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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
two-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
by competent authority reviewed data

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Remarks:
systemic toxicity
Effect level:
300 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: general systemic toxicity, not further specified in SIDS Initial Assessment report
Dose descriptor:
NOAEL
Remarks:
reproduction
Effect level:
300 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: see remarks

Target system / organ toxicity (P0)

Critical effects observed:
no

Results: F1 generation

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: no effect on the pre- and postnatal development of the progeny in both generations up to the limit dose level

Target system / organ toxicity (F1)

Critical effects observed:
no

Results: F2 generation

Effect levels (F2)

Dose descriptor:
NOAEL
Generation:
F2
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: no effect on the pre- and postnatal development of the progeny in both generations up to the limit dose level

Overall reproductive toxicity

Reproductive effects observed:
no

Applicant's summary and conclusion

Conclusions:
A two-generation reproduction toxicity study in rats with dietary MEA-HCl administration demonstrated clear NOAELs for systemic and reproductive toxicity including effects on fertility at 300 mg/kg bw/day. Only at 1000 mg/kg bw/day, which is generally accepted as a limit dose level, minor effects were noted. Males at this dose showed a minor functional impairment of fertility in the form of decreased weights of epididymides and cauda epididymidis and reductions in the number of homogenization resistant caudal epididymal sperm. However, there was neither an effect on mating success nor histomorphological evidence of testicular toxicity. Females at this dose had decreased numbers of implants and increased resorption rates resulting in smaller litters associated with indications of systemic toxicity. There was virtually no effect on the pre- and postnatal development of the progeny in both generations up to the limit dose level of 1000 mg/kg bw/day representing a NOAEL for developmental toxicity.