Sodium ethanolate

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: short-term inhalation

Type of information:

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

Adequacy of study:

supporting study

Study period:

1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A published study containing sufficient details to regard it as reliable for use in hazard assessment. Basic experimental detail provided. Route of exposure highly relevant.

Data source

Reference

Reference Type:

publication

Title:

Neurochemical but not behavioral deviations in the offspring of rats following prenatal or paternal inhalation exposure to ethanol.

Author:

Nelson BK, Brightwell WS, Mackenzie-Taylor DR, Burg JR, Massari VJ

Year:

1988

Bibliographic source:

Neurotoxicol Teratol 10, 15-22.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 414 (Prenatal Developmental Toxicity Study) Behavioural study

Deviations:

yes

Remarks:

yes low number of pregnant females; no necropsy or pathology conducted; males treated prior to mating

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

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: females 176-200g; males >300g

ENVIRONMENTAL CONDITIONS
- Temperature: 24+/-2°C
- Humidity: ~40%
- Photoperiod: 12hr light/dark cycle.

Administration / exposure

Route of administration:

inhalation

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 (one air change per minute.) Dosing method described in detail.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

IR analyser - exposures found to be +/-200ppm of nominal. Independently cross-checked with charcoal adsorption tubes analysed by gas chromatography.

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 1-19 of gestation

Frequency of treatment:

daily

Doses / concentrations

Remarks:

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

No. of animals per sex per dose:

Females, 15 per group, males,18 per group.

Control animals:

yes

Details on study design:

Duration of test: see method details

Examinations

Observations and clinical examinations performed and frequency:

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE: Yes, as measures of maternal toxicity.

WATER CONSUMPTION AND COMPOUND INTAKE: Yes, as measures of maternal toxicity.
- Time schedule for examinations:

Other examinations:

All litters weighed within 16 hrs. Litters less than 3 pups per sex discarded. Offspring weighed on PND 7 and checked for abnormalities

Statistics:

Behavioral data were analyzed using multivariate analysis of variance or an m-ranking procedure. Repeated measures analyses were conducted where appropriate to p<0.05. Neurochemical data were analyzed using Analysis of Variance followed by Duncan's Multiple Range post-hoc tests where a significance was found.

Results and discussion

Results of examinations

Details on results:

No effect on weight gain. Feed intake retarded during 1st week but normal thereafter at 16000ppm. No effects on litter size, still births, length of pregnancy, offspring survival. No effect observed in behavioural study tests. No effect on dopamine, substance P, beta-endorphin and acetylcholine levels. Significant effects on norepinephrine, 5-hydroxytryptamine but magnitude and direction of changes not correlated with dose. Level of Met-enk phalin affected at lower but not higher dose.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

>= 1 600 ppm

Basis for effect level:

other: no effects observed

Remarks on result:

other: Generation: maternal (migrated information)

2

Dose descriptor:

NOEL

Effect level:

< 1 000 ppm (nominal)

Basis for effect level:

other: Significant changes in 5-hydroxytryptamine levels in different parts of the brain.

Remarks on result:

other: Generation: other: - Neurotransmiter levels in offspring brain (migrated information)

3

Dose descriptor:

NOAEL

Effect level:

>= 1 600 mg/m³ air (nominal)

Basis for effect level:

other: No effects observed

Remarks on result:

other: Generation: other: - Behavioural development (migrated information)

Any other information on results incl. tables

Males: weight gain retarded during 1st week but normal thereafter.

Control values of behavioural results are described in Nelson et al 1985. Neurobehavioral Toxicology and Teratology, 7, 779 -783, 1985.

Applicant's summary and conclusion

Conclusions:

Ethanol treatment did not affect the performance of offspring in behavioural tests. Some biochemical changes were observed in the brain but not dose related and not cosistent across brain regions.

Executive summary:

Male Sprague-Dawley rats were exposed 7 hours per day for six weeks to 10,000 or 16,000ppm ethanol by inhalation and then mated with untreated rats. Pregnant females received the same experimental treatment from day 1 -19 of gestation and were allowed to deliver their offspring. Treatment with ethanol did not affect the weight gain of parental animals. Offspring from paternally or maternally exposed animals performed as well as controls in tests of neuromotor coordination, activity levels, and learning ability. Levels of acetylcholine, dopamine, substance P, and beta-endorphin were unchanged in the brain in the offspring of ethanol exposed rats. Complex, but significant changes in the levels of norepinephrine occurred only in paternally exposed offspring. 5 -Hydroxytryptamin levels were reduced in the cerebrum, and met-enkephalin levels were increased in all brain regions of offspring from both maternally and paternally exposed rats.