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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
Oral gavage application of different doses to mouse 5 days/week, 13 weeks;
Type of information:
experimental study
Adequacy of study:
key study
Study period:
90 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES are commonly accepted as trustworthy and useful reference books in REACh endpoint specific guidance.

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1989

Materials and methods

Principles of method if other than guideline:
Oral gavage application of different doses to mouse 5 days/week, 13 weeks; Determination of survival and body weight, clinical signs, gross pathology and histopathology.
GLP compliance:
yes
Limit test:
no
Justification for study design:
Oral gavage application of different doses to mouse 5 days/week, 13 weeks; Determination of survival and body weight, clinical signs, gross pathology and histopathology.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:

- Name of test material (as cited in study report): Benzyl alcohol, NF grade (Stauffer Chemical Co., Westport, Connecticut)
- Purity 99 %
- Lot/batch No.: 4T 215P1

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: B6C3F1 mice
- Source: Charles River Breeding Laboratories (Portage, MI)
- Age at study initiation: 7-9 weeks
- Weight at study initiation (mean): males 27.3-28.9 g; females: 20.6-21.0 g
- Housing: 5 per cage
- Diet ad libitum
- Water ad libitum
- Acclimation period: 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-27 (68-81 °F)
- Humidity (%): 30-90
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Administration volume: 10 ml/kg
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
extraction of benzyl alcohol with methanol followed by gas chromatographic analysis
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
once daily, 5 days/week
Doses / concentrationsopen allclose all
Dose / conc.:
50 mg/kg bw/day (actual dose received)
Dose / conc.:
100 mg/kg bw/day (actual dose received)
Dose / conc.:
200 mg/kg bw/day (actual dose received)
Dose / conc.:
400 mg/kg bw/day (actual dose received)
Dose / conc.:
800 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
10
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.
- Post-exposure period: no

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes, all animals
- Time schedule: twice daily

BODY WEIGHT: Yes, all animals
- Time schedule for examinations: weighed individually initially and at the end of the studies; weighed by group at other times 1 x week

CLINICAL PATHOLOGY: No
Oestrous cyclicity (parental animals):
GROSS PATHOLOGY: Yes, all animals

HISTOPATHOLOGY: Yes, histopathological examination performed on all vehicle controls and on all animals in the 800 mg/kg bw-group, including reproductive organs. Brains were examined from rats in the 400 mg/kg bw-group.
Statistics:
According to Kaplan and Meier, method of Coc (1972) and Tarone's (1975) life table test.

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
gross pathology
histopathology: non-neoplastic
histopathology: neoplastic
Dose descriptor:
NOAEL
Effect level:
800 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive performance
Remarks on result:
other: no compound related effects on reproductive organs (gross and histopatology examination) up to highest dose (800 mg/kg bw/day)

Target system / organ toxicity (P0)

Critical effects observed:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not examined
Mortality / viability:
not examined
Body weight and weight changes:
not examined
Haematological findings:
not examined
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed

Details on results (F1)

No compound related effects on reproductive organs (gross and histopatology examination) could be found in this subchronic study.

Effect levels (F1)

Remarks on result:
not measured/tested

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

No compound related effects on reproductive organs (gross and histopatology examination) could be found in this subchronic study.

Applicant's summary and conclusion

Conclusions:
In a 13 week dose-finding study male and female mice received once daily on 5 days/week 0, 50, 100, 200, 400, 800 mg/kg bw benzyl alcohol via gavage. Based on clinical signs and reduced body weight development in males and females the NOAEL was considered to be 200 mg/kg bw/day. Regarding reproductive organs no compound related effects could be found (gross and histopathologic examination).