Barium oxide, obtained by calcining witherite

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

fertility, other

Remarks:

based on test type (migrated information)

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

BaO rapidly hydrolyzes to Ba(OH)2, a strongly alkaline substance, upon contact with water. Barium chloride dihydrate as well soluble barium salt was used to assess the potential of BaO to cause barium toxicity. The study did not follow a guideline, but the experimental setup meets basic scientific criteria.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Four dose levels were tested with 20 males and 20 females each: 0, 1000, 2000, and 4000 ppm Barium Chloride Dihydrate in drinking water. Males were treated for 60 consecutive days, females for 30 days. At the end of the treatment period, one male and one female were co-housed until signs of mating were detected, but for maximum 8 days. Live offspring were counted, weighed and examined on day 0 (day of birth) and again on day 5. Dead pups were colleced and examined. All females were terminated on days 96 or 97 and vagina, cervix, oviduct and ovaries were examined and implantation sites were counted.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: Fischer-344/N

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Simonsen Laboratories, Gilroy (CA)
- Age at study initiation: 32 days
- Housing: 5 per cage
- Diet (e.g. ad libitum): NIH-07 pellets ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 10-11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24
- Air changes (per hr): 13.5
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: drinking water

Vehicle:

water

Details on mating procedure:

- M/F ratio per cage: 1/1
- Length of cohabitation: until detection of signs of mating, but for max. 8 days
- Proof of pregnancy: sperm in vaginal smear
- No replacement of male after unsuccessful pairing (no explanation)
- After successful mating each pregnant female was caged (how): no data

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Dosage analyses were conducted on all dose levels, once at the beginning and midway through the testing period. Detected dose levels were within 1-6% of expected dosage.

Duration of treatment / exposure:

Males: 60 days, Females: 30 days prior to mating

Frequency of treatment:

continuous

Details on study schedule:

- Males were treated for 60 days, females for 30 days with test substance in drinking water prior to mating
- 1 male was mated with 1 female
- animals were checked daily for signs of co-habitation and separated if positive, at the latest however 8 days after begin of the mating period
- live pups were counted and examined on day of birth and 5 days after
- females were sacrificed at days 96 and 97 and reproductive organs were examined

Remarks:

Doses / Concentrations:
1000, 2000, 4000 ppm
Basis:
nominal in water

No. of animals per sex per dose:

20

Control animals:

yes, concurrent vehicle

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Females were weighed on the day of mating and on the day of parturition

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

Oestrous cyclicity (parental animals):

not determined

Sperm parameters (parental animals):

Parameters examined in male parental generation:
testis weight, epididymis weight, sperm count, sperm motility, sperm morphology

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical abnormalities

GROSS EXAMINATION OF DEAD PUPS:
yes, for external abnormalities

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: no data
- Maternal animals: All surviving were terminated at days 96 and 97.

GROSS NECROPSY
- Gross necropsy consisted of vagina, cervix, oviducts, and ovaries (females). Implantation sites in uteri were counted.

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS): In the highest dose group (4000 ppm), one dam had to be sacrificed in a moribound state 21 days after impregnation. Necropsy revealed seven fetuses and one resorption site. No other mortalities were reported.

REPRODUCTIVE FUNCTION (PARANTAL ANIMALS):
- No differences in sperm count, motility or morphology were found.
- No effects on testis or epididymal weight.
- Vaginal cytology was negative for abnormalities.

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS): Pregnancy rates ranged between 40% in controls to 65% in the highest treatment group.

Dose descriptor:

NOAEL

Effect level:

2 000 ppm (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Animals did not show increased mortality, fertility rates, live pup numbers and weights were comparable to controls. No effects on sperm count, motility, and morphology, testis or epididymal weight.

The average litter sizes on D0 and D5 as well as the number of implants per pregnant dam were marginally reduced in the highest dose group (4000 ppm) compared to controls, however these changes were not statistically significant. The live pup weight on day of birth (D0) was significantly lower than that of controls, however at D5 no significant differences in pup weights could be found.

No external abnormalities were observed.

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

2 000 ppm (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Pup numbers, birth weight, and weight gain after birth were normal, no external abnormalities were detected.

Reproductive effects observed:

not specified

Reproductive toxicity:

	0 ppm	4000 ppm
Pregnancy rate	40%	65%
Average litter size D0	9.0± 1.37	7.2± 0.52
Average litter size D5	9.3± 1.16	7.1± 0.56
Implants / pregnant dam	9.6± 1.10	7.7± 0.52
Live pup weight D0	5.7± 0.09	5.2± 0.06*
Live pup weight D5	10.55± 0.26	9.93± 0.20

*p≤0.01

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2 000

Study duration:

subchronic

Species:

rat

Quality of whole database:

BaO rapidly hydrolyzes to Ba(OH)2, a strongly alkaline substance, upon contact with water. Barium chloride dihydrate as well soluble barium salt was used to assess the potential of BaO to cause barium toxicity.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

BaO rapidly hydrolyzes to Ba(OH)₂, a strongly alkaline substance, upon contact with water. Barium chloride dihydrate as well soluble barium salt was used to assess the potential of BaO to cause barium toxicity. Barium chlorid dihydrate and barium oxide share the barium ion as cation which may be the toxophore of the registered compound barium oxide. For details on comparability of the two compunds, please refer to the weight-of-evidence justification.

Available data on the reproduction toxicity of soluble barium is derived from one publication (Dietz et al.), which tested both rats and mice. Female and male animals were exposed to barium chloride dihydrate in the drinking water (high dose was 4000 ppm for rats and 2000 ppm for mice). Males that were treated for 60 days were then mated with females that had been exposed for 30 days prior to co-housing. It is unclear from the data and description whether the animals were further exposed during mating period and pregnancy. The authors did not find any changes in pregnancy rate between treated and control rats and mice. Further, sperm count, motility, and morphology as well as examination of female reproductive organs were normal. Treated dams produced slightly less pups in the high dose group, which also showed marginally reduced birth weights. However, both findings were not statistically significant. Therefore, the NOAEL for both parental (P) and F1 toxicity was set at 2000 ppm.

Short description of key information:
repeated dose study on fertility (Dietz, 1992): NOAEL (rat) = 2000 ppm, NOAEL (mouse) = 2000 ppm

Justification for selection of Effect on fertility via oral route:
The study does fulfill basic scientific principles. Reproductive toxicity was tested in both rats and mice. Documentation is incomplete and the lack of drinking water consumption data does not allow for determination of actual compound consumption.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Since there were no indications for reproductive toxicity in the studies addressing reproduction toxicity or in the repeated-dose exposure (both in mice and rats), a non-classification for BaO is warranted according to Regulation (EC) 1272/2008 (CLP).