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Diss Factsheets

Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
two-generation reproductive toxicity
Type of information:
experimental study
Remarks:
Ethanol has been demonstrated to form during hydrolysis in gastric fluid. Any oral toxicity on the xanthate needs to consider oral effects of carbon disulphide and the corresponding alcohol
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Ethanol has been demonstrated to form during hydrolysis in gastric fluid.
Any oral toxicity on the xanthate needs to consider oral effects of carbon disulphide and the corresponding alcohol
Further animal testing on the xanthate cannot be justified
Administration route was by inhalation. Toxicokinetic assessment suggests that this is a suitable route of exposure for chronic effects

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
GLP compliance:
yes
Remarks:
Primary data source not found
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethanol
EC Number:
200-578-6
EC Name:
Ethanol
Cas Number:
64-17-5
Molecular formula:
C2H6O
IUPAC Name:
Ethanol
Test material form:
liquid

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
Continuous
Details on mating procedure:
Male - female ratio per cage: 1:1
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Samples weeks 1, 6, 12, and 18 of main study with Parental animals.
Duration of treatment / exposure:
F0-males minimum of 18 weeks, including 1 week prior to mating and during the mating period,
F0-females minimum of 18 weeks, including 1 week prior to mating,
F1 animals 10 weeks exposure

Frequency of treatment:
Daily, ad-libitum
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
Water only
Dose / conc.:
6 660 mg/kg bw/day
Remarks:
Based on 5% in drinking water
Dose / conc.:
13 300 mg/kg bw/day
Remarks:
Based on 10% in drinking water
Dose / conc.:
20 000 mg/kg bw/day
Remarks:
Based on 15% in drinking water
No. of animals per sex per dose:
20
Control animals:
yes, concurrent vehicle
Details on study design:
Dose level selection based on rangefinder study showing reduction in bodyweight gain at top dose.
Positive control:
No

Examinations

Parental animals: Observations and examinations:
At least daily observations
Weekly weight assessment and full physical assessment
Food consumption assessed for each group
Drinking water monitored
Oestrous cyclicity (parental animals):
Yes
Sperm parameters (parental animals):
Checked on necropsy as part of post-mortum examinations
Litter observations:
Number and vigour
Postmortem examinations (parental animals):
Full necropsy and gross examination of organs at scheduled termination
Postmortem examinations (offspring):
Pups found dead and at scheduled termination
Statistics:
Statistical analysis was applied as needed

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, non-treatment-related
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Endocrine findings:
not specified
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
> 20 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity (P0)

Critical effects observed:
no

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, non-treatment-related
Water consumption and compound intake (if drinking water study):
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Histopathological findings: neoplastic:
no effects observed

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed

Effect levels (P1)

Dose descriptor:
NOAEL
Effect level:
> 20 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity (P1)

Critical effects observed:
no

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
mortality observed, non-treatment-related
Description (incidence and severity):
Mortality across groups not considered to be significantly different to historical levels
No treatment related effects
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Slight reduction of bodyweight
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Sexual maturation:
no effects observed
Anogenital distance (AGD):
effects observed, non-treatment-related
Nipple retention in male pups:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings:
effects observed, treatment-related
Description (incidence and severity):
Significantly decreased % motile sperm but no changes in sperm concentration, % abnormal sperm or % tailless sperm
There was a significant decrease in testis, epididymis and seminal vesicle weight but not when adjusted for body weight.

Developmental neurotoxicity (F1)

Behaviour (functional findings):
no effects observed

Details on results (F1)

Effects on F1 similar to those seen in parental animals

Effect levels (F1)

Dose descriptor:
NOAEC
Generation:
F1
Effect level:
ca. 13 300 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
other: Sperm parameters

Target system / organ toxicity (F1)

Critical effects observed:
no

Results: F2 generation

General toxicity (F2)

Clinical signs:
effects observed, non-treatment-related
Mortality / viability:
mortality observed, non-treatment-related
Description (incidence and severity):
Within historical parameters
Body weight and weight changes:
effects observed, non-treatment-related
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, non-treatment-related

Effect levels (F2)

Dose descriptor:
NOAEL
Generation:
F2
Effect level:
ca. 20 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain

Target system / organ toxicity (F2)

Critical effects observed:
no

Overall reproductive toxicity

Reproductive effects observed:
no

Any other information on results incl. tables

Result: No observed effect on fertility.


 


Parental/F1 data: Ethanol treatment had no effect on bodyweights and on the proportion of breeding pairs producing at least 1 litter during the continuous breeding phase or the number of litters per pair. 


 


Effects on sperm and male reproductive organs: In the F1, 15% ethanol group there was a significantly decreased % motile sperm but no changes in sperm concentration, % abnormal sperm or % tailless sperm. There was a significant decrease in testis, epididymis and seminal vesicle weight but not when adjusted for body weight.


 

Applicant's summary and conclusion

Conclusions:
Slight effect on male reproductive organs and sperm
Reduction in weight of off-spring