Registration Dossier

Toxicological information

Toxicity to reproduction: other studies

Currently viewing:

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Cross-referenceopen allclose all
Reason / purpose:
read-across source
Reference
Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: additional investigations in mice within a 90 day study
Reason / purpose:
reference to same study
Principles of method if other than guideline:
Subchronic toxicity study with determination of sperm motility and concentration in males and length of oestrus cycle and vaginal cytology following repeated dose according EPA OPP 82-1. For details on test method and general toxicity please refer to 7.5.1.
GLP compliance:
yes
Type of method:
in vivo
Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Duration of treatment / exposure:
90 d
Frequency of treatment:
daily
Dose / conc.:
1 250 ppm (nominal)
Dose / conc.:
2 500 ppm (nominal)
Dose / conc.:
5 000 ppm (nominal)
Dose / conc.:
10 000 ppm (nominal)
Dose / conc.:
20 000 ppm (nominal)
Control animals:
yes, concurrent no treatment
Key result
Dose descriptor:
NOAEL
Remarks:
general toxicity
Effect level:
1 250 ppm (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: >=2500 ppm: increased relative and absolute liver and kidney weights
Remarks on result:
other: corresponds to 199 (males) and 237 mg/kg bw/d (females), respectively
Key result
Dose descriptor:
NOAEL
Remarks:
reproduction
Effect level:
20 000 ppm (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other:
Remarks on result:
other: corresponds to 2733 (males) and 1663 mg/kg bw/d (females), respectively

Male:

Reproductive organ weights (R. testicle and R. epididymidis) showed no difference to the respective controls; epididymal tail weight was significantly reduced when compared to the respective control at the high dose.

Spermatogonial measurements revealed no findings.

 

Female:

Mean estrous cycle length was significantly prolonged at 20000 ppm.

Conclusions:
No effects on reproduction were observed.
Reason / purpose:
read-across source
Reference
Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: additional investigations in rats within a 90 day study
Reason / purpose:
reference to same study
Principles of method if other than guideline:
Subchronic toxicity study in rats with determination of sperm motility and concentration in males and length of oestrus cycle and vaginal cytology following repeated dose according EPA OPP 82-1. For further details on method and general toxicity please refer to 7.5.1.
GLP compliance:
yes
Type of method:
in vivo
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Duration of treatment / exposure:
90 d
Frequency of treatment:
daily
Dose / conc.:
1 880 ppm (nominal)
Dose / conc.:
7 500 ppm (nominal)
Dose / conc.:
30 000 ppm (nominal)
Control animals:
yes, concurrent vehicle
Key result
Dose descriptor:
NOAEL
Remarks:
general toxicity
Effect level:
3 750 ppm (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: >= 7500 ppm: increased relative liver and kidney weights
Remarks on result:
other: males ca. 247 mg/kg bw/day; females ca. 256 mg/kg bw/day
Key result
Dose descriptor:
NOAEL
Remarks:
reproduction
Effect level:
30 000 ppm (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Males: Reproductive organ weights and Spermatozoal measurements (including % motility) and concentration showed no difference to the respective control values; Females: No significant changes in the medium oestrous cycle length.
Remarks on result:
other: males ca. 2028 mg/kg bw/day; females ca. 2024 mg/kg bw/day

Males: Reproductive organ weights (R. testicle, R. epididymis, R. epididymis tail) and Spermatozoal measurements (including % motility) and concentration showed no difference to the

respective control values

Females: >= 7500 ppm: Medium oestrous cycle length was significant increased, especially at 7500 ppm in 2/10 females the length exceeded 7 days and at 30000 ppm in 2/10 females the

oestrous cycle length was not determined or exceeded 7 days. However, these changes were not statistically significant.

Conclusions:
No effects on reprotoxicity was observed.

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Remarks:
general toxicity, rat
Effect level:
3 750 ppm (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: >= 7500 ppm: increased relative liver and kidney weights
Remarks on result:
other: males ca. 247 mg/kg bw/day; females ca. 256 mg/kg bw/day; Source, CAS 95-48-7, o-cresol, NTP, 1991
Key result
Dose descriptor:
NOAEL
Remarks:
reproduction, rat
Effect level:
30 000 ppm (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Males: Reproductive organ weights and Spermatozoal measurements (including % motility) and concentration showed no difference to the respective control values; Females: No significant changes in the medium oestrous cycle length.
Remarks on result:
other: males ca. 2028 mg/kg bw/day; females ca. 2024 mg/kg bw/day; Source, CAS 95-48-7, o-cresol, NTP, 1991
Key result
Dose descriptor:
NOAEL
Remarks:
general toxicity, mouse
Effect level:
1 250 ppm (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: >=2500 ppm: increased relative and absolute liver and kidney weights
Remarks on result:
other: corresponds to 199 (males) and 237 mg/kg bw/d (females), respectively; Source, CAS 95-58-7, o-cresol, NTP, 1991
Key result
Dose descriptor:
NOAEL
Remarks:
reproduction, mouse
Effect level:
20 000 ppm (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other:
Remarks on result:
other: corresponds to 2733 (males) and 1663 mg/kg bw/d (females), respectively; Source, CAS 95-58-7, o-cresol, NTP, 1991

Applicant's summary and conclusion

Conclusions:
No effects on reproductive parameters were observed in sub-chronic studies in rats and mice with the source substance o-cresol. Similar effects are considered for the target substance as explained in the analogue justification.