/kg/day in rats after oral administration.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Justification for the read-across approach is included in section 13
Reason / purpose for cross-reference:
read-across source
Conclusions:
No relable data with the target substance is available. Data from the supporting substance DHEA is used to cover this endpoint.
No effects on embryonic or fetal development were observed in New Zealand White rabbits , dosed orally during GD7-20 with DHEA at dose levels of 0, 20, 50 or 125 mg/kg/day.
In the same study, CD rats were dosed orally with DHEA during GD6-17 at dose levels 0, 5, 15 or 50 mg/kg/day. Embryolethality and increased early resorptions occurred at all dose levels in rats, including complete litter loss. Skeletal malformations were also observed. DHEA may may interfere with the energy requirements of the developing embryo or perturb to hormonal balance necessary to maintain implantation.
It can be assumed that the LOAEL is 5 mg/kg/day in rats after oral administration.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
5 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

No reliable reproductive or developmental toxicity data is available for T008506. Data from the supporting substance DHEA is used to cover this endpoint. The substance T008506 is considered classified as reproductive toxicant category 1B according to CLP regulation.

Additional information