Androst-4-ene-3,17-dione

Endpoint summary

Description of key information

Oral, 4 weeks (Rat-Wistar, GLP, non-audited draft, doses: 0 / 15 / 50 / 150 mg/kg, once daily, equivalent to OECD TG407): LOAEL 15 mg/kg [Schering AG, report no. AG16, 1996-11-12]
Subcutaneous, 4 weeks (Rat-Wistar, GLP, non-audited draft, doses: 0 / 5 / 15 / 50 mg/kg, once daily): LOAEL: 5 mg/kg [Schering AG, report no. AY75, 2000-04-10]
Results of repeated oral studies published within scope of NTP (NIH, US) assessment [NTP Technical Report 560, NIH Publication No. 10-5901, September 2010]:
Oral, 14 weeks (Rat-Wistar, GLP, doses 0 / 1 / 5 / 10 / 20 / 50 mg/kg, once daily, OECD TG408): NOAEL 5 mg/kg
Oral, 14 weeks (Mouse-B6C3F1, GLP, doses 0 / 1 / 5 / 10 / 20 / 50 mg/kg, once daily, OECD TG408): LOAEL 50 mg/kg

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: NTP laboratory health and safety guidelines

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Version / remarks:

2008

Deviations:

yes

Remarks:

NTP protocol followed – dose range finding for 2-year study (no testing of sensory reactivity/motor activity, not all mandatory endpoint with regard to ED investigated (no thyroid hormones)

Principles of method if other than guideline:

Cited from report: "The NTP conducts its studies in compliance with its laboratory health and safety guidelines and FDA Good Laboratory Practice Regulations and must meet or exceed all applicable federal, state, and local health and safety regulations. Animal care and use are in accordance with the Public Health Service Policy on Humane Care and Use of Animals. Studies are subjected to retrospective quality assurance audits before being presented for public review."

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Androstendione
- Lot/batch No.: H408
- Purity: > 98 %
- Stability under test conditions: The stability of the substance in the formulation was analytically verified for at least 35 days (sealed amber glass bottles; 5 °C).

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: F344/N
- Source: Taconic Farms, Inc. (Germantown, NY, USA)
- Age at study initiation: 5 to 6 weeks old
- Weight at study initiation (mean): males 101 g, females 91 g
- Housing: in groups of five per cage (solid bottom polycarbonate cages)
- Diet and Water: ad libitum
- Acclimation period: 12 to 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 22 +/- 1.6 (72 +/- 3 °F)
- Humidity (%): 50 +/- 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

Administration volume: 5 mL/kg

VEHICLE: 0.5 % aqueous methylcellulose

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Dose formulations were analysed three times during the 3-month study; animal room samples were also analysed. The analytical method used was HPLC.

Duration of treatment / exposure:

14 weeks

Frequency of treatment:

once daily, 5 days/week

Dose / conc.:

1 mg/kg bw/day (actual dose received)

Dose / conc.:

5 mg/kg bw/day (actual dose received)

Dose / conc.:

10 mg/kg bw/day (actual dose received)

Dose / conc.:

20 mg/kg bw/day (actual dose received)

Dose / conc.:

50 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

10; additionally 10 animals per sex and dose were treated for clinical pathology studies.

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: For dose selection results from a previously conducted 2-week study were used. In this study groups of five male and five female rats were administered 0, 1, 5, 10, 20, or 50 mg androstenedione/kg body weight in a 0.5 % aqueous methylcellulose solution by gavage, 5 days per week for 12 days. All rats survived to the end of the study, and the mean body weights of dosed groups were similar to those of the vehicle control groups. The development of cytoplasmic vacuoles within centrilobular hepatocytes in male rats was the only treatment-related effect observed.

- Rationale for selecting satellite groups: Additional 10 animals per sex and dose were treated for 23 days for clinical pathology studies.

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes, all animals
- Time schedule: observed twice daily; clinical findings were recorded weekly for core study animals.

BODY WEIGHT: Yes, all animals
- Time schedule for examinations: Animals were weighed initially, on day 2 (female mice), day 3 (males), day 4 (female rats), weekly, and at the end of the studies.

CLINICAL PATHOLOGY:
Blood was collected from the retroorbital sinus of clinical pathology study rats on days 4 and 24 and from core study rats at the end of the studies for hematology and clinical chemistry.
- Hematology: automated and manual hematocrit; hemoglobin concentration; erythrocyte, nucleated erythrocytes, reticulocyte, and platelet counts; mean cell
volume; mean cell hemoglobin; mean cell hemoglobin concentration; leukocyte count and differentials
- Clinical chemistry: urea nitrogen, creatinine, total protein, albumin, alanine aminotransferase, alkaline phosphatase, creatine kinase, sorbitol dehydrogenase, and total bile acids

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, necropsies were performed on core study animals
Organs weighed were heart, right kidney, liver, lung, right testis, thymus, and uterus.

