Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

A single dose of the test substance was administered to male rats by oral route. 3 days after the treatment, the testes were removed for histopathological observations. Under the study conditions, no effect on the weight of the testes and on the spermatogenesis was observed in the test substance treated groups (Lloyd, 1988).

Link to relevant study records
Reference
Endpoint:
fertility, other
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A scientifically sound study/ publication. No guideline available for such kind of investigation. However, the result obtained is valuable.
Qualifier:
no guideline followed
Principles of method if other than guideline:
In this in vivo study a single dose of the test substance was administered to male rats by oral route. 3 days after the treatment, the testes were removed for histopathological observations.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
other: Alpk/AP (Wistar derived)
Sex:
male
Route of administration:
oral: unspecified
Vehicle:
water
Details on mating procedure:
Not applicable: no mating was performed. Male fertility was investigated.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
single dose
Frequency of treatment:
single dose
Details on study schedule:
not applicable
Remarks:
Doses / Concentrations:
0, 10, 25 mg/kg bw
Basis:
other: nominal in water in 5 mL water/kg bw, adjusted to pH 7 using 1.0 M NaOH
No. of animals per sex per dose:
10 males per dose
Control animals:
yes, concurrent vehicle
Key result
Dose descriptor:
NOAEL
Remarks:
fertility
Effect level:
25 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: after single dose treatment
Basis for effect level:
other: F1 generation was not assessed
Remarks on result:
not measured/tested
Reproductive effects observed:
not specified
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
25 mg/kg bw/day
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

In a developmental toxicity test rats were administered high oral doses (75 or 150 mg/kg bw x d, on gestation days 10 - 20). There was no influence on reproductive-toxic parameters (litter size, surviving rate, growth). Functional disturbances of the liver and kidneys were reversible (for approximately 50 days) (Ema, 2010).

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1997
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary literature
Qualifier:
no guideline followed
Principles of method if other than guideline:
Female rats were exposed by oral route to trifluoroacetic acid during the gestation (from day 10 to day 20). On day 21, the delivery occured and then the pups were examined until day 49 postnatal (PND 49).
GLP compliance:
not specified
Remarks:
No information available.
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Route of administration:
oral: gavage
Vehicle:
water
Details on mating procedure:
not indicated
Duration of treatment / exposure:
10 days: the test substance was administered from GD 10 to GD 20.
Frequency of treatment:
daily
Duration of test:
not indicated
Remarks:
Doses / Concentrations:
0, 75, 150 mg/kg bw/d
Basis:
nominal in water
No. of animals per sex per dose:
not indicated (around 40 pregnant females per dose and control)
Control animals:
yes, concurrent vehicle
Dose descriptor:
NOAEL
Effect level:
> 150 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Basis for effect level:
other: not specified
Remarks on result:
not determinable because of methodological limitations
Abnormalities:
not specified
Developmental effects observed:
not specified
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
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
Additional information

The NOAEL for the effect on developmental toxicity: via oral route was determined to be > 150 mg/kg bw/d (maternal animals).

Toxicity to reproduction: other studies

Description of key information

Three cell culture systems such as isolated Leydig cells, Sertoli cells and Sertoli-germ cell co-cultures were exposed to the test substance. Cell parameters like protein content, lactate and pyruvate production, hormonally stimulated testosterone production and morphology depending on the cell culture type were analysed and the results compared with reference values to assess the effect of the test substance.

Under the test conditions, the test item enhanced the lactate production (Sertoli cells) significantly in a dose-dependent manner and inhibited testosterone output (Leydig cells) but only in the presence of hormone at 5 hours. The no observed-effect level (NOEL) for this effect was established to be less than 1 mM. The test item thus showed only a small effect on the function of Leydig cells and no effect on Sertoli cells (ECHA disseminated dossier, 2014).

Link to relevant study records
Reference
Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
March - October 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: It is a well documented non-guideline study which was performed in compliance with GLP
Qualifier:
no guideline followed
GLP compliance:
yes
Type of method:
in vitro
Dose descriptor:
NOEL
Remarks:
effect on testosterone production in Leydig cells under hCG stimulation
Effect level:
1 other: mM
Conclusions:
The test item was exposed to three cell culture systems such as isolated Leydig cells, Sertoli cells and Sertoli-germ cell co-cultures. The cell culture systems used are known to be responsive to some positive control compounds and the effects obtained used as reference values for the assessment of the test item. Cell parameters like protein content, lactate and pyruvate production, hormonally stimulated testosterone production and morphology depending on the cell culture type were analysed. Under the test conditions, the test item enhanced the lactate production (Sertoli cells) significantly in a dose-dependent manner and inhibited testosterone output (Leydig cells) but only in the presence of hormone at 5 hours. The no observed-effect level (NOEL) for this effect was established to be less than 1 mM. The test item thus showed only a small effect on the function of Leydig cells and no effect on Sertoli cells.

Justification for classification or non-classification

Toxicity to reproduction (oral)

The available experimental test data is reliable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for reproductive toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Directive 2017/776.

Developmental toxicity (oral)

The available experimental test data is reliable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for developmental toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Directive 2017/776.