Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Purity: 98,96 %

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Duration of treatment / exposure:
Male: 46 days,
female: from 14 days before mating to day 3 of lactation
Control animals:
yes

Results and discussion

Results of examinations

Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Body weight gain was reduced in 500 mg/kg females in the pregnancy and lactation periods
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Food consumption was decreased in the 500 mg/kg group on day 2 of administration in males and on day 10 of administration and day 3 of pregnancy in females.
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
On the haematological and blood chemical analyses, the 500 mg/kg males exhibited decreased numbers of platelets and increased cholinesterase values.
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Increases in relative organ weights were seen for the livers of males and females, and kidneys of males at 500 mg/kg. On gross necropsy, dark brown discoloration of the liver was observed in 9/12 males receiving 500 mg/kg.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Hypertrophy of hepatocytes in the centrilobular zones of the livers: 500 mg/kg males and 2/12 79 mg/kg males. Atrophy and regeneration of kidney tubular epithelium and dilation of tubules: 2/12 males and 1/12 females 500 mg/kg, and 1/12 79 mg/kg males.

Effect levels

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Dose descriptor:
NOEL
Remarks:
for P generation
Effect level:
12.5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: repeated dose toxicity
Dose descriptor:
NOEL
Remarks:
for P generation
Effect level:
79 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Basis for effect: fertility
Dose descriptor:
NOEL
Remarks:
for P generation
Effect level:
79 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Basis for effect: maternal
Dose descriptor:
NOEL
Remarks:
for F1 generation
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: Bodyweight of the offspring

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

This was a combined repeated dose and reproductive/developmental toxicity test, see also section 7.8.1.

Applicant's summary and conclusion

Conclusions:
Repeat dose toxicity
NOEL: 12.5 mg/kg/day
Reproductive and developmental toxicity
NOEL for P generation: 79 mg/kg/day
NOEL for F1 generation: 500 mg/kg/day