Titanium(4+) ethanolate

Toxicity to reproduction

Some information in this page has been claimed confidential.

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A published study containing sufficient details to conclude results reliable for use in hazard assessment. Limited experimental detail provided. Study incomplete as a comprehensive assessment of effects on male fertility.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Comparison of Behavioural Teratogenic Effects of Ethanol and n-propanol administered by inhalation to rats.

Author:

Nelson BK; Brightwell, WS, Burg JR

Year:

1985

Bibliographic source:

Neurobehav Toxicol Teratol 7, 779-83.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Deviations:

yes

Remarks:

short paternal exposure period; no pathology conducted; number of pregnant females low; male treated rats mated to untreated females.

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Constituent 2

Reference substance name:

Ethanol

EC Number:

200-578-6

EC Name:

Ethanol

Cas Number:

64-17-5

Molecular formula:

C2H6O

IUPAC Name:

ethanol

Details on test material:

- Name of test material (as cited in study report): ethanol

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 400-500g males; 200-300g females
- Housing: Females housed individually.

ENVIRONMENTAL CONDITIONS
- Temperature: 73 +/- 3F.
- Humidity: 40-50%.
- Light/dark cycle (hrs): 12/12

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

whole body

Vehicle:

other: air in chamber

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Exposure was conducted in 0.5m3 chambers with dynamic air flow
- Air change rate: (one air change per minute.)

Details on mating procedure:

After 2 day non-exposure period males were mated individually with untreated virgin females. Mating period 5 days. Mating confirmed by presence of sperm plugs under cages or vaginal smears.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Exposure period: 7 hours /day
Premating exposure period (males): 6 weeks
Premating exposure period (females): none
Postmating exposure period (females): Days 1-20 gestation
Duration of test: see method details

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 10000, 16000ppm
Basis:
nominal conc.

No. of animals per sex per dose:

18/group male
15/group female (pregnant)

Control animals:

yes

Details on study design:

Analytical monitoring: Yes (IR analyser) - exposure found to be within 11% of nominal). Independently cross-checked with charcoal adsorption tubes.

Examinations

Parental animals: Observations and examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: Daily

FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food intake were measured.

WATER CONSUMPTION AND COMPOUND INTAKE: Yes

Litter observations:

Pups were individually weighed weekly for five weeks.

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

> 16 000 ppm

Sex:

male

Basis for effect level:

reproductive function (oestrous cycle)

reproductive function (sperm measures)

Remarks on result:

not determinable due to absence of adverse toxic effects

Results: F1 generation

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Sex:

not specified

Remarks on result:

not determinable because of methodological limitations

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Result: negative

No effect on weight gain, feed or water intake.  No effect on fertility or litter sizes.  Offspring numbers averaged 14/litter. Previous studies quoted as showing exposures to 10000 and 16000 ppm (30 400mg/m3) ethanol typically give rise to blood ethanol concentrations of 30 and 500 mg/l ethanol.  Authors calculate that for rats exposures in excess of 11000 ppm are required to begin accumulating ethanol in the blood and that ethanol is no more toxic by the inhalation route than by other routes.

No data on offspring body weight gain provided but it is presumed that there was no change from controls.

6 weeks treatment period for males does not cover one complete cycle of spermatogenesis.

Applicant's summary and conclusion

Conclusions:

Ethanol treatment did not affect the fertility of male rats determined by number of litters and litter size.

Executive summary:

Male rats were exposed to ethanol in an inhalation chamber at concentrations of 11,000ppm or 16,000ppm for six weeks. After a two day non-exposure period they were mated to untreated females for 5 days. The pregnant females received the same experimental exposure from day 1 -20 of gestation and were then allowed to deliver their litters. Ethanol treatment did not affect fertility or litter sizes.