HISTOPATHOLOGY: Yes, complete histopathology was performed on vehicle control and 50 mg/kg core study rats
In addition to gross lesions and tissue masses, the following tissues were examined: adrenal gland, bone, brain, clitoral gland, esophagus, eye, harderian gland, heart, large intestine (cecum, colon, rectum), small intestine (duodenum, jejunum, ileum), kidney, liver, lung, lymph nodes (mandibular and mesenteric), mammary gland, nose, ovary, pancreas, parathyroid gland, pituitary gland, preputial gland, prostate gland, salivary gland, seminal vesicle, skin, spleen, stomach (forestomach and glandular), testis with epididymis, thymus, thyroid gland, trachea, urinary bladder, and uterus. In addition, the adrenal gland, heart, liver, mammary gland, ovary, prostate gland, and thyroid gland of rats were examined in the remaining dosed groups.

SPERM MOTILITY AND VAGINAL CYTOLOGY: At the end of the studies, sperm samples were collected from male animals in the 0, 10, 20, and 50 mg/kg groups for sperm motility evaluations. The following parameters were evaluated: spermatid heads per testis and per gram testis, spermatid counts, and epididymal spermatozoal motility and concentration. The left cauda, left epididymis, and left testis were weighed. Vaginal samples were collected for up to 12 consecutive days prior to the end of the studies from females administered 0, 10, 20, or 50 mg/kg for vaginal cytology evaluations. The percentage of time spent in the various estrous cycle stages and estrous cycle length were evaluated.

Statistics:

Survival Analysis: The probability of survival was estimated by the product-limit procedure of Kaplan and Meier (1958). Statistical analyses for possible dose-related effects on survival used Cox¿s (1972) method for testing two groups for equality and Tarone¿s (1975) life table test to identify dose-related trends. All reported P values for the survival analyses are two sided.
Calculation of Incidences were performed: Incidences of neoplasms or nonneoplastic lesions as the numbers of animals bearing such lesions at a specific anatomic site and the numbers of animals with that site examined microscopically.
Analysis of Neoplasm and Nonneoplastic Lesion Incidences: Poly-k test (Bailer and Portier, 1988; Portier and Bailer, 1989; Piegorsch and Bailer, 1997) to assess neoplasm and nonneoplastic lesion prevalence. Tests of significance included pairwise comparisons of each dosed group with controls and a test for an overall dose-related trend. Continuity-corrected Poly-3 tests were used in the analysis of lesion incidence, and reported P values are one sided.
Analysis of Continuous Variables: Two approaches were employed to assess the significance of pairwise comparisons between dosed and control groups in the analysis of continuous variables. 1) Parametric multiple comparison procedures of Dunnett (1955) and Williams (1971, 1972). 2) Nonparametric multiple comparison methods of Shirley (1977) (as modified by Williams, 1986) and Dunn (1964).

Clinical signs:

not specified

Mortality:

no mortality observed

Description (incidence):

All rats survived to the end of the study.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

The mean body weights of the 20 mg/kg female group was significantly greater than those of the vehicle control group and there was significant increased weight gain in the 1, 20, and 50 mg/kg female groups.

Haematological findings:

no effects observed

Description (incidence and severity):

There were no changes in hematology variables that were considered attributable to androstenedione administration.

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

There were no changes in clinical chemistry variables that were considered attributable to androstenedione administration.

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Female thymus weights were significantly increased in the 20 and 50 mg/kg groups, which may be related to the increase in mean body weight.

Gross pathological findings:

no effects observed

Description (incidence and severity):

No lesions were observed through gross observation that could be attributed to the administration of androstenedione.

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

No treatment-related histological lesions were observed in males or females.

Other effects:

effects observed, treatment-related

Description (incidence and severity):

SPERM MOTILITY AND VAGINAL CYTOLOGY
The numbers of sperm per mg cauda epididymis in the 10, 20, and 50 mg/kg male groups and the total number of sperm per cauda epididymis in 50 mg/kg males were significantly less than those of the vehicle controls.

Dose descriptor:

NOAEL

Effect level:

5 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: Steroid hormone-related effect on male fertility in the next higher dose group based on sperm investigations (The numbers of sperm per mg cauda epididymis were significantly decreased).

Critical effects observed:

yes

Lowest effective dose / conc.:

10 mg/kg bw/day (actual dose received)

System:

male reproductive system

Organ:

cauda epididymis

Treatment related:

yes

Dose response relationship:

yes

Relevant for humans:

yes

Survival and body Weights of Rats in the 3-Month Gavage Study of androstenedione

	dose (mg/kg)	Survival a	Mean Body Weight b (g) Final Weight			Final Weight Relative to Controls (%)
			Initial	Final	Change
Male	0	10/10	101 ± 2	333 ± 7	232 ± 6
	1	10/10	101 ± 2	340 ± 6	239 ± 6	102
	5	10/10	101 ± 1	344 ± 4	243 ± 4	103
	10	10/10	102 ± 2	343 ± 5	241 ± 4	103
	20	10/10	102 ± 1	343 ± 3	241 ± 3	103
	20	10/10	101 ± 2	340 ± 5	239 ± 4	102
Female	0	10/10	92 ± 1	189 ± 2	97 ± 3
	1	10/10	89 ± 1	200 ± 4*	111 ± 4*	106
	5	10/10	92 ± 1	198 ± 2*	107 ± 2	105
	10	10/10	93 ± 1	198 ± 2*	106 ± 2	105
	20	10/10	90 ± 2	206 ± 3**	116 ± 3**	109
	20	10/10	89 ± 1	199 ± 4**	111 ± 4**	105

 

* Significantly different (P#0.05) from the vehicle control group by Williams’ test

** P#0.01

a Number of animals surviving at 2 weeks/number initially in group

b Weights and weight changes are given as mean ± standard error.

 

 

Summary of Reproductive Tissue Evaluations for Male Rats in the 3-Month Gavage Study

of Androstenedione

	Vehicle Control	10 mg/kg	20 mg/kg	50 mg/kg
N	10	10	10	10
Weights (g)
Necropsy body wt	333 ± 8	343 ± 5	343 ± 3	340 ± 5
L. Cauda epididymis	0.1954 ± 0.0057	0.2082 ± 0.0044	0.2050 ± 0.0034	0.2083 ± 0.0048
L. Epididymis	0.4562 ± 0.0119	0.4610 ± 0.0075	0.4540 ± 0.0082	0.4303 ± 0.0110
L. Testis	1.5171 ± 0.0277	1.5272 ± 0.0259	1.5135 ± 0.0175	1.5053 ± 0.0220
Spermatid measurement
Spermatid heads (1E03 /mg testis)	124.86 ± 3.27	127.11 ± 4.83b	131.80 ± 4.53	126.49 ± 3.56
Spermatid heads (1E06 /testis)	169.38 ± 5.53		178.00 ± 6.85	169.38 ± 5.91
Epididymal spermatozoal measurements
Sperm (1E03 /mg cauda epididymis)	575 ± 27	475 ± 28*	463 ± 27*	407 ± 21**
Sperm (1E06 /cauda epididymis)	112 ± 5	98 ± 5	95 ± 6	85 ± 5**
Sperm motility (%)	75.7 ± 2.2	76.0 ± 2.1	73.8 ± 2.4	74.7 ± 1.5

* Significantly different (P</=0.05) from the vehicle control group by Shirley’s test

** (P</=0.01)

a Data are presented as mean ± standard error. Differences from the vehicle control group are not significant by Dunnett’s test (body and tissue weights) or Dunn’s test (spermatid measurements).

b n = 9

Estrous Cycle Characterization for Female Rats in the 3-Month Gavage Study of Androstenedione a

	Vehicle Control	10 mg/kg	20 mg/kg	50 mg/kg
Number weighed at necropsy	10	10	10	10
Necropsy body wt	189 ± 2	198 ± 2	206 ± 3**	199 ± 4
Proportion of regular cycling females b	10/10	10/10	9/10 c	7/10 d
Estrous cycle length (days)	4.8 ± 0.2	5.0 ± 0.1	4.9 ± 0.1	5.2 ± 0.2
Estrous stages (% of cycle)
Diestrus	60.0	60.0	60.2	61.1
Proestrus	10.0	16.7	13.0	7.4
Estrus	29.2	22.5	21.3	22.2
Metestrus	0.8	0.8	5.6	7.4
Uncertain diagnoses	0.0	0.0	0.0	1.9

 

** Significantly different (P#0.01) from the vehicle control group by Dunnett’s test

a Necropsy body weights and estrous cycle length data are presented as mean ± standard error. Differences from the vehicle control group are not significant by Dunn’s test (estrous cycle length). By multivariate analysis of variance, dosed females do not differ significantly from the vehicle control females in the relative length of time spent in the estrous stages.

b Number of females with a regular cycle/number of females cycling

c Estrous cycle was longer than 12 days or unclear in 1 of 10 animals.

d Estrous cycle was longer than 12 days or unclear in 3 of 10 animals.

Executive summary:

Cited from NTP report:

"Groups of 10 male and 10 female core study rats were administered 0, 1, 5, 10, 20, or 50 mg androstenedione/kg body weight in a 0.5 % aqueous methylcellulose solution by gavage, 5 days per week for 14 weeks; additional groups of 10 male and 10 female clinical pathology study rats received the same doses for 23 days. All rats survived to the end of the study. The mean body weights of the 20 mg/kg female group was significantly greater than those of the vehicle control group and there was significant increased weight gain in the 1, 20, and 50 mg/kg female groups. Female thymus weights were significantly increased in the 20 and 50 mg/kg groups, which may be related to the increase in mean body weight. The numbers of sperm per mg cauda epididymis in the 10, 20, and 50 mg/kg male groups and the total number of sperm per cauda epididymis in 50 mg/kg males were significantly less than those of the vehicle controls. No treatment-related histological lesions were observed in males or females."

No NOAEL was concluded in the report, as the study served only for the purpose of dose selection for a 2 -year carcinogenicity study. As effects on male fertility revealed the most sensitive health effect in the study a NOAEL of 5 mg/kg is concluded as point of departure for the delineation of a DNEL.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

5 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a subacute repeated dose toxicity study similar to OECD TG 407 Androstendione in physiological saline containing 0.085 % Myrj 53 was administered to 6 Wistar rats/sex/dose daily by gavage at dose levels of 15, 50 and 150 mg/kg bw/d.

Another group of 6 M/6 F received the vehicle at the same volume and served as control. The effects of the test item were evaluated using clinical, biochemical and hematological parameters as well as bone marrow examination, urinalysis, coagulation studies, necropsy findings, organ weight analysis and microscopic examination.

The administration of the substance led to dose-dependent effects such as increased body weight, atrophy of uterus, cervix, pituitary gland and adrenals, as well as increased numbers of erythrocytes and increased hemoglobin in females. For males, alterations in thymus were reported. These effects were regarded to represent endocrine effects typical for a steroid hormone. Regarding these effects a NOAEL could not be established in the study.

An increase in liver weights together with increased liver transaminases was additionally observed at 150 mg/kg in both sexes and was considered to indicate beginning liver toxicity. A NOAEL could not be established; the LOAEL was established at 15 mg/kg.

In this study, no clear androgenic mode of action could be identified. No alterations of male genital organs at all were observed which would have been expected if the compound had comparable androgenic potential to testosterone. The atrophy of the uterus in the females of the mid- (50 mg/kg) and high-dose (150 mg/kg) groups, however, indicates that the compound has an antiestrogenic potential. However, the ovaries were not affected. They appeared to be normal and active in all groups. The dosage might have been too low to provoke effects at the ovaries. It is known of gestagens hat effects on the endometrium are induced at a lower dosage than effects on the ovaries. On the whole, the effects observed are regarded to represent endocrine action of a steroid hormone on various target organs such as pituitary gland, adrenal glands, endometrium, thymus etc. without a clear hormonal pattern of action. The increase in liver weight in both sexes after the high dose probably reflects an adaptive growth stimulation which is known after prolonged application of other steroid hormones as well. The slight increase in liver enzymes in the high-dose group is considered to be an indication of beginning liver toxicity (NTP, 2010).

 

Groups of 10 male and 10 female mice were administered 0, 1, 5, 10, 20, or 50 mg androstenedione/kg body weight in a 0.5 % aqueous methyl cellulose solution by gavage, 5 days per week for 14 weeks. Except for one 10 mg/kg female that died early due to a dosing accident, all mice survived to the end of the study. The mean body weights of dosed groups were similar to those of the vehicle control groups. The number of spermatids per mg testis and the total number of spermatids per testis in 20 mg/kg males were significantly greater than those of the vehicle controls. Sperm motility in 50 mg/kg males was significantly lower than that in the vehicle controls.

The incidences of x-zone atrophy of the adrenal cortex, an androgen-sensitive endpoint, were significantly increased in females administered 5 mg/kg or greater. There were also significant decreases in the incidences of x-zone cytoplasmic vacuolization in 20 and 50 mg/kg females. The incidences of bone marrow hyperplasia were significantly increased in 5 and 50 mg/kg males.

The leading health effect in this study is concluded to be the effect on male fertility starting at 50 mg/kg (= LOAEL). Concerning the incidences of x-zone atrophy this is not regarded to be of relevance for humans, as the x-zone of the adrenal gland is located at the junction of the cortex and medulla, and is unique to the mouse (NTP, 2010).

 

In a subacute repeated dose toxicity study similar to OECD TG 407 Androstendione in physiological saline containing 0.085 % Myrj 53 was administered to 6 Wistar rats/sex/dose daily by gavage at dose levels of 15, 50 and 150 mg/kg bw/d.

Another group of 6 M/6 F received the vehicle at the same volume and served as control. The effects of the test item were evaluated using clinical, biochemical and hematological parameters as well as bone marrow examination, urinalysis, coagulation studies, necropsy findings, organ weight analysis and microscopic examination.

The administration of the substance led to dose-dependent effects such as increased body weight, atrophy of uterus, cervix, pituitary gland and adrenals, as well as increased numbers of erythrocytes and increased hemoglobin in females. For males, alterations in thymus were reported. These effects were regarded to represent endocrine effects typical for a steroid hormone. Regarding these effects a NOAEL could not be established in the study.

An increase in liver weights together with increased liver transaminases was additionally observed at 150 mg/kg in both sexes and was considered to indicate beginning liver toxicity. A NOAEL could not be established; the LOAEL was established at 15 mg/kg.

In this study, no clear androgenic mode of action could be identified. No alterations of male genital organs at all were observed which would have been expected if the compound had comparable androgenic potential to testosterone. The atrophy of the uterus in the females of the mid- (50 mg/kg) and high-dose (150 mg/kg) groups, however, indicates that the compound has an antiestrogenic potential. However, the ovaries were not affected. They appeared to be normal and active in all groups. The dosage might have been too low to provoke effects at the ovaries. It is known of gestagens hat effects on the endometrium are induced at a lower dosage than effects on the ovaries. On the whole, the effects observed are regarded to represent endocrine action of a steroid hormone on various target organs such as pituitary gland, adrenal glands, endometrium, thymus etc. without a clear hormonal pattern of action. The increase in liver weight in both sexes after the high dose probably reflects an adaptive growth stimulation which is known after prolonged application of other steroid hormones as well. The slight increase in liver enzymes in the high-dose group is considered to be an indication of beginning liver toxicity (Treher, 1996).

The once daily subcutaneous administration of the substance to male and female rats over 4 weeks at doses of 0, 5, 15 and 50 mg/kg led to dose-dependent effects such as decrease of thymus and testes weights, increase of organ weights of prostate, seminal vesicles or uterus and related histological alterations, which can be attributed to the endocrine action of the test compound with partial androgenic, estrogenic and progestagenic action. Additional signs of general toxicity like decreased body weight gain, decreased food and increased water consumption together with occurence of protein in the urine and increased kidney weight were observed at higher doses. Due to the onset of some of the described hormonal effects already at the low dose, a NOAEL could not be established (Steger-Hartmann, 2000).

 

Further study results are cited in RTECS database (April 2013):

The once daily oral administration of androstendion over 14 days results in endocrine effects on menstrual cycle; TDLo: 14 mg/kg/14D-I [Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- v. 42, p. 917, 2004 (FCTOD7)]

 

The daily application of androstendion to rats over 34 days results in endocrine effects not further specified; TDLo: 34 mg/kg/34D-I [Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- v. 42, p. 917, 2004 (FCTOD7)]

 

The daily oral administration to rats over 33 days leads to not specified changes in the liver and enzyme inhibition, induction, or change in blood or tissue levels: Phosphatases; TDLo: 1980 mg/kg/33D-I [Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- v. 44, p. 579, 2006 (FCTOD7)]

 

Androstendion applied once daily orally over 33 days results in changes in serum composition (e.g., TP, bilirubin, cholesterol) and metabolism (intermediary): Lipids, including transport; TDLo: 165 mg/kg/33D-I [Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- v. 44, p. 579, 2006 (FCTOD7)]

 

The daily intramuscular administration to mice over 4 days results in maternal effects in uterus, cervix, vagina ; TDLo: 200 mg/kg/4D-I [Journal of Pharmacology and Experimental Therapeutics. (Williams and Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- v. 297, p. 1099, 2001 (JPETAB)]

 

A lot of human data is available from the use of androstendione to achieve a pharmacological effect (e.g. hormone replacement therapy, over-the-counter sports supplementation). As these data does not give relevant information in the context of REACH they were not included in the IUCLID.

Justification for classification or non-classification

No classification required for repeated dose toxicity according to Regulation (EC) 1272/2008, as the leading health effect after repeated exposure to the substance is reproductive toxicity, and the substance is classified accordingly (see chapter Toxicity to reproduction